Immunotherapy of Recurrent Herpes Labialis With Squaric Acid.
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ABSTRACT:
SUBMITTER: Palli MA
PROVIDER: S-EPMC5817593 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Immunotherapy of Recurrent Herpes Labialis With Squaric Acid.
Palli Maria Alora MA McTavish Hugh H Kimball Alexa A Horn Thomas D TD
JAMA dermatology 20170801 8
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Project description:IntroductionDifferences in immune characteristics, including immune gene expression by peripheral blood mononuclear cells (PBMCs), correlating with herpes labialis and good or poor immune control of herpes simplex virus type 1 (HSV-1), and how these characteristics change after dosing with squaric acid dibutyl ester (SADBE), were investigated.MethodsPBMCs were collected from persons positive for IgG against HSV-1 and having frequent, infrequent, or no herpes labialis outbreaks. The PBMCs were tested for proliferation against HSV-1 and a fungal antigen (Candida) and immune gene expression in the presence of HSV-1 and Candida. On day 1 after blood collection the subjects with frequent outbreaks were dosed topically on the arm once with SADBE, and their PBMCs were collected and tested 8 weeks later.ResultsThose with good immune control of their HSV-1 infection (fewer outbreaks) differ from those with poorer immune control in these ways: (1) Greater PBMC proliferation in vitro to HSV-1, HSV-1-infected cell extracts, and Candida considered together (P < 0.01). (2) Higher expression of IFNG and five other immune-related genes (P < 0.05 for each) and lower expression of IL5 and two other immune-related genes (P < 0.05 for each) in PBMCs in vitro stimulated with HSV-1 virus. The subjects with frequent outbreaks were treated once with SADBE, and 56 days later the PBMCs of these subjects differed from PBMCs from the same subjects taken on day 1 before treatment in exactly the same ways listed above as differences between those with good and poor immune control of HSV-1, and at the same levels of significance.ConclusionsHigher IFNG and lower IL5 expression by PBMCs in the presence of HSV-1 correlate with fewer herpes labialis outbreaks, and a single topical dose of SADBE to the arm of subjects with frequent herpes labialis episodes improves immune response to HSV-1.
| S-EPMC6416766 | biostudies-literature
Project description:ObjectivesThis study aims to compare the therapeutic effects of acyclovir nanofiber and acyclovir-clobetasol nanofiber formulations with their non-nano formulations (cream formulation) on recurrent labial herpes.Materials and methodsEighty patients with labial herpes lesions were divided into four groups, each receiving one of the following treatments: acyclovir-clobetasol nano patch, acyclovir-clobetasol cream, acyclovir nano patch, or acyclovir cream. Pain levels and recovery times were assessed. The Wilcoxon test compared pain levels, while the log-rank test compared healing and scabbing times.ResultsAcyclovir-clobetasol nanofiber and cream, along with acyclovir nanofiber, significantly reduced symptoms compared to the acyclovir cream. The recovery and scabbing times were shorter in patients who received acyclovir-clobetasol formulations compared to those receiving acyclovir alone.ConclusionAcyclovir-clobetasol combinations accelerated recovery times compared to acyclovir alone. Additionally, nanofiber formulations demonstrated enhanced healing efficacy over cream formulations.Trial registrationThis trial was retrospectively registered by Iranian Registry of Clinical Trials (IRCT) at 14/11/2023.Trial registration numberIRCT20230926059521N1.
| S-EPMC11539845 | biostudies-literature
Project description:BackgroundRecurrences of herpes simplex virus (HSV) in the orofacial region (herpes labialis or cold sores) impact quality-of-life. We aimed to study whether the bacille Calmette-Guérin (BCG) vaccine can attenuate cold sore recurrences through off-target immunomodulatory effects.MethodsIn this nested randomised controlled trial within the multicentre, phase 3 BRACE trial, 6828 healthcare workers were randomised in 36 sites in Australia, the Netherlands, Spain, the United Kingdom and Brazil, to receive BCG-Denmark or no BCG (1:1 ratio using a web-based procedure) and followed for 12 months with 3-monthly questionnaires. Exclusion criteria included contraindication to BCG vaccine or previous vaccination with BCG within the past year, any other live-attenuated vaccine within the last month, or any COVID-specific vaccine. The intervention group received one intradermal dose of 0.1 mL of BCG-Denmark corresponding to 2-8 x 105 colony forming units of Mycobacterium bovis, Danish strain 1331. The primary outcome was the difference in restricted mean survival time (i.e., time to first cold-sore recurrence), in participants with frequent recurrent herpes labialis (≥4 recurrences/year), analysed by intention-to-treat. Secondary outcomes addressed additional questions, including analyses in other sub-populations. Adverse events were monitored closely during the first 3 months and were reported in all participants who received one dose of study drug according to intervention received. The BRACE trial is registered with ClinicalTrials.gov, NCT04327206.FindingsBetween March 30, 2020 and February 18, 2021, 84 individuals with frequent recurrent cold sores were randomly assigned to BCG (n = 38) or control (n = 46). The average time to first cold-sore recurrence was 1.55 months longer in the BCG group (95% CI 0.27-2.82, p = 0.02) than the control group (hazard ratio 0.54, 95% CI 0.32-0.91; intention-to-treat). The beneficial effect of BCG was greater in the as-treated population (difference 1.91 months, 95% CI 0.69-3.12, p = 0.003; hazard ratio 0.45, 95% CI 0.26-0.76). In prespecified subgroup analyses, only sex modified the treatment effect (interaction p = 0.007), with benefit restricted to males. Over 12 months, a greater proportion of participants in the BCG group compared with the control group reported a decrease in duration (61% vs 21%), severity (74% vs 21%), frequency (55% vs 21%), and impact on quality of life (42% vs 15%) of cold sore recurrences. In participants who had ever had a cold sore, there was also a decrease in self-reported burden of recurrences in the BCG group. In participants who had never had a cold sore, there was an increased risk of a first episode in the BCG group (risk difference 1.4%; 95% CI 0.3-2.6%, p = 0.02). There were no safety concerns.InterpretationBCG-Denmark vaccination had a beneficial effect on herpes labialis, particularly in males with frequent recurrences, but may increase the risk of a first cold sore.FundingBill & Melinda Gates Foundation, the Minderoo Foundation, Sarah and Lachlan Murdoch, the Royal Children's Hospital Foundation, Health Services Union NSW, the Peter Sowerby Foundation, SA Health, the Insurance Advisernet Foundation, the NAB Foundation, the Calvert-Jones Foundation, the Modara Pines Charitable Foundation, the UHG Foundation Pty Ltd, Epworth Healthcare, and individual donors.
| S-EPMC10500555 | biostudies-literature
Project description:Recurrent herpes labialis (RHL) is a common skin disease that is often caused by herpes simplex virus type I (HSV-1), but its immunology and pathogenesis remain unclear. The balance of Th17/Treg cells is crucial for maintaining immune homeostasis. This study aimed to investigate whether the balance of Th17/Treg cells and related cytokines may be a determinant occurrence in patients with RHL. This is a clinical experimental research based on clinical observation and analysis. We collected RHL patients from the outpatient clinic of the Department of Dermatology of Zhejiang Chinese Medical University (Hangzhou, China) in 2017, conducted questionnaire survey and signed informed consent. Peripheral blood was collected from 30 patients with RHL and 30 healthy volunteers. Flow cytometry was used to detect the percentages of Treg cells and Th17 cells. Protein microarrays coated with 20 cytokines related to T-cell subsets were performed. Enzyme-linked immunosorbent assay (ELISA) assay was conducted to further verify the expression levels of the cytokines that were screened by protein microarrays. Percentages of Th17/Treg cells in peripheral blood of RHL patients were significantly increased compared to those in healthy volunteers. The fold changes of GM-CSF, IL-4, TGF-β, IL-12, IL-10, IL-17F, and TNF-α were significantly increased compared with healthy volunteers. In addition, the expression of IL-4, IL-10, and TGF-β in the serum of RHL patients increased significantly. Our results indicated an imbalance of Th17/Treg cells in RHL, and this imbalance is probably an important factor in the occurrence, development, and recovery of RHL.
| S-EPMC7401041 | biostudies-literature
Project description: Not available
| S-EPMC6461191 | biostudies-literature
Project description:PurposeThese studies describe the testing of a novel, daily-use lip cream designed for individuals with lips prone to recurrent herpes labialis (RHL) that protects against environmental triggers.Subjects and methodsIn vitro occlusive and in vitro and in vivo photoprotection analyses, a characterization of normal vs dry lips, and a randomized, evaluator-blinded, clinical trial that assessed the lip cream in healthy subjects with dry lips were conducted. In the clinical trial, subjects applied the lip cream or were untreated and evaluated using transepidermal water loss (TEWL), corneometry, visual assessments of lip dryness, expert photographic evaluations, and subject-rated outcomes.ResultsThe lip cream's in vitro water vapor transmission rate (84.1 g/(m2 h)) indicated moderate occlusivity. The lip cream, but not placebo or control (water), reduced ultraviolet A (UVA)- and UVB-induced DNA damage, and tumor necrosis factor-α (EpiDermFT) and pros-taglandin E2 release (EpiDermFT and EpiGingival™). The lip cream's in vivo sun protection factor (SPF) was 12.2 (lower confidence limit, 11.3) and SPF/UVA protection factor ratio was 0.9. The characterization of dry vs normal lips identified differences in moisturization. In the clinical trial, the lip cream significantly decreased TEWL (difference: -7.19 [95% CI: -11.41, -2.98]; P<0.01), increased corneometry (difference: 4.62 [95% CI: 1.05, 8.19]; P<0.05), and reduced visual dryness (difference: -1.48 [95% CI: 2.24, -0.71]; P<0.001) compared to untreated subjects. Significant benefits were also observed on expert photographic assessments of scaling (difference: -0.89 [95% CI: -1.75, -0.03]; P< 0.05), cupping (difference: -1.50 [95% CI: -2.30, -0.70]; P<0.001), and healthy appearance (difference: -1.44 [95% CI: -2.29, -0.58]; P<0.01); differences in overall healthy appearance were not significant (P=0.51). Subject-rated assessments indicated improvements in cracking, dryness, and flaking in the lip cream group but worsening in untreated subjects.ConclusionThese studies indicate that this novel, daily-use lip cream protects against UV radiation, drying, and chapping, which are established environmental RHL triggers.
| S-EPMC6432897 | biostudies-literature
Project description:BackgroundThe incidence of recurrent herpes zoster (HZ) and the relationship between initial and recurrent HZ are not clear.MethodsThe Miyazaki Dermatologist Society has surveyed ~5000 patients with HZ annually since 1997. A questionnaire regarding HZ and its recurrence was completed by the dermatologists.ResultsA total of 34 877 patients with HZ were registered at 43 clinics between June 2009 and November 2015. Among 16 784 patients seen at 10 of the 43 clinics, 1076 patients (6.41%) experienced recurrence. Herpes zoster was more frequent in female than in male patients (5.27 vs 4.25 in 1000 person-years, P < .001), as was HZ recurrence (7.63% vs 4.73%, P < .001). Two and three recurrences were observed in 49 and 3 patients, respectively. Recurrence in the same dermatome was observed in 16.3% of patients, and more frequently this occurred in the left side (P = .027). The number of HZ-experienced persons increased with age, and one third of the population had experienced HZ by the age of 80.ConclusionsRecurrent HZ was observed in 6.41% of patients, with a higher incidence in women. Moreover, HZ experience reduced the HZ incidence to 31.7% of the incidence in the HZ-naive population.
| S-EPMC5414100 | biostudies-literature
Project description:[structure: see text] A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 microM. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 microM.
| S-EPMC2527039 | biostudies-literature
Project description:Our group has recently described a gene on human chromosome 21, the Cold Sore Susceptibility Gene-1 (CSSG-1, also known as C21orf91), which may confer susceptibility to frequent cold sores in humans. We present here a genotype-phenotype analysis of CSSG-1 in a new, unrelated human population. Seven hundred fifty-eight human subjects were enrolled in a case/control Cold Sore Study. CSSG-1 genotyping, herpes simplex virus 1 (HSV1) serotyping, demographic and phenotypic data was available from 622 analyzed subjects. Six major alleles (H1-H6) were tested for associations with each of the self-reported phenotypes. The statistical analysis was adjusted for age, sex and ethnicity. Genotype-phenotype associations were analyzed from 388 HSV1-seropositive subjects. There were significant CSSG-1 haplotype effects on annual cold sore outbreaks (P=0.006), lifetime cold sores (P=0.012) and perceived cold sore severity (P=0.012). There were relatively consistent trends toward protection from frequent and severe cold sores among those with the H3 or H5/6 haplotypes, whereas those with H1, H2, and H4 haplotypes tended to have more frequent and more severe episodes. Different alleles of the newly described gene CSSG-1 affect the expression of cold sore phenotypes in this new, unrelated human population, confirming the findings of the previous family-based study.
| S-EPMC4785534 | biostudies-literature
Project description:ObjectiveTo compare New Zealand medical grade kanuka honey with topical aciclovir for the treatment of herpes simplex labialis.DesignProspective parallel randomised controlled open-label superiority trial.Setting76 community pharmacies across New Zealand between 10 September 2015 and 13 December 2017.Participants952 adults randomised within the first 72 hours of a herpes simplex labialis episode.InterventionsRandom assignment 1:1 to either 5% aciclovir cream or medical grade kanuka honey (90%)/glycerine (10%) cream, both applied five times daily.Outcome measuresThe primary outcome was time from randomisation to return to normal skin (stage 7). Secondary outcomes included time from randomisation to stage 4 (open wound), time from stage 4 to 7, maximal pain, time to pain resolution and treatment acceptability.ResultsPrimary outcome variable: Kaplan-Meier-based estimates (95% CI) for the median time in days for return to normal skin were 8 (8 to 9) days for aciclovir and 9 (8 to 9) for honey; HR (95% CI) 1.06 (0.92 to 1.22), p=0.56. There were no statistically significant differences between treatments for all secondary outcome variables. No related serious adverse events were reported.ConclusionThere was no evidence of a difference in efficacy between topical medical grade kanuka honey and 5% aciclovir in the pharmacy-based treatment of herpes simplex labialis.Trial registration numberACTRN12615000648527;Post-results.
| S-EPMC6530412 | biostudies-literature