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1.
Nat Commun ; 13(1): 5481, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123328

RESUMO

Herpes simplex virus (HSV) naturally infects skin and mucosal surfaces, causing lifelong recurrent disease worldwide, with no cure or vaccine. Biomimetic human tissue and organ platforms provide attractive alternatives over animal models to recapitulate human diseases. Combining prevascularization and microfluidic approaches, we present a vascularized, three-dimensional skin-on-chip that mimics human skin architecture and is competent to immune-cell and drug perfusion. The endothelialized microvasculature embedded in a fibroblast-containing dermis responds to biological stimulation, while the cornified epidermis functions as a protective barrier. HSV infection of the skin-on-chip displays tissue-level key morphological and pathophysiological features typical of genital herpes infection in humans, including the production of proinflammatory cytokine IL-8, which triggers rapid neutrophil trans-endothelial extravasation and directional migration. Importantly, perfusion with the antiviral drug acyclovir inhibits HSV infection in a dose-dependent and time-sensitive manner. Thus, our vascularized skin-on-chip represents a promising platform for human HSV disease modeling and preclinical therapeutic evaluation.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Herpes Simples/tratamento farmacológico , Humanos , Interleucina-8
2.
Ital J Pediatr ; 48(1): 165, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068631

RESUMO

Intraosseous (IO) access offers a fast and reliable route for administration of fluids and drugs when intravenous (IV) accesses like umbilical, peripheral, or peripherally inserted central lines fail in critically ill neonates. Several medications can be successfully administered via the IO route, however only limited information is available regarding IO administration of antiviral agents.We present the case of a 2-week-old neonate, admitted to the Neonatal Intensive Care Unit (NICU) due to suspected meningitis, who received acyclovir through IO infusion after the venous access was lost and a new one could not be established. No complications were reported within 12 months of follow up.This report highlights the feasibility of IO acyclovir infusion when IV accesses fail in a critically ill neonate.


Assuntos
Estado Terminal , Infusões Intraósseas , Aciclovir , Humanos , Recém-Nascido , Tíbia
3.
Viruses ; 14(9)2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36146785

RESUMO

BACKGROUND: HSV-1, HSV-2 and VZV are alpha Herpesviruses, neurotropic viruses that are associated with various neurologic complications upon primary infection or reactivation. Cases of myelitis and radiculomyelitis are rare and appropriate etiologic diagnoses can be tricky. CASE PRESENTATION: Here we describe the case of a young immunocompetent woman who developed painful and extended vesicular genital lesions, with subsequent radiculomyelitis. HSV-1/-2 PCRs in the cerebrospinal fluid were misleadingly negative, whereas HHV-6 PCR was positive. Positive anti-HSV-2 IgM and IgG in serum was consistent with HSV-2 primary infection. On the other hand, the detection of HHV-6 DNA was explained by inherited chromosomally integrated HHV-6. The clinical course was favorable with high-dose IV acyclovir and corticosteroids. CONCLUSION: HSV-2-related radiculomyelitis is a rare clinical entity, which can be difficult to diagnose. In this case report, the causative virus was not detected in the patient's CSF, whereas HHV-6 DNA, non-pathogenic in this situation, was paradoxically positive. The diagnosis was based on the clinical features typical for HSV-2 primary infection, confirmed by the serology results. The delay between the genital lesions and the appearance of the radiculomyelitis, along with the absence of HSV-2 detection in the CSF, suggests a possible immuno-mediated physiopathological process. As for the HHV-6 DNA detection in the patient's CSF, it was explained by inherited chromosomally integrated HHV-6. This case illustrates how both negative and positive clinical virology results need careful interpretation according to the clinical findings.


Assuntos
Herpesviridae , Herpesvirus Humano 1 , Herpesvirus Humano 6 , Aciclovir , DNA Viral/análise , DNA Viral/genética , Feminino , Herpesviridae/genética , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Herpesvirus Humano 6/genética , Humanos , Imunoglobulina G , Imunoglobulina M
4.
Rev Med Chil ; 150(4): 559-563, 2022 Apr.
Artigo em Espanhol | MEDLINE | ID: mdl-36155766

RESUMO

Central nervous system infections are a medical emergency, due to their high fatality and sequelae. Timely treatment is essential, and should be initially indicated empirically by clinical guidance, without microbiological certainty. Hence the importance of cerebrospinal fluid (CSF) analysis as an etiological and therapeutic guide in the crucial initial hours of management. We report a 57-year-old woman consulting for fever and altered mental status. A brain CAT scan was normal. A lumbar puncture disclosed a CSF with predominance of neutrophils. Suspecting a bacterial meningitis, antimicrobial treatment was started but 48 hours after, the patient did not improve. A new lumbar puncture disclosed a CSF with predominance of lymphocytes. The lymphocyte shift prompted a PCR that was positive for herpes virus. The patient was treated with acyclovir with a good evolution.


Assuntos
Anti-Infecciosos , Encefalite por Herpes Simples , Aciclovir/uso terapêutico , Anti-Infecciosos/uso terapêutico , Antivirais/uso terapêutico , Encefalite por Herpes Simples/líquido cefalorraquidiano , Encefalite por Herpes Simples/tratamento farmacológico , Humanos , Linfócitos
5.
Front Public Health ; 10: 942377, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968424

RESUMO

Objective: The objective of this study was to assess the status and trends of antiviral treatment in outpatients with herpes zoster in China. Methods: Prescription data on antiviral drugs were extracted from the database of the Hospital Prescription Analysis Program of China according to the inclusion criteria. Yearly prescriptions and costs were calculated, and trends were analyzed. The trends were further stratified by age, sex, and specific drug use. The distribution of defined daily costs (DDCs) of valaciclovir and famciclovir were analyzed, and trends in the median DDCs were identified. Results: A total of 132,911 prescriptions from 49 hospitals located in six major areas of China were included in the analysis. The yearly prescriptions containing antivirals increased from 8,819 in 2010 to 16,361 in 2019. The percentage of prescriptions for patients aged 65 years and above also increased (27.7% in 2010 to 31.0% in 2019), and the number of prescriptions for females was higher than those for males (P < 0.001). The average cost of antivirals per prescription decreased; thus, the yearly cost showed no increasing trend. The main prescribed antivirals were valaciclovir and famciclovir, which progressively increased in prescriptions. The use of acyclovir decreased during the study period. Prescriptions containing topical formulations, acyclovir and penciclovir, both increased. The DDCs of valaciclovir and famciclovir decreased dramatically. Conclusion: The use of antivirals has increased over the decade, while the cost has not. Antiviral treatments adhere well to recent recommendations, except for the use of topical antivirals. The findings of this study may benefit the healthcare source allocation and management of herpes zoster in China.


Assuntos
Antivirais , Herpes Zoster , Aciclovir/efeitos adversos , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , China , Famciclovir/uso terapêutico , Feminino , Herpes Zoster/induzido quimicamente , Herpes Zoster/tratamento farmacológico , Herpes Zoster/epidemiologia , Humanos , Masculino , Pacientes Ambulatoriais , Valaciclovir/uso terapêutico
6.
Turk Neurosurg ; 32(5): 861-865, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35929032

RESUMO

Central and peripheral nervous system involvement of COVID-19 has been reported in 25% of cases. COVID-19 is associated with encephalitis and most often presenting with confusion and disorientation, and mortality decreases with early diagnosis and treatment.The patient who was admitted with confusion and fever and found COVID-19 PCR positivity in both cerebrospinal fluid (CSF) and the nasopharyngeal swab is presented here. A 71-year-old female patient who underwent transsphenoidal pituitary tumor surgery 4 months ago, was in an acute confusional state with fluctuations in consciousness and agitation. It was suggested that bilateral temporal areas of the brain and paramedian region of the pons compatible with encephalitis in the T2 and FLAIR axial sections of magnetic resonance imaging (MRI). Nasopharyngeal and CSF SARS-CoV-2 RNA PCR was studied since thorax CT was compatible with COVID-19 pneumonia and in both samples, PCR was found positive. Encephalitis for toxic and metabolic causes was excluded. In this case, COVID-19 encephalitis was treated with dual antiviral (favipiravir and acyclovir) and steroid therapy. The uniqueness of this case is not only the presence of a very few reported cases of both Nasopharyngeal and CSF SARS-CoV-2 RNA PCR positivity but also previous history of transsphenoidal pituitary surgery 4 months ago.


Assuntos
COVID-19 , Encefalite , Doenças da Hipófise , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Feminino , Humanos , RNA Viral , SARS-CoV-2 , Esteroides
7.
Biomater Adv ; 136: 212785, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35929318

RESUMO

Herpetic dermatitis and oral recurrent herpes (ORH) are among the most common human infections. Antiviral drugs such as acyclovir (ACV) are used in the standard treatment for ORH. Despite its therapeutic efficacy, ACV is continuously and repetitively administered in high doses. In this sense, the development of controlled release drug delivery systems such as core-shell fibers have a great potential in the treatment of ORH. In this work, poly(lactic acid)/poly(ethylene glycol) (PLA/PEG) fibers were produced by solution blow spinning (SBS) for the controlled release of ACV encapsulated in the core. PLA/PEG nanofibers containing four different blend ratios (100:0, 90:10, 80:20 and 70:30 wt%) without or with 10 wt% ACV were characterized by scanning electron microscopy (SEM), thermogravimetry (TG) and differential scanning calorimetry (DSC). The ACV release profile for 21 days was accessed by UV-Vis spectroscopy. Static water contact angles of the spun fiber mats were measured by the sessile drop method to evaluate fiber wettability upon contact with skin for transdermal release. Cytotoxicity and antiviral efficacy against Herpes simplex viruses (HSV-1) were evaluated using Vero cells. ACV addition did not impact on morphology, but slightly improved thermal stability of the fibers. Addition of hydrophilic PEG in PLA/PEG blends, however, increased drug release as confirmed by contact angle measurements and release profile. The in vitro tests showed the effectiveness of the drug delivery systems developed in reducing HSV-1 viral titer, which is related to the judicious combination of polymers used in the fibrous mats, in addition to not being cytotoxic to Vero cells. These results show the great potential of PLA/PEG solution blow-spun fibers in the controlled release of ACV to develop practical devices for the treatment of cold sores, while favoring the aesthetic appearance by covering them with a soft tissue patch (fibrous mats).


Assuntos
Nanofibras , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Chlorocebus aethiops , Preparações de Ação Retardada/farmacologia , Humanos , Nanofibras/química , Poliésteres/química , Polietilenoglicóis/farmacologia , Células Vero
8.
J Investig Med High Impact Case Rep ; 10: 23247096221117785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35968563

RESUMO

Adverse cutaneous reactions to medications are not uncommon and may resemble viral infection and vice versa, complicating diagnosis. We describe the case of a 79-year-old male with cholangiocarcinoma with liver and presumed lung metastasis who presented with abdominal pain and was admitted with ileitis with partial small bowel obstruction. He had a widespread papulovesicular rash with hemorrhagic center, mostly on his face, chest, and back. The rash was initially thought to be a drug eruption, but was eventually diagnosed via dermatopathological examination as disseminated varicella zoster virus (VZV) infection. Steroid treatment was discontinued, and airborne precautions were initiated. Polymerase chain reaction for VZV was obtained and intravenous acyclovir treatment was begun. This case of VZV, initially suspected to be an adverse drug reaction, highlights the importance of early identification of a highly infectious lesion and the importance of early infection control measures, given the implications of exposure to VZV for health care personnel.


Assuntos
Erupção por Droga , Exantema , Herpes Zoster , Aciclovir/efeitos adversos , Idoso , Erupção por Droga/complicações , Exantema/etiologia , Herpes Zoster/complicações , Herpes Zoster/diagnóstico , Herpesvirus Humano 3 , Humanos , Masculino
9.
Am J Ophthalmol ; 242: 215-220, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35809660

RESUMO

PURPOSE: To examine risk factors associated with cerebrovascular accident (CVA) following herpes zoster ophthalmicus (HZO). DESIGN: Retrospective cohort study. METHODS: Review of medical records of all patients with HZO seen at the department of Ophthalmology, Auckland District Health Board, New Zealand, between January 1, 2006, and December 31, 2016. The main outcome measure was cerebrovascular accident within 12 months of diagnosis. RESULTS: A total of 869 patients diagnosed with HZO were included in the study. The median age at onset of HZO was 65.5 years (interquartile range [IQR] 52.9-75.4), and 52.5% (n=456) were male. Antiviral therapy was started in 765 participants (88.0%), not used in 95 (10.9%), and not documented in 9 participants (1.0%). Four hundred sixty-eight participants (54.9%) received prompt oral antiviral therapy (≤72 hours of rash onset). A CVA occurred in the 12 months following HZO in 14 patients (1.6%) and was most common in older patients, occurring in 2.5% aged ≥65 years, 0.7% aged 40-65 years, and 0.9% aged <40 years. Hazard of CVA was highest immediately following HZO, with median time to CVA of 2.3 months (IQR 0.8-5.9 months). Patients who received prompt acyclovir had a 76.2% lower hazard of CVA (0.9% vs 2.6%, P = .022) on multivariate analysis. CONCLUSIONS: Cerebrovascular accident occurs in a low proportion of individuals within 1 year following HZO. Antiviral treatment for HZO may reduce the risk of subsequent CVA when given within 72 hours of rash onset.


Assuntos
Exantema , Herpes Zoster Oftálmico , Acidente Vascular Cerebral , Aciclovir/uso terapêutico , Idoso , Antivirais/uso terapêutico , Feminino , Herpes Zoster Oftálmico/complicações , Herpes Zoster Oftálmico/diagnóstico , Herpes Zoster Oftálmico/tratamento farmacológico , Humanos , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/etiologia
10.
BMC Complement Med Ther ; 22(1): 181, 2022 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-35804339

RESUMO

BACKGROUND: Anthocyanin-containing plant extracts and carotenoids, such as astaxanthin, have been well-known for their antiviral and anti-inflammatory activity, respectively. We hypothesised that a mixture of Ribes nigrum L. (Grossulariaceae) (common name black currant (BC)) and Vaccinium myrtillus L. (Ericaceae) (common name bilberry (BL)) extracts (BC/BL) with standardised anthocyanin content as well as single plant extracts interfered with the replication of Measles virus and Herpesviruses in vitro. METHODS: We treated cell cultures with BC/BL or defined single plant extracts, purified anthocyanins and astaxanthin in different concentrations and subsequently infected the cultures with the Measles virus (wild-type or vaccine strain Edmonston), Herpesvirus 1 or 8, or murine Cytomegalovirus. Then, we analysed the number of infected cells and viral infectivity and compared the data to non-treated controls. RESULTS: The BC/BL extract inhibited wild-type Measles virus replication, syncytia formation and cell-to-cell spread. This suppression was dependent on the wild-type virus-receptor-interaction since the Measles vaccine strain was unaffected by BC/BL treatment. Furthermore, the evidence was provided that the delphinidin-3-rutinoside chloride, a component of BC/BL, and purified astaxanthin, were effective anti-Measles virus compounds. Human Herpesvirus 1 and murine Cytomegalovirus replication was inhibited by BC/BL, single bilberry or black currant extracts, and the BC/BL component delphinidin-3-glucoside chloride. Additionally, we observed that BC/BL seemed to act synergistically with aciclovir. Moreover, BC/BL, the single bilberry and black currant extracts, and the BC/BL components delphinidin-3-glucoside chloride, cyanidin-3-glucoside, delphinidin-3-rutinoside chloride, and petunidin-3-galactoside inhibited human Herpesvirus 8 replication. CONCLUSIONS: Our data indicate that Measles viruses and Herpesviruses are differentially susceptible to a specific BC/BL mixture, single plant extracts, purified anthocyanins and astaxanthin. These compounds might be used in the prevention of viral diseases and in addition to direct-acting antivirals, such as aciclovir.


Assuntos
Hepatite C Crônica , Herpesviridae , Ribes , Vaccinium myrtillus , Aciclovir , Animais , Antocianinas/farmacologia , Antivirais/farmacologia , Cloretos , Frutas/química , Humanos , Vírus do Sarampo , Camundongos , Extratos Vegetais/farmacologia
11.
Med Arch ; 76(2): 146-148, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35774041

RESUMO

Background: Ocular herpes simplex is usually caused by herpes simplex virus type 1 (HSV-1) and less commonly by the type 2 virus (HSV-2). Ocular manifestations of HSV include blepharitis, conjunctivitis, lacrimal system obstruction, corneal involvement, and uveitis. Corneal involvement is one of the causes of loss of vision and can be epithelial herpetic keratitis or stromal herpetic keratitis. Objective: A significant population has a colonization of herpes viruses. Under certain circumstances, these viruses can reactivate with a significant ocular morbidity. Globally, COVID-19 vaccines are recommended; however, the vaccine safety data are limited. Case report: Herein, we reported a case of herpetic keratitis reactivation that occurred 2 days after receiving SARS-CoV-2 mRNA vaccine. The patient is a 50-year-old man who underwent penetrating keratoplasty (PKP) in 2020 for corneal opacity caused by a previous herpes simplex keratitis in 2013. Herpetic keratitis was treated successfully with topical antiviral acyclovir along with topical moxifloxacin and artificial tears. After treatment, prophylactic oral acyclovir was started. Conclusion: Both ophthalmologist and patients should be aware of this phenomenon. Long-term prophylactic antiviral treatment may be recommended for those patients.


Assuntos
COVID-19 , Ceratite Herpética , Aciclovir/uso terapêutico , Antivirais/uso terapêutico , Vacinas contra COVID-19/efeitos adversos , Humanos , Ceratite Herpética/tratamento farmacológico , Ceratite Herpética/etiologia , Ceratite Herpética/prevenção & controle , Masculino , Pessoa de Meia-Idade , RNA Mensageiro , Recidiva , SARS-CoV-2 , Vacinação , Vacinas Sintéticas , Vacinas de mRNA
12.
Clin Chim Acta ; 533: 156-167, 2022 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-35787990

RESUMO

OBJECTIVE: To develop a suitable clinical laboratory assay for detecting the activity of circulating immune complexes (CICs) that activate complement (ACIC). METHODS: CICs measured in serum were initially used to activate complement, and the remaining complement was activated through sensitized human O-erythrocytes. ACIC was quantified by the degree of hemolysis. Each serum sample was tested for ten consecutive days to determine its stability. Reference ranges are suggested. ACIC was measured in both healthy individuals and patients with autoimmune diseases as well. RESULTS: The OD values of the hemolysis degree index were inversely proportional to ACIC (r = -0.986, P = 0.002). A pooled serum was used to eliminate interference and optimize the experiment. The hemolysis degree (HD) was used to indicate the detection result. HD = (detection value OD/negative value OD)*100. Both the intra-batch and the inter-batch results showed good stability with a CV of 6.5% and 8.1%, respectively. HD differences between males and females were significant (P = 0.015) while the normal distribution for both genders was conformed. The HD recommended reference range for men is 56-88 while for women is 51-86. Serum HD of healthy subjects and autoimmune disease patients showed a significant difference (P = 0.001). Autoimmune disease patients have lower HD which was a result of having stronger ACIC. CONCLUSION: The ACIC assay while utilizing human O-erythrocytes as an indicator system is sensitive and accurate, and has potential in clinical applications.


Assuntos
Doenças Autoimunes , Hemólise , Aciclovir , Complexo Antígeno-Anticorpo , Proteínas do Sistema Complemento , Eritrócitos , Feminino , Humanos , Masculino
13.
PLoS Pathog ; 18(7): e1010688, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35793357

RESUMO

Herpes simplex virus type 1 (HSV-1) is a common virus of mankind and HSV-1 infections are a significant cause of blindness. The current antiviral treatment of herpes infection relies on acyclovir and related compounds. However, acyclovir resistance emerges especially in the long term prophylactic treatment that is required for prevention of recurrent herpes keratitis. Earlier we have established antiviral siRNA swarms, targeting sequences of essential genes of HSV, as effective means of silencing the replication of HSV in vitro or in vivo. In this study, we show the antiviral efficacy of 2´-fluoro modified antiviral siRNA swarms against HSV-1 in human corneal epithelial cells (HCE). We studied HCE for innate immunity responses to HSV-1, to immunostimulatory cytotoxic double stranded RNA, and to the antiviral siRNA swarms, with or without a viral challenge. The panel of studied innate responses included interferon beta, lambda 1, interferon stimulated gene 54, human myxovirus resistance protein A, human myxovirus resistance protein B, toll-like receptor 3 and interferon kappa. Our results demonstrated that HCE cells are a suitable model to study antiviral RNAi efficacy and safety in vitro. In HCE cells, the antiviral siRNA swarms targeting the HSV UL29 gene and harboring 2´-fluoro modifications, were well tolerated, induced only modest innate immunity responses, and were highly antiviral with more than 99% inhibition of viral release. The antiviral effect of the 2'-fluoro modified swarm was more apparent than that of the unmodified antiviral siRNA swarm. Our results encourage further research in vitro and in vivo on antiviral siRNA swarm therapy of corneal HSV infection, especially with modified siRNA swarms.


Assuntos
Herpes Simples , Herpesvirus Humano 1 , Aciclovir/metabolismo , Aciclovir/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Células Epiteliais/metabolismo , Herpes Simples/genética , Herpes Simples/terapia , Herpesvirus Humano 1/fisiologia , Humanos , RNA de Cadeia Dupla/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Replicação Viral/genética
15.
Int J Mol Sci ; 23(15)2022 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-35897709

RESUMO

Herpes simplex virus type-1 (HSV-1) infection causes several disorders, and acyclovir is used as a reference compound. However, resistant strains are commonly observed. Herein, we investigate the effects of N-heterocyclic compounds (pyrazolopyridine derivatives), named ARA-04, ARA-05, and AM-57, on HSV-1 in vitro replication. We show that the 50% effective concentration (EC50) values of the compounds ARA-04, ARA-05, and AM-57 were 1.00 ± 0.10, 1.00 ± 0.05, and 0.70 ± 0.10 µM, respectively. These compounds presented high 50% cytotoxic concentration (CC50) values, which resulted in a selective index (SI) of 1000, 1000, and 857.1 for ARA-04, ARA-05, and AM-57, respectively. To gain insight into which step of the HSV-1 replication cycle these molecules would impair, we performed adsorption and penetration inhibition assays and time-of-addition experiments. Our results indicated that ARA-04 and ARA-05 affected viral adsorption, while AM-57 interfered with the virus replication during its α- and γ-phases and decreased ICP27 content during initial and late events of HSV-1 replication. In addition, we also observed that AM-57 caused a strong decrease in viral gD content, which was reinforced by in silico calculations that suggested AM-57 interacts preferentially with the viral complex between a general transcription factor and virion protein (TFIIBc-VP16). In contrast, ARA-04 and ARA-05 interact preferentially in the proteins responsible for the viral adsorption process (nectin-1 and glycoprotein). Thus, our results suggest that the 1H-pyrazolo[3,4-b]pyridine derivatives inhibit the HSV-1 replicative cycle with a novel mechanism of action, and its scaffold can be used as a template for the synthesis of promising new molecules with antiviral effects, including to reinforce the presented data herein for a limited number of molecules.


Assuntos
Herpes Simples , Infecções por Herpesviridae , Herpesvirus Humano 1 , Aciclovir/farmacologia , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Chlorocebus aethiops , Herpes Simples/tratamento farmacológico , Infecções por Herpesviridae/tratamento farmacológico , Herpesvirus Humano 1/fisiologia , Pirazóis , Piridinas/farmacologia , Piridinas/uso terapêutico , Células Vero , Replicação Viral
16.
Yakugaku Zasshi ; 142(7): 771-774, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35781507

RESUMO

We report a haemodialysis patient with end-stage renal failure whom a pharmacist aided in the management of acyclovir (ACV) encephalopathy, which may have been related to valacyclovir hydrochloride (VACV) administered without sufficient dose reduction. The patient 78 years was admitted with a tentative diagnosis of varicella zoster viral meningitis. A pharmacist suspected ACV encephalopathy related to excessive VACV administration and raised a query with the attending physician. According to the pharmacist's proposal, ACV administration was discontinued and continuous hemodiafiltration (CHDF) was performed. On day 5 of hospitalisation, the consciousness disorder was improved. In this report, we showed the detailed CHDF conditions of the present case, and the contribution of a pharmacist to treating and avoiding ACV encephalopathy was discussed.


Assuntos
Encefalopatias , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Aciclovir/efeitos adversos , Encefalopatias/induzido quimicamente , Encefalopatias/tratamento farmacológico , Humanos , Farmacêuticos , Valaciclovir
17.
Viruses ; 14(6)2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35746758

RESUMO

Two-thirds of the world's population is infected with HSV-1, which is closely associated with many diseases, such as Gingival stomatitis and viral encephalitis. However, the drugs that are currently clinically effective in treating HSV-1 are Acyclovir (ACV), Ganciclovir, and Valacyclovir. Due to the widespread use of ACV, the number of drug-resistant strains of ACV is increasing, so searching for new anti-HSV-1 drugs is urgent. The oleanolic-acid derivative AXX-18 showed a CC50 value of 44.69 µM for toxicity to HaCaT cells and an EC50 value of 1.47 µM for anti-HSV-1/F. In addition, AXX-18 showed significant inhibition of ACV-resistant strains 153, 106, and Blue, and the anti-HSV-1 activity of AXX-18 was higher than that of oleanolic acid. The mechanism of action of AXX-18 was found to be similar to that of oleanolic acid, except that AXX-18 could act on both the UL8 and UL52 proteins of the uncoupling helicase-primase enzyme, whereas oleanolic acid could only act on the UL8 protein. We have elucidated the antiviral mechanism of AXX-18 in detail and, finally, found that AXX-18 significantly inhibited the formation of skin herpes. In conclusion, we have explored the anti-HSV-1 activity of AXX-18 in vitro and in vivo as well as identification of its potential target proteins, which will provide a theoretical basis for the development of subsequent anti-HSV-1 drugs.


Assuntos
Herpesvirus Humano 1 , Ácido Oleanólico , Aciclovir/farmacologia , Antivirais/metabolismo , Antivirais/farmacologia , Genes Virais , Herpesvirus Humano 1/genética , Ácido Oleanólico/farmacologia , Proteínas Virais/genética
19.
Am J Case Rep ; 23: e936707, 2022 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-35666704

RESUMO

BACKGROUND Varicella zoster virus (VZV) infection can increase the risk of cerebrovascular disease, involving small and large arteries, especially in immunosuppressed patients with ophthalmic division of the trigeminal nerve involvement. We present the case of a patient with intracerebral VZV vasculopathy without overt clinical manifestation but with abnormal imaging findings in the brain magnetic resonance (MR). CASE REPORT A 59-year-old woman with systemic lupus erythematosus (SLE), without other traditional cardiovascular risk factors, presented to the hospital due to headache, vertical diplopia, decreased of visual acuity of right eye, and disseminated varicella zoster virus (VZV) infection with predominant skin lesions distributed along the ophthalmic division of the right trigeminal nerve. Cerebrospinal fluid (CSF) testing revealed meningitis and positive polymerase chain reaction (PCR) for VZV, and a brain MRI scan showed a right occipital hemorrhagic lesion; thus, she was diagnosed with disseminated VZV infection with neurological involvement. She received intravenous acyclovir for 10 days. One month later, a physical examination was unremarkable and she was asymptomatic, but control brain MR angiography showed stenosis of the right internal carotid and the right middle cerebral artery, compatible with VZV vasculopathy. The PCR for VZV turned negative in CSF but the titers of anti-VZV IgG antibodies in CSF were high, and no increase of plasma autoimmune biomarkers were detected at any time in the course of the clinical evolution. CONCLUSIONS Discordance between imaging findings and clinical manifestations can appear in intracerebral VZV vasculopathy. A differential diagnosis is mandatory, especially if there is underlying immunosuppression.


Assuntos
Herpes Zoster , Lúpus Eritematoso Sistêmico , Aciclovir , Feminino , Herpesvirus Humano 3 , Humanos , Lúpus Eritematoso Sistêmico/complicações , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
20.
Early Hum Dev ; 170: 105616, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35763957

RESUMO

BACKGROUND: Neonatal herpes simplex virus (HSV) disease has been treated with high-dose (20 mg/kg/dose) acyclovir since 1991. AIMS: Determine the safety of acyclovir in infants with neonatal HSV treated with high-dose acyclovir; examine the association between acyclovir dose and exposure with adverse events (AEs). STUDY DESIGN: We obtained demographic information and acyclovir dosing via medical records. Acyclovir exposure was calculated using an established pharmacokinetic model. SUBJECTS: Infants <120 days of age with neonatal HSV discharged from four academic children's hospitals. OUTCOME MEASURES: We identified clinical and laboratory adverse events (AEs). RESULTS AND CONCLUSIONS: We identified 49 infants with neonatal HSV treated with acyclovir; 42 infants had complete 21-day dosing information. Median mean daily dose was 59 mg/kg/day. Clinical AEs were common among all gestational and postnatal age groups. Rash was the most common clinical AE (37 %). Mild laboratory AEs occurred in 2-37 % of infants. The median maximum doses (mg/kg/day) were higher among infants with hypokalemia, elevated blood urea nitrogen, and thrombocytosis. For all other laboratory AEs, the median maximum doses for infants without events were higher or equal to the median maximum dose of infants with the AE. The odds of experiencing any clinical or laboratory AE did not differ by predicted acyclovir exposure for either area under the curve (AUC) or maximum concentration (Cmax) (odds ratio [OR] = 1.00 [0.98, 1.03] and OR = 1.01 [0.93, 1.12], respectively). Although AEs were common with high-dose acyclovir exposure, severe AEs were rare. Acyclovir exposure was not associated with AEs.


Assuntos
Aciclovir , Herpes Simples , Aciclovir/efeitos adversos , Antivirais/efeitos adversos , Criança , Feminino , Herpes Simples/induzido quimicamente , Herpes Simples/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Complicações Infecciosas na Gravidez , Simplexvirus
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