A 49-year-old liver transplant patient with 4-year history of epilepsy after initiation of cyclosporine developed increasingly frequent seizures over 3 months. Serial brain magnetic resonance imaging showed left temporoparietal cortical edema that gradually improved despite clinical decline. Herpes simplex virus type-1 (HSV-1) DNA was detected in cerebrospinal fluid by polymerase chain reaction. Cerebrospinal fluid HSV-1&2 IgM was negative. Seizures were controlled after acyclovir treatment, and the patient remained seizure free at 1-year follow-up.
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Rat pheochromocytoma (PC12) cells differentiated with nerve growth factor (Nd-PC12) were used to investigate the establishment of a non-productive herpes simplex virus type 1 (HSV-1) infection that is reversible. The results of this work are as follows: (i) Nd-PC12 cultures could be maintained as long term (>7 weeks) non-dividing cultures only when plated on collagen-coated dishes in the absence of serum; (ii) Infection of Nd-PC12 with HSV-1 strains KOS and 17 in the transient presence of acycloguanosine (ACV) resulted in all cultures free of detectable levels of infectious virus at the time of ACV removal and ACV was not needed to maintain the non-productive quiescent state in the subsequent 8 weeks; (iii) These persistently infected and quiescent (QIF)-PC12 cultures demonstrated both spontaneous and forskolin-inducible virus production, at low (5%) and high frequencies (92-100%), respectively during the first 2 weeks post-ACV withdrawal. (iv) In contrast to other in vitro models, HSV-1 failed to reactivate following removal of nerve growth factor. (v) A high percentage of QIF-PC12 cultures (50-100%) produced virus in response to forskolin treatment as long as 7 weeks post-ACV withdrawal. (vi) Expression of HSV-1 productive genes (i.e. alpha0, alpha4, alpha27, UL30 and UL18) dropped precipitously in the presence of ACV and remained undetectable or continued to decline following its removal, whereas the levels of LAT and the host gene G3PDH remained relatively constant throughout the 31 day study period as measured by RT-PCR. These results indicate that QIF-PC12 cells offer a novel, neuronal cell culture system that may enhance our ability to study HSV-1 reactivation from a cryptic, latent-like, non-productive state in the absence of replication inhibitors.
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Prophylaxis-based antiviral treatment and intensive monitoring followed by pre-emptive antiviral treatment are both commonly used management strategies to reduce risk of cytomegalovirus (CMV) infection following renal transplantation. This study employed a decision-model approach using published efficacy data and information from a recent survey of French clinical practice to consider the relative costs and outcomes associated with CMV prevention strategies for high-risk patient groups. The cost per case of treating tissue invasive and symptomatic CMV disease was estimated at euro 15,431 and euro 10,852, respectively. In the highest infection-risk patient group (positive donor with no previous CMV history) prophylactic oral valaciclovir was shown to avoid the greatest number of CMV disease cases (35 cases per 100 transplanted patients) and reduced the overall CMV-related costs per transplanted patient by around 14% over a'wait-and-treat' baseline strategy. In contrast, intensive monitoring and preemptive treatment resulted in a much higher cost per transplanted patient. This analysis suggests that prophylactic treatment remains the most cost-effective approach to the management of CMV in renal-transplanted patients. Further comparative studies between prophylactic and pre-emptive treatment would be a valuable addition to the current evidence based on CMV prevention.
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Bio-based nanocomposites were prepared using starch nanocrystals obtained by acid hydrolysis of native starches using different acid sources. In recent times, focuses on starch nanocrystals (SNCs) have been increasing in number of research works dedicated to the development of bio-nanocomposites by blending with different biopolymeric matrices. The work mainly deals with the preparation of starch nanocrystals using different native starches by acid hydrolysis using hydrochloric acid and trifluroacetic acid. The as-prepared starch nanocrystals are having high crystallinity and more platelet morphologies, and used as a drug carrying filler material in the hydrogel formulations with the care of different polymer matrices. The condensed work also concentrates on the dispersion of antiviral drug in the hydrogels, which are applied onto biocompatible bio-membrane to be formulating a complete transdermal patch. The acid hydrolysed starch nanocrystals were thoroughly characterized using TEM, SEM, particle size analysis and zeta potential. Their thermal stability and the crystalline properties were also characterized using TG-DSC and XRD respectively. The physiochemical interaction and compatibility between the drug and the SNCs filler in the polymeric hydrogels were evaluated using FT-IR analysis. The formulated hydrogels were subjected to evaluation of in vitro permeation studies using Franz diffusion studies. The in vitro study was indicated substantial guarantee for the fabrication of drug dispersed in polymeric hydrogels using SNCs as filler matrices for a successful transdermal drug delivery.
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We have previously reported that a retrovirus vector (LNAF0.3TK) carrying a herpes simplex virus thymidine kinase gene regulated only by the 0.3-kb human alpha-fetoprotein (AFP) promoter provides ganciclovir (GCV)-mediated cytotoxicity in high AFP-producing human hepatoma cells but not in low AFP-producing cells. In the present study, a retrovirus vector (LNAF0.3(E+)TK), in which herpes simplex virus thymidine kinase gene expression is under the control of a human AFP enhancer directly linked to its promoter, was constructed and compared with LNAF0.3(E+)TK. In the intermediate and low AFP-producing human hepatoma cells PLC/PRF/5 and huH1/cl.2, respectively, as well as in the high AFP-producing human hepatoma cells (HepG2), LNAF0.3(E+)TK sensitized these cells to GCV in vitro but did not affect cell growth in nonhepatoma cells (HeLa). In an animal model using athymic mice harboring PLC/PRF/5 cells, GCV treatment resulted in more pronounced growth inhibition in the LNAF0.3(E+)TK virus-infected cells than in the LNAF0.3(E+)TK virus-infected cells. These results indicate that the human AFP enhancer that is directly linked to its promoter involves selective and enhanced tumoricidal activity in gene therapy for hepatocellular carcinoma.
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We report an AIDS patient with cytomegalovirus (CMV) retinitis that developed from an early minor lesion and progressed to extended involvement of the retina and severe deterioration of vision due to poor compliance with ganciclovir treatment. A 33-year-old man was known to have acquired immunodeficiency syndrome (AIDS) for eight months. The patient had no complaint of visual symptoms. A routine eye examination revealed his visual acuity to be 6/6 in both eyes. The dilated eye fundus examination using indirect ophthalmoscopy disclosed a localized white yellowish granular lesion in the peripheral retina of the right eye and a completely normal left eye. CMV retinitis with initial manifestation in the right eye was diagnosed. Due to incomplete treatment with ganciclovir, the retinal lesion rapidly enlarged and extended to the posterior pole, with eventual destruction of the nerve fiber layer and optic disc. The visual acuity of right eye dropped from 6/6 to 1/60 within six months. This case report indicates the importance of early, dilated eye fundus examination and recognition of early CMV retinitis in order to salvage visual function in AIDS patients. Completion of the anti-CMV treatment course in halting the progression of CMV retinitis is also emphasized.
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To ascertain the antitumor effect of retroviral transduction of the pancreatic cancer cell lines MIA PaCa 2, CAPAN-1, PANC1, and PSN1 with the herpes simplex virus thymidine kinase (HSV-TK) gene.
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852 renal transplantation recipients, including asymptomatic CMV replication and CMV disease, received antiviral therapies of intravenous acyclovir or comprehensive anti-infection solution, mainly with intravenous ganciclovir. Effect, time, acute allograft rejection, and safety were analyzed during the antiviral therapy
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The activation of TK was increased after transfection of the pVLTR-tk into the EBV-LMP1 positive cells. After GCV treatment, the clonogenicity and survival of the cells substantially declined, and a bystander effect was also observed. The LMP1 positive cells exhibited remarkable apoptosis following pVLTR-tk/GCV treatment, and the pVLTR-tk/GCV restrained tumor growth in vivo for EBV-LMP1 positive cancers.
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Human herpesvirus-6 (HHV-6) has been implicated in bone marrow suppression, interstitial pneumonitis, and fatal meningoencephalitis in bone marrow transplant (BMT) recipients.
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Clinical improvement reported by most of our patients warrants further investigation in a larger, randomized, double-blind, placebo-controlled trial.
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Lymphoproliferative syndromes are the most common tumors in transplant recipients. More than 90% of posttransplantation lymphoproliferative syndromes (PTLS) are considered to be associated with Epstein-Barr virus, and 86% are of the B-cell line. Histopathology ranges from polymorphic-reactive to monomorphic forms. Clonality should be studied using molecular biology techniques. Clinically, a differentiation is usually made between early PTLS (occurring within 1 year after transplantation) and late PTLS, which occur as localized or disseminated nodal lymphomas. In localized forms, immunosuppression should be discontinued or decreased, and the involved area should be subsequently resected or irradiated. In disseminated cases, immunosuppression should be decreased and administration of acyclovir/ganciclovir should be considered. If this is not effective, treatment should be started with anti-CD20 monoclonal antibodies (rituximab). If no response occurs, use of chemotherapy, possibly with interferon, should be considered. Our aim was to report the incidence, clinical signs, and treatment in a series of patients undergoing lung transplantation (LTx).
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Herpes zoster leukoencephalitis is a rare complication of varicella-zoster virus infection. Associated with high mortality, the majority of cases have been discovered postmortem; today, however, magnetic resonance imaging is being used successfully as an aid in the diagnosis of this disease. The first two reported cases of HIV-infected patients with herpes zoster leukoencephalitis who recovered clinically and showed complete resolution of the magnetic resonance demyelination images after acyclovir treatment are described. In addition, the cases of herpes zoster leukoencephalitis reported in the literature to date are reviewed.
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Multicentre retrospective study of clinical records of all patients consecutively hospitalized for varicella during the last decade, in ten tertiary care clinical centres of Pediatrics and Infectious Diseases, throughout Italy.
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Infections due to herpes simplex virus (HSV) resistant to acyclovir (ACV) represent an important clinical concern in immunocompromised patients. In order to switch promptly to an appropriate treatment, rapid viral susceptibility assays are required. We developed herein a genotyping analysis focusing on thymidine kinase gene (TK) mutations in order to detect acyclovir-resistant HSV in clinical specimens. A total of 85 HSV-1 positive specimens collected from 69 patients were analyzed. TK gene could be sequenced directly for 81 clinical specimens (95%) and 68 HSV-1 specimens could be characterized as sensitive or resistant by genotyping (84%). Genetic characterization of 67 susceptible HSV-1 specimens revealed 10 polymorphisms never previously described. Genetic characterization of 14 resistant HSV-1 revealed 12 HSV-1 with either TK gene additions/deletions (8 strains) or substitutions (4 strains) and 2 HSV-1 with no mutation in the TK gene. DNA polymerase gene was afterwards explored. With this rapid PCR-based assay, ACV-resistant HSV could be detected directly in clinical specimens within 24 h.
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Data are available describing short-course (2 or 3 d) therapy with acyclovir and valacyclovir. Short-course acyclovir therapy was superior to placebo. Three- and 5-day regimens of valacyclovir were equivalent. Early initiation of therapy may be more important than duration of therapy.
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We report three patients with ophthalmic herpes zoster (HZ) manifestations on the background diagnosis of multiple myeloma (MM). It seems that immunocompromised status has caused reactivation of the varicella zoster virus (VZV) producing a well-characterised neurological syndrome and subsequent postherpetic neuralgia in two patients. One patient experienced lymphocytic leptomeningitis resulting in unilateral optic neuritis. All patients received similar myeloma disease-specific treatment prior to HZ reactivation. All patients were treated with thalidomide and steroids, and they thereafter underwent autologous stem cell transplantation. Prior to HZ reactivation they received new immunomodulatory drugs in the form of thalidomide in addition to bortezomib (2 patients) and lenalidomide (1 patient). Immediate specific antiviral therapy was successfully applied with intravenous acyclovir for 10 days, followed by long-term oral famciclovir maintenance. Two patients progressed to have chronic HZ ophthalmicus and postherpetic neuralgia requiring ongoing antiviral therapy and neuroepileptic medications for the neuropathic pain.
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Interventional case report. One patient was diagnosed with cytomegalovirus retinitis in the left eye while receiving immunosuppressive treatment following renal transplantation. The retinitis resolved completely with systemic ganciclovir. Further reduction of immunosuppressive treatment, causing a rapid increase in CD4-T lymphocyte count, was associated in the same eye with the occurrence of IRU consisting of anterior uveitis, vitritis, and macular edema.
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Replication-competent recombinant adenoviral vector (Ad-DeltaE1B19/55) was used in this study, whereas replication-incompetent adenovirus (Ad-DeltaE1A) was generated as a control. Both Ad-DeltaE1B19/55-TK and Ad-DeltaE1A-TK comprise the HSVtk gene inserted into the E3 region of the viruses. YCC-2 cells were infected with the viruses and incubated with 2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl-5-iodouracil (I-131 FIAU) to measure amount of radioactivity. The cytotoxicity of the viruses was determined, and gamma ray imaging of HSVtk gene was performed. MTT assay was also performed after GCV treatment.
A retrospective analysis was performed.
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Two studies were performed to assess the relative bioavailability of Lovrak (Julphar, UAE) compared with Zovirax (Glaxo Wellcome, UK) at the International Pharmaceutical Research Center (IPRC), Amman, Jordan. One study involved acyclovir tablets and the other acyclovir suspension. Each study enrolled 24 volunteers and in both studies, after an overnight fasting, the two brands of acyclovir were administered as a single dose on 2 treatment days separated by 1 week washout period. After dosing, serial blood samples were collected for a period of 16 h. Plasma harvested from blood, was analysed for acyclovir by an HPLC method with UV detection. Various pharmacokinetic parameters including AUC0-t, AUC0-infinity, Cmax, Tmax, T1/2 and Kelm were determined from plasma concentrations for both formulations and found to be in good agreement with the reported values. AUC0-t, AUC(0-proportional to), and Cmax were tested for bioequivalence after log-transformation of data. No significant difference was found based on ANOVA; 90% confidence intervals for the test/reference ratio of these parameters were found within the bioequivalence acceptance range 80%-125%. Based on these statistical inferences it was concluded that a Lovrak tablet is bioequivalent to a Zovirax tablet and that Lovrak suspension is bioequivalent to Zovirax suspension.
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Cx43 expression was examined with flowcyto-metry, Western Blot, and immunofluorescence in two ovarian tumor cells OVCAR3, CAOV3 before and after RA treatment. Bystander effect was determined by the cells growth inhibitory rate with methyl thiazolyl tetrazolium.
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Feline herpesvirus 1 (FHV-1) is a common cause of respiratory and ocular disease in cats. Especially in young kittens that have not yet reached the age of vaccination, but already lost maternal immunity, severe disease may occur. Therefore, there is a need for an effective antiviral treatment. In the present study, the efficacy of six antiviral drugs, i.e. acyclovir, ganciclovir, cidofovir, foscarnet, adefovir and 9-(2-phosphonylmethoxyethyl)-2, 6-diaminopurine (PMEDAP), against FHV-1 was compared in Crandell-Rees feline kidney (CRFK) cells using reduction in plaque number and plaque size as parameters.
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Multidrug and toxin extrusion (MATE; SLC47A) proteins are membrane transporters mediating the excretion of organic cations and zwitterions into bile and urine and thereby contributing to the hepatic and renal elimination of many xenobiotics. Transported substrates include creatinine as endogenous substrate, the vitamin thiamine and a number of drug agents with in part chemically different structures such as the antidiabetic metformin, the antiviral agents acyclovir and ganciclovir as well as the antibiotics cephalexin and cephradine. This review summarizes current knowledge on the structural and molecular features of human MATE transporters including data on expression and localization in different tissues, important aspects on regulation and their functional role in drug transport. The role of genetic variation of MATE proteins for drug pharmacokinetics and drug response will be discussed with consequences for personalized medicine.
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PEG-PEI Fe(3)O(4) nano-magnetic fluid-DNA complexes could protect the DNA from degradation of DNaseI, serum and sonication. AFP positive cells transfected by pAFP-TK were highly sensitive to the GCV treatment, and the survival of cells declined obviously. HSV-TK/GCV suicide gene therapy system had direct cell toxicity.
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Twenty cases (12 female and 8 male patients) of KVE were seen. The mean age of the patients was 46.4 years. There were seven cases of erythroderma, four of pemphigus vulgaris, three of toxic epidermal necrolysis, two of airborne contact dermatitis (ABCD), one each of lichenoid drug rash, and drug rash with eosinophilia and systemic symptoms (DRESS). Underlying dermatoses for erythroderma were: ABCD (3), psoriasis (3), and cutaneous T-cell lymphoma (1). Possible source of infection could be identified in five cases: exogenous sources in four cases and endogenous source in one case. The mean incubation period for cases with known source was 5 days (range, 2-9 days). Eighteen patients responded favorably to acyclovir. None of our patients had recurrent KVE during the study period.