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Scientific Reports Sep 2023The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid...
The success of many drugs in ophthalmic treatments is hindered by their physico-chemical properties and the limited precorneal retention time. Here, lyotropic liquid crystals are proposed as a new ophthalmic drug delivery system. Acyclovir was chosen as model drug for its solubility and its controlled release from cubic phase was achieved. We demonstrated the effortless application of lamellar phase on corneal surface and its ability to convert itself in cubic phase in situ. While the complex viscosity of lamellar phase was affected by temperature (5.1 ± 1.4 kPa·s at 25 °C and 0.12 ± 0.001 Pa·s at 35 °C, respectively), the cubic phase shown no changes in viscosity values and shear thinning behaviour at both temperatures and even in presence of the drug The degradation kinetic of drug-loaded cubic phase was slightly slower than the empty formulation, recording 27.92 ± 1.43% and 33.30 ± 3.11% of weight loss after 8 h. Ex vivo studies conducted on porcine eyeballs and isolated cornea confirmed the instantaneous transition to cubic phase, its ability to resist to gravity force, and forced dripping of simulated tear fluid. Histopathological investigation showed how treated cornea did not report changes in epithelial and stroma structures. In summary, lyotropic liquid crystals could represent an advantageous ophthalmic drug delivery system.
Topics: Animals; Swine; Liquid Crystals; Drug Delivery Systems; Solubility; Cornea; Acyclovir
PubMed: 37758768
DOI: 10.1038/s41598-023-42185-z -
International Journal of Molecular... Jul 2023Previous studies have found that -mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis...
Previous studies have found that -mediated herpes simplex virus-TK/ganciclovir (BF-TK/GCV) reduces the expression of VEGF and CD146, implying tumor metastasis inhibition. However, the mechanism by which BF-TK/GCV inhibits tumor metastasis is not fully studied. Here, we comprehensively identified and quantified protein expression profiling for the first time in gastric cancer (GC) cells MKN-45 upon BF-TK/GCV treatment using quantitative proteomics. A total of 159 and 72 differential expression proteins (DEPs) were significantly changed in the BF-TK/GCV/BF-TK and BF-TK/GCV/BF/GCV comparative analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis enriched some metastasis-related pathways such as gap junction and cell adhesion molecules pathways. Moreover, the transwell assay proved that BF-TK/GCV inhibited the invasion and migration of tumor cells. Furthermore, immunohistochemistry (IHC) demonstrated that BF-TK/GCV reduced the expression of HIF-1α, mTOR, NF-κB1-p105, VCAM1, MMP13, CXCL12, ATG16, and CEBPB, which were associated with tumor metastasis. In summary, BF-TK/GCV inhibited tumor metastasis, which deepened and expanded the understanding of the antitumor mechanism of BF-TK/GCV.
Topics: Mice; Animals; Ganciclovir; Simplexvirus; Bifidobacterium longum subspecies infantis; Genetic Therapy; Disease Models, Animal; Stomach Neoplasms; Thymidine Kinase; Antiviral Agents
PubMed: 37511481
DOI: 10.3390/ijms241411721 -
Bioinformation 2023The atomic resolution model of US9, UL20, and gH protein of HSV is known. Hence, the ligand protein interaction of the US9, UL20, and gH protein models were carried out...
The atomic resolution model of US9, UL20, and gH protein of HSV is known. Hence, the ligand protein interaction of the US9, UL20, and gH protein models were carried out with synthetic drugs like acyclovir, bexarotene, vinorelbine, foscarnet, famciclovir, cidofovir and two plant derived natural drug acacetin and anthraquinone. Based on structure and docking study, it is predicted that protein US20 and gH binds with particular anti-HSV drug i.e. acyclovir, cidofovir, acacetin and famciclovir, acacetin respectively, while interaction of different protein is different with drugs.
PubMed: 37928488
DOI: 10.6026/97320630019981 -
Indian Journal of Ophthalmology Aug 2023To demonstrate viral proteins/inflammatory cytokines in a patient with unilateral keratouveitis. Retrospective case report. A 70-year-old Asian-Indian male presented...
To demonstrate viral proteins/inflammatory cytokines in a patient with unilateral keratouveitis. Retrospective case report. A 70-year-old Asian-Indian male presented with acute onset of blurring of vision in the left eye (OS) of 2 days duration. He had was coronavirus disease 2019 (COVID-19)-positive 3 months earlier. He had undergone cataract surgery/retinal laser photocoagulation in both the eyes. The corrected distance visual acuity (CDVA) (Snellen) in the right eye (RE) (OD) and left eye (LE) (OS) was 20/20 and 20/80, respectively. OS showed decreased corneal sensation, Descemet's folds, mild stromal edema, and fine and pigmented keratic precipitates with anterior chamber 1+ flare and 1+ cells. Fundus evaluation showed scattered laser marks in the OD and temporal sectoral laser marks in OS. He was diagnosed with viral keratouveitis in OS. Tear samples were collected on Schirmer's strips and tear wash for mass spectrometry and cytokines, which had 368 and 451 viral proteins in the RE and LE, respectively, using nano liquid chromatography-mass spectrometry, which were more than controls. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and varicella zoster virus proteins were detected. Cytokine analysis using flow cytometer analysis showed higher inflammation in OS as compared to OD. The patient was treated with oral acyclovir and topical steroids and resulted in resolution of his keratouveitis. SARS-CoV-2 proteins were present in the tear sample 3 months after COVID-19. The presence of viral proteins does not indicate causality.
Topics: Humans; Male; Aged; Retrospective Studies; COVID-19; SARS-CoV-2; Keratitis; Uveitis; Viral Proteins
PubMed: 37530289
DOI: 10.4103/IJO.IJO_593_23 -
The Journal of Dermatological Treatment Dec 2024Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVE
Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.
METHODS
Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.
RESULTS
The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy ( = .0002) and incidence of postherpetic neuralgia ( = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups ( = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ ( > .05).
CONCLUSIONS
Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.
Topics: Humans; Herpes Zoster; Neuralgia, Postherpetic; Antiviral Agents; Randomized Controlled Trials as Topic; Treatment Outcome; Incidence; Bromodeoxyuridine
PubMed: 38811010
DOI: 10.1080/09546634.2024.2355256 -
Viruses Aug 2023The thymidine kinase (TK) and DNA polymerase (pol) genes of the herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are two important genes involved in antiviral...
The thymidine kinase (TK) and DNA polymerase (pol) genes of the herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) are two important genes involved in antiviral resistance. We investigated the genetic polymorphisms of the HSV-TK and pol genes in clinical isolates from Korean HSV-infected patients using next-generation sequencing (NGS) for the first time in Korea. A total of 81 HSV-1 and 47 HSV-2 isolates were examined. NGS was used to amplify and sequence the TK and pol genes. Among the 81 HSV-1 isolates, 12 and 17 natural polymorphisms and 9 and 23 polymorphisms of unknown significance in TK and pol were found, respectively. Two HSV-1 isolates (2.5%) exhibited the E257K amino acid substitution in TK, associated with antiviral resistance. Out of 47 HSV-2 isolates, 8 natural polymorphisms were identified in TK, and 9 in pol, with 13 polymorphisms of unknown significance in TK and 10 in pol. No known resistance-related mutations were observed in HSV-2. These findings contribute to our understanding of the genetic variants associated with antiviral resistance in HSV-1 and HSV-2 in Korea, with frequencies of known antiviral resistance-related mutations of 2.5% and 0% in HSV-1 and HSV-2, respectively.
Topics: Humans; Acyclovir; Antiviral Agents; DNA-Directed DNA Polymerase; Herpesvirus 1, Human; Herpesvirus 2, Human; Mutation; Republic of Korea; Thymidine Kinase; Drug Resistance, Viral
PubMed: 37632051
DOI: 10.3390/v15081709 -
Brazilian Journal of Microbiology :... Sep 2023Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as...
Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infect, respectively, 67% and 13% of the world population, most commonly causing mild symptoms, such as blisters/ulcers. However, severe conditions such as keratitis, encephalitis, and systemic infections may occur, generally associated with the patient's immunological condition. Although Acyclovir® (ACV) and its analogs are the reference drugs for herpetic infections, the number of ACV-resistant HSV infections is growing exponentially. Therefore, new natural products' bioactive compounds have been studied to develop novel effective anti-herpetics. Trichilia catigua is a plant widely used in traditional medicine, including the treatment of skin diseases and sexual infections. In our study, 16 extracts from the bark of T. catigua, obtained with different solvents and their combinations, were evaluated against HSV-1 AR and HSV-2, respectively, ACV resistance and genital strains in vitro. The extracts with the highest selectivity index were used to prepare new topical anti-herpetic formulations and confirmed in vivo. Two new topical formulations were suggested to treat cutaneous and genital herpetic recurrent lesions. The cytotoxicity and antiviral activity were tested using the MTT method. The cytotoxic (CC) and inhibitory (IC) concentrations of 50% and the selectivity index (SI: CC/IC) were determined. Tc12, Tc13, and Tc16 were added to the formulations. Infected BALB/c mice were treated for 8 days, and the severity of the herpetic lesions was analyzed daily. All CEs showed a CC value ranging from 143 to 400 µg/mL, except for Tc3 and Tc10. Tc12, Tc13, and Tc16 showed the best SI in the 0 h, virucidal, and adsorption inhibition assays. In the in vivo test against HSV-1 AR, the infected animals treated with creams were statistically different from the infected non-treated animals and similar to ACV-treated mice. In HSV-2-infected genitalia, similar effects were found for Tc13 and Tc16 gels. The present study demonstrated that extracts from the bark of T. catigua, traditionally used in folk medicine, are a valuable source of active compounds with anti-herpetic activity. The extracts showed a virucidal mechanism of action and prevented the initial stages of viral replication. The cutaneous and genital infections were strongly inhibited by the Tc12, Tc13, and Tc16 extracts. New topical therapeutic alternatives using Trichilia catigua extracts are suggested for patients infected with ACV-resistant strains of HSV.
Topics: Mice; Animals; Acyclovir; Reinfection; Antiviral Agents; Herpes Simplex; Herpesvirus 1, Human; Herpesvirus 2, Human; Meliaceae; Genitalia
PubMed: 37338788
DOI: 10.1007/s42770-023-01027-w -
Skin Health and Disease Oct 2023Some studies emphasise the relationship between the herpes simplex virus (HSV) and pemphigus. Although the possible role of HSV in the pathogenesis of pemphigus and the...
BACKGROUND
Some studies emphasise the relationship between the herpes simplex virus (HSV) and pemphigus. Although the possible role of HSV in the pathogenesis of pemphigus and the severity of the disease is obscure, we aimed to evaluate the presence of herpes simplex viruses (HSV 1/2) in the oral lesions of patients with pemphigus vulgaris and also assess its association with disease severity and types of lesions.
METHODS
A retrospective study was conducted on collected data in the form of collecting paraffin blocks, slides, and relevant pathology reports and referring to patients' medical records. A questionnaire containing details on the degree of skin, scalp, and mucosal involvement (Pemphigus Disease Area Index (PDAI)) was fulfiled. The immunoassay result was also collected to check the anti-desmoglein 3 and 1 antibodies (using ELISA technique).
RESULTS
In this study, 52 patients of pemphigus vulgaris with oral lesions (case) and 52 patients with oral lesions not related to the disease (control) were evaluated. HSV1 was detected in 13.5% of oral pemphigus lesions and 1.9% of the control group ( = 0.0598). There were no positive cases of HSV2 in either group. There was no significant association between the positivity of HSV1 and the site of lesions ( = 1.00) or disease severity ( = 0.28). However, we found a strong correlation between the PDAI disease severity score with the titre of the AntiDsg3 antibody ( = 0.487, = 0.001) and AntiDsg1 antibody ( = 0.309, = 0.026).
CONCLUSION
This study demonstrated a significant prevalence of HSV1 in oral pemphigus lesions, and acyclovir therapy may play a significant role in managing these patients. However, HSV's role in the of pemphigus vulgaris cannot be clearly determined.
PubMed: 37799351
DOI: 10.1002/ski2.261 -
RSC Advances Oct 2023, also known as the Indian Elm Tree, has been used in Ayurvedic medicine for its medicinal properties. In this study, two biologically active metabolites, 5(6)...
, also known as the Indian Elm Tree, has been used in Ayurvedic medicine for its medicinal properties. In this study, two biologically active metabolites, 5(6) dihydrostigmast 22en 3--β-glucoside (DHS) and 1--eicosanoyl glycerol-2'--β-galactouronic (EGG), were isolated for the first time from the -butanol fraction of using a chromatographic technique and identified by NMR, and HRESI-MS. The antiviral and multidrug-resistant activities of these metabolites were evaluated as well as the -butanol fraction. The -butanol fraction of exhibited weak antiviral effects, but DHS and EGG demonstrated significant antiviral activity against herpes simplex type-1 (HSV-1) and Coxsackie (CoxB4) viruses. Both metabolites showed lower IC values than the standard antiviral drug acyclovir, indicating their potency in inhibiting viral replication. EGG showed potent antiviral activity with minimal cytotoxicity at the highest concentration tested, presenting a selectivity index (SI) of 18.18 and 15.58 against HSV-1 and CoxB4 viruses, respectively. A preliminary assessment of the antibacterial activity of the -butanol fraction and metabolites revealed that DHS had the highest inhibitory potency against drug-resistant strains, including MRSA and Carbapenem-resistant . It also exhibited significant inhibitions against Fluconazole-resistant and ESBL - . DHS displayed the lowest minimum inhibitory concentration (MIC) values, indicating its superiority as an antibacterial agent compared to EGG and the -butanol fraction. Molecular docking analysis confirmed the antiviral and antibacterial actions of DHS and EGG by demonstrating their strong binding.
PubMed: 37928846
DOI: 10.1039/d3ra05978b -
American Journal of Ophthalmology Case... Dec 2023To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and...
PURPOSE
To present a case of irreversible corneal edema after 10 years of amantadine use. A literature review was carried out to describe the clinical characteristics and outcomes of amantadine-induced corneal edema.
OBSERVATIONS
A 36-year-old woman presented with a 6-week history of gradually progressive bilateral painless visual loss with visual acuity (VA) of 20/350 and 20/300 in the right and left eye, respectively. Examination showed bilateral diffuse central corneal edema with multiple Descemet membrane folds without endothelial guttata, keratic precipitates or intraocular inflammation. This did not respond to hypertonic saline drops and empirical treatment for presumed herpetic endotheliitis with oral acyclovir. Medication review revealed the use of amantadine 100mg daily for the past 10 years, prescribed by her neurologist for fatigue. Despite discontinuing amantadine, corneal edema was irreversible due to a markedly reduced endothelial cell count of 625 (right) and 680 cells/mm (left).
CONCLUSIONS AND IMPORTANCE
This case highlights the need to consider amantadine as a cause of unexplained bilateral non-guttae corneal edema. A literature review of 33 case reports revealed broadly similar features of amantadine-induced corneal edema; whilst most cases had favorable outcomes with median VA 20/25 (interquartile range IQR 20/20-20/30) and complete resolution of corneal edema within 30 days (IQR 14-35) of amantadine discontinuation, most experienced low endothelial cell density 759 cells/mm (IQR 621-1078). Taken together, screening specular microscopy ought to be considered for those in whom amantadine is likely required long-term.
PubMed: 37840541
DOI: 10.1016/j.ajoc.2023.101881