• Proceedings of the Korean Society of Applied Pharmacology
• /
• 1997.04a
• /
• pp.119-119
• /
• 1997

Valacyclovir is a L-valyl ester prodrug of acyclovir which is a highly effective and selective antiviral agent in the treatment of herpes virus diseases. Valacyclovir is rapidly and almost completely converted to acyclovir and increases the oral bioavailability of acyclovir three to five fold. However, the intestinal absorption mechanism of valacyclovir is not clear. If the improved absorption mechanism of valacyclovir is fully understood, it will provide a rationale of designing the amino acid ester prodrugs of polar drugs containing hydroxyl group. The main objective of our present study is to characterize the membrane transport mechanism of valacyclovir. Methods : Intestinal absorption of valacyclovir was investigated by using in-situ rat perfusion study and its wall permeability was estimated by modified boundary layer model. The membrane transport mechanism was also investigated through the uptake study in Caco-2 cells and in CHO-hPepTl cells. Results : In the rat perfusion study, the wall permeability of valacyclovir was ten times higher than acyclovir and showed concentration dependency, Valacyclovir also demonstrated a D,L stereo-selectivity with L-isomer having an approximately five-fold higher permeability than D-isomer. Mixed dipeptides and cephalexin, which are transported by dipeptide carriers, strongly competed with valacyclovir for the intestinal absorption, while L-valine did not show any competition with valacyclovir. This indicated that the intestinal absorption of valacyclovir could be dipeptide carrier-mediated. In addition, the competitive uptake study in Caco-2 cells presented that dipeptides reduced the valacyclovir uptake but valine did not. Also, in IC$\sub$50/ study, valacyclovir showed strong inhibition on the $^3$H-gly-sar uptake in CHO-hPepTl cells over-expressing a human intestinal peptide transporter. Taken together, the result from our present study indicated that valacyclovir utilized the peptide transporter for the intestinal absorption.

• Annals of Clinical Neurophysiology
• /
• v.3 no.1
• /
• pp.9-14
• /
• 2001

Background : Bell's palsy(BP) is defined as an idiopathic peripheral facial paralysis of acute onset, accounting for more than 50% of all cases of facial paralysis. Different theories on the etiology of BP have been proposed. Herpes simplex virus-1(HSV) has been the most suspicious causative agent, but varicella zoster virus(VZV) also is suspected. Objectives : We evaluated the serological changes of IgG and IgM titer of HSV and VZV to know the causative agent of BP. Materials and Methods : Subjects consisted of 35 patients who developed acute idiopathic unilateral facial palsy(16 men and 19 women from 9 to 78 years old) within a week of onset. We took the serum of the acute and convalescent stages, respectively. Serum IgG and IgM titer of HSV and VZV were measured in acute and convalescent stages by EIA method. Results : Only the HSV IgG titer showed statistically significant elevation in the convalescent stage(p=0.0291). Others did not show any significant change between the acute and convalescent stage. Conclusion : We concluded that HSV may be related to the causative agent of BP.

• The Korean Journal of Pain
• /
• v.21 no.3
• /
• pp.217-223
• /
• 2008

Background: Lumbar transforaminal epidural injections (LTEIs) have been utilized in the treatment of radicular pain, and LTEIs have the advantage of target-specificity. However, there have not been enough studies on the contrast patterns in LTEIs with using fluoroscopy. The purpose of this study was to evaluate the spreading epidural contrast patterns that are seen during real-time fluoroscopic guided LTEIs. Methods: A total of 131 patients who underwent fluoroscopic guided LTEIs were studied. The inclusion criteria were those patients with low back pain and/or lower extremity pain that was caused by a herniated nucleus pulposus, lumbar spinal stenosis, failed back surgery syndrome, and herpes zoster-associated pain. We classified the contrast patterns in regard to the contrast flow spreading to the nerve root and/or the unilateral, bilateral or cylinderic type of epidural spreading on the AP view of the fluoroscopy and the ventral or dorsal epidural filling on the lateral view. In addition to the pattern analysis, we evaluated the range of contrast spreading from the cranial to the caudal epidural filling and the incidence of an intravascular flow pattern. Results: Epidural spreading was seen in 126 cases (96.2%) of the total patients through the nerve root. Ventral spreading occurred in 120 cases (95.2%). On the AP view, a nerve root with unilateral, bilateral and cylinderic epidural filling was noted for 108 (85.7%), 9 (7.1%) and 9 (7.1%) cases, respectively. The contrast spreading to vertebral segments was smaller for the patients with lumbar spinal stenosis and failed back surgery syndrome than for the other groups (P < 0.0083). The incidence of intravascular injection was 11.1% (14/126). Conclusions: LTEIs using fluoroscopic visualization provided excellent assessment of the ventral epidural filling as well as nerve root filling. However, unilateral epidural spreading was prominent for the LTEIs.

• Journal of Microbiology and Biotechnology
• /
• v.11 no.2
• /
• pp.234-241
• /
• 2001

The C-terminal 393 bp region of the human interleukin-16 (IL-16) gene was cloned and expressed in E. coli along with mammalian cell lines. Recombinant IL-16 expressed from E. coli was 22 kDa on SDS-PAGE and showed 260% of chemoattractant activity at a concentration of $0.1\;{\mu}g/ml$. HeLa, COS, and Neuro-2a cells were transduced by recombinant retrovirus vector pLNC/IL-16/IRES/TK and the intracellular and secreted amounts of IL-16 produced by HeLa/IL-16/TK, COS/IL-16/TK, and Neuro-2a/IL-16/TK cells were determined by enzyme-linked immunosorbent assay (ELISA). HeLa/IL-16/TK $(1{\times}10^5)$ and COS/IL-16/TK $(1{\times}10^5)$ cells secreted 36.1 and 13.3 ng of IL-16 for 48 h, respectively. Forty-nine ng and 86.4 ng of IL-16 remained in the cell lysates of HeLa/IL-16/TK and COS/IL-16/TK. Intracellular and secreted amounts of IL-16 from Neuro-2a/IL-16/TK $(5{\times}10^5)$ cells during 24 h cultivation were 50 ng and 3.3 ng, respectively. Also, HeLa and COS cells wee stably transfected with mammalian expression vector pCRIII/IL-16. Both culture media and cell lysates prepared from HeLa/IL-16 cells and COS/IL-16 cells showed chemoattractant activity ranging from 190% to 460% as compared to the control experiment. Expression of the herpes simplex virus thymidine kinase (HSV0tk) gene in pLNC/IL-16/ IRES/TK bicistronic retroviral expression vector was verified by performing a genciclovir (GCV) sensitivity assay. Finally, IL-16 repressed Tat-transactivated human immunodeficiency virus type 1 long terminal repeat (HIV-1 LTR) promoter activity.

• Journal of Pharmaceutical Investigation
• /
• v.23 no.3
• /
• pp.139-144
• /
• 1993

Microencapsulation of acyclovir, an effective antiviral agent which acts as a specific inhibitor of herpes DNA polymerase, by carbopol-gelatin complex coacervation has been carried out to develop an oral controlled release preparation, which could improve the absorption characteristics in GI tract. After dissolving carbopol and gelatin separately in distilled water at $40^{\circ}C$, gelatin solution was mixed with carbopol solution while stirring at the same temperature. The pH of the mixture was lowered gradually by dropwise addition of 10% HCI with continuous stirring, and then, at pH 3.5, positively charged gelatin molecules were attracted to negatively charged carbopol. These coacervation processes were observed by optical microscopy during preparation. Plasma concentrations of acyclovir in rats after an oral administration of microcapsule suspension were assayed by HPLC, and pharmacokinetic parameters were calculated based on the model-independent analyses. Two standard formulations, oral solution and intravenous bolus injection, were used as references to compare the bioavailability. It has been revealed that $C_{max}$, $T_{max}$, and MRT of microcapsule suspension were greater than those of oral solution, which results in about two-fold increases in bioavailability. Therefore, in conclusion, the carbopol-gelatin microcapsule of acyclovir might be evaluated as an effective oral controlled release preparation which could increase the bioavailability of acyclovir.

• Journal of Microbiology and Biotechnology
• /
• v.19 no.9
• /
• pp.1070-1076
• /
• 2009

Telomerase reverse transcriptase (TERT), which prolongs the replicative life span of cells, is highly upregulated in 85-90% of human cancers, whereas most normal somatic tissues in humans express limited levels of the telomerase activity. Therefore, TERT has been a potential target for anticancer therapy. Recently, we described a new approach to human cancer gene therapy, which is based on the group I intron of Tetrahymena thermophila. This ribozyme can specifically mediate RNA replacement of human TERT (hTERT) transcript with a new transcript harboring anticancer activity through a trans-splicing reaction, resulting in selective regression of hTERT-positive cancer cells. However, to validate the therapeutic potential of the ribozyme in animal models, ribozymes targeting inherent transcripts of the animal should be developed. In this study, we developed a Tetrahymena-based trans-splicing ribozyme that can specifically target and replace the mouse TERT (mTERT) RNA. This ribozyme can trigger transgene activity not only also in mTERT-expressing cells but hTERT-positive cancer cells. Importantly, the ribozyme could selectively induce activity of the suicide gene, a herpes simplex virus thymidine kinase gene, in cancer cells expressing the TERT RNA and thereby specifically hamper the survival of these cells when treated with ganciclovir. The mTERT-targeting ribozyme will be useful for evaluation of the RNA replacement approach as a cancer gene therapeutic tool in the mouse model with syngeneic tumors.

• Journal of Acupuncture Research
• /
• v.18 no.1
• /
• pp.237-247
• /
• 2001

Background : infection associated with otalgia, herpetic eruptions, facial palsy, trigeminal pain and cochleovestibular dysfunction such as hearing dishubance, tinnitus, vertigo and other symptoms, and is not frequently encountered in otolaryngologic field. And facial paralysis occured by this syndrome is rapid in onset, usually severe in degree, and poor in prognosis. Objectives : To evaluate the Oriental Medicine's treatment and prognosis of Herpes zoster oticus and to classify of peripheral Facial palsy on Oriental Medicine. Methods : Clinical observation and analysis about a case of Ramsay-Hunt syndrome III type was done, who visited Dongguk University Gangnam Hospital. This case is managed by integrated therapy of oriental and western medicine. In oriental medicine, to treate ear pain, heonggae-yeongoetang(荊芥蓮翹湯) was given and to treat herpetic eruption, 8 constitution acupuncture treatement was done. In western medicine, antiviral agent, acyclovir and steroid hormone, prednisolon were treated. Result : About 6 weeks treatment, this case which has worse prognosis than Bell's palsy, was completed cured without any complication. Conclusion : 1. Futher divided classification about non-infectious and infectious facial palsy include "Ramsay Hunt Syndrome" is needed. 2. In acute state, Jeonyohwadan's (纏腰火丹) treatement can be applied, but the difference of invasion part, primary symptom such as ear pain and herpetic eruption is needed another treatment. 3. Ear pain and herpetic eruption can be treated in part of poongyeol(風熱) and subyeol(濕熱). 4. In Acupuncture treatement, Jeonyohwadan's (纏腰火丹) treatement can be applied in acute stage and guanwasa's treatement can be applied in chronic stage. but futher research is needed. 5. This case, Ramsay Hunt Syndrome IlI type, was managed by integrated therapy such as heonggae-yeongoetang(荊芥蓮翹湯), 8 constitution acupuncture treatement, acyclovir and prednisolon and this treatement was good effect.

• Korean Journal of Poultry Science
• /
• v.35 no.1
• /
• pp.39-55
• /
• 2008

Like the other herpesviruses, the virion of MDV consists of an envelope, which surrounds an amorphous tegument. Within the tegument, and icosahedral capsid encloses a linear double-stranded DNA core. Although the genome structure of MDV indicates that it is an ${\alpha}-herpesvirus$ like herpes simplex and varicella-zoster viruses, biological properties indicate MDV is more akin to the ${\gamma}-herpesvirus$ group, which includes Epstein-Barr and Kaposi's sarcoma herpesviruses. These herpesviruses replicate lytically in lymphocytes, epithelial and fibroblastic cells, and persist in lymphoblastoid cells. MDV has a complex life cycle and uses two means of replication, productive and non-productive, to exist and propagate. The method of reproduction changes according to a defined pattern depending on changes in virus-cell interactions at different stages of the disease, and in different tissues. Productive (lytic) interactions involve active invasion and take-over of the host cell, resulting in the production of infectious progeny virions. However, some herpesviruses, including MDV, can also establish a non-productive (abortive) infection in certain cell types, resulting in production of cell-associated progeny virus. Non-productive interactions represent persistent infection, in which the viral genome is present but gene expression is limited, there is no structural or regulatory gene translation, no replication, no release of progeny virions and no cell death. Reactivation of the virus is rare, and usually the infectious virus can be re-isolated only after cultivation in vitro. MDV establishes latency in lymphoid cells, some of which are subsequently transformed. In this review article, recent knowledges of the pathogenesis mechanisms followed by MDV infection to sensitive cells and chickens are discussed precisely.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.1705-1712
• /
• 2016

Background: The aim of this study was to determine and evaluate the association of different viral infections, with hepatitis B and C viruses, Epstein-Barr virus, cytomegalovirus and human herpes virus-8 (HBV, HCV, EBV, CMV, HHV-8) with the risk of lymphomas (Hodgkin and non-Hodgkin) among Egyptian patients, and correlate with the histopathological staging and typing as well as the prevalence of combined infections. Materials and Methods: A total of 100 newly diagnosed lymphoma patients with 100 healthy age and sex matched normal controls were assayed for viral infection using enzyme linked immunosorbant assay (ELISA) followed by real time polymerase chain reaction (RT-PCR). Results: Our results showed a high statistical significant difference between cases and controls as regards clinical and laboratory findings (P<0.001 and=0.003). A high statistical difference was seen for the association of most viruses and lymphoma cases (p<0.001) except for positive HBs Ag, positive CMV IgG and HHV-8 (p=0.37, 0.70 and 1.0 respectively). No statistical significant difference was found between Hodgkin (HL) and non-Hodgkin (NHL) as regards viral prevalence except HCV antigen, 57.1% for HL and 26.5% for NHL (p = 0.03). Only, HBV DNA showed a high significant value among infiltrated bone marrow cases (p=0.003) and finally, a high significant association of 2 combined viral infections with infiltrated bone marrow lymphoma cases (p=0.04). Conclusions: Our results showed that infection with HBV, HCV, CMV and EBV were associated with increased risk of lymphoma among the Egyptian population. Detection of new associations between infectious agents and risk of cancer development will facilitate progress in elaboration of prophylactic measures, early diagnostic methods and, hopefully, novel therapy of malignant tumours.

• Journal of Microbiology and Biotechnology
• /
• v.9 no.5
• /
• pp.541-547
• /
• 1999

Constructions of a transfer vector and a recombinant baculovirus using the thymidine kinase gene of the Herpes simplex virus type 1 strain F (HSV -1) were carried out. Newly cloned transfer vector, pHcgXIIIB, was constructed by insertion of the glycoprotein gX gene signal peptide sequence of Pseudorabies virus into the baculovirus vector pHcEV-IV. The gX sequence was inserted just downstream from the promoter for the polyhedrin gene of the Hyphantria cunea nuclear polyhedrosis virus (HcNPV). HSV-1 thymidine kinase(tk) gene (1.131 kb) was used as a candidate gene for transferring into the baculovirus expression system. The tk gene was inserted into a BamHI site downstream from the gX sequence-promoter for the polyhedrin gene in the pHcgXIIIB transfer vector and was transferred into the infectious lacZ-HcNPV expression vector. Recombinant virus was isolated and was named gX-TK-HcNPV. The recombinant virus produced a 45 kDa gX-TK fusion protein in Spodoptera frugiperda cells, which was confirmed by Western blot analysis. Microscopic examination of gX-TK-HcNPV-infected cells revealed normal multiplication. Fluorescent antibody staining indicated that the gX-TK fusion protein was present in the cytoplasm. These results indicated that the transfer vector successfully transferred the gX-tk gene into the baculovirus expression system.