• YAKHAK HOEJI
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• v.43 no.1
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• pp.77-84
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• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural naringenin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Naringenin inhibited plaque formations of HSV-l and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-l with selectivity index (SI) of 19.1 than on HSV-2 with SI of 5.7 The combined antiherpetic effects of naringenin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of naringenin with acyclovir on HSV-l and HSV-2 showed more potent synergism with CI values of 0.28∼0.81 for 50%, 70%, 90% effective levels than those with vidarabine with CI values of 0.86-3.28.

• Korean Journal of Pharmacognosy
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• v.29 no.4
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• pp.277-282
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• 1998

In order to search for anti-Herpes simplex virus type 1(HSV-1) agents, we screened 80 specimens of Korean traditional medicine by SRB assay. The methanol extracts of Thujae orientalis Semen (Cupressaceae) showed strong anti-HSV activity among samples tested. From the butanol fraction of Thujae orientalis Semen anti-HSV-1 agent was isolated by chromatographic separation using Amberlite XAD-4 and Sephadex LH-20. The structure was elucidated by spectroscopic methods, and was identified as ${\beta}-sitosterol$ (compound I). Compound I exhibited anti-HSV-1 activity with $EC_{50}$ of 0.6 mg/ml and $CC_{50}$ of 5.99 mg/ml, respectively.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.298-309
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• 2000

Background : The antitumor effects of herpes simplex virus thymidine kinase (HSV-tk) and ganciclovir (GCV) strategies for cancer gene therapy have a the following advantages : 1) a direct cytotoxicity to HSV-tk modified cancer cells by GCV 2) a cell death by the local transfer of toxic metabolites from the HSV-tk modified cells to nearby unmodified tumor cells (bystander effect), and 3) in vivo bystander effect such as antitumor-immunity. Retroviral and adenoviral sequences can silence transgene expression in cells and mice. In this study, we investigated the above described advantages of HSV-tk/GCV strategy in Lewis lung cell and mouse lung cancer model using retroviral vector and adenoviral vector. Also, we observed whether the expression of a silenced gene can be reactivated by treating cells with butyrate. Methods : Retrovirus-HSV-tk and adenovirus-HSV-tk vectors were used for the transduction of Lewis lung carcinoma (LLC) cells. The change of HSV-tk expression by butyrate was measured by Western blol The antitumor activities containing bystander effect were observed in vivo (by MTT assay) and in vivo tumor models of various combinations of LLC and LLC-tk. Results : 1. Butyrate induced the enhancement of HSV-tk expression from adenovirally transduced cells but not from retrovirally transduced cells. 2. Both retrovirus-HSV-tk and adenovirus-HSV-tk vectors with GCV treatment were effective for killing of tumor cell in vitro and suppression of LLC tumorigenicity. Bystander effect was responsible for killing of mixture of LLC-tk and LLC in vitro and in vivo-tumorigenicity model. Conclusion : Butyrate could augment adenovirus-mediated HSV -tk gene expression. Cancer gene therapy with HSV-tk suicide gene by retroviral and adenoviral vector seems to be an effective approach for lung cancer therapy.

• IMMUNE NETWORK
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• v.15 no.2
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• pp.91-99
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• 2015

Herpes simplex virus (HSV) is a common causative agent of genital ulceration and can lead to subsequent neurological disease in some cases. Here, using a genital infection model, we tested the efficacy of vinegar-processed flos of Daphne genkwa (vp-genkwa) to modulate vaginal inflammation caused by HSV-1 infection. Our data revealed that treatment with optimal doses of vp-genkwa after, but not before, HSV-1 infection provided enhanced resistance against HSV-1 infection, as corroborated by reduced mortality and clinical signs. Consistent with these results, treatment with vp-genkwa after HSV-1 infection reduced viral replication in the vaginal tract. Furthermore, somewhat intriguingly, treatment of vp-genkwa after HSV-1 infection increased the frequency and absolute number of $CD3^-NK1.1^+NKp46^+$ natural killer (NK) cells producing interferon (IFN)-${\gamma}$ and granyzme B, which indicates that vp-genkwa treatment induces the activation of NK cells. Supportively, secreted IFN-${\gamma}$ was detected at an increased level in vaginal lavages of mice treated with vp-genkwa after HSV-1 infection. These results indicate that enhanced resistance to HSV-1 infection by treatment with vp-genkwa is associated with NK cell activation. Therefore, our data provide a valuable insight into the use of vp-genkwa to control clinical severity in HSV infection through NK cell activation.

• Pediatric Infection and Vaccine
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• v.3 no.2
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• pp.207-213
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• 1996

Herpes simplex virus(HSV) infections of the CNS are associated with significant morbidity and mortality even when appropriate antiviral therapy is administered. HSV infections of the brain can be subdivided into two categories : neonatal HSV infections, which usually are caused by HSV type 2, and herpes simplex encephalitis(HSE), which occur in patients over 3 months old and is nearly uniformly caused by HSV type 1. The clinical presentation of HSE is one of the focal encephalopathic process associated with altered levels of consciousness, fever, focal seizures and hemiparesis. But because of the lack of pathognomic clinical presentation and diagnostic procedure, the efforts to develop alternative diagnostic procedure have led to the use of new diagnostic technique such as polymerase chain reaction(PCR). We report a case of HSV type 1 encephalitis in 13 month old male infant who presented with altered level of consciousness, fever and focal seizures. With the use of the PCR, HSV-1 DNA was detected in cerebrospinal fluid from the patient. The symptoms and signs of encephalitis subsided by treatment with acyclovir in 14 days.

• Korean Journal of Microbiology
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• v.42 no.3
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• pp.177-184
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• 2006

This study was performed to evaluate the prevalence of high risk Human papilloma virus (HPV), Herpes simplex virus type 1, 2 (HSV-1,2), Hepatitis B virus (HBV) and Human Immuno deficiency virus (HIV) infection with sexual transmitted viral diseases in Busan during 2004 to 2005. six hundred seventy four samples of cervical swabs were tested for sexually transmitted viral diseases. Among the isolated viruses, 23 (3.4%) samples were HPV and 3 (0.4%) and 9 (1.3%) samples were HSV 1 and 2, respectively. Among the 586 serum samples tested for viruses, HSV IgM 121 (3.6%), HSV-1 IgG 487 (83.1%), HSV-2 IgG 135 (23.0%), HBsAg 26 (4.4%), HBeAg 7 (1.2%), and HIV (0%) types were found. HPV genotypes were detected in 16 patients, of which 13 cases were high risk type HPV, 3 cases were low risk type HPV, and multi infection were detected in 7 cases. In the age distribution of the patients, 7.2% of infection tested from cervical swabs occurred in under the age of 20, while 100% of infection was found to occur in those who were 40 years old or older in the serum samples. The outbreak pattern in their occupations was found to be the highest at the health organization (amusement quarter) for the cervical swabs, and at infirmary (commercial sex worker) for the serum samples, respectively.

• Korean Journal of Oriental Medicine
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• v.1 no.1
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• pp.495-508
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• 1995

In order to search for anti-HSV agents from natural complex products, we extended the number of specimens. Both methanol extract and boiling water extract of the natural complex products were screened to detect anti-HSV activity by MTT assay. Anti-HSV activities of thirteen natural complex products extracted by methanol and boiling water were screened. Three of 13 natural complex products extracted by methanol showed efficacy against HSV. Natural complex products showing anti-HSV activities as methanol extracts were No.3, 6, 11 and their Sl were 323.809, 2811.041 and 708.20. As water boiling extracts, No.8 and No.11 have displayed Sl of 16.45 and 60.39 respectively. Especially anti-HSV activities of natural complex products extracted by methanol No.6 was stronger than other ones.

• Korean Journal of Pharmacognosy
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• v.30 no.1
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• pp.40-47
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• 1999

To search for less toxic antiherpetic agents, the inhibitory effects of natural hesperetin on the plaque formation of herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in Vero cells were examined by the plaque reduction assay in vitro. Hesperetin inhibited plaque formations of HSV-1 and HSV-2 in a dose dependent manner. It also exhibited more potent antiherpetic activity on HSV-2 with selectivity index (SI) of 9.8 than on HSV-1 with SI of 8.4. The combined antiherpetic effects of hesperetin with nucleoside antiherpetic agents, acyclovir and vidarabine, were examined on the multiplication of these two strains of herpesviruses in Vero cells by the combination assay. The results of combination assay were evaluated by the combination index (CI) that was calculated by the multiple drug effect analysis. The combinations of hesperetin with acyclovir on HSV-1 and HSV-2 showed synergistic effects with CI values of $0.29{\sim}0.73$ for 50%, 70%, 90% effective levels and those with vidarabine showed partially synergistic or additive effects with CI values of $0.83{\sim}1.33$.

• Korean Journal of Oriental Medicine
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• v.2 no.1
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• pp.417-429
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• 1996

Herpes simplex viruses(HSV) are one of the most common infectious virus of man. Though chemotherapies and antibiotics against HSV have been developed in many countries, but anti-HSV agents were not satisfactory to mankind by their toxic reaction and side effects. In order to search for anti-HSV agents from Korean traditional prescriptions, we extended the number of specimens. Both methanol extract and boilling water extract of the Korean traditional prescriptions were screened to detect anti-HSV activities by MTT assay. Korean traditional prescriptions showing anti-HSV activities as methanl extracts were Paekyopsan, Chesupwilyungtang, Yongdamsagantang, and prescription 11. Four methanol extracts showing anti-HSV activities were freationated by hexane and their efficacies were tested. Hexane freationations of Paekyopsan, Chesupwilyungtang, and prescription 11 showed in anti-HSV activities both haxane and methanol fractionation.

• The Journal of the Korean Society for Microbiology
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• v.35 no.2
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• pp.191-201
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• 2000

The viruses of Herpes Simplex Virus 1 (HSV-1), Herpes Simplex Virus 2 (HSV-2) and Varicella-Zoster virus (VZV) which belong to the alpha herpes subfamily are important human pathogens. When eruptions were not fully developed from these viral infections, clinical diagnosis was not always easy and required virological confirmation test. The above viruses were reactivated in individuals who were compromised in immune competence for one reason or another. Polymerase chain reaction (PCR) enables rapid and sensitive detection of HSV and VZV DNAs. Its sensitivity was largely influenced by choice of primers. Authors conducted a study to detect of those three viruses in human specimens including vesicle fluid and joint fluid and serum using PCR methods. Primers used for this study were the general primer pair GPHV-RU which was known to amplify within the genes enjoying the highest degree of homology between UL15 of HSV and UL42 of VZV. PCR with primers hybridized pair GPHV-RU amplifies a 396 bp with THP-1 and HSV-2 standard strain DNA and 405 bp with VZV standard strain DNA. Restriction enzyme cleavage with HpaII and DdeI were used to detect and distinguish DNAs of THP-1 and HSV-2 and VZV. The purpose of this study was a rapid and easy detection of VZV and THP-1 or HSV-2 from various clinical specimens (vesicle fluid, serum and joint fluid) by PCR method. Used methods were: HSV PCR with primer 1, 2 and HpaII RE digestion; VZV nested PCR; HSV PCR with primer A, Band BssHII RE digestion. 1) In 33 cases (33/42, 78.6%) VZV was detected single or mixed infection from 42 clinical specimens which included vesicle fluid (5), serum form respiratory infected children (10), serum from immune suppressed adult cancer patients (7) and joint fluid from arthritis patients (20). 2) In 20 cases (20/42, 47.6%) HSV was detected singly or mixed infection and 19 of those cases were HSV-2 and 1 case was THP-1. 3) In 19 cases (19/42, 45.2%) VZV was singly detected which included serum from respiratory infected children (6 cases), joint fluid from arthritis patients (9 cases), vesicle fluid (2 cases) and serum form immunosuppressed cancer patients (2 cases). 4) HSV was singly detected in 6 cases (6/42, 14.3%) which included joint fluid from arthritis patients (5 cases) and serum form respiratory infected children (1 cases). 5) 14 cases of VZV and HSV mixed infection (14/42, 33.3%) were detected. They included vesicle fluid (3 cases), serum form immunosuppressed cancer patients (4 cases), serum from respiratory infected children (2 cases) and joint fluid from arthritis patients (5 cases). 6) HSV-1 and HSV-2 detection and typing by HSV PCR with primer A, Band BssHII RE digestion method was more sensitive and the results were easier to detect than on other method.