• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.849-859
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• 2018

Herpes simplex virus type 2 (HSV-2) infection has been a public health concern worldwide. It is the leading cause of genital herpes and a contributing factor to cervical cancer and human immunodeficiency virus (HIV) infection. No vaccine is available yet for the treatment of HSV-2 infection, and routinely used synthetic nucleoside analogs have led to the emergence of drug resistance. The small molecule $Retro-2^{cycl}$ has been reported to be active against several pathogens by acting on intracellular vesicle transport, which also participates in the HSV-2 lifecycle. Here, we showed that Retro-2.1, which is an optimized, more potent derivative of $Retro-2^{cycl}$, could inhibit HSV-2 infection, with 50% inhibitory concentrations of $5.58{\mu}M$ and $6.35{\mu}M$ in cytopathic effect inhibition and plaque reduction assays, respectively. The cytotoxicity of Retro-2.1 was relatively low, with a 50% cytotoxicity concentration of $116.5{\mu}M$. We also preliminarily identified that Retro-2.1 exerted the antiviral effect against HSV-2 by a dual mechanism of action on virus entry and late stages of infection. Therefore, our study for the first time demonstrated Retro-2.1 as an effective antiviral agent against HSV-2 in vitro with targets distinct from those of nucleoside analogs.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.192-198
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• 2006

Background: Investigating strategy to enhance efficiency of gene transfer via adenovirus is critical to sustain gene expression in targeted cells or tissues to regulate immune responses. However, the use of adenovirus as a gene delivery method has been limited by the native tropism of the virus. In this study, the critical parameter is to improve the efficient binding of viral particles to the plasma membrane prior to cellular uptake. Methods: Human immunodeficiency virus (HIV-1) trans-acting activator of transcription (TAT), a protein transduction domain, was fused to the ectodomain of the coxsackie-adenovirus receptor (CAR). The CAR-TAT protein was produced from a Drosophila Schneider 2 cells (S2) transfected with CAR-TAT genes. The function of CARTAT was analyzed the efficiency of adenoviral gene transfer by flow cytometry, and then immunizing AdVGFP with CAR-TAT was transduced on dendritic cells (DCs). Results: S2 transfectants secreting CAR-TAT fusion protein has been stable over a period of 6 months and its expression was verified by western blot. Addition of CAR-TAT induced higher transduction efficiency for AdVGFP at every MOI tested. When mice were vaccinated with DC of which adenoviral transduction was mediated by CAR-TAT, the number of IFN-${\gamma}$ secreting T-cells was increased as compared with those DCs transduced without CAR-TAT. Conclusion: Our data provide evidence that CAR-TAT fusion protein enhances adenoviral transduction and immunogenecity of transgenes on DCs and may influence on the development of adenoviral-mediated anti-tumor immunotherapy.

• Korean Journal of Veterinary Research
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• v.46 no.1
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• pp.7-12
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• 2006

We have studied pharmacokinetics of a new anti-human immunodeficiency virus (HIV) agent VP-0501 and its amino acid prodrug VP-0501AL which is designed to improve oral bioavailability. After oral administration at 100 mg/kg dose in rats (n = 4), VP-0501 was not detectable in plasma (<50 ng/ml), while after the administration of VP-0501AL, VP-0501 was quantitatively detected, at least for 8 hrs, with Cmax of ca. $2.5{\mu}g/ml$ and AUC of $8hr^{\ast}{\mu}g/ml$. When VP-0501 was intravenously administered at 50mg/kg, this compound appeared at a marginal level in plasma with AUC of $2hr^{\ast}{\mu}g/ml$, $t_{1/2}$ of 2 hr, $C_0$ of $0.7{\mu}g/ml$, and MRT of 3 hr. On the other hand, with intravenous VP-0501AL at the same dose, both the prodrug VP-0501AL and its metabolite VP-0501 appeared comparatively at higher level in the plasma: pharmacokinetic parameters of VP-0501AL including $Vd_{\beta}$, AUC, $t_{1/2,{\beta}}$, $C_0$, $CL_{tot}$, and MRT were ca. 2 L/kg, $70hr^{\ast}{\mu}g/ml$, 2 hr, $180{\mu}g/ml$, 0.7 L/hr/kg, and 1 hr, respectively. These results demonstrate that attachment of amino acid alanine to VP-0501 is an effective approach for improvement of its oral bioavailability. Therefore, VP-0501AL is expected to become a new highly bioavailable and potent anti-AIDS drug candidate/lead compound.

• Journal of Periodontal and Implant Science
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• v.48 no.2
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• pp.92-102
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• 2018

Purpose: This study investigated the validity of the Charlson comorbidity index (CCI) as a predictor of periodontal disease (PD) over a 12-year period. Methods: Nationwide representative samples of 149,785 adults aged ${\geq}60$ years with PD (International Classification of Disease, 10th revision [ICD-10], K052-K056) were derived from the National Health Insurance Service-Elderly Cohort during 2002-2013. The degree of comorbidity was measured using the CCI (grade 0-6), including 17 diseases weighted on the basis of their association with mortality, and data were analyzed using multivariate Cox proportional-hazards regression in order to investigate the associations of comorbid diseases (CDs) with PD. Results: The multivariate Cox regression analysis with adjustment for sociodemographic factors (sex, age, household income, insurance status, residence area, and health status) and CDs (acute myocardial infarction, congestive heart failure, peripheral vascular disease, cerebral vascular accident, dementia, pulmonary disease, connective tissue disorders, peptic ulcer, liver disease, diabetes, diabetes complications, paraplegia, renal disease, cancer, metastatic cancer, severe liver disease, and human immunodeficiency virus [HIV]) showed that the CCI in elderly comorbid participants was significantly and positively correlated with the presence of PD (grade 1: hazard ratio [HR], 1.11; P<0.001; grade ${\geq}2$: HR, 1.12, P<0.001). Conclusions: We demonstrated that a higher CCI was a significant predictor of greater risk for PD in the South Korean elderly population.

• Journal of Preventive Medicine and Public Health
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• v.45 no.3
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• pp.156-163
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• 2012

Objectives: It is necessary to examine groups carrying out sexually risky behavior because the prevalence of sexually transmitted diseases (STDs) is high among them. In this study, the prevalence of STDs among homosexuals and sexbuying men in South Korea was investigated, along with their sexual risk factors. Methods: Men who have sex with men (MSMs, n=108) were recruited in Seoul and Busan by applying the time location sampling method, while sex-buying men (n=118) were recruited from a john school in Gyeonggi province, the suburbs of Seoul. Dependent variables included past or present infection with syphilis, Chlamydia, gonorrhea, and human immunodeficiency virus. Independent variables included health behavior, social support, sexual behavior, and safe sex. Results: It was found that when the MSMs were non-drunk while having sexual intercourse (odds ratio [OR], 0.132), they showed a higher STD infection rate when they had a higher number of anal sex partners (OR, 5.872), rarely used condoms (OR, 1.980), had lower self-efficacy (OR, 0.229), and were more anxious about becoming infected with an STD (OR, 3.723). However, the men who paid for sex showed high STD infections when they had more sex partners (OR, 2.286) and lower education levels (OR, 3.028). Conclusions: STD infections among the two groups were high when they were engaged with many sex partners and not having protected sex. In other words, there was a gap in risky sex behavior within such groups, which was significantly related to the possibility of developing an STD. Therefore, the preventive intervention against STDs for these groups needs to be expanded to include management of sex behaviors.

• Journal of Yeungnam Medical Science
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• v.29 no.2
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• pp.102-105
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• 2012

Collapsing glomerulopathy (CG) has become an important cause of end-stage renal disease (ESRD). First delineated from other proteinuric glomerular lesions in the 1980s, CG is now recognized as a common, distinct pattern of proliferative parenchymal injury that portends a rapid loss of renal function and poor responses to empirical therapy. The first cases in the literature trace back to human-immunodeficiency-virus(HIV)-negative patients who underwent biopsy in 1979. A 45-year-old male patient complained of hematuria and proteinuria eight years ago. He showed an abrupt serum creatinine increase from 1.75 to 2.65 mg/dL in the last preceding months. Afterwards, his serum creatinine progressively increased up to 6.82 mg/dL. Moreover, his 24 h urine protein level was determined to have reached 6,171 mg/day, as opposed to 670 mg/day a year earlier. Consequently, renal biopsy was performed, and its result showed collapsing glomerulopathy, compatible with the diagnosis. He has undergone continuous ambulatory peritoneal dialysis as renal replacement therapy. Thus, it is reported herein that a patient clinically diagnosed with chronic kidney disease eight years ago showed a sudden renal-function decrease and was clinicopathologically diagnosed with collapsing glomerulopathy based on the results of his renal biopsy.

• KSBB Journal
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• v.25 no.1
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• pp.18-24
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• 2010

Juglans mandshurica belongs to the family Juglandaceae is known to contain a wide range of pharmacological activities including anti-cancer, anti-inflammation, astringent, and anti-human immunodeficiency virus-type 1 (HIV-1). Melanogenesis refers to the biosynthesis of melanin pigment in melanocytes. In this study, to investigate the whitening activity of the extracts from Juglans mandshurica, we measured effects on a tyrosinase activity, a melanogenesis, and a tyrosinase synthesis in the B16/BL6 melanoma cells and an antioxidant activity. The extracts significantly scavenged a 1,1-diphenyl-2-picrylhydrazyl (DPPH) and a superoxide anion radicals in a dose-dependent manner with a $SC_{50}$ value of $20\;{\mu}g/mL$ and $25\;{\mu}g/mL$, respectively. Also, the tyrosinase activity and melanogenesis were significantly inhibited by the extracts. Furthermore, the synthesis of tyrosinase protein was significantly decreased by the extracts in enzyme-linked immunosorbent assay. Double blind study on the clinical efficacy of a cream containing 2% of the extracts showed that the extracts have a significant skin whitening effect. Therefore, this study demonstrates that the extracts from Juglans mandshurica may be useful as a potential agent for skin whitening.

• Journal of Ginseng Research
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• v.41 no.2
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• pp.144-150
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• 2017

Background: The presence of gross deletions in the human immunodeficiency virus nef gene ($g{\Delta}nef$) is associated with long-term nonprogression of infected patients. Here, we investigated how quickly genetic defects in the nef gene are associated with Korean Red Ginseng (KRG) intakein 10 long-term slow progressors. Methods: This study was divided into three phases over a 20-yr period; baseline, KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef gene amplicons were obtained using reverse transcription polymerase chain reaction (PCR) and nested PCR from 10 long-term slow progressors (n = 1,396), and nested PCR from 36 control patients (n = 198), and 28 ART patients (n = 157), and these were then sequenced. The proportion of $g{\Delta}nef$, premature stop codons, and not in-frame insertion or deletion of a nucleotide was compared between three phases, control, and ART patients. Results: The proportion of defective nef genes was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%), control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p < 0.01). Small in-frame deletions or insertions were significantly more frequent among patients treated with KRG alone compared with controls (p < 0.01). Significantly fewer instances of genetic defects were detected in samples taken during the KRG plus ART phase (7.8%; p < 0.01). The earliest defects detected were $g{\Delta}nef$ and small in-frame deletions after 7 mo and 67 mo of KRG intake, respectively. Conclusion: KRG treatment might induce genetic defects in the nef gene. This report provides new insight into the importance of genetic defects in the pathogenesis of AIDS.

• International Journal of Oral Biology
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• v.44 no.4
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• pp.173-181
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• 2019

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with age-matched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

• Tuberculosis and Respiratory Diseases
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• v.57 no.2
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• pp.101-117
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• 2004

현증 결핵환자가 감소하고, 면역억제환자가 증가하고 있는 국내 추세에서 잠복결핵(latent tuberculosis)의 진단 및 치료 지침이 필요한 실정이다. 그러나 결핵의 유병률, 발생률 그리고 비씨지 접종률 등이 외국과 다른 국내의 현실에서 현증이 없는 잠복결핵의 진단 및 치료에 대한 방침은 필연적으로 외국과 다를 수 밖에 없으며, 현 시점에 국내에서 이에 대한 자료가 불충분하여 국내의 환경에 적합한 근거 중심의 지침을 설정하기는 어려운 상황이다. 그러나 결핵의 기본 병태 생리를 근거로 하여 최소한 결핵균 감염 이후 결핵 발병의 위험성이 높은 대상 환자에서는 잠복결핵 진단을 위한 검사를 시행하여 치료 여부를 결정하여야 한다. 고위험군은 사람면역결핍바이러스(human immunodeficiency virus, HIV) 감염자, 장기이식환자, 면역억제제를 장기간 사용하는 환자, 6세 이하의 소아 중 최근 전염성 결핵환자 접촉자 등을 우선적으로 고려해야 한다. 미국은 발병 위험도의 고, 중, 저에 따라 투베르쿨린 검사(tuberculin skin test, Mantoux test)의 양성기준을 달리 하여 잠복결핵을 진단하고 있으나, 국내에는 아직 이에 대한 자료가 부족하므로 발병의 위험이 높은 상기 고위험군을 대상으로 하여 PPD RT-23 2TU (Tuberculin unit)를 이용한 피부반응검사에서 10mm이상의 경결(induration)이 생성되는 경우를 양성으로 정하고 추후 연구 결과에 따라 재조정이 필요하다. 그 동안은 투베르쿨린 검사 결과 5-10 mm 사이의 경결반응을 보이는 면역억제 환자에 대하여는 개별적으로 의사의 판단에 따라 잠복결핵의 진단 및 치료 여부를 결정한다. 그러나 면역억제제를 사용하는 등 결핵 발병의 고위험군에서는 피부반응검사상 음성이라도 과거 결핵 치료력이 없이 흉부사진상 명백하게 과거에 결핵을 앓은 흉터가 남아있는 경우(석회화된 1차 결핵 소견은 제외)에는 잠복결핵의 치료를 시행한다. 상기 잠복결핵의 진단 및 검사의 적응증은 최소한 시행하여야 할 경우를 나열한 것으로 이외의 환자에 대하여는 환경 및 대상에 따라 개별화되어야 한다. 치료제로는 isoniazid (INH) 9개월 매일 치료(최소 한 6개월 이상, HIV양성 환자인 경우는 9개월), rifa-mpicin (RFP) 4개월 치료 및 INH/RFP 3개월 매일 치료를 시행할 수 있다. 상기 치료가 어려운 경우에는 RFP/pyrazinamide (PZA) 2개월 매일 치료를 고려할 수 있으나 중증 간독성의 가능성에 대한 철저한 교육 및 추적검사가 필요하다. 향후 국내 환경의 변화 및 연구결과에 따라 추후 부족한 부분에 대한 지침의 재정립이 필요하다.