Non-Thermal Plasma Reduces HSV-1 Infection of and Replication in HaCaT Keratinocytes In Vitro.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG), with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. The antiviral effect of NTP was investigated using an in vitro model of HSV-1 epithelial infection that involved the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. It was found that NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggests the potential of NTP as a therapeutic agent effective against HSV-1 infection.

THE COMBINATION OF ORAL VALACYCLOVIR WITH TOPICAL CLOBETASOL THERAPY WAS THE MOST EFFECTIVE IN REDUCING THE TIME TO HEAL FROM HERPES LABIALIS.

ARTICLE TITLE AND BIBLIOGRAPHIC INFORMATION: Koe KH, Veettil SK, Maharajan MK, Syeed MS, Nair AB, Gopinath D. comparative efficacy of antiviral agents for prevention and management of herpes labialis: A systematic review and network meta-analysis. J Evid Based Dent Pract. 2023 Mar; 23(1):101778. doi: 10.1016/j.jebdp.2022.101778. Epub 2022 Sep 14. PMID: 36914303. SOURCE OF FUNDING: None. TYPE OF STUDY/DESIGN: Systematic review with meta-analysis.

Efficacy of photobiomodulation therapy in recurrent herpes labialis management: a randomized controlled trial.

OBJECTIVES: This study is aimed at assessing the therapeutic efficacy of photobiomodulation therapy (PBMT) for the management of recurrent herpes labialis (RHL) by evaluating both pain and clinical recovery. MATERIAL AND METHODS: A randomized, double-blind, controlled trial was conducted on 40 patients with RHL, and they were randomly divided into two groups, where 20 patients received treatment with PBMT (650 nm, 100 mW, 4.7 J/cm2), continuous mode, for 120 s, and placebo cream, while another 20 patients (control group) were treated with acyclovir cream 5% (5 times/5 days) and passive laser. Pain was assessed at five different times. The day when the complete disappearance of the pain was observed and the day when the crust fell off spontaneously were also recorded. RESULTS: The pain level in the control group was significantly higher than that in the PBMT group after the second application of the laser, while the differences were not significant between the two groups at other times. The pain in the PBMT group disappeared faster than that in the control group, but the difference was not significant in terms of clinical recovery. CONCLUSIONS: Photobiomodulation therapy of herpes labialis reduced pain significantly faster than acyclovir, but there was no difference in healing time between the groups in light of the parameters used in this study. CLINICAL RELEVANCE: PBMT is a promising treatment that may be an effective alternative to acyclovir in the management of recurrent herpes labialis. TRIAL REGISTRATION ISRCTN: com ID: ISRCTN87606522.

Quality-Adjusted Life Year Proxies for Caries in Primary Dentition: A Discrete Choice Experiment.

INTRODUCTION: Cost-utility analysis (CUA)-a method to evaluate intervention cost-effectiveness-transforms benefits of alternatives into a measure of quantity and quality of life, such as quality-adjusted life year (QALY), to enable comparison across heterogeneous programs. Measurement challenges prevent directly estimating utilities and calculating QALYs for caries in primary dentition. Proxy disease QALYs are often used as a substitute; however, there lacks quantitative evidence that these proxy diseases are comparable to caries. OBJECTIVE: To employ a discrete choice experiment (DCE) to quantitatively determine the most comparable proxy disease for different levels of caries in primary dentition. METHODS: A cross-sectional DCE survey was administered to respondents (N = 461) who resided in California, were aged ≥18 y, and were primary caretakers for ≥1 child aged 3 to 12 y. Four attributes were included: pain level, disease duration, treatment cost, and family life impacts. Mixed effects logistic regression and conditional logistic regression were used to analyze the survey data. RESULTS: Respondents from the overall sample preferred no pain over mild (odds ratio [OR] = 0.50, P < 0.05), moderate (OR = 0.57, P < 0.05), and severe pain (OR = 0.48, P < 0.05). Acute gastritis (OR = 0.44, P < 0.05), chronic gastritis (OR = 0.31, P < 0.01), and cold sore (OR = 0.38, P < 0.05) were less preferred than stage 1 caries. Acute tonsilitis (OR = 0.43, P < 0.05), acute gastritis (OR = 0.38, P < 0.05), chronic gastritis (OR = 0.26, P < 0.01), and cold sore (OR = 0.33, P < 0.01) were less preferred than stage 2 caries. Chronic gastritis (OR = 0.42,P < 0.05) was less preferred than stage 4 caries. CONCLUSIONS: Parents viewed the characteristics of many diseases with similar QALYs differently. Findings suggest that otitis media and its QALY-as commonly used in CUAs-may be a suitable proxy disease and substitute. However, other disease states with slightly different QALYs may be suitable. As such, the recommendation is to consider a range of proxy diseases and their QALYs when conducting a CUA for child caries interventions. KNOWLEDGE TRANSFER STATEMENT: This study reviews and systematically compares pediatric diseases that are comparable to caries in primary dentition. The findings may inform future research using cost-utility analysis to examine the incremental cost-effectiveness ratio of interventions to prevent and treat caries as compared with an alternative.

Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.

BACKGROUND AND PURPOSE: Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. METHODS: For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. RESULTS: In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. CONCLUSION: These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.

[What is known about the diagnosis and treatment of herpes labialis?] / Wat is er bekend over de diagnostiek en behandeling van herpes labialis?

Herpes labialis is one of the most common skin infections. In most people it is asymptomatic or mildly symptomatic, but very severe cases do occur. Herpes remains latent and can recur. Herpes labialis is a clinical diagnosis. If in doubt, additional testing can be carried out, usually polymerase chain reaction. There are no treatments that can eliminate the virus. In case of more severe symptoms and frequent recurrences, there may be an indication for treatment. In case of mild complaints, topical zinc sulphate/zinc oxide and analgesics (systemic or topical lidocaine) will suffice. More severe complaints and frequent recurrences can be treated with antiviral creams (Aciclovir) or with systemic antiviral medication (Valaciclovir). In frequent recurrences, prophylactic Valaciclovir can also be given for a period of many months. Treatment should be started as soon as possible and will slightly shorten the duration of the disease.

Vitamin D serum level in participants with positive history of recurrent herpes labialis.

AIM: Vitamin D plays an important role in immune system regulation, also its deficiency is assumed to affect the patients' predisposition to viral diseases such as recurrent herpes labialis. In this cross-sectional study, we tried to compare the mean serum level of vitamin D in participants with a positive history of recurrent herpes labial lesions and healthy controls. MATERIALS AND METHODS: The vitamin D serum level of 43 participants with a positive history of recurrent herpes labial lesions who were referred to the Motahhari laboratory in Shiraz during 2020-2022, was compared with 42 healthy controls. It was assessed by an Elisa kit. An Independent T-test was used to compare the vitamin D serum level between two genders. In order to assess the mean age value and gender distribution, an independent T-test and Pearson Chi-Square were used, respectively for the two groups. The serum vitamin D level was compared between both control and test groups. RESULTS: There was no significant difference between vitamin D mean serum levels in the two evaluated groups (p.value = 0.72). Although the age (p.value = 0.09) and recurrence (p.value = 0.13) of herpes labialis had no statistically significant relation to the vitamin D serum level, the healing duration of herpes labialis was inversely related (p.value = 0.01). Lower-level of serum vitamin D were accompanied by a longer healing duration of the lesions. CONCLUSION: Although the vitamin D serum level of participants with a history of recurrent herpes labialis had no relation with age and herpes virus recurrence frequency, a longer healing duration of lesions had been reported in patients with lower serum levels of vitamin D.

COMPARATIVE EFFICACY OF ANTIVIRAL AGENTS FOR PREVENTION AND MANAGEMENT OF HERPES LABIALIS: A SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS.

OBJECTIVE: To compare the relative efficacy and safety of antiviral agents used in the prevention and management of herpes labialis through a network meta-analysis of clinical trials. METHODS: A systematic search was performed in Ovid Medline PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus and Clinicaltrials.gov for randomized controlled trials (RCTs) reporting a comparison of antiviral agents in the management and prevention of herpes labialis in healthy/immunocompetent adults. The data extracted from the selected RCTs were assessed and a network meta-analysis (NMA) was performed. The interventions were ranked according to the surface under the cumulative ranking (SUCRA). RESULTS: A total of 52 articles were included for qualitative synthesis and for the quantitative part, 26 articles were analyzed for the primary treatment outcome and 7 studies were analyzed for the primary prevention outcome. The combination therapy of oral valacyclovir and topical clobetasol was the best ranked with a mean reduction in healing time of -3.50 (95% CI -5.22 to -1.78) followed by vidarabine monophosphate of -3.22 (95% CI -4.59 to -1.85). No significant inconsistencies, heterogeneity, and publication bias were reported for TTH outcome analysis. For primary prevention outcomes, only 7 RCTs fulfilled the inclusion criteria, and none of the interventions was shown to be superior to each other. The absence of adverse events was reported by 16 studies, whereas other studies reported mild side effects only. CONCLUSION: NMA highlighted that several agents were effective in the management of herpes labialis among which the combination of oral valacyclovir with topical clobetasol therapy was the most effective in reducing the time to heal. However, further studies are required to determine which intervention is the most effective in preventing the recurrence of herpes labialis.

A Comprehensive Overview of Epidemiology, Pathogenesis and the Management of Herpes Labialis.

Herpes labialis remains exceedingly prevalent and is one of the most common human viral infections throughout the world. Recurrent herpes labialis evolves from the initial viral infection by herpes simplex virus type 1 (HSV-1) which subsequently presents with or without symptoms. Reactivation of this virus is triggered by psychosocial factors such as stress, febrile environment, ultraviolet light susceptibility, or specific dietary inadequacy. This virus infection is also characterized by uninterrupted transitions between chronic-latent and acute-recurrent phases, allowing the virus to opportunistically avoid immunity and warrant the transmission to other vulnerable hosts simultaneously. This review comprehensively evaluates the current evidence on epidemiology, pathogenesis, transmission modes, clinical manifestations, and current management options of herpes labialis infections.

Neighborhood disadvantage and immune-related illnesses among residents living in the US Gulf States.

PURPOSE: Neighborhood disadvantage has been associated with increased risk for pneumonia and influenza-associated hospitalizations. Few studies, however, have investigated how neighborhood disadvantage may influence immune-related illnesses. The aim of this study was to examine the association between neighborhooddisadvantage and immune-related illnesses. METHODS: We used data from the Gulf Long-term Follow-up (GuLF) Study (n = 32,608). Our analytic sample included home visit participants (n = 11,193) who had complete information on exposure and covariates (n = 10,543). Neighborhood disadvantage was assessed using the 2013 Area Deprivation Index (ADI), which assigns a ranking of 1 to 100 for lowest to highest disadvantage. We linked ADI to participants' geocoded enrollment addresses at the census block group level. ADI was categorized into quartiles based on the national distribution with the first quartile as the referent. Immune-related illnesses self-reported at the home visit (May 2011-May 2013) included occurrence of shingles, pneumonia, cold sores, flu, and colds since the Deepwater Horizon oil spill (April 2010). Frequent colds and frequent flu were defined as ≥4 colds and ≥2 episodes of flu since the spill. An aggregated outcome, based on occurrence of any pneumonia, cold sores, flu, and ≥4 colds since the spill, was also examined. We assessed the association of each outcome with ADI using multivariable log-binomial regression adjusting for individual-level demographics, behavioral factors, kids at home, and season of interview completion. RESULTS: We found elevated prevalence ratios (PR) and 95% confidence intervals (CI) for pneumonia associated with ADI in the third (PR: 2.04, 95% CI: 1.04, 4.02) and fourth (PR: 2.00; 95% CI: 1.00, 3.98) quartiles. PRs for frequent colds were also elevated for increasing ADI quartiles, but with confidence intervals including the null value. CONCLUSIONS: The observed associations of frequent colds and pneumonia with increasing neighborhood disadvantage may warrant further research on this topic.

Associations between host genetic variants and Herpes Simplex Labialis in the TwinsUK cohort.

OBJECTIVE: Previous literature supports controversial results about the role of host genetic factors in the reactivation of Herpes Simplex Labialis (HSL). The objective of this study is to explore the association between different putative single nucleotide polymorphisms (SNPs) and self-reported HSL reactivation in the TwinsUK cohort. DESIGN: 1761 participant were recruited for this study from the TwinsUK register. Blood collection and HSL questionnaire were completed for a subset of 595 participants (age 61.9, dizygotic twins 62.8%). Blood was stored at -80 °C and DNA analysed from all samples. The potential associations between candidate SNPs and HSL were assessed using a set of 40 SNPs, including SNPs previously correlated with HSL disease and other SNPs previously associated with the oral microbiota. RESULTS: 235 participants reported to have experienced 'cold sores' at least once in their lives, and 160 reported reinfection episodes. No association was detected between rs243588, rs1047978, rs1062202 genotypes and both occurrence of cold sores (p = 0.172, p = 0.360, p = 0.742) and their recurrence (p = 0.160, p = 0.105,p = 0.746). Among other investigated SNPs, a nominal significant association was detected between Vitamin D Receptor (VDR) Fok I (rs2228570) and both history of HSL (p = .001) and its recurrence (p = .007). CONCLUSIONS: A single nucleotide polymorphism in the VDR gene may be correlated with cold sores and their recurrence.

A phase 3, randomized, double-blind, placebo-controlled study evaluating a single, patient-initiated dose of amenamevir for recurrent herpes labialis.

Amenamevir (ASP2151), a novel, non-nucleoside analog, antiviral drug, inhibits the enzyme activities of helicase and primase, which are essential for replication of herpes viral genomic DNA. In this phase 3, randomized, double-blind, placebo-controlled, multicenter study, the authors investigated the efficacy and safety of a single patient-initiated dose of amenamevir to treat recurrent herpes labialis. Adult immunocompetent patients with recurrent herpes labialis who had the experience and ability to recognize prodromal symptoms were randomly assigned to administer amenamevir 1200 mg or placebo as a patient-initiated therapy within 6 hours after onset of prodromal symptoms. The primary efficacy end point was time to healing of all herpes labialis lesions in the modified intention-to-treat population. Secondary efficacy end points were time to crusting of all herpes labialis lesions, time to resolution of pain accompanying herpes labialis, proportion of patients with aborted lesions, and time to resolution of subjective symptoms accompanying herpes labialis. The modified intention-to-treat population, which excluded patients with aborted lesions, comprised 298 patients who self-initiated amenamevir and 307 who took placebo. Amenamevir demonstrated superiority over placebo for the primary end point; the median time to all lesion healing was 5.1 days for amenamevir versus 5.5 days for placebo (hazard ratio, 1.24; 95% confidence interval, 1.06-1.46; p = 0.0085). Time to crusting of all lesions was significantly shorter with amenamevir versus placebo (p = 0.0065); there were no significant between-group differences in other secondary outcomes. Treatment-emergent adverse events in both groups were generally mild in severity; there were two moderate events that were judged unrelated to study treatment, and no severe or serious events. In summary, a single patient-initiated dose of amenamevir 1200 mg taken within 6 hours of prodromal symptom onset significantly shortened the time to all lesion healing of recurrent herpes labialis compared with placebo, with no clinically important safety concerns.

Photobiomodulation for Preventive Therapy of Recurrent Herpes Labialis: A 2-Year In Vivo Randomized Controlled Study.

Objective: The present study aimed to evaluate the effectiveness of the application of photobiomodulation therapy (PBMT) in the prevention of recurrent herpes labialis (RHL) through a randomized controlled clinical trial. Background data: RHL is a lifelong infection that effects patients' quality of life. In the literature PBMT has shown positive results preventing RHL, decreasing recurrences and severity of lesions. Despite the good results reported, there are still few controlled clinical studies published on the subject. Methods: For this study, 158 volunteers were recruited and were randomly divided into three study groups: Laser 1-1 J/point (L1J): n = 61, Laser 2-2 J/point (L2J): n = 50, and placebo-0 J/point: n = 47. The treatment consisted of a protocol of 15 sessions throughout 6 months and 2 years of follow-up posttreatment. Results: The results showed that L1J presented the most satisfactory results concerning the reduction of the number of lesions per year and less severity of recurrences in the long-term evaluation when compared with L2J. Both Laser Groups (L1J and L2J) were statistically more efficient than placebo in all aspects analyzed. All patients who received laser treatment (L1J and L2J) and presented recurrences had significant improvement in frequency and/or severity of lesions. No patient had side effects from treatment. Conclusions: PBMT can be effective in the reduction of the frequency of recurrences of RHL and in the severity of postirradiation lesions that may appear.

Is low-level laser therapy effective in the treatment of herpes labialis? Systematic review and meta-analysis.

The objective of this systematic review is to evaluate the effectiveness of low-level laser therapy in the treatment of herpes labialis. The searches were carried out independently by 2 researchers and the articles were selected through the electronic databases according to the inclusion and exclusion criteria previously established. Initially, 480 articles were found, of which 7 randomized clinical trials and 1 clinical trial were selected. In total, 928 patients were included. In the meta-analysis, the mean healing time for laser use was significant, showing a mean reduction of 1.37 [CI 95% = 0.92 to 1.82] days for tissue healing (p < 0.0001). In the meta-analysis to evaluate the time for crust formation, there was no significant difference between the groups and no significant reduction in the mean time for crust formation (p = 0.150). Only one of the selected studies had a low risk of bias. The use of low-level laser proved to be effective in the treatment of herpes labialis. However, due to the high risk of bias in the included studies, there is a need to carry out new standardized studies to prove the effectiveness of this therapy.

Uncommon cause of trigeminal neuritis and central nervous system involvement by herpes labialis: a case report.

BACKGROUND: Trigeminal neuropathy is characterized by numbness in the region innervated by the trigeminal nerves, with or without neuropathic weakness in the muscles of mastication. Trigeminal neuritis is a form of trigeminal neuropathy in which the lesion is caused by an inflammation. Herein, we report a patient with trigeminal neuritis due to central nervous system (CNS) involvement of herpes labialis (HL) infection, which was successfully treated with anti-viral and anti-inflammatory agents. CASE PRESENTATION: A young healthy female presented with numbness in the left hemiface for two weeks. She had a preceding typical HL infection on left facial lip one week before the sensory symptom onset. Brain magnetic resonance imaging revealed high signal intensities and asymmetrical thickening with enhancement along the cisternal segment of the left trigeminal nerve. Additionally, brain MR angiography showed multifocal stenoses in the M1 segment of the middle cerebral artery and the cavernous portion of the internal carotid artery. Cerebrospinal fluid (CSF) examination showed mild pleocytosis with normal protein level, glucose ratio, but CSF polymerase chain reaction assay for specific anti-viral antibodies including herpes simplex virus was negative, and CSF culture also did not identify a specific pathogen. The results of serologic testing including tumor markers and autoimmune markers were all unremarkable. A tentative diagnosis of trigeminal neuritis as a complication of HL involving the CNS was made considering the clinical, neuroradiological, and laboratory findings of the patient. Therefore, the patient was treated with intravenous methylprednisolone and acyclovir for 10 days. After the treatments, her sensory disturbance was markedly improved. Brain MRI at the 3-month follow-up also demonstrated improvement of previously identified high signal intensity lesions and multifocal intracerebral artery stenoses. CONCLUSION: HL is usually a self-limiting, benign disease without complications, but rarely presents as trigeminal neuritis due to CNS involvement. Therefore, meticulous evaluation may be necessary if trigeminal neuritis or CNS involving symptoms occur after HL.

Association of Photodynamic Therapy and Photobiomodulation As a Promising Treatment of Herpes Labialis: A Systematic Review.

Background: This systematic review aims to analyze the effectiveness of the association of photodynamic therapy (PDT) and photobiomodulation (PBM) in the treatment of recurrent herpes labialis and to analyze the very many variables of parameters applied, number of sessions, photosensitizer concentration, and the timing of the intervention to offer clinicians an indication of the most likely optimal techniques and parameters required to achieve clinical success. Methods: This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA Checklist and registered at the International Prospective Register of Systematic Reviews (PROSPERO). We searched and identified articles of the subsequent bibliographic databases: PubMed and Cochrane. Results: Since there are no clinical trials regarding the association of PDT and PBM in the treatment of herpes labialis, we only included case reports in our review. All studies used methylene blue solution as the photosensitizer and the laser (diode laser or low-power laser) with a wavelength of 660 nm as the light source. Power output, power density, number of irradiation points, number of PBM sessions, and irradiation duration varied between the included studies. Despite the diversity in parameters between studies, all case reports showed good results regarding relieving symptoms, accelerating healing, as well as reducing the incidence of recurrence without side effects. Conclusions: The association of PDT in the vesicular phase and PBM in the crust phase can be considered a promising solution for recurrent labial herpes. Despite the many successful cases reported, establishing an effective clinical protocol for the treatment of herpes labialis using PDT followed by PBM will only be possible through double-blind placebo studies that would elucidate the exact action of this treatment modality, the appropriate irradiation parameters for both therapies, optimal timing, and number of PBM sessions following PDT. This review has been registered at the International Prospective Register of Systematic Reviews (PROSPERO) under number CRD42021290757.

Low-dose Oral Thimerosal for the Treatment of Oral Herpes: Clinical Trial Results and Improved Outcome After Post-hoc Analysis.

BACKGROUND: Thimerosal (TML) is an organomercury antimicrobial. Low doses (1/250th of the amount in a typical vaccine dose) may promote an antiviral immune response. Low-dose TML (BTL-TML) was evaluated for safety and efficacy against herpes labialis in two FDA-approved, randomized, double blind, placebo-controlled clinical trials. METHODS: BTL-TML was evaluated in a Phase IIa trial for its ability to block progression to lesion in subjects with recurrent oral herpes caused by dental trauma. Subjects were administered BTL-TML or a saline control over a 7-day period. In a Phase IIb trial, BTL-TML was evaluated for its ability to block progression to lesion over a 7-day period in subjects with herpes lip infections induced by exposure to ultraviolet (UV) radiation. RESULTS: Progression to lesion post-dental procedure was prevented in 54.5% (12/22) TML subjects versus 22.2% (2/9) control subjects (p = 0.106). Progression to lesion post-UV irradiation was blocked in 47.8% (11/23) BTL-TML treatment subjects and 42.8% (6/14) control subjects. A post-hoc analysis yielded 52.2% (12/23) BTL-TML subjects with no progression to lesion versus 28.6% (6/21) control subjects with no progression (p = 0.099). There were no significant differences in adverse effects between treatment and control groups in either trial. CONCLUSIONS: Neither clinical trial showed a statistically significant effect of BTL-TML on progression to lesion. However, the post-hoc analysis suggested there is a 48-hour period following UV radiation exposure during which the anti-herpes activity of antivirals such as BTL-TML is reduced. Accordingly, BTL-TML may have promise in subsequent, properly designed and powered clinical trials.

Formulation of acyclovir (core)-dexpanthenol (sheath) nanofibrous patches for the treatment of herpes labialis.

Topically applied antiviral creams and patches are the commercially available options for the treatment of herpes labialis. The nanofibrous patches could be a new direction in the formulation. The project aimed to formulate core-shell type nanofibrous scaffolds loaded with dexpanthenol (shell) and acyclovir (core). To achieve the fast dissolution of the antiviral agent, hydroxypropyl-beta-cyclodextrin was used as a complexation agent. The further aim was to study the prepared electrospun scaffolds' morphological- and physicochemical properties and antiviral activity. The fibrous samples were prepared by electrospinning using polyvinylpyrrolidone (PVP) as a shell, hypromellose (HPMC), and poly(ethylene oxide)(PEO) composite or poly(vinyl alcohol) (PVA) as a core polymer. The morphology of the prepared sample was studied by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Raman spectroscopy. The SEM photos showed that fibrous structures were obtained. In the case of the PVA/PVP composition, the desired structure was obtained. While when HPMC-PEO was used as a core, the core-shell structure could not be observed. The Raman measurements revealed the mixed fibre structure of this sample. All of the fibrous samples released about 100% of acyclovir and also the dexpanthenol within 20 min. Coaxially electrospun fibres of different compositions were successfully prepared with various structural homogeneities, furthermore, a better antiviral activity could be achieved compared to the commercially available Zovirax cream.