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International Journal of Molecular... Mar 2024Kaposi's sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its...
Kaposi's sarcoma-associated herpesvirus (KSHV) can cause a variety of malignancies. Ganciclovir (GCV) is one of the most efficient drugs against KSHV, but its non-specificity can cause other side effects in patients. Nucleic acid miR-34a-5p can inhibit the transcription of KSHV RNA and has great potential in anti-KSHV therapy, but there are still problems such as easy degradation and low delivery efficiency. Here, we constructed a co-loaded dual-drug nanocomplex (GCV@ZIF-8/PEI-FA+miR-34a-5p) that contains internally and adsorbs miR-34a-5p externally. The folic acid (FA)-coupled polyethyleneimine (PEI) coating layer (PEI-FA) was shown to increase the cellular uptake of the nanocomplex, which is conducive to the enrichment of drugs at the KSHV infection site. and miR-34a-5p are released at the site of the KSHV infection through the acid hydrolysis characteristics of ZIF-8 and the "proton sponge effect" of PEI. The co-loaded dual-drug nanocomplex not only inhibits the proliferation and migration of KSHV-positive cells but also decreases the mRNA expression level of KSHV lytic and latent genes. In conclusion, this co-loaded dual-drug nanocomplex may provide an attractive strategy for antiviral drug delivery and anti-KSHV therapy.
Topics: Humans; Herpesvirus 8, Human; Ganciclovir; MicroRNAs; Sarcoma, Kaposi
PubMed: 38474177
DOI: 10.3390/ijms25052932 -
International Journal of Molecular... Feb 2024Acyclovir and ganciclovir comprise the prophylaxis and treatment of herpesvirus and cytomegalovirus infections occurring in immunocompromised patients. Their therapeutic...
Acyclovir and ganciclovir comprise the prophylaxis and treatment of herpesvirus and cytomegalovirus infections occurring in immunocompromised patients. Their therapeutic drug monitoring is fundamental because of interindividual variability leading to side effects and drug resistance and is performed through several techniques, such as liquid chromatography coupled with UV spectrophotometry (HPLC-UV) or mass spectrometry (LC-MS/MS). Therefore, we developed and validated a low-cost, non-time-consuming, and low-sample-consuming HPLC-UV method. Briefly, 100 µL of sample was used for sample preparation, mainly consisting of precipitation through organic solvent. In total, 20 µL was injected into the instrument. Chromatographic separation was obtained eluting mobile phases A (10 mM ammonium formiate 0.01% formic acid) and B (acetonitrile) on a Poroshell 120 SB-C8 2.1 × 150 mm, 2.7 µm for 12 min isocratically (97:3; A:B) at a flow rate of 0.2 mL/min. The linearity range (0.5-40 mg/L) of the method allowed us to quantify both the Cmin and Cmax of acyclovir and ganciclovir. Plasma concentrations measured on a small cohort of patients undergoing acyclovir (31) and ganciclovir (9) treatment by the proposed method and the LC-MS/MS methods, already in use, were significantly correlated. The proposed HPLC-UV method may be implemented in diagnostics as an alternative method in case of the unavailability of the LC-MS/MS system.
Topics: Humans; Child; Acyclovir; Ganciclovir; Chromatography, High Pressure Liquid; Chromatography, Liquid; Tandem Mass Spectrometry; Sensitivity and Specificity; Reproducibility of Results
PubMed: 38473930
DOI: 10.3390/ijms25052685 -
Medicine Mar 2024In rare occasions, coxsackievirus infections can cause serious illness, such as encephalitis and myocarditis. The immunotherapies of cancer could increase the risk of... (Review)
Review
INTRODUCTION
In rare occasions, coxsackievirus infections can cause serious illness, such as encephalitis and myocarditis. The immunotherapies of cancer could increase the risk of myocarditis, especially when applying immune checkpoint inhibitors. Herein, we report a rare case of Coxsackie B virus-induced myocarditis in a patient with a history of lymphoma.
CASE PRESENTATION
A 32-year-old woman was admitted to the hospital with recurrent fever for more than 20 days, and she had a history of lymphoma. Before admission, the positron emission tomography/computed tomography result indicated that the patient had no tumor progression, and she was not considered the cancer-related fever upon arriving at our hospital. Patient's red blood cell, platelet count, and blood pressure were decreased. In addition, she had sinus bradycardia and 3 branch blocks, which was consistent with acute high lateral and anterior wall myocardial infarction. During hospitalization, the patient had recurrent arrhythmia, repeated sweating, poor mentation, dyspnea, and Coxsackie B virus were detected in patient's blood samples by pathogen-targeted next-generation sequencing. The creatine kinase, creatine kinase MB, and N-terminal pro-brain natriuretic peptide were persistently elevated. Consequently, the patient was diagnosed with viral myocarditis induced by Coxsackie B virus, and treated with acyclovir, gamma globulin combined with methylprednisolone shock therapy, trimetazidine, levosimendan, sildenan, continuous pump pressors with m-hydroxylamine, entecavir, adefovir, glutathione, pantoprazole, and low-molecular-weight heparin. Her symptoms worsened and died.
CONCLUSION
We reported a case with a history of lymphoma presented with fever, myocardial injury, who was ultimately diagnosed with Coxsackie B virus-induced myocarditis. Moreover, pathogen-targeted next-generation sequencing indeed exhibited higher sensitivity compared to mNGS in detecting Coxsackie B virus.
Topics: Humans; Female; Adult; Myocarditis; Enterovirus B, Human; Coxsackievirus Infections; Virus Diseases; Fever; Lymphoma
PubMed: 38457543
DOI: 10.1097/MD.0000000000037248 -
Cureus Mar 2024Herpetic uveitis is an easy diagnosis to miss, which can lead to devastating consequences. The aim of this report is to create awareness of how this disease can present,...
Herpetic uveitis is an easy diagnosis to miss, which can lead to devastating consequences. The aim of this report is to create awareness of how this disease can present, appropriate clues to the diagnosis, and how it should be managed. We report a case of a 70-year-old female who presented with redness and painless blurry vision in her right eye and was treated with topical corticosteroid drops for presumed idiopathic anterior uveitis. Despite initial symptomatic improvement, she reattended with a significant deterioration in vision and was found to have a large corneal infiltrate and associated perforation. The perforation was sealed with corneal gluing, and she was treated for presumed herpetic anterior uveitis with oral acyclovir. Corneal polymerase chain reaction (PCR) specimen was positive for herpes simplex virus DNA. The perforation started to leak again despite repeat corneal gluing, so an emergency therapeutic penetrating keratoplasty was performed. She has remained on prophylactic oral acyclovir for the last 24 months, with no recurrence and the graft remains clear.
PubMed: 38444929
DOI: 10.7759/cureus.55471 -
Open Forum Infectious Diseases Mar 2024Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are...
BACKGROUND
Acyclovir-resistant mucocutaneous herpes simplex virus (HSV) infection is an uncommon problem typically seen in immunocompromised hosts. Systemic treatment options are limited. The performance of foscarnet and its toxicities in this population are poorly characterized.
METHODS
This was a multicenter retrospective study of adults treated with foscarnet for HSV infection between January 2012 and December 2017. Relevant data were collected including demographics, baseline conditions, previous anti-HSV medications, concomitant medications, HSV outcomes, and adverse events. Acyclovir-resistant HSV infection was defined based on genotypic or phenotypic testing results; refractory infection was defined as infection not improving after 5 days of treatment-dosed antiviral therapy in those not tested for resistance.
RESULTS
Twenty-nine patients had 31 episodes of HSV (15/18 resistant; among episodes without resistance testing, 7/10 refractory; 3 not evaluable) treated with foscarnet. All patients were immunocompromised including 19 (66%) with hematologic malignancy and 9 (31%) with HIV. Median duration of foscarnet was 16 days (range, 6-85 days). Fifteen episodes (48%) healed by the end of or after foscarnet. Median time to healing among those with resolution was 38 days (range, 9-1088 days). At least 1 adverse event during therapy was reported in 26 (84%) treatment episodes including 23 (74%) that were considered drug related. Common adverse events were electrolyte disturbance (20 [65%]) and kidney dysfunction (13 [42%]). Foscarnet was discontinued in 10 episodes (32%) due to an adverse event, including 6 due to kidney dysfunction.
CONCLUSIONS
Among 31 episodes of HSV treated with foscarnet, only half resolved with treatment, and adverse events were common.
PubMed: 38444818
DOI: 10.1093/ofid/ofae046 -
Encephalitis (Seoul, Korea) Apr 2024Herpes simplex encephalitis (HSE) is a common viral encephalitis that can be fatal if not adequately treated. Fever, cerebrospinal fluid (CSF) pleocytosis, and typical...
Herpes simplex encephalitis (HSE) is a common viral encephalitis that can be fatal if not adequately treated. Fever, cerebrospinal fluid (CSF) pleocytosis, and typical neuroimaging findings are commonly observed in HSE cases. We encountered a patient with HSE who did not exhibit these classic clinical features. A 63-year-old male presented with his first-ever seizure. Fever did not develop until the fourth day of admission, and neither neuroimaging nor CSF analysis revealed abnormalities. Under suspicion of autoimmune encephalitis, methylprednisolone was administered. Subsequently, when the patient developed fever, a follow-up neuroimaging study was performed and revealed abnormalities consistent with HSE. The patient was promptly treated with acyclovir, which led to a full recovery. Diagnosing HSE in patients who present without fever or CSF pleocytosis and with typical neuroimaging findings poses a challenge. Therefore, prior to initiating immunosuppressive treatment, it is crucial to closely observe patients and to conduct follow-up tests, including neuroimaging and CSF analysis.
PubMed: 38442545
DOI: 10.47936/encephalitis.2023.00220 -
ACS Omega Feb 2024Acyclovir (ACV), a synthetic nucleoside derivative of purine, is one of the most potent antiviral medications recommended in the specific management of varicella-zoster...
Acyclovir (ACV), a synthetic nucleoside derivative of purine, is one of the most potent antiviral medications recommended in the specific management of varicella-zoster and herpes simplex viruses. The molecularly imprinted polymer (MIP) was utilized to create an effective and specific electrochemical sensor using a straightforward photopolymerization process to determine ACV. The polymeric thin coating was developed using the template molecule ACV, a functional monomer acrylamide, a basic monomer 2-hydroxyethyl methacrylate, a cross-linker ethylene glycol dimethacrylate, and a photoinitiator 2-hydroxy-2-methyl propiophenone on the exterior of the glassy carbon electrode (GCE). Scanning electron microscopy, attenuated total reflectance-Fourier transform infrared spectroscopy, electrochemical impedance spectroscopy, and cyclic voltammetry were employed for the purpose of characterizing the constructed sensor (AM-ACV@MIP/GCE). Differential pulse voltammetry and a 5 mM ferrocyanide/ferricyanide ([Fe(CN)]) redox reagent were used to detect the ACV binding to the specific cavities on MIP. The study involves density functional theory (DFT) calculations, which were conducted to investigate template-functional monomer interactions thoroughly, calculate template-functional monomer interaction energies, and determine the optimal template/functional monomer ratio. DFT calculations were performed using Becke's three-parameter hybrid functional with the Lee-Yang-Parr correlation functional (B3LYP) method and 6-31G(d,p) basis set. The sensor exhibits linear performance throughout the concentration region 1 × 10 to 1 × 10 M, and the limit of detection and limit of quantification were 7.15 × 10 M and 2.38 × 10 M, respectively. For the electrochemical study of ACV, the sensor demonstrated high accuracy, precision, robustness, and a short detection time. Furthermore, the developed electrochemical sensor exhibited exceptional recovery in tablet dosage form and commercial human blood samples, with recoveries of 99.40 and 100.44%, respectively. The findings showed that the AM-ACV@MIP/GCE sensor would effectively be used to directly assess pharmaceuticals from actual specimens and would particularly detect ACV compared to structurally similar pharmaceutical compounds.
PubMed: 38434833
DOI: 10.1021/acsomega.3c09399 -
Sultan Qaboos University Medical Journal Feb 2024Ramsay Hunt syndrome (RHS) is a triad of peri-auricular pain, ipsilateral facial nerve palsy and vesicular rash around the ear pinna. It is caused by reactivation of...
Ramsay Hunt syndrome (RHS) is a triad of peri-auricular pain, ipsilateral facial nerve palsy and vesicular rash around the ear pinna. It is caused by reactivation of varicella-zoster virus (VZV) that lies dormant in the geniculate ganglia. It can be complicated by VZV encephalitis rarely. We report the case of an 8-year-old previously healthy boy who presented to a tertiary care hospital in Muscat, Oman in 2021 with fever, progressive left ear pain, vesicular rash around his ear pinna and left-sided facial nerve palsy. His course was complicated by VZV encephalitis where he was managed with intravenous (IV) acyclovir and IV corticosteroids. He improved significantly and was asymptomatic with a normal neurology examination at the 6-months follow-up.
Topics: Male; Child; Humans; Herpes Zoster Oticus; Herpesvirus 3, Human; Encephalitis; Pain; Exanthema; Paralysis
PubMed: 38434459
DOI: 10.18295/squmj.3.2023.020 -
Scientific Reports Feb 2024Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin...
Jatropha variegata and Jatropha spinosa (family: Euphorbiaceae) are utilized in Yemeni traditional medicine to treat respiratory tract infection and in different skin conditions such as wound healing, as antibacterial and hemostatic. In this study, we evaluated the cytotoxicity and the antiviral activities of the methanolic J. variegata (leaves: Ext-1, stems: Ext-2, and roots: Ext-3), and J. spinosa extracts (aerial parts: Ext-4 and roots: Ext-5), in addition to their methylene chloride fractions of roots extracts (F-6 and F-7, respectively). All samples were tested against three human cancer cell lines in vitro (MCF-7, HepG2, and A549) and two viruses (HSV-2 and H1N1). Both plants showed significant cytotoxicity, among them, the methylene chloride fractions of roots of J. variegata (F-6) and J. spinosa roots (F-7) showed the highest activity on MCF-7 (IC = 1.4 and 1 μg/mL), HepG2 (IC = 0.64 and 0.24 μg/mL), and A549 (IC = 0.7 and 0.5 μg/mL), respectively, whereas the IC values of the standard doxorubicin were (3.83, 4.73, and 4.57 μg/mL) against MCF-7, HepG2, and A549, respectively. These results revealed that the roots of both plants are potential targets for cytotoxic activities. The in vitro results revealed potential antiviral activity for each of Ext-3, Ext-5, F-6, and F-7 against HVS-2 with IC of 101.23, 68.83, 4.88, 3.24 μg/mL and against H1N1 with IC of 51.29, 27.92, 4.24, and 3.06 μg/mL respectively, whereas the IC value of the standard acyclovir against HVS-2 was 83.19 μg/mL and IC value of the standard ribavirin against H1N1 was 52.40 μg/mL .The methanol extracts of the roots (Ext-3 and Ext-5) of both plants were characterized using UPLC/MS. A total of 73 metabolites were annotated, including fourteen diterpenoids, eleven flavonoids, ten phenolic acid conjugates, twelve fatty acids and their conjugates, five triterpenes and steroids, two sesquiterpenes, and six coumarins. The cytotoxicity and antiviral activities determined in the present work are explained by the existence of flavonoids, coumarins and diterpenes with commonly known cytotoxicity and antiviral activities.
Topics: Humans; Plant Extracts; Jatropha; Influenza A Virus, H1N1 Subtype; Methylene Chloride; Antineoplastic Agents; Flavonoids; Coumarins; Antiviral Agents
PubMed: 38418513
DOI: 10.1038/s41598-024-55196-1 -
The American Journal of Case Reports Feb 2024BACKGROUND Infectious keratitis after pterygium surgery is a rare but potentially devastating complication. The present study presents 5 cases of herpes simplex... (Review)
Review
BACKGROUND Infectious keratitis after pterygium surgery is a rare but potentially devastating complication. The present study presents 5 cases of herpes simplex keratitis (HSK) after pterygium surgery. CASE REPORT This study was conducted in our clinic in a 5-year period from February 2017 to September 2021. The 5 patients were men, aged between 42 and 73 years, with no prior history of herpes simplex virus (HSV) infections. Symptoms appeared near 1 month (median 30 days, range 10 to 70 days) after primary pterygium surgery. Diagnosis was based on clinical symptoms and laboratory test results, such as tear HSV-sIgA, corneal tissue polymerase chain reaction, and next-generation sequencing of metagenomics. The epithelial (1/5) and stromal (4/5) subtypes of HSK were identified. The patients received topical ganciclovir gel, immunosuppressive eyedrops, and oral acyclovir tablets, along with additional surgical interventions if necessary. Three were healed with conservative therapy, 1 eye required amniotic membrane transplantation due to corneal melt, and 1 was perforated and followed by corneal grafting. Finally, a literature review of previous publications on HSK after ocular surgeries was conducted. CONCLUSIONS HSK is a rare but serious complication that can arise after uneventful pterygium surgery. It is worthy of attention that both epithelial and stromal forms can occur. Timely diagnosis and treatment are crucial to prevent unfavorable outcomes. Consequently, routine corneal fluorescein staining, tear sIgA examination, and corneal scraping for polymerase chain reaction or next-generation sequencing of metagenomics should be performed in any suspected cases.
Topics: Male; Humans; Adult; Middle Aged; Aged; Female; Antiviral Agents; Pterygium; Keratitis, Herpetic; Acyclovir; Immunoglobulin A, Secretory
PubMed: 38400535
DOI: 10.12659/AJCR.942401