Administration Of Ganciclovir Research Articles

An adult with hemorrhagic varicella co-infects with cytomegalovirus: a case report

BackgroundHemorrhagic varicella (HV) is a particular form of chicken pox.,with high mortality in adults. This form of the disease is rare, to date, approximately 4 cases have been reported. Occasional cases of HV have been documented in adults with hematologic disorders or other diseases. While there is one reported case of simultaneous reactivation of cytomegalovirus in an adult with chickenpox, there is a lack of information regarding changes in liver function indicators for such patients. This is unfortunate, as CMV reactivation can further exacerbate liver failure and increase mortality. In this report, we present a case of hemorrhagic varicella reactivation with cytomegalovirus and provide some relevant discussions.Case presentationWe present the case of a 25-year-old male with HV, who had a history of nephrotic syndrome generally controlled with orally administered prednisone at a dosage of 50 mg per day for two months. The patient arrived at the emergency room with complaints of abdominal pain and the presence of hemorrhagic vesicles on his body for the past 3 days. Despite medical evaluation, a clear diagnosis was not immediately determined. Upon admission, the leukocyte count was recorded as 20.96 × 109/L on the first day, leading to the initiation of broad-spectrum antibiotic treatment. Despite the general interpretation that a positive IgG and a negative IgM indicate a previous infection, the patient’s extraordinarily elevated IgG levels, coupled with a markedly increased CMV DNA quantification, prompted us to suspect a reactivation of the CMV virus. In light of these findings, we opted for the intravenous administration of ganciclovir as part of the treatment strategy. Unfortunately,,the patient succumbed to rapidly worsening symptoms and passed away. Within one week of the patient’s demise, chickenpox gradually developed in the medical staff who had been in contact with him. In such instances, we speculate that the patient’s diagnosis should be classified as a rare case of hemorrhagic varicella.ConclusionSwift identification and timely administration of suitable treatment for adult HV are imperative to enhance prognosis.

Clinical efficacy of ganciclovir combined with transfer factor oral solution for pediatric infectious mononucleosis

This study investigates the clinical efficacy of ganciclovir combined with transfer factor oral solution in the treatment of patients with infectious mononucleosis (IM) to provide a reference for clinical application. A total of 150 children with IM who received treatment in our hospital from 2020 to 2022 were randomly selected as the research subjects. They were randomly divided into a control group receiving intravenous administration of ganciclovir (n = 75) and an observation group receiving transfer factor oral liquid in combination with intravenous administration of ganciclovir (n=75). The results showed that after treatment, the serum levels of CK-MB, CK, CRP, IL-6, and TNF-α were significantly reduced in both groups. The observation group showed lower levels than the control group. Additionally, peripheral blood CD4+ T cells, CD4+/CD8+ ratio, and Tfr expression were higher in the observation group compared to the control group, while the level of CD8+ T cells was lower than that of the control group. Furthermore, there were no significant changes in the levels of IgA, IgM, and IgG antibodies in the two groups before and after treatment. In conclusion, the combination therapy of transfer factor oral solution and ganciclovir demonstrates favorable clinical efficacy and safety in the treatment of children with IM, as it effectively reduces inflammatory reactions, regulates cellular immune function, promotes Tfr differentiation, and shortens recovery time.

Cellular senescence is a double-edged sword in regulating aged immune responses to influenza.

Clearance of senescent cells has demonstrated therapeutic potential in the context of chronic age-related diseases. Little is known, however, how clearing senescent cells affects the ability to respond to an acute infection and form quality immunological memory. We aimed to probe the effects of clearing senescent cells in aged mice on the immune response to influenza (flu) infection. We utilized a p16 trimodality reporter mouse model (p16-3MR) to allow for identification and selective clearance of p16-expressing cells upon administration of ganciclovir (GCV). While p16-expressing cells may exacerbate dysfunctional responses to a primary infection, our data suggest they may play a role in fostering memory cell generation. We demonstrate that although clearance of p16-expressing cells enhanced viral clearance, this also severely limited antibody production in the lungs of flu-infected aged mice. 30 days later, there were fewer flu-specific CD8 memory T cells and lower levels of flu-specific antibodies in the lungs of GCV-treated mice. Furthermore, GCV-treated mice were unable to mount an optimal memory response and demonstrated increased viral load following heterosubtypic challenge. These results suggest that targeting senescent cells may potentiate primary responses while limiting the ability to form durable and protective immune memory with age.

Adoptive transfer of CMV-specific TCR-T cells for the treatment of CMV infection after haploidentical hematopoietic stem cell transplantation

BackgroundCytomegalovirus (CMV) reactivation after unmanipulated haploidentical stem cell transplantation (SCT) frequently occurs, causing life-threatening morbidities and transplantation failure. Pre-emptive therapy upon the detection of CMV viremia using antiviral agents is...

Inhibition of orthotopic castration-resistant prostate cancer growth and metastasis in mice by JC VLPs carrying a suicide gene driven by the PSA promoter.

Metastatic castration-resistant prostate cancer (mCRPC) is challenging to treat. Virus-like particles (VLPs), originating from JC polyomavirus (JCPyV) and carrying a suicide gene driven by the PSA promoter (PSAtk-VLPs), can inhibit tumor growth in animal models of human prostate cancer. However, the efficacy of suppression of orthotopic PCa growth and metastasis by PSAtk-VLPs remains undetermined. Here, we established an iRFP stable expression CRPC cell line suitable for deep-tissue observation using fluorescence molecular tomography (FMT). These cells were implanted into murine prostate tissue, and PSAtk-VLPs were systemically administered via the tail vein along with the prodrug ganciclovir (GCV), allowing for the real-time observation of orthotopic prostate tumor growth and CRPC tumor metastasis. Our findings demonstrated that systemic PSAtk-VLPs administration with GCV and subsequent FMT scanning facilitated real-time observation of the suppressed growth in mouse iRFP CRPC orthotopic tumors, which further revealed a notable metastasis rate reduction. Systemic PSAtk-VLPs and GCV administration effectively inhibited orthotopic prostate cancer growth and metastasis. These findings suggest the potential of JCPyV VLPs as a promising vector for mCRPC gene therapy. Conclusively, systemically administered JCPyV VLPs carrying a tissue-specific promoter, JCPyV VLPs can protect genes within the bloodstream to be specifically expressed in specific organs.

Adoptive Transfer of CMV-Specific TCR-T Cells for the Treatment of CMV Infection after Haploidentical Hematopoietic Stem Cell Transplantation

Background: CMV reactivation after unmanipulated haploidentical stem cell transplantation (SCT) frequently occurs, causing life-threatening morbidities and transplantation failure. Preemptive therapy upon the detection of CMV viremia using antiviral agents is currently the standard of care but its efficacy is quite limited and associated with significant toxicity. The CMV antigen-specific cytotoxic T lymphocytes (CTLs) therapy was limited by the time-consuming manufacture process and relatively low success rate. More effective and safer approaches for the treatment of CMV reactivation after haploidentical SCT are in urgent need. Methods: A single-arm, open-label Phase I clinical trial evaluating the safety and efficacy of CMV-targeting TCR-T (CMV-TCR-T) cell therapy as the first-line preemptive therapy for patients with CMV reactivation post haploidentical PBSCT was conducted in the Chinese PLA General Hospital (ClinicalTrials.gov Identifier: NCT05140187). Six patients with CMV reactivation after haploidentical SCT were adoptively transferred by 1 to 3 doses of SCT donors-derived CMV-TCR-T cells. This trial was a dose-escalation study with doses ranging from 1×10 3 CMV-TCR-T cells/kg body weight per dose to 5×10 5 CMV-TCR-T cells/kg per dose Results: Except for the Grade 1 CRS observed in one patient and mild fever in 2 patients, no other adverse events were observed. Four patients had complete response within a month after CMV-TCR-T cells infusion without the administration of any antiviral agents. The other two patients who initially didn't completely respond to CMV-TCR-T cell therapy had salvage ganciclovir and foscarnet administration and then had rapid CMV clearance. The CMV-TCR-T cells displayed overall robust expansion and persistence in the peripheral blood after infusion. The CMV-TCR-T cells were firstly detected in the peripheral blood of these patients 3 to 7 days after the 1 st dose of CMV-TCR-T infusion, rapidly expanded and persisted for at least 1~4 months, providing long-term protections against CMV reactivation. In one patient, the CMV-TCR-T cells started to expand even when the anti-GvHD reagents were still being used , further indicating the proliferation potential of CMV-TCR-T cells. Conclusions: Our study firstly showed CMV-targeting TCR-T cell as a highly feasible, safe and effective first-line preemptive treatment for CMV reactivation after haploidentical PBSCT.

Acute Hemorrhagic Rectal Ulcer Complicated by Cytomegalovirus Enteritis following Steroid Pulse Therapy for Acute Exacerbation of Interstitial Pneumonia: A Case Report.

We herein report a rare case of acute hemorrhagic rectal ulcer (AHRU) complicated by cytomegalovirus enteritis following steroid pulse therapy for interstitial pneumonia. An 86-year-old woman underwent steroid pulse therapy for interstitial pneumonia. She was bedridden with dyspnea and suddenly developed melena. Colonoscopy revealed AHRU, which did not improve with conservative treatment, but did improve with ganciclovir administration for cytomegalovirus enteritis. Pulmonologists administer steroid pulse therapy for interstitial pneumonia; however, this gastrointestinal complication does not receive its due attention. Delayed treatment of this complications can be fatal. Caution should be taken when administering steroid pulse therapy to bedridden patients with interstitial pneumonia.

Hearing Following Prolonged and Delayed Ganciclovir Treatment in a Murine Cytomegalovirus Model.

Compare hearing outcomes utilizing standard, prolonged and delayed ganciclovir (GCV) therapy in a murine model of cytomegalovirus (CMV). BALB/c mice were inoculated with mouse cytomegalovirus (mCMV) or saline via intracerebral injection on postnatal day 3 (p3). Intraperitoneal GCV or saline was administered at 12 h intervals for the duration of the standard (p3-p17), delayed (p30-p44), or prolonged treatment windows (p3-p31). Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Blood and tissue samples were harvested from mice on p17 and p37 one hour after GCV administration, and their concentrations were assessed via liquid chromatography-mass spectrometry. A delayed course of GCV improved ABR but not DPOAE thresholds in mCMV-infected mice. A prolonged course of GCV did not provide better hearing thresholds than those administered standard treatment. The average GCV concentration in all 17-day-old mice tissue was significantly higher than those in older 37-day-old mice. Delayed GCV treatment provided a hearing benefit on ABR over untreated mCMV infected mice. Prolonged CGV administration showed no benefit compared to a shorter duration GCV treatment. GCV drug concentrations both systemically and in the cochlea are much lower in older mice. These results have potential implications for the clinical management of cCMV infected children. NA Laryngoscope, 134:433-438, 2024.

Cytomegalovirus enteritis resistant to antiviral drugs improved following total colectomy

BackgroundCytomegalovirus (CMV) infection, often subclinical in childhood, is reactivated during a state of cell-mediated immunodeficiency. In cases of organ damage, patients can require medical treatment for an infectious disease, generally through the use of antiviral drugs. There are no reports of surgical treatment in cases, where infection was found, and medical treatment was difficult. We encountered a case of CMV enteritis that was difficult to treat because of resistance to antivirals but improved after total colectomy.Case presentationA previously healthy, 74-year-old woman visited a doctor with a chief complaint of watery diarrhea persisting for 2 weeks; she was transferred to our hospital because of hypoxemia and hypovolemic shock. Computed tomography scan indicated wall thickening over the entire colon and the patient was diagnosed with infectious colitis. Conservative and antibacterial therapies were started with fasting fluid replacement. Subsequently, bloody stools were observed 11 days after admission. Colonoscopy was then performed, which showed mucosal edema and longitudinal ulcer, while a histopathological examination of the colon mucosa revealed C7HRP positive on 22 days after admission. CMV enteritis was diagnosed, and the antiviral medication, ganciclovir, was started. Diseases causing immunosuppression and other possible causes of enteritis were also closely examined; however, all were negative. Furthermore, the patient’s symptoms and her endoscopic findings did not improve with ganciclovir administration; therefore, the antiviral drug was changed to foscarnet. Unfortunately, the patient did not improve despite the additional administration of gamma globulin and methylprednisolone, and she was determined to have enteritis resistant to medical therapy. A total colon resection was performed 88 days after the admission. Her condition gradually stabilized postoperatively, and oral intake was initiated and tolerated. The patient was transferred to another hospital for rehabilitation for home discharge. She is now at home and has had no recurrences.ConclusionsIn previous reports of surgical treatment for CMV enteritis, many cases were initially undiagnosed, emergency surgery was performed after perforation or stenosis was recognized, and then CMV was diagnosed and treated. In CMV enteritis without immunodeficiency, surgical treatment may be an option if medical treatment is ineffective.

Comparison of Three Renal Function Formulas for Ganciclovir/Valganciclovir Dose Individualization in CMV-Infected Solid Organ Transplantation Patients Using a Population Approach.

The gold standard treatment of established cytomegalovirus infection or prevention in solid organ transplantation is the intravenous administration of ganciclovir (GCV) or oral administration of valganciclovir (VGCV), both adjusted to the renal function. In both instances, there is a high interindividual pharmacokinetic variability, mainly owing to the wide range of variation of both the renal function and body weight. Therefore, accurate estimation of the renal function is crucial for GCV/VGCV dose optimization. This study aimed to compare three different formulas for estimating the renal function in solid organ transplantation patients with cytomegalovirus infection, for individualizing antiviral therapy with GCV/VGCV, using a population approach. A population pharmacokinetic analysis was performed using NONMEM 7.4. A total of 650 plasma concentrations obtained after intravenous GCV and oral VGCV administrations were analyzed, from intensive and sparse sampling designs. Three different population pharmacokinetic models were built with the renal function given by Cockcroft-Gault, Modification of Diet in Renal Disease, or Chronic Kidney Disease EPIdemiology Collaboration (CKD-EPI) formulas. Pharmacokinetic parameters were allometrically scaled to body weight. The CKD-EPI formula was identified as the best predictor of between-patient variability in GCV clearance. Internal and external validation techniques showed that the CKD-EPI model had better stability and performed better compared with the others. The model based on the more accurate estimation of the renal function with the CKD-EPI formula and body weight as a size metric most used in the clinical practice can refine initial dose recommendations and contribute to GCV and VGCV dose individualization when required in the prevention or treatment of cytomegalovirus infection in solid organ transplantation patients.

Therapeutic effects of anti-GM2 CAR-T cells expressing IL-7 and CCL19 for GM2-positive solid cancer in xenograft model.

While chimeric antigen receptor (CAR)-T cell therapy has demonstrated excellent efficacy in hematopoietic malignancies, its clinical application in solid cancers has yet to be achieved. One of the reasons for such hurdle is a lack of suitable CAR targets in solid cancers. GM2 is one of the gangliosides, a group of glycosphingolipids with sialic acid in the glycan, and overexpressed in various types of solid cancers. In this study, by using interleukin (IL)-7 and chemokine (C-C motif) ligand 19 (CCL19)-producing human CAR-T system which we previously developed, a possibility of GM2 as a solid tumor target for CAR-T cell therapy was explored in a mouse model with human small-cell lung cancer. Treatment with anti-GM2 IL-7/CCL19-producing CAR-T cells induced complete tumor regression along with an abundant T cell infiltration into the solid tumor tissue and long-term memory responses, without any detectable adverse events. In addition, as measures to control cytokine-release syndrome and neurotoxicity which could occur in association with clinical use of CAR-T cells, we incorporated Herpes simplex virus-thymidine kinase (HSV-TK), a suicide system to trigger apoptosis by administration of ganciclovir (GCV). HSV-TK-expressing anti-GM2 IL-7/CCL19-producing human CAR-T cells were efficiently eliminated by GCV administration in vivo. Our study revealed the promising therapeutic efficacy of anti-GM2 IL-7/CCL19-producing human CAR-T cells with an enhanced safety for clinical application in the treatment of patients with GM2-positive solid cancers.

Putting PLX5622 into perspective: microglia in central nervous system viral infection.

Putting PLX5622 into perspective: microglia in central nervous system viral infection.

Treatment with hepatocyte transplantation in a novel mouse model of persistent liver failure

Background and AimCell-based transplantation therapy using hepatocytes, hepatic stem cells, hepatocyte-like cells induced from stem cells, etc. is thought to be an attractive alternative to liver transplantation, and have been studied to date. For its clinical application, however, it is extremely important to develop a model that reproduces the pathological conditions with indication for treatment and enables the study for the ideal treatment strategy. MethodsThe transgenic mice which express the thymidine kinase (TK) gene of human herpes simplex virus (HSV) in their hepatocytes with normal immunity has been developed (designated as HSVtk). After ganciclovir (GCV) administration which injure TK-expressing hepatocytes, the primary hepatocytes (PHs) isolated from green fluorescent protein (GFP) transgenic mouse (GFP-tg) were transplanted to HSVtk intrasplenically, and replacement index (RI) with transplanted PHs in the liver, liver histology, and mRNA expressions in the liver were analyzed up to 8 weeks after transplantation. ResultsHSVtk without PH transplantation after GCV administration developed persistent liver failure with degenerated hepatocytes, persistent elevation of ALT and hepatic p16 mRNA levels, suggesting the existence of cellular senescence in the base of the disease. When autologous GFP-PHs were transplanted to HSVtk, the transplanted cells were successfully engrafted in the liver. Eight weeks after transplantation, serum ALT levels and liver histology were almost normalized, while RIs varied from 19.8 to 73.8%. Since the hepatic p16 mRNA levels were decreased significantly in these mice, the senescence of hepatocytes associated with liver injury was thought to be resolved. On the other hand, allogenic GFP-PHs transplanted to HSVtk were eliminated as early as 1 week after transplantation. In these mice, hepatic p16 mRNA levels were significantly increased at 8 weeks after transplantation, suggesting the aggravation of hepatocyte senescence. FK506 administration to HSVtk protected the transplanted hepatocytes with allogenic background from rejection at 2 weeks after transplantation, but the condition of mice and the senescent status in the liver seemed worsened. ConclusionsThe mouse model with HSVtk/GCV system was useful for studying the mechanism of liver regeneration and the immune rejection responses in the hepatocyte transplantation treatment. It may also be utilized to develop the effective remedies to avoid immune rejection.

Tissue-Engineered Endothelial Cells Induce Sustained Vascular Healing Through Early Induction of Vascular Repair

BackgroundPerivascular implantation of tissue-engineered endothelial cells (TEEC) after vascular injury profoundly inhibits neointimal hyperplasia. However, the time course and mechanism by which this effect occurs remain unknown. By developing genetically modified TEEC that express a “suicide gene,” we can control the time during which the TEEC could exert their effect and determine the length of time TEEC need to be present following vascular injury to exert their inhibitory effect on long-term neointimal hyperplasia.MethodsBovine aortic endothelial cells (BAE) were transfected with the human herpes simplex virus thymidine kinase (tk) gene to render them sensitive to ganciclovir (GCV). These BAE+tk were grown to confluence on Gelfoam and shown to have the same growth kinetics and biologic potency as control cells but were sensitive to GCV at low concentrations. The BAE+tk were grown on Gelfoam and placed in the perivascular space around balloon-injured rat carotid arteries. Rats randomly received BAE-tk, BAE+tk, or nothing (control) after balloon injury. GCV was administered early (days 1–7), late (days 5–11), or not at all.ResultsTwo weeks after injury, extensive neointimal hyperplasia was observed in control animals with an intima:media (I:M) area ratio of 0.80 ± 0.19. Early administration of GCV killed the BAE in constructs with TK sensitivity and eliminated the impact of TEEC regulation of intimal hyperplasia (0.45 ± 0.06). Intimal hyperplasia was still effectively reduced in animals with implants containing BAE-tk or BAE+tk which received GCV late (0.11 ± 0.04 and 0.19 ± 0.05). Immunohistochemistry demonstrated the lethal effect of GCV on TK-sensitive cells.ConclusionsThe application of perivascular TEEC for only the first few days after injury had a significant inhibitory effect on intimal hyperplasia. This is in contrast to the results obtained in this same animal model with the infusion of isolated anti-smooth muscle cell proliferative agents. This suggests that the mechanism of action of TEEC may be upstream from smooth muscle cell proliferation. Moreover, the use of this technique to further elucidate biologic mechanisms will prove invaluable in the tissue engineering field.Lay SummaryWe report a novel, genetically altered tissue-engineered endothelial cell (TEEC) implant that inhibits neointimal hyperplasia after experimental vascular injury. The viability of these implants can be carefully controlled and suggest a putative mechanism by which TEEC recapitulate control over the vascular response to injury.

Efficacy of HSV-TK/GCV system suicide gene therapy using SHED expressing modified HSV-TK against lung cancer brain metastases

Lung cancer is one of the most common cancers, and the number of patients with intracranial metastases is increasing. Previously, we developed an enzyme prodrug suicide gene therapy based on the herpes simplex virus thymidine kinase (HSV-TK)/ganciclovir (GCV) system using various mesenchymal stem cells to induce apoptosis in malignant gliomas through bystander killing effects. Here, we describe stem cells from human exfoliated deciduous teeth (SHED) as gene vehicles of the TK/GCV system against a brain metastasis model of non-small cell lung cancer (NSCLC). We introduced the A168H mutant TK (TKA168H) into SHED to establish the therapeutic cells because of the latent toxicity of wild type. SHED expressing TKA168H (SHED-TK) exhibited chemotaxis to the conditioned medium of NSCLC and migrated toward implanted NSCLC in vivo. SHED-TK demonstrated a strong bystander effect in vitro and in vivo and completely eradicated H1299 NSCLC in the brain. SHED-TK cells implanted intratumorally followed by GCV administration significantly suppressed the growth of H1299 and improved survival time. These results indicate that the TKA168H variant is suitable for establishing therapeutic cells and that intratumoral injection of SHED-TK followed by GCV administration may be a useful strategy for therapeutic approaches.

Astrocyte depletion alters extracellular matrix composition in the demyelinating phase of Theiler's murine encephalomyelitis.

Astrocytes produce extracellular matrix (ECM) glycoproteins contributing to the blood-brain barrier and regulating the immune response in the central nervous system (CNS). The aim of this study was to investigate the impact of astrocyte depletion upon the clinical outcome and the composition of ECM glycoproteins in a virus-induced animal model of demyelination. Glial fibrillary acidic protein (GFAP)-thymidine-kinase transgenic SJL (GFAP-knockout) and wildtype mice were infected with Theiler’s murine encephalomyelitis virus (TMEV). Astrocyte depletion was induced during the progressive, demyelinating disease phase by ganciclovir administration once daily between 56 and 77 days post infection (dpi). At 77 dpi GFAP-knockout mice showed a significant deterioration of clinical signs associated with a reduction of azan and picrosirius red stained ECM-molecules in the thoracic spinal cord. Basement-membrane-associated ECM-molecules including laminin, entactin/nidogen-1 and Kir4.1 as well as non-basement membrane-associated ECM-molecules like collagen I, decorin, tenascin-R and CD44 were significantly reduced in the spinal cord of GFAP-knockout mice. The reduction of the investigated ECM-molecules demonstrates that astrocytes play a key role in the production of ECM-molecules. The present findings indicate that the detected loss of Kir4.1 and CD44 as well as the disruption of the integrity of perineuronal nets led to the deterioration of clinical signs in GFAP-knockout mice.

Eosinophilic enteritis accompanied by cytomegalovirus disease: a case report

BackgroundEosinophilic enteritis is a chronic inflammatory disorder of the intestinal tract that is characterized by eosinophil infiltration. Cytomegalovirus (CMV), a common virus, has a broad infectivity range. CMV is retained in the host body after infection. Impairment of host immune defences may reactivate the latent CMV, leading to symptoms of overt disease.Case presentationA Japanese female in her 70 s was admitted to a hospital due to diarrhoea and then transferred to our hospital. Laboratory data showed hypoalbuminemia. Computed tomography (CT) revealed oedema of the small intestine. Lower gastrointestinal endoscopy revealed oedema of the submucosa, without any remarkable changes in the mucosa of the terminal ileum. Histological examination of the terminal ileum revealed infiltration of > 20 eosinophils per high-power field (HPF). These findings aided in diagnosing eosinophilic enteritis. We administered methylprednisolone (500 mg/day) for three days, followed by tapering prednisolone. However, the patient’s general condition and hypoalbuminemia failed to improve. Immunoglobulin (Ig) G- CMV and IgM-CMV tests were positive. CMV antigenemia was extremely high. Therefore, we administered ganciclovir intravenously, which improved the patient’s condition. Furthermore, azathioprine was administered to taper and discontinue prednisolone without relapse of eosinophilic enteritis. This treatment helped stabilize the patient’s condition for approximately four years.ConclusionWe present a case of eosinophilic enteritis accompanied by CMV disease during prednisolone treatment. The patient’s condition improved after administration of ganciclovir. Azathioprine aided in discontinuing prednisolone and stabilizing the patient’s condition for approximately four years.

Congenital Cytomegalovirus Infection: Transmission, Diagnosis and Treatment.

Introduction: Cytomegalovirus (CMV) is a linear, dsDNA virus that is regarded as the prototype of the Betaherpesvirinae subfamily of viruses. It has an established endemic status in certain locations around the globe, and is also reported to be the most prevalently occurring congenital infection in humans. Furthermore, Cytomegalovirus is notorious for being a persistent lifelong pathogen that poses a threat of reactivation as well. Discussion: Congenital cytomegalovirus infection causes numerous ophthalmologic, and neurologic sequelae, and is also known for being the principal reason behind sensorineural hearing loss of non-genetic etiology in neonates. These symptoms, if present, may give rise to a premonition of congenital Cytomegalovirus disease, and so, a diagnosis can be established through serology, radiology, and PCR of salivary, urinary, or dried blood spot samples. Timely administration of ganciclovir or valganciclovir has proven to be effective in managing symptomatic cases of congenital CMV. Conclusion: A well-timed delivery of pharmacological and non-pharmacological interventions is necessary to achieve healthy developmental outcomes for the neonate. Moreover, there is still a need to study the role of antiviral therapy in silent cases since asymptomatic patients are at a risk of developing long-term clinical sequelae as well. Relevance: An estimated 60-90% of women of child-bearing age get infected with Cytomegalovirus, and Congenital CMV disease is reported in 0.2-2.4% of all live births. Therefore, in order to develop effective screening and management protocols, it is vital to educate healthcare professionals regarding the various aspects of this congenital infection.

Cytomegalovirus Infection After Lung Transplantation

<h3>Purpose</h3> Cytomegalovirus (CMV) is one of the most important pathogens causing infections after lung transplantation (LTx), since it is known to have influences on postoperative outcomes after LTx and occurrence of chronic lung allograft dysfunction (CLAD). In this study, we retrospectively reviewed the frequency and managements of CMV infection after LTx. <h3>Methods</h3> This study included 227 lung transplants (92 living-donor lobar lung transplants [LDLLTs] and 135 deceased-donor lung transplants [DDLTs]) performed between 2008 and 2019. In our institution, we usually give antivirus prophylaxis until 1 year after LTx with oral administration of valganciclovir (VGCV). <h3>Results</h3> CMV infection after LTx occurred in 64 recipients (28.2%), and the median duration between LTx and CMV infection was 215 days (range: 6-2566 days). Among these 64 recipients, 18 recipients (28.1%) were CMV-mismatched (donor + /recipient -). CMV viremia was observed in 50 recipients, while end-organ CMV disease occurred in 14 recipients. Among 55 recipients having CMV infection after the completion or discontinuation of antivirus prophylaxis with VGCV, the median time from the end of prophylaxis to CMV infection was 3 months (range: 1-83 months). As treatments for CMV infection, the administration of ganciclovir (GCV) was mainly performed in most cases. Foscarnet was used for 5 recipients due to the myelosuppression (n = 2) and the suspicion of GCV resistance (n = 3). Both overall survival (OS) and CLAD-free survival of recipients having CMV infection were significantly worse than those of recipients not having CMV infection both in LDLLT (p = 0.013 [OS] and p = 0.035 [CLAD-free survival], Figure A and B) and in DDLT (p<0.001 [OS] and p = 0.003 [CLAD-free survival], Figure C and D). <h3>Conclusion</h3> The frequency of CMV infection after LTx was relatively high, and many CMV infections occurred early after the completion or discontinuation of VGCV administration. The prognoses of LTx recipients having CMV infection were worse than those not having CMV infection both in LDLLT and in DDLT.

CBMS-3 Potent bystander effect in suicide gene therapy using genetically engineered stem cells from human exfoliated deciduous teeth

HSV thymidine kinase (TK)/ganciclovir (GCV) has a long history of application in malignant glioma and we have previously demonstrated its bystander effect on gliomas using several stem cell types as a vehicle. The main reason for applying stem cells is that they have a unique tumor-trophic activity that allows them to deliver TK genes efficiently to nearby the tumor. Stem cells from human exfoliated deciduous teeth (SHED) are mesenchymal stem cells easily harvested from dental pulp and no studies have reported suicide gene therapy using SHED as a carrier for malignant gliomas. For transduction of SHED with the HSVTK gene (SHEDTK), we used HSVTK retrovirus-producing cells.In vitro experiments showed a significant migration ability of SHEDTK toward tumor-conditioned medium and representative tumor growth factors. We also detected a significant bystander effect of SHEDTK on gliomas in the presence of GCV. In vitro time-lapse imaging showed that both SHEDTK and glioma cells underwent gradual morphological apoptosis and activation of caspase 3/7 was observed in both cell types. In intracranial tumor models using nude mice, SHEDTK migrated around the U87 cell mass implanted in the contralateral hemisphere. Additionally, coculture suspensions of SHEDTK and U87-luciferase cells were xeno-transplanted followed by intraperitoneal administration of GCV for 10 days. All mice of treatment group survived for more than 100 days, whereas those treated without GCV died of tumor growth with median survival of 42 days after tumor implantation. Furthermore, pre-existing intracranial U87 model mice were injected intratumorally with SHEDTK followed by GCV administration as described above. The tumor volume was significantly reduced during the treatment period, and over-all surivial in treatment group is prolonged significantly to that of control groups. These results indicate that SHEDTK-based suicide gene therapy might offer a new promising therapeutic modality for human malignant gliomas.