• Title/Summary/Keyword: Administration and dosage

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Neuroprotective effects of herbal mixture HT070 on global cerebral ischemia in rats

  • Song, Jungbin;Lee, Donghun;Kim, Young-Sik;Lee, Hyun Jeong;Lee, Seunggyeong;Kim, Dong Kuk;Kang, Shin Ho;Shin, Yong Kook;Choi, Ho-Young;Kim, Hocheol
    • The Korea Journal of Herbology
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    • v.31 no.4
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    • pp.101-109
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    • 2016
  • Objectives : HT070 is a mixture of herbal extracts from root of Scutellaria baicalensis and stem bark of Eleutherococcus senticosus , which have long been used for stroke therapy in traditional Korean Medicine. The purpose of this study was to investigate the neuroprotective effects of HT070 on global cerebral ischemia and its potential mechanisms.Methods : Transient global cerebral ischemia was produced by 10 min of four-vessel occlusion (4-VO) in male Wistar rats. HT070 was administered orally at a dosage of 200 mg/kg twice at 0 and 90 min after reperfusion. Hippocampal neuronal damage was measured 7 days after reperfusion. To explore the potential mechanisms, we used hydrogen peroxide (H2O2)-induced rat pheochromocytoma (PC12) cells as an in vitro model. PC12 cells were pretreated with HT070 for 1 h and then exposed to 100 μM H2O2 for 6 h in the presence of HT070. Cell viability was measured by MTT assay and the mRNA expression of Bax, Bcl-2, iNOS and COX-2 were measured by quantitative RT-PCR.Results : Oral administration of HT070 at a dose of 200 mg/kg significantly reduced neuronal death in the hippocampal CA1 region by 13.4% as compared to the vehicle-treated group. HT070 increased cell viability, reversed the down-regulated Bcl-2 mRNA level, and suppressed the up-regulated mRNA expressions of Bax, iNOS, and COX-2 in H2O2-treated PC12 cells.Conclusions : HT070 protects against delayed neuronal death after global cerebral ischemia and its neuroprotection properties might be attributed to the inhibition of mitochondrial apoptosis and ROS-generating enzymes.

Dissolution Characteristics of Hydrophobic Drug-Soluble Carrier Coprecipitates(III) -Dissolution Behaviour of Indomethacin from Several Fast Release Solid Dispersions of Indomethacin-

  • Jeon, In-Koo;Lee, Min-Hwa;Kim, Shin-Keun
    • Journal of Pharmaceutical Investigation
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    • v.6 no.3
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    • pp.58-69
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    • 1976
  • It is well established that dissolution is freruently the rate limiting step in the gastrointestinal absorpton of a drug from a solid dosage from. The relationship between the dissolution rate and absorption is particularly distinct when considering drugs of low solubility. Consequently, numerous attempts have been made to modify the dissolution characteristics of poorly water soluble drugs. Since dissolution rate is directly proportional to surface area, one may increase the rate by decreasing the particle size of the drug. Levy has considered a number of methods by which a drug may be presented to the GI fludids in finely divided from. The direct method is the utilization of microcrystalline or micronized particles. A second method involves the administration of solutions from which, upon dilution with gastric fluids, the dissolved drug will precipitate in the form of very fine particles. A more unique way of obtaining microcrystalline dispersions of a drug has been ercently suggested by Sekiguchi et al. They have first proposed the formation of a eutectic mixture of a poorly water soruble drug with a physiologically inert, easily soluble carrier. When such systems are exposed to water or GI fluids, the soluble carrier will dissolve rapidly and the finely dispersed drug particles will then be released. It has been suggested by Shefter and Higuchi that the formation of crystalline solvate could be a powerful tool in affecting rapid disslution of highly insoluble substances. Goldberg et al. have noted that the formation of solid solution could reduce the particle size to a minimum and increase the dissolution rate as well as the solubility of the durgs. It has also been shown that the rates of solution of drugs were appreciably increased by coprectipitating the drug with soluble polymers. The increase was found to be sensitive to the method of preparation, the molecular weight of polymer and the particular ratio of drugs to polymer. Although several investigations have demontrated that the solubility and/or dissolution rates of drugs can be increased in this manner, little information is available in the literature related to the in vivo absorption pattern of drugs orally administered as PVP coprecipitates. Recently, however, it was demonstrated that both the rate and extent of absorption of the insoluble drug could be markedly enhanced when orally administered to rats in the form of a coprecipitate with PVP. The purpose of the present investigation was to ascertain the general appility of soluble polymer coprectation technique as a method for enhancing the in vitro dissolution rate of hydrophobic indomethacin. To accomplish this aim, the dissolution characteristics of pure indomethacin, indomethcin-polymer physical mixtures and indomethacin-polymer coprecipitates were quantitatively studied by comparing their relative dissolution rates. The solubility and dissolution behavior of these systems were also examined.

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Suppressive effects of Sojinjiyangtang(SJJY) on Der f-induced Atopic Dermatitis in NC/Nga Mice. (NC/Nga 생쥐에 유발된 아토피 피부염에 대한 소진지양탕(消疹止痒湯)의 억제 효과와 면역 조절 작용)

  • Lee, Won-Gu;Jin, Mi-Rim;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.16 no.2
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    • pp.171-190
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    • 2007
  • Atopic dermatitis is a chronic inflammatory skin disease characterized by pruritic and erythromatous skin lesions. In this study we examined the suppressive effects of SJJY on der f induced atopic dermatitis in NC/Nga mic, and concluded as follows: Oral administration of SJJY significantly decreased the severity score in the skin lesions at the dosage of 6.6 mg/25g/day for 8 weeks. SJJY significantly suppressed the infiltration of inflammatory cells into skin compared with control, and decreased the expression of CD4, CD8, CD20 and CCR3 in the skin lesions. SJJY significantly decreased the level of IgE in the serum compared with control, and the levels of IgM, IgG2a and IgG2b were also decreased. SJJY significantly decreased the levels of IL-6, but not TNF-a, in the serum compared with control. The levels of IFN-$\gamma$ was significantly increased in the supernatant of CD3/CD28 activated cultured splenocytes from the SJJY treated mice. The levels of IL-4 and IFN-$\gamma$ in the supernatants was much less in the der f activated splenocytes from SJJY treated mice than control. SJJY significantly increased the total number of cells in lymph node, while decreased the total number of skin compared with control. SJJY increased the number of CD3+ and CD4+ cell compared with control, while decreased the number of CD4+/CD25+ and CCR3+ cells in the PBMC. SJJY increased the number of CD3+, CD4+, CD8+, CD4+/CD25+, NKT+, CD3+/CD69+ cells compared with control, while decreased the number of B220+/IgE+, B220+/CD23+ cells in the lymph node. SJJY significantly decreased the number of CD3+/CD69+, CCR3+, B220+/IgE+, CD11b+/Gr-1+ compared with control in the skin lesions. Taken together, these results suggested that SJJY has suppressive effects on atopic dermatitis by the regulation of immune system and has potential as a therapeutics for atopic dermatitis. Further studies on molecular mechanisms on immune regulation are needed.

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Effect of 2-2'-dipyridyl in culture media and combined advantage of Streptococcus parauberis vaccine for preparation of Vibrio harveyi vaccine on olive flounder, Paralichthys olivaceus (Vibrio harveyi 백신의 효능 향상을 위한 배양 배지내 2-2'-dipyridyl 첨가 및 연쇄구균 백신과 혼합 투여의 효과)

  • Kim, Myoung Sug;Jung, Sung Hee;Hong, Suhee
    • Journal of Fisheries and Marine Sciences Education
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    • v.26 no.6
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    • pp.1366-1372
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    • 2014
  • This study was conducted to select the media for the formalin killed vaccine (FKC) production of Vibrio harveyi and its application for olive flounder, Paralichthys olivaceus. For this, we have investigated the immune effects of Vibrio harveyi FKC vaccines grown in 3 different media i.e. Tryptic Soy Broth (TSB), TSB containing 2-2'-dipyridyl (TSB-D), Brain Heart Infusion Broth (BHIB) on the production of agglutinating antibody and protection against Vibrio harveyi in olive flounder. Additionally, a dual vaccine was prepared by combining Streptococcus parauberis vaccine to V. harveyi vaccine and its efficacy was also analyzed with the determination of optimal administration dosage. Consequently, olive flounder immunized with FKC grown in TSB-D showed the same protection with the vaccine grown in BHIB and the optimal dose of the vaccine was 10mg/kg of body weight. Indeed the dual vaccine showed higher agglutination titer and protection than control fish. The optimal dose for dual vaccine was 10mg/kg body weight for each of two vaccines.

Determination of Optimal Dosage of Ethanol Extract of Houttuynia cordata Thunberg Against Benign Prostatic Hyperplasia (전립선 비대증에 대한 Houttuynia cordata Thunberg 에탄올 추출물의 최적용량 결정)

  • Lee, Jin Young;Kim, Hyung Hoi;Kang, Jae Seon
    • Journal of Life Science
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    • v.31 no.7
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    • pp.631-640
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    • 2021
  • Houttuynia cordata Thunberg has been studied for a variety of pharmacological actions in traditional oriental medicine. In this study, we investigated the effects of Houttuynia cordata ethanol extract (HCE) on benign prostatic hyperplasia (BPH) models induced by castration and testosterone propionate (TP) injection. Thirty rats were divided into six groups. One group was used as a normal control, and the other groups were castrated and had intraperitoneal injections of TP for 14 days to induce BPH. A positive control group was given daily doses of finasteride (5 mg/kg) to the BPH model. Rats administered HCE (0.5, 1 or 2 mg/kg) instead of finasteride were compared with controls as experimental groups. There was no statistical significance in terms of prostate weight based on 100 g of body weight. The concentrations of 5-α reductase and dehydroxytestosteronre (DHT) were determined via ELISA tests, and there was a significant decrease in all experimental groups. The 0.5 mg/kg HCE group had the lowest level of 5-α reductase, and the 2 mg/kg HCE group had the lowest level of DHT. In the histopathological observation of prostates, the control and the 2 mg/kg HCE groups had normal cell shapes and no swelling. However, in the negative control group and the 1 mg/kg HCE group, the cells were swollen, and the gap between the cells was narrowed. In particular, in the 0.5 mg/kg HCE group, some cells were bursting. Therefore, the administration of more than 2 mg/kg of HCE is suitable to protect against BPH.

Real-World Efficacy and Safety of Everolimus with Low Dose Tacrolimus in Liver Transplantation Recipients (실제 임상현장에서의 간이식 환자 대상 Everolimus와 저용량 Tacrolimus 병용요법의 유효성 및 안전성 평가)

  • Jang, Seoyoun;Kim, Boram;Jeon, Sujeong;Choi, Kyung Suk;Lee, Eunsook;Lee, Ju-Yeun;Lee, Euni;Han, Ho-Seong;Cho, Jai Young
    • Korean Journal of Clinical Pharmacy
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    • v.31 no.1
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    • pp.44-52
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    • 2021
  • Background: Post-transplant immunosuppression with calcineurin inhibitors (CNIs) is associated with kidney function impairment while mammalian target of rapamycin (mTOR) inhibitors, such as everolimus, can be used for its renal-sparing effects. In this study, we compared the efficacy and safety of everolimus with low dose tacrolimus (EVR+Low TAC) and conventional dose tacrolimus (TAC) in liver transplantation recipients. Methods: Medical records of recipients who received liver transplantation at Seoul National University Bundang Hospital from January 1st 2009 to December 31st 2018 were retrospectively reviewed. Cohort entry date was defined as the day everolimus was initiated and tacrolimus dosage was reduced. All patients were followed up for 1 year. Indicator of efficacy was the incidence of rejection and safety was evaluated by incidence of drug adverse events including renal function. Results: Among 118 patients, there were 40 patients (33.9%) in EVR+Low TAC group. Incidence of rejection, including both biopsy proven acute rejection and clinical rejection, was similar in two groups [7.5% (n=3) vs. 6.4% (n=5), p=1.000]. Renal dysfunction was less frequent in EVR+Low TAC [17.5% (n=7) vs. 35.9% (n=28), p=0.038]. However, incidence rates of dyslipidemia, oral ulcer were more frequent in EVR+Low TAC [45.0% (n=18) vs. 21.8% (n=17), p=0.009; 15.0% (n=6) vs. 1.3% (n=1), p=0.006]. Conclusions: In terms of prevention of rejection, EVR+Low TAC was as effective as TAC and had renal-sparing effect but was associated with increased risk of dyslipidemia and oral ulcer. This study demonstrates that EVR+Low TAC could be an alternative to liver transplant recipients with nephrotoxicity after administration of conventional dose tacrolimus.

Prospective Study on the Development of Glaucoma after Interferon alfa Therapy for Chronic Hepatitis B (만성 B형 간염 환자에서 인터페론 치료 후 녹내장 발생 여부의 전향적 연구)

  • Kwon, Young-Se;Choe, Yon-Ho;Hong, Sung-Bum
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.3 no.2
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    • pp.169-174
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    • 2000
  • Purpose: Previously reported ocular complications of interferon alfa administration are extremely rare. We experienced a 15-year-old boy with chronic hepatitis B who developed glaucoma after interferon alfa therapy. The purpose of this prospective study was to evaluate the possible development of glaucoma after interferon alfa therapy for chronic hepatitis B. Methods: Nine patients with chronic hepatitis B who visited Inha university hospital between February 1998 and July 1999 received interferon alfa therapy. We measured visual acuity, intraocular pressure, C/D ratio, and visual field examination at pre-interferon therapy, three and six months after therapy, respectively. Results: The total number of patients was 9 (4 boys and 5 girls). Mean age was $11.7{\pm}4.1$ years. The duration of therapy was 6 months and mean dosage of interferon was 5 million units. Compared with visual acuity, intraocular pressure, and C/D ratio at pre-therapy, those parameters at 3 months and 6 months after therapy showed no significant differences and none showed visual field defect after therapy. Conclusion: Our prospective study showed no evidence of development of glaucoma after interferon therapy. However, it is necessary to be concerned about the possibility of developing glaucoma or other ophthalmologic diseases after interferon therapy in chronic hepatitis B.

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Beneficial Effect of Curcumin on Epidermal Permeability Barrier Function in Hairless Rat (무모쥐에서 자외선에 의한 피부 장벽 손상에 미치는 커큐민의 보호 효과)

  • Jeon, Hee-Young;Kim, Jeong-Kee;Kim, Wan-Gi;Lee, Sang-Jun
    • Korean Journal of Food Science and Technology
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    • v.40 no.6
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    • pp.686-690
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    • 2008
  • Recent research has shown that curcumin has beneficial effects in a variety of skin diseases, including scleroderma, psoriasis, and skin cancer. In this study, we assessed the effects of curcumin on epidermal permeability barrier function in vivo and in vitro. In order to evaluate the effects of curcumin on epidermal permeability barrier function in vivo, hairless rats were exposed to UVB irradiation, and curcumin was administered orally at a dosage of 150 mg/kg per day for 8 weeks. Transepidermal water loss (TEWL) and epidermal thickness were measured at the end of the experiment. The expression of filaggrin, a marker of keratinocyte differentiation, and serine palmitoyltransferase (SPT), a marker of the formation of the stratum corneum lipid barrier, in human HaCat keratinocytes were analyzed. The in vivo results showed that an 8 week administration of curcumin markedly prevented the UVB-induced increase in TEWL. The UV-induced increase in epidermal thickness was also reduced significantly by curcumin treatment. The in vitro results demonstrated the concentration-dependent effects of curcumin on the expression of both filaggrin and SPT in HaCat cells, reflecting the notion that curcumin can induce epidermal keratinocyte differentiation and can improve the recovery of skin barrier functions. These results show that curcumin is a promising candidate for the improvement of epidermal permeability barrier function.

Effects of Baikal Skullcap (Scutellaria baicalensis Georgi) extracts on the recovery of liver function in $CCl_4$-exposed rats (황금 추출물이 $CCl_4$ 중독 쥐의 간장기능 회복에 미치는 영향)

  • Lim, Sang-Cheol
    • Korean Journal of Plant Resources
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    • v.23 no.1
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    • pp.54-59
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    • 2010
  • The objective of present study was to investigate the effect of Baikal Skullcap (Scutellaria baicalensis Georgi) extracts on recovery of liver function in $CCl_4$-exposed rats. The values of RBC, Hb and PCV did not show significant difference among all treatment groups. The counts of WBC was lower in Skullcap extracts groups than in control group. The ratio of neutrophils and eosinophiles were decreased, and the ratio of lymphocytes and monocytes were increased with increased administration of Skullcap extracts dosage. The ratio of basophils was, however, not significantly different among all treatment groups. The concentration of plasma total protein and albumin showed no significant difference among all treatment groups. The ratio of albumin/globulin was higher in Skullcap extracts groups than in control group. The activities of GOT, GPT and LDH were lower in Skullcap extracts groups, compared to control group. The liver IL-$1{\beta}$, IL-6 and TNF-$\alpha$ concentration were decreased, and IL-10 was increased in Skullcap extract groups, compared to control group. Results of this study suggested that Skullcap may alleviate liver inflammatory reaction induced by liver toxicity.

Validation of Voriconazole Therapeutic Drug Monitoring in Lung Transplant Recipients Receiving Voriconazole alone for Treatment of Invasive Aspergillosis (침습성 아스페르길루스증의 치료 목적으로 voriconazole을 단독으로 투여받는 폐이식 환자에서 voriconazole 약물혈중농도 모니터링의 유효성 검증)

  • Son, Yu Jeong;Lee, Kyung A;Jo, Ju Hee;Kim, Jae Song;Son, Eun Sun;Park, Moo Suk
    • Korean Journal of Clinical Pharmacy
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    • v.29 no.2
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    • pp.89-100
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    • 2019
  • Background: Invasive aspergillosis (IA) is associated with high morbidity and mortality, particularly among immunocompromised patients, such as lung transplant recipients. Voriconazole, the first-line therapy for IA, shows a non-linear pharmacokinetic profile and has a narrow therapeutic range. Careful and appropriate administration is necessary, primarily because it is used for critically ill patients; however, the clinical usefulness of therapeutic drug monitoring (TDM) has not been sufficiently verified. Therefore, in this study, we validated the safety and efficacy of voriconazole TDM in lung transplant recipients receiving only voriconazole for IA treatment. Methods: The electronic medical records of lung transplant recipients (${\geq}19$ years of age) administered only voriconazole for > 7 days for treatment of IA from June 1, 2013 to May 31, 2018 were analyzed retrospectively. Results: Among the 54 patients, 27 each were allocated to TDM and non-TDM groups, respectively. There were no significant differences in patient characteristics between the two groups except for ICU-hospitalization status. Of the TDM group patients, 81.5% needed adjustment of voriconazole dosage because the levels were out of target range. Comparison of two groups showed that treatment response was higher throughout treatment and switching rates of second-line agents were significantly lower in the TDM group, but it was insufficient to confirm safety improvements through voriconazole TDM. Conclusions: Considering that the treatment response tended to be higher and the rates of switching to second-line antifungal agents were lower in the TDM group, voriconazole TDM may increase the therapeutic effect on IA in lung transplant patients.