Ganciclovir

The connexin 26 (Cx26) gene suppresses the growth of HeLa cells in vitro and in vivo. We explored the possibility that the Cx26genenot only suppresses growth but can also mediate the bystander effect that is observed in some gene therapy. In gene therapy mediated by the herpes simplex virus thymidine kinase, the toxicity of ganciclovir affects not only the cells transduced with the gene but also affects neighboring tumor cells; it has been suggested that gap junctional intercellular communication (GJIC) may play a role in such a bystander effect. HeLa cells expressing the Cx26 gene(Cx26―@) or not expressingthe Cx26genewere transfected with the herpes simplex virus thymidine kinase (tki gene, producing Cx26-tlC, Cx26'-tk―, Cx26@-tk', and Cx26@-tk' cells. By making different kinds of cocultures of these cells, we observed a clear bystander killing effect, assessed by the neutral red toxicity test, in the coculture of Cx26@-tk/Cx26@-tk@ cells. The bystander effect was m...

The purpose of this work is to develop empirical equations for describing the in vitro ganciclovir (GCV) release from PLGA microspheres and also to develop and characterize a formulation containing GCV loaded PLGA microspheres dispersed in thermogelling PLGA-PEG-PLGA polymer gel. Effect of polymer chain length and polymer blending on GCV entrapment and release from PLGA microspheres is also examined. PLGA microspheres of GCV were prepared from two polymers PLGA 6535 (d,l-lactide:glycolideColon, two colons65:35, Mw=45,000-75,000 Da) and Resomer RG 502H (d,l-lactide:glycolideColon, two colons50:50, Mw=8000 Da) and a 3:1 mixture. PLGA-PEG-PLGA polymer was synthesized and characterized. In vitro GCV release studies were conducted with microspheres and microspheres dispersed in 23% w/v PLGA-PEG-PLGA solution. Polymer blended microspheres entrap more GCV (72.67+/-2.49%) than both PLGA 6535 (51.37+/-2.7%) and Resomer RG 502H (47.13+/-1.13%) microspheres. In vitro drug release data was fit ...

Nephrotic syndrome is the most common glomerular disease in children. Most cases are idiopathic and the first episode is rarely related to cytomegalovirus infection, particularly after 3 months of age. We present a 7-month-old infant who developed atypical presentation of nephrotic syndrome secondary to cytomegalovirus infection. The patient was referred to undergo orchiopexy due to right-sided undescended testis. Following the surgery, he developed fever, gastroenteritis and renal failure. A few days later, generalized edema and proteinuria were detected. Due to positive test results for cytomegalovirus, ganciclovir was  administered. Remission of nephrotic syndrome was obtained within the first two weeks of the treatment. No relapse of nephrotic syndrome was detected during 12 months of follow up. We may conclude that in unexplained infantile nephrotic syndrome, CMV should be considered as one of the possible
etiologies.

A novel doughnut-shaped minitablet (DSMT) was developed and evaluated as a biodegradable intraocular drug delivery system for rate-modulated delivery of antiviral bioactives. The DSMT device was manufactured using a special set of punches fitted with a central-rod in a Manesty tableting press. The DSMT device released the antiretrovirals foscarnet and ganciclovir at a first-order rate. The erosion kinetics was assessed by gravimetric analysis and scanning electron microscopy. The device gradually eroded when immersed in simulated vitreous humor (SVH) (pH 7.4, 37 degrees C) and released bioactives in a sustained manner. The novel geometric design and veracity of the DSMT device was retained even after 24 weeks of erosion. When considering the duration of the bioactive released from the DSMT device, it was found that by the careful selection of the type and concentration of polymer employed in formulating the DSMT device, it was possible to produce a device that could release drug for...

Abstract Ogilvie's syndrome, or acute colonic pseudo-obstruction, is a rare complication following liver transplantation. We describe two cases in which the onset of Ogilvie's syndrome is strongly temporally associated with acute cytomegaloviral (CMV) infection in immunosuppressed liver transplant recipients. The pseudo-obstruction resolved rapidly in both cases following treatment with intravenous ganciclovir. Acute CMV infection therefore appeared to be causally linked to pathogenesis of Ogilvie's syndrome in these two cases. This association has not been described previously to our knowledge, and should be considered in any transplant patient presenting with Ogilvie's syndrome.

Patients with refractory or recurrent B-lineage hematologic malignancies have less than 50% of chance of cure despite intensive therapy and innovative approaches are needed. We hypothesize that gene modification of hematopoietic stem cells (HSC) with an anti-CD19 chimeric antigen receptor (CAR) will produce a multi-lineage, persistent immunotherapy against B-lineage malignancies that can be controlled by the HSVsr39TK suicide gene. High-titer third-generation self-inactivating lentiviral constructs were developed to deliver a second-generation CD19-specific CAR and the herpes simplex virus thymidine kinase HSVsr39TK to provide a suicide gene to allow ablation of gene-modified cells if necessary. Human HSC were transduced with such lentiviral vectors and evaluated for function of both CAR and HSVsr39TK. Satisfactory transduction efficiency was achieved; the addition of the suicide gene did not impair CAR expression or antigen-specific cytotoxicity, and determined marked cytotoxicity ...

The efficacy and safety of valganciclovir (VGCV) for cytomegalovirus (CMV) prophylaxis in liver transplant recipients has not been established. We retrospectively compared the efficacy and safety of low-dose oral VGCV (450 mg once daily for 90 days) and standard oral ganciclovir (1 g three times a day for 90 days, GCV) in preventing CMV disease in 109 adult liver transplant recipients who survived at least 1 month between January 2001 and April 2003 (49 GCV and 60 VGCV). The incidence of CMV disease at 1 year post-transplant was similar among patients treated with VGCV and GCV (3% and 4%, respectively). Three of the four CMV disease cases occurred in high-risk recipients with CMV serotype of donor+/recipient− (D+/R−) and all cases presented after completion of CMV prophylaxis, ranging 114-152 days post-transplant. Severe neutropenia was rare, and thrombocytopenia and anemia occurred at similar frequencies with both prophylaxis regimens. In conclusion, a 90-day regimen of low-dose oral VGCV has a similar efficacy and safety profile to high-dose oral GCV in adult liver transplant recipients. D+/R− liver transplant recipients remain at risk of developing CMV disease after completion of antiviral prophylaxis. Additional prospective studies with close monitoring for CMV viremia and drug resistance are needed to further establish the optimal dose and duration of VGCV in liver transplant recipients. Liver Transpl 12:112–116, 2006. © 2005 AASLD.

Assessments of herpes simplex virus 1 thymidine kinase (HSV-tk)/ganciclovir (GCV) treatment response, early in the course of therapy, are important in the evaluation and clinical management of patients. This study addresses whether imaging amino acid transport, glucose utilization, and passive vascular permeability provides an early indication of treatment response and can predict long-term outcome.

Transfer of the herpes simplex virus-thymidine kinase (HSV-tk) gene followed by the administration of ganciclovir (GCV) into hepatocellular carcinoma (HCC)-derived cell lines either in vitro or transplanted into nude mice has been shown to provide a potential ...