• Archives of Pharmacal Research
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• v.23 no.5
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• pp.501-506
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• 2000

We examined the antifibrotic effect of a methanol extract from Stephania tetrandra (ST) on experimental liver fibrosis. liver fibrosis was induced by bile duct ligation and scission (BDL/S) in rats. In BDL/S rats, activity levels of aspartate transaminase (AST), alanine transaminse (ALT), alkaline phosphatase (ALP), concentration of total bilirubin in serum, and hydroxyproline content of the liver were significantly increased. The ST treatment (either 100 ${m}g/kg/day$ or 200 ${m}g/kg/day$, p.o. for 4 weeks) in BDL/S rats reduced the serum AST, ALT and ALP activity levels significantly (p<0.01). Similarly, when compared to the control group, the concentration of hydroxyproline in the livers of the BDL/S rats treated with 100${m}g$ or 200${m}g$ ST treated rats decreased by 40% and 33% respectively, when compared to the BDL/S control group (p<0.01). The morphological characteristics of fibrotic liver that were observed in the BDL/S control group, improved in the ST treated BDL/S group. In the fibrotic liver of BDL/S rats treated with ST, a marked reduction in the numbers of alpha smooth muscle cell actin positive stellate cells was observed. These results indicate that doses of either 100 or 200 ${m}g/kg/day$ of methanol extract from S. tetrandra, had an antifibrotic effect in rats with liver fibrosis induced by bile duct ligation and scission.

• KSBB Journal
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• v.30 no.4
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• pp.182-190
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• 2015

The Zostera marina ethanolic extract (ZMEE) was tested in this study to investigate the anti-inflammatory activity in LPS-induced RAW 264.7 cells and mouse model. Nitric oxide production and inducible nitiric oxide synthase expression in cells treated with ZMEE was reduced significantly in a dose-dependent manner. Similarly, the secretion of pro-inflammatory cytokines such as interleukin (IL)-6, IL-$1{\beta}$, and TNF-${\alpha}$ was inhibited markedly. In addition, the expression of nuclear factor kappa B (NF-${\kappa}B$) and the phosphorylation of JNK, ERK, and p38 MAPKs was suppressed by ZMEE as well. In vivo test, ZMEE attenuated the croton oil-induced mouse ear edema and there were no mortalities in mice administered 5,000 mg/kg body weight of ZMEE during the observation periods. The results in photomicrograph of mice ear tissue showed the reduction of dermal thickness and the number of infiltrated mast cells. These results indicate that ZMEE inhibits the production of LPS-induced pro-inflammatory mediators, suggesting that ZMEE may be a potential material for anti-inflammatory therapies.

• YAKHAK HOEJI
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• v.52 no.5
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• pp.331-344
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• 2008

Recently, the FDA (Food and Drug Administration) of the United States and many advanced countries remark biomarkers and surrogate endpoints as a critical path tool on model based drug development. Economic, technical and social profit on model based drug development like a reduction of the length of research and development have been achieved. Therefore we summarize previous studies about biomarkers and surrogate endpoints and suggest a development direction of therapeutic agents. In diabetes mellitus (DM) and osteoporosis, there are remarkable increases in number of patients and most of patients take medicine during their whole lifetime. For this reason, many patients with DM and osteoporosis have a tolerance on their medicine. We expect that research and development on biomarkers and surrogate endpoints will contribute to new drug development on DM and osteoporosis. Biomarkers for DM are blood levels of glucose, insulin, ${HbA}_{1c}$, CRP, alpha-glucosidase, adiponectin and DPP-4. Among these, validated surrogate endpoints for DM are blood levels of glucose, insulin and ${HbA}_{1c}$ Biomarkers for osteoporosis are BMD, BMC, trabecular volume, ICTP, DPD, osteocalcin, the activity of osteoclast and production of osteoblast. The validated surrogate endpoints for osteoporosis are BMD only. This review summarizes all suggested biomarkers and surrogate endpoints in DM and osteoporosis. The biomarkers are classified by drugs, and the method of validation for surrogate endpoints is suggested. This information would contribute to suggest a direction of DM and osteoporosis therapeutic agent development.

• Food Science and Biotechnology
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• v.18 no.3
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• pp.630-635
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• 2009

This study was performed to analyze various antioxidants, to evaluate the antioxidative activities, and to measure the protective effect for gap junction intercellular communication (GJIC) to assess the functional potency of the cherry tomato. The ascorbic acid, lycopene, and ${\beta}-carotene$ were measured at $503.4{\pm}9.6$, $39.7{\pm}1.5$, and $7.4{\pm}0.3$ mg/100 g d.w., and ${\alpha}-$, ${\beta}+{\gamma}-$, ${\delta}-tocopherol$ contents were measured at $8.3{\pm}0.1$, $1.7{\pm}0.0$, and $0.1{\pm}0.0$ mg/100 g d.w., respectively. Cherry tomato extract using hexane/acetone/EtOH (2:1:1, CTE) exhibited a ABTS radical scavenging activity with an $IC_{50}$ value of $48.83{\pm}0.30\;{\mu}g/mL$. The cherry tomato protected against the inhibition of GJIC induced by $H_2O_2$ in WB-F344 rat liver epithelial cells, and the reduction in phosphorylated Cx43 was most clearly correlated with the concentration of CTE. These results demonstrated that the cherry tomato harbors a wealth of potent antioxidants and might be protect human body against the inhibition of the GJIC by toxic components.

• Journal of The Korean Society of Integrative Medicine
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• v.11 no.1
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• pp.63-70
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• 2023

Purpose : Excessive alcohol causes damage to skeletal muscles, leading to the development of a specific disease entity called alcoholic myopathy. Chronic inflammation is related as an underlying mechanism for the loss of muscle mass induced by alcohol. Pro-inflammatory cytokines such as TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) play a role in this process. The acupuncture point Feng Shi (GB 31) is located on the midline of the lateral aspect of the thigh, above the transverse popliteal crease. This acupoint is used for the treatment of weakness, atrophy, numbness, and post-stroke symptoms of lower limbs. The purpose of this study was to investigate the effect of Feng Shi stimulation on muscle atrophy caused by chronic alcohol administration. Method : Young male Sprague-Dawley rats were randomly divided into three groups of eight each: Normal, Control, and GB31. The rats in the Control and GB31 groups were orally given 25 % ethanol (5 ㎖/kg, body weight) daily for 4 weeks. The Normal group was similarly administered saline. The acupressure at Feng Shi was treated to rats in the GB31 group. After 4 weeks, the body weight, muscle weight and cross-sectional area of gastrocnemius were assessed and the histological changes in gastrocnemius muscle fiber were observed by hematoxylin and eosin staining. Moreover, TNF-α and IL-6 expressions were immunohistochemistrically evaluated. Results : Acupressure stimulation at Feng Shi had a protective effect on the weight reduction of the gastrocnemius muscle caused by alcohol intake, and had an effect of suppressing anatomical change in muscle fiber and decreasing the average cross-sectional area. Also, the immunoreactivities of TNF-α and IL-6 in the GB31 group were decreased. Conclusion : These results suggest that acupressure at Feng Shi has protective effects on chronic alcohol-induced muscle atrophy by inhibiting pre-inflammatory proteins such as TNF-α and IL-6.

• Tuberculosis and Respiratory Diseases
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• v.44 no.2
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• pp.360-378
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• 1997

Background : Severe acute lung injury(ALI), also known as the adult respiratory distress syndrome(ARDS), is a heterogenous nature of dynamic and explosive clinical synrome that exacts a mortality of approximately 50%. Endotoxin(ETX) is an abundant component of the outer membrane of gram-negative bacteria capable of inducing severe lung injury in gram-negative sepsis and gram-negative bacterial pneumonia, which are among the most common predisposing causes of ARDS. The influx of PMNs into airway tissue is a pathological hallmark of LPS-induced lung injury. And there is a substantial evidence suggesting that cytokines are important mediators of lung injury in gram-negative sepsis. However, the kinetics of phagocytes and cytokines by an exact time sequence and their respective pathogenic importance remain to be elucidated. This study was performed to investigate the role of phagocytes and proinflammatory cytokines in ETX-induced ALI through a time course of changes in the concentration of protein, $TNF{\alpha}$ and IL-6, and counts of total and its differential cells in BALF. The consecutive histologic findings were also evaluated. Method : The experimental animals, healthy male Sprague-Dawley, weighted $200{\pm}50g$, were divided into control- and ALI- group. ALI was induced by an intravenous administration of ETX, 5mg/kg. Above mentioned all parameters were examined at 0(control), 3, 6, 24, 72 h after administration of ETX. $TNF{\alpha}$ and IL-6 cone. in BALF were measured by a bioassay. Results : The protein concentration and total leukocyte count(TC) in BALF was significantly increased at 3h compared to controls(p < 0.05). The protein conc. was significantly elavated during observation period, but TC was significantly decreased at 72h(p < 0.05 vs. 24h). There was a close relationship between TC and protein cone. in BALF(r = 0.65, p < 0.001). The PMN and monocyte count was well correlated with TC in BALF, and the correlation of PMN(r = 0.97, p < 0.001) appeared to be more meaningful than that of monocyte(r = 0.61, p < 0.001). There was also a significant correlation between protein cone. and PMN or monocyte count in BALF(PMN vs. monocyte : r = 0.55, p < 0.005 vs. r = 0.64, p < 0.001). The count of monocyte was significantly elavated during observation period though a meaningful reduction of PMN count in BALF at 72h, this observation suggested that monocyte may, at least, partipate in the process of lung injury steadly. In this study, there was no relationship between IL-6 and $TNF{\alpha}$ cone., and $TNF{\alpha}$ but not IL-6 was correlated with TC(r = 0.61, p < 0.05) and monocyte(r = 0.67, p < 0.05) in BALF only at 3, 6h after ETX introduced. In particular, the IL-6 cone. increased earlier and rapidly peaked than $TNF{\alpha}$ cone. in BALF. In histologic findings, the cell counts of lung slices were increased from 3 to 72h(p < 0.001 vs. NC). Alveolar wall-thickness was increased from 6 to 24h(p < 0.001 vs. NC). There was a significant correlation between the cell counts of lung slices and alveolar wall-thickness(r= 0.61, p < 0.001). This result suggested that the cellular infiltrations might be followed by the alterations of interstitium, and the edematous change of alveolar wall might be most rapidly recovered to its normal condition in the process of repair. Conclusion : We concluded that although the role of PMN is partly certain in ETX-induced ALI, it is somewhat inadequate to its known major impact on ALL Alveolar macrophage and/or non-immune cells such as pulmonary endothelial or epithelial cells, may be more importantly contributed to the initiation and perpetual progression of ETX-induced ALI. The IL-6 in ETX-induced ALI was independent to $TNF{\alpha}$, measured by a bioassay in BALF. The early rise in IL-6 in BALF implies multiple origins of the IL-6.

• Korean Journal of Materials Research
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• v.8 no.12
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• pp.1158-1164
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• 1998

Aluminium sulfate solution was prepared by sulfuric acid treatment from gibbsite. Aluminium sulfate hydrate [$Al_2(SO_4)_3$ · $nH_2O$] was precipitated from aluminium sulfate solution by adding it into ethylalcohol. From XRD analysis as-prepared $Al_2(SO_4)_3$ · $nH_2O$ was confirmed to have mixed-crystalization water(n=18, 16, 12, 6). The average water of crystalization calculated from thermogravimetry(TG) was 14.7. Aluminium sulfate hydrate [$Al_2(SO_4)_3$ · $nH_2O$] was thermally decomposed and converted to $Al_2(SO_4)_3$ at $800^{\circ}C$, $\gamma-Al_2O_3$ at $900-1000^{\circ}C$, and $\alpha-Al_2O_3$ at $1200^{\circ}C$. Ni-doped $\gamma-Al_2O_3$, was synthesized from the slurry of as-prepared $\gamma-Al_2O_3$, with the ratio of [Ni]/[Al]=0.5. The reaction conditions of synthesis were determined as initial pH 9.0 and temperature $80^{\circ}C$ The basicity(pH) of slurry was controlled by using urea and $NH_4OH$ solution. Urea was also used for deposition-precipitation. For determining termination of reaction, the data acquisition was performed by oxidation reduction potential(ORP), conductivity and pH value in the process of reaction. Termination of the reaction was decided by observing the reaction steps and rapid decrease in conductivity. On the other hand, BET(Brunauer, Emmett and Teller) and thermal diffusity of Ni- doped $\gamma-Al_2O_3$, with various content of Ni were measured and compared. Thermal stability of Ni- doped $\gamma-Al_2O_3$ at $1250^{\circ}C$ was confirmed from BET and XRD analysis. The surface state of Ni-doped $\gamma-Al_2O_3$ was investigated by X-ray photoelectron spectroscopy(XPS). The binding energy at $Ni2P_{3/2}$ increased with increasing the formation of $NiAl_2O_4$ phase.

• Journal of Biosystems Engineering
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• v.4 no.1
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• pp.1-23
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• 1979

The use of barley seeder attached to rotary tiller in the rural area has a significant meaning not only for the solution of labor peak season, but also for the increase of land utilization efficiency. The facts that presently being used barley seeders are all based on the mechanical principles of the reverse rotation, center drive and are all using forward rotating tine, which is used to be easily and heavily worn out when it rotates reversely, raise problem of recommending them to rural area in Korea. Therefore, the main objective of the study was to develop new type of rotary tine attachable to barley seeders. To attain the objective the following approaches were applied. (1) The kinematic analysis of reverse rotating barley seeders. (2) The studies on the soil bin and artificial soil. (3) The comparative experiment on the power requirement of prototype tine. The results obtained from the studies are summarized as follow: 1. The kinematic analysis of barley seeder attached to rotary tiller: The following results were obtained from the kinematic analysis for deriving general formulae of the motion and velocity characterizing the rotary tine of barley seeders presently being used by farmers. a) The position vector (P) of edge point (P) in the rotary tine of reverse rotating, center drive was obtained by the following formula. $$P=(vt+Rcos wt)i+Rsin wt j+ \{ Rcos \theta r sin \alpha cos (wt- \beta +\theta r) +Rsin \theta r sin \alpha sin (wt-\beta + \theta r) \} lk $$ b) The velocity of edge point $(P^')$ of reverse rotating, center drive rotary tine was obtained by the following formula. $$(P^')=(V-wR sin wt)i+(w\cdot Rcoswt)j + \{ -w\cdot Rcos \theta r\cdot sin \alpha \cdot sin (wt-\beta +\theta r) + w\cdot Rsin \theta r\cdot sin \alpha \cdot cos (wt- \beta + \theta r \} k $$ c) In order to reduce the power requirement of rotary tine, the angle between holder and edge point was desired to be reduced. d) In order to reduce the power requirement, the edge point of rotary tine should be moved from the angle at the begining of cutting to center line of machine, and the additional cutting width should be also reduced. 2. The studies on the soil bin and artificial soil: In order to measure the power requirement of various cutting tines under the same physical condition of soil, the indoor experiments Viere conducted by filling soil bin with artificially made soil similar to the common paddy soil and the results were as follows: a) When the rolling frequencies$(x)$ of the artificial soil were increased, the densIty$(Y)$ was also increased as follows: $$y=1.073200 +0.070780x - 0.002263x^2 (g/cm^3)$$ b) The absolute hardness $(Y)$ of soil had following relationship with the rolling frequencies$(x)$ and were increased as the rolling frequencies were increased. $$Y=37.74 - \frac {0.64 + 0.17x-0. 0054x^2} {(3.36-0.17x + 0.0054x^2)^3} (kg/cm^3)$$ c) The density of soil had significant effect on the cohesion and angle of internal friction of soil. For instance, the soil with density of 1.6 to 1.75 had equivalent density of sandy loam soil with 29.5% of natural soil moisture content. d) The coefficient of kinetiic friction of iron plate on artificial soil was 0.31 to 0.41 and was comparable with that of the natural soil. e) When the pulling speed of soil bin was the 2nd forward speed of power tiller, the rpm of driving shaft of rotary was similar to that of power tiller, soil bin apparatus is indicating the good indoor tester. 3. The comparative experiment on the power requirement of prototype tine of reverse rotating rotary: According to the preliminary test of rotary tine developed with various degrees of angle between holder and edge pcint due to the kinematic analysis, comparative test between prototype rotary tine with $30 ^\circ $ and $10 ^\circ$ of it and presently being used rotary tine was carried out 2nd the results were as follows: a) The total cutting torque was low when the angle between holder and edge point was reduced. b) $\theta r$ (angle between holder and edge point) of rotary tine seemed to be one: of the factors maximizing the increase of torque. c) As the angle between holder and edge point ($\theta r$) of rotary tine was $30 ^\circ $ rather than $45 ^\circ $, the angle of rotation during cutting soil was reduced and the total cutting torque was accordingly reduced about 10%, and the reduction efficiency of total cutting torque was low when the angle between holder and edge point ($\theta r$) of rotary tine was $10 ^\circ $, which indicates that the proper angle between holder and edge point of rotary tine should be larger than $10 ^\circ $ and smaller than $30 ^\circ $ . From above results, it could be concluded that the use of the prototype rotary tine which reduced the angle between holder and edge point to $30 ^\circ $, insted of $45 ^\circ $, is disirable not only decreasing the power requirements, but also increasing the durabie hour of it. Also forward researches are needed, WIlich determine the optimum tilted angle of rotary brocket, and rearrangement of the rotary tine on the rotary boss.

• The Journal of Korean Academy of Prosthodontics
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• v.34 no.2
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• pp.246-265
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• 1996

After adjusting glazed surface of laminate veneer porcelain by reduction in the clinical procedure, an additional polishing procedure is required to smoothen the roughened surface by reduction, as it is difficult to glaze it again in the furnace. In this study, four kinds of laminate veneer porcelain were ground with diamond points as done in the clinical procedure. The adjusted porcelain surface was polished with Durawhite stone, Ceramiste points, Exa cerapol, Porcelain polishing wheel, Diamond polishing paste. The degree of surface roughness was evaluated with SEM and profilometer at each step, The self glazed surface and the glazed surface with glazing powder were compared with the polished surface and surface roughness of four kinds of laminate veneer porcelain according to the polishing method and step were obserbed. The following results were obtained : 1. There was no difference in the average surface roughness Ra value and the surface roughness obserbed under SEM according to the polishing methods and steps used, among the four kinds of laminate veneer porcelain including Colorlogic, Exelco, Vintage, and Vitadur alpha product. 2. Due to porosities, the surface in the course of polishing by polishing instruments was rougher than the glazed surface, evaluated with a SEM. 3. Insta-Glaze diamond polishing paste has no statistical difference with self glazed group 1, although it has a lower value in average surface roughness Ra value. 4. Group 2 which was glazed with galzing powder was lowest in view of SEM, but it revealed higher surface roughness Ra value than group 1, the glazed surface and group 8, polished by diamond polishing paste, due to surface waveness. 5. Proper surface smoothness could not be in the surface roughness analysis of SEM and profilometer by Shofu laminate polishing kit composed of Diamond point, Durawhite stone and Ceramiste points. Based on the results of this study, the following conclusions can be drawn. We obtain low surface roughness than glazed surface by polishing instruments, but not perfect results clinically. In order to obtain a perfect clinical result or a surface smoothness comparable to glazed porcelain there is a need for further improvement of porcelain materials, condensa-tion techniques, polishing instruments and polishing methods. Furthermore card should be taken not to breakdown the glazed surface during the clinical and laboratory procedure.

• The Korean Journal of Pharmacology
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• v.25 no.1
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• pp.115-134
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• 1989

Combined effects of ganciclovir (GCV) and vidarabine (ara-A) on the replication, DNA synthesis, and gene expression of wild type-1 herpes simplex virus (HSV-1) and three acyclovir (ACV)-resistant HSV-1 mutants were studied. These mutants include a virus expressing no thymidine kinase $(ACV^r)$, a virus expressing thymidine kinase with altered substrate specificity $(IUdR^r)$, and a mutant expressing altered DNA polymerase $(PAA^r5)$. GCV, an agent activated by herpesvirus specific thymidine kinase, showed potent antiviral activity against the wild type HSV-1(KOS) and DNA polymerase mutant $(PAA^r5)$. The ACV-resistant mutants with thymidine kinase gene $(ACV^r\;and\;IUdR^r)$ were resistant to GCV. All tested wild type HSV-1 or ACV-resistant HSV-1 mutants did not display resistance to vidarabine (are-A). Combined GCV and ara-A showed potentiating synergistic antiviral activity against wild type KOS and $PAA^r5$, and showed subadditive combnined ativiral activity against thymidine kinase mutants. Combined GCV and ara-A more significantly inhibited the viral DNA synthesis in wild type KOS and $PAA^r5-infected$ cells to a greater extent than either agent alone, but the synergism was not determined in $ACV^r$ or $IUdR^r-infected$ cells. These data clearly indicate that combined GCV and ara-A therapy might be useful for the treatment of infections caused by wild type HSV-1 or ACV-resistant HSV-1 with DNA polymerase mutation. ACV-resistant viruses with the mutation in thymidine kinase gene are also, resistant to GCV, but susecptible to ara-A, indicating that ara-A would the drug of choice for the treatment of ACV-resistant HSV-1 which does not express thymidine kinase or expresses thymidine kinase with altered substrate specificity. While the synthesis of viral ${\alpha}-proteins$ of wild type HSV-1 was not affected by ACV, GCV, ara-A, or combined GCV and ara-A, the synthesis of ${\beta}-proteins$ was slightly but significantly increased at the later stage of viral infection by the antiviral agents. The synthesis of ${\gamma}-proteins$ of wild type HSV- 1 was significantly inhibited by ACV, GCV, ara-A, and combined GCV and ara-A. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ also significantly altered the expression of viral ${\beta}-and$ ${\gamma}-proteins$, of which efffct was similar to that of GCV $(10-{\mu}M)$ alone. Although ACV at the concentration of $10-{\mu}M$ did not alter the expression of ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ of ACV-resistant $PAA^r5$, GCV and ara-A significantly alter the epression of ${\beta}-and$ ${\gamma}-proteins$, not ${\alpha}-protein$, as same manner as they altered the expression of those proteins in cells inffcted with wild type HSV-1. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ altered the expression ${\beta}-and$ ${\gamma}-proteins$ in $PAA^r5$ infected cells, and the effect of combined regimen was comparable of that of GCV $(10-{\mu}M)$. These data indicate that the alteration in the expression of ${\beta}-and$ ${\gamma}-proteins$ in wild type HSV-1 or $PAA^r5$ infected cells could be more significantly affected by combined GCV and are-A than individual GCV or ara-A. In view of the fact that (a) viral ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ are synthesized in a cascade manner; (b) ${\beta}-proteins$ are essential for the synthesis of viral DNA; (c) the synthesis of ${\beta}-proteins$ are inhibited by ${\gamma}-proteins$; and (d) most ${\gamma}-proteins$ are made from the newly synthesized progeny virus, it is suggested that GCV and ara-A, alone or in combination, primarily inhibit the synthesis of viral DNA, and by doing so might exhibit their antiherpetic activity. The alteration in viral protein synthesis in the presence of tested antiviral agents could result from the alteration in viral DNA synthesis. From the present study, it can be concluded that (a) combined GCV and ara-A therapy would be beneficial for the control of inffctions caused by wild type HSV-1 or ACV-resistant DNA polymerase mutants; (b) the combined synergistic activity of GCV and ara-A is due to further decrease in the viral DNA by the combined regimen; (c) ara-A is the drug of choice for the infection caused by ACV-resistant HSV-1 with thymidine kinase mutation; and (d) the alteration in viral protein synthesis by GCV and ars-A, alone or in combination, is mostly due to the decreased synthesis of viral DAN.