• Title/Summary/Keyword: Dosing

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Effect of Eurycoma longifolia Jack on Laevator Ani Muscle in Both Uncastrated and Testosterone-Stimulated Castrated Intact Male Rats

  • Ang, Hooi-Hoon;Cheong, Hung-Seong
    • Archives of Pharmacal Research
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    • v.24 no.5
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    • pp.437-440
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    • 2001
  • It has been reported that Eurycoma longifolia Jack commonly known as Tongkat Ali has gained notoreity as a symbol of man's ego and strength by the Malaysian men because it increases male virility and sexual prowess during sexual activities. As such, the effects of 200, 400 and 800 mg/kg of butanol, methanol, water and chloroform fractions of E. longifolia Jack were studied on the laevator am muscle in both uncastrated and testosterone-stimulated castrated intact male rats after dosing them for 12 consecutive weeks. Results showed that 800 mg/kg of butanol, methanol, water and chloroform fractions of E. longifolia Jack significantly increased (p<0.05) the leavator am muscle to 58.56$\pm$1.22, 58.23 $\pm$0.31, 60.21 $\pm$0.86 and 62.35 $\pm$0.98 mg/100 g body weight, respectively, when compared with the control (untreated) in the uncastrated intact male rats and 49.23 $\pm$0.82, 52.23 $\pm$ 0.36, 50.21 $\pm$ 0.66 and 52.35 $\pm$ 0.58 mg/100 g body weight, respectivety, when compared to control (untreated) in the testosterone-stimulated castrated intact male rats. Hence the proandrogenic effect as shown by this study further supported the traditional use of this plant as an aphrodisiac.

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Pharmacodynamics of Potassium Channel Opener Lemakalim in the Isolated Rat Hearts and Conscious SHRs under Hyperkalemic and Hypokalemic Condition (칼륨채널 활성물질 Lemakalim의 고칼륨혈증 및 저칼륨혈증에서의 심기능에 대한 영향 및 항 고혈압작용)

  • 신홍섭;신화섭;권광일
    • YAKHAK HOEJI
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    • v.37 no.5
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    • pp.463-475
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    • 1993
  • Pharmacological effects of lemakalim on cardiovascular system were investigated using isolated rat hearts and conscious SHRs subjected to hyperkalemic and hypokalemic condition. In the isolated hearts perfused with normal physiological salt solution(4.7 mM KCI), lemakalim increased cardiac function and coronary flow, and these effects were significantly potentiated under hypokalemic(1.2, 2.5 mM KCI), but attenuated under hyperkalemic(IO mM KCI) condition. In conscious SHRS, lemakalim(0.1, 0.2, 0.3mg/kg, p.o.) produced a dose-related decrease in systolic blood pressure, the maximal hypotensive effect being reached around 0.5 hr after dosing. The intensity and the duration of hypotensive effect of lemakalim were significantly increased when administered in combination with dihydrochlorothiazide (2 mg/kg, p.o.), but decreased with triamterene(32 mg/kg, p.o.). It appears that the differential effects of two types of diuretics on the hypotensive action of lemakalim are due to their hypokalemic and hyperkalemic action, respectively. It is conclued that the concomitant use of $K^{+}$ channel openers and hypokalemic diuretics may be an appropriate model of combination therapy in the treatment of hypertension.

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Comprehension of Capsaicin for a Experimental Part of Physical Therapy (물리치료의 실험적 측면에 대한 Capsaicin의 이해)

  • Kim, Dong-Hyun;Kim, Jin-Sang
    • The Journal of Korean Physical Therapy
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    • v.13 no.1
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    • pp.219-227
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    • 2001
  • Capsaicin. a vanillyl amide(8-methy1-N-vanilly1-6-nonenamide) with a molecular weight of 305.42, was substance, interrupting the pain conducting pathway Until recently the neurotoxic effects of Capsaicin to adult animals were thought to be limited to the peripheral nervous system. But several reports suggest the possibility of central nervous system changes after Capsaicin administration to the adult rat. Capsaicin desensitization is defined as long lasting, reversible suppression of sensory neuron activity. How fast and for how long the desensitization develops is related to the dose and time of exposure to Capsaicin, and the interval between consecutive dosing. In the long term Capsaicin treatment can lead to morphological degeneration and changes in some small sensory neurons, predominantly unmyelinated C fiber afferent nerve fibers. Clinical interest has recently been roused by evidence that Capsaicin's desensitizing action may be of therapeutic value and that an endogenous Capsaicin-1 ike substance may exist. This study summarizes the fundamental knowledge(mechanism, receptors, et al of Capsaicin) of Capsaicin for physical therapists.

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Single Oral Dose Toxicity Test of Yukmijihwangtanggamibang, a Polyherbal Formula in ICR Mice (육미지황탕가미방(六味地黃湯加味方)의 마우스 경구 단회 투여 독성 평가)

  • Park, Mee-Yeon
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.25 no.1
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    • pp.122-131
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    • 2011
  • The object of this study was to evaluate the single dose toxicity of Yukmijihwangtanggamibang (YMJHTGMB), a polyherbal formula have been traditionally used as prevention or treatment agent for various lung diseases including chronic obstructive pulmonary disease (COPD), in male and female mice. Aqueous extracts of YMJHTGMB (Yield = 16.33%) wasadministered to female and male ICR mice as an oral dose of 2,000, 1,000 and 500 mg/kg (body weight) according to the recommendation of Korea Food and Drug Administration (KFDA) Guidelines. Animals were monitored for the mortality and changes in body weight, clinical signs and gross observation during 14 days after dosing, upon necropsy; organ weight and histopathology of 12 principle organs were examined. As results, we could not find any mortality, clinical signs, and changesin the body and organ weight except for soft feces restricted to YMJHTGMB 2,000 mg/kg treated two male mice (2/5; 40%) at 1 day after administration. In addition, no YMJHTGMB-treatment related abnormal gross findings and changes in histopathology of principle organs were detected except for some sporadic accidental findings. The results obtained in this study suggest that the 50% lethal dose and approximate lethal dose of YMJHTGMB aqueous extracts in both female and male mice were considered as over 2,000 mg/kg, the limited highest dosage recommended by KFDA Guidelines.

Micronucleus Test of Kong-Jin-Dan, a Polyherbal Formula, in Bone Marrow Cells of Male ICR Mice

  • Lee, Sang-Nam;Park, Ji-Ha;Ku, Sae-Kwang
    • Toxicological Research
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    • v.24 no.3
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    • pp.213-218
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    • 2008
  • In this research, the genotoxic effects of Kong-Jin-Dan(KJD), a polyherbal formula were evaluated using the mouse micronucleus test. KJD was administered once a day for 2 continuous days by oral gavage to male ICR mice at doses of 2000, 1000 and 500 mg/kg. Cyclophosphamide was used as a known genotoxic agent in a positive control. The appearance of a micronucleus is used as an index for genotoxic potential. In addition, the changes on the total white blood cells and differential counts on the lymphocytes, neutrophils, eosinophils, basophils and monocytes in the prepared blood smears were also conducted to observe the possible immunosuppress. The results obtained indicated that KJD shows no genotoxicity effects up to 2000 mg/kg dosing levels, but KJD shows slight increased trends in the blood total leukocyte numbers as pharmacological effects of immune stimulation. In addition, it is also considered that there were no problems from cytotoxicity of KJD tested in this study because the polychromatic erythrocyte ratio was detected as > 0.42 in all tested groups.

Effect of Hepatotoxicants on the Biliary and Urinary Excretion of Acetaminophen and its Metabolites in Rats (간독성물질들이 아세트아미노펜의 대사와 배설에 미치는 영향)

  • 박기숙;서경원;정태천;황세진;김효정
    • Biomolecules & Therapeutics
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    • v.1 no.1
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    • pp.50-57
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    • 1993
  • This study characterized the effect of liver injury produced by hepatotoxicants on the biliary and urinary excretion of acetaminophen(AA) metabolites. Liver damage was produced in male S.-D. rats, 24 hr after dosing with carbon tetrachloride(4CCl_4,$ 0.75 mι/kg, ip) or thioacetamide(TA, 200 mg/kg, ip), or 16 hr after administration of cadmium chloride(4CdCl_2,$ 3.9 mg/kg, iv). Liver damage without renal injury was confirmed by measuring serum enzymes, creatinine and BUN levels as well as by histopathological examination. AA and its metabolites were measured for 3 hr by HPLC in rats injected iv with 1 mmo1/kg of AA. The excreted amounts of AA-glucuronide into bile were reduced to 60~70% of control rats by hepatotoxicants, but did not change urinary excretion of AA-glucuronide and AA-sulfate. Treatments with $CCl_4,\; CdCl_2$ and TA decreased the total (biliary plus urinary) excretion of thioethers of AA(30~50% of control), suggesting that these toxicants decrease cytochrome P-450-mediated toxification of AA. However, treatments of $CdCl_2$and TA markedly enhanced the excretion of AA-mercapturate into urine. Thus, 4CdCl_2$ and TA not only influence the formation of AA-glutathione, but may also alter the excretory routes (i.e. bile and urine) for the elimination of AA-metabolite.

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Pharmacokinetics of CJ-50001i Recombinant Human Granulocyte-Colony Stimulating Factor, in Rats and Dogs (CJ-50001 (recombinant human granulocyte-colony stimulating factor)의 흰쥐와 개에서의 약물동태학적 연구)

  • 김성남;신재규;이수정;정용환;하석훈;김기완;고형곤;김제학
    • Biomolecules & Therapeutics
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    • v.6 no.4
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    • pp.400-405
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    • 1998
  • The pharmacokinetics of CJ-50001 (recombinant human granulocyte-colony stimulating factor, developed by R&D center of Cheil Jedang Corp.) were investigated in rats and dogs. The serum concentrations of CJ-50001 were measured by a sandwich enzyme immunoassay. After single intravenous (iv) administration of Cf-50001 to rats at a dose of 5 $\mu$g/kg, the mean terminal half-life and area under the concentration-time curve (AUC) were 0.96 h and 124.497g . h/ml, respectively. After single subcutaneous (sc) administration at the same dose, maximum serum concentration was observed at about 2 hours after administration, and the mean terminal half-life, AUC and the bioavailability were 1.11 h,63.58$\mu$g . h/ml and 51.07%, respectively. In repeated dosing studies, CJ-50001 was administered iv and sc to rats at a daily dose of 5$\mu$g/kg for 7 days. The pharmacokinetic parameters, such as mean AUC and terminal half-life, were no significantly different from those of single administration. Following single iv and sc administration of CJ-50001 to dogs at a dose of 5 $\mu$g/kg, mean AUCs were much higher than those of rats, due to the decreased clearence (CL). After sc administration to dogs, maximum serum concentration was observed at 2~4 hours after administration and the bioavailability was 54.60%.

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Immunotoxicological Effects of Mouse CpG Oligodeoxynucleotides in Lupus-prone NZB/NZW F1 Mice

  • Kim, Bo-Hwan;Seo, Dong-Jin;Jung, Soon-Hee;Kim, Soo-Ki
    • Molecular & Cellular Toxicology
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    • v.5 no.3
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    • pp.207-215
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    • 2009
  • Despite wide therapeutic use of CpG ODN against infection, allergy and cancer, the safety and toxicity of CpG ODNs were poorly delineated. Thus, we investigated whether optimal dosing of CpG ODN would affect immunotoxicological parameters in NZB/NZW F1 mice. Comparisons were made among control, non-CpG ODN and mouse CpG ODN ($10{\mu}g$)-treated groups for 4 weeks. To gauge the immunotoxicity of CpG ODNs, we measured nonspecific parameters, degree of lupus nephritis, proteinuria, or autoantibody, and cytokine expression in mRNA level of lymphocytes. We found that there were no significant differences among groups in nonspecific immunotoxicological profiles and in evaluation profiles of glomerulonephritis. However, titer of anti-dsDNA and anti-cardiolipin antibodies in mouse CpG ODN group rose three or eight-fold higher than in control group. Collectively, CpG ODN might be clinically less immunotoxic in terms of clinical profiles in lupus-prone NZB/NZW F1 mice, in spite of high autoantibody titer in CpG ODN treated groups.

Morphological studies on kidney in cyclophosphamide-treated NOD mice (Cyclophosphamide를 투영한 NOD 마우스의 신장에 대한 형태학적 연구)

  • Lee, Joon-sup;Seong, Je-kyung
    • Korean Journal of Veterinary Research
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    • v.34 no.4
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    • pp.653-664
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    • 1994
  • This study was carried out to investigate diabetic renal changes in cyclophosphamide(CY) treated nonobese diabetic(NOD) mice and to develop animal model of diabetic human nephropathy. The 8-week-old NOD and ICR mice were injected with cyclophosphamide intraperitoneally at 200mg/kg body weight and compared the chemical effects on these mice with the non-treated NOD and ICR mice respectively. The renal glomeruli in ICR, cyclophosphamide-treated ICR(ICR+CY), NOD and cyclophosphamide-treated NOD(NOD+CY) mice were observed by the light and electron microscopes. The results obtained were summarized as follows ; 1. Spontaneous incidences of diabetes mellitus in NOD mice were significantly promoted by dosing with cyclophosphamide. 2. Glomerulohypertrophy, proliferation of mesangium, partial thickening of glomerular basement membrane, and partial fusion of pedicels of podocyte were observed in NOD mice and NOD+CY mice. These changes were not observed in both ICR mice and ICR+CY mice. 3. The diabetic nephropathy observed in NOD+CY mice was more severe than that of non-treated NOD mice.

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Corrosion Control in Water Distribution System using Lime and Carbon Dioxide(I) - Determination of Optimum Operational Conditions in Lime Adding Process (소석회와 CO2를 이용한 상수관로의 부식제어(I) - 소석회 주입공정의 최적 운전인자 도출)

  • Sohn, Byung-Young;Byun, Kyu-Sik;Kim, Young-Il;Lee, Doo-Jin
    • Journal of Korean Society of Water and Wastewater
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    • v.22 no.3
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    • pp.373-378
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    • 2008
  • The pH & alkalinity adjustment method by lime and carbon dioxide($CO_2$) for corrosion control in water distribution system was investigated to determine the optimum operational condition in lime adding process in water treatment plant(WTP). The mixing time at dissolution tank and sedimentation time at saturator for maintaining optimal turbidity condition of lime supernatant were 60~75 minutes and 75~95 minutes, respectively. There was no difference according to $CO_2$ adding methods such as $CO_2$ saturated water or $CO_2$ gas. But, $CO_2$ saturated water could be convenience at WTP in terms of pH control and quantitative dosing. To minimize generation of calcium carbonate products, the short time interval between adding of lime and $CO_2$ is most important. The lime should be added below 32 mg/l for preventing pH rising and generation of calcium carbonate products at the heating condition.