• Title/Summary/Keyword: dose index

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Studies on the Dopaminergic Neuronal Toxicity of MPTP and its Pyridium Metabolite, $MPP^+$ (MPTP와 대사물인 $MPP^+$의 도파민 신경세포에 대한 독성효과에 관한 연구)

  • Kim, Yong-Sik;Park, Chan-Woong;Yoon, Young-Ran;Youn, Yong-Ha
    • The Korean Journal of Pharmacology
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    • v.31 no.2
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    • pp.165-177
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    • 1995
  • Dissociated cell cultures from rat embryonic ventral mesencephalon were used to evaluate the mechanisms of $MPP^+$ neurotoxicity. The cells were treated with MPTP or $MPP^+$ and the viability of the cells was assessed biochemically; tyrosine hydroxylase (TH) immunoreactivity, protein, intracellular ATP and lactate content and lipid peroxidation. Also the generation of the intracellular oxidants was measured after loading 2', 7‘-dichlorofluorescin diacetate to the cells. When cultures were exposed to 0.1 mM $MPP^+$, at 2 hour incubation lactate was significantly accumulated in the cells and then the intracellular ATP content and TH immunoreactivity were decreased dose- and time-dependently. But, malondialdehyde as an index for lipid peroxidation was not changed even though the generation of the intracellular oxidants was stimulated by the addition of $MPP^+$. On the other hand, 1 mM MPTP significantly reduced the TH immunoreactivity at 24 hour exposure without any change in the intracellular A TP, lactate and MDA content until 6 hour exposure. And also MPTP inhibited the generation of the intracellular oxidants from control cells and $MPP^+$ exposed cells. These results indicate that cytotoxicity of $MPP^+$ is mediated by inhibiting the mitochondrial energy metabolism rather than generating the intracellular oxidants. And MPTP would have direct action in addition to conveting to the toxic metabolite, $MPP^+$ to exert the toxicity on the dopaminergic neurons.

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YKP1447, A Novel Potential Atypical Antipsychotic Agent

  • Dong, Seon-Min;Kim, Yong-Gil;Heo, Joon;Ji, Mi-Kyung;Cho, Jeong-Woo;Kwak, Byong-Sung
    • The Korean Journal of Physiology and Pharmacology
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    • v.13 no.2
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    • pp.71-78
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    • 2009
  • (S)-Carbamic acid 2-[4-(4-fluoro-benzoyl)-piperidin-1-yl]-1-phenyl-ethyl ester hydrochloride (YKP1447) is a novel "atypical" antipsychotic drug which selectively binds to serotonin (5-$HT_{2A}$, Ki=0.61 nM, 5-$HT_{2C}$, Ki=20.7 nM) and dopamine ($D_2$, Ki=45.9 nM, $D_3$, Ki=42.1 nM) receptors with over $10\sim100$-fold selectivity over the various receptors which exist in the brain. In the behavioral studies using mice, YKP1447 antagonized the apomorphine-induced cage climbing ($ED_{50}$=0.93 mg/kg) and DOI-induced head twitch ($ED_{50}$=0.18 mg/kg) behavior. In the dextroamphetamine-induced hyperactivity and conditioned avoidance response (CAR) paradigm in rats, YKP1447 inhibited the hyperactivity induced by amphetamine ($ED_{50}$=0.54 mg/kg) and the avoidance response ($ED_{50}$=0.48 mg/kg); however, unlike other antipsychotic drugs, catalepsy was observed only at much higher dose ($ED_{50}$=68.6 mg/kg). Based on the CAR and catalepsy results, the therapeutic index (TI) value for YKP1447 is over 100 (i.p.). These results indicate that YKP1447 has an atypical profile and less undesirable side effects than currently available drugs.

Anti-hyperglycemic and Anti-hyperlipidemic Effects of the Triterpenoid-Rich Fractions from Rubus coreanus and Rubus crataegifolius and Their Main Component, Niga-ichigoside $F_1$, in Streptozotocin-induced Diabetic Rats

  • Choi, Jong-Won;Yoo, Yeong-Min;Kim, Min-Young;Nam, Jung-Hwan;Nugroho, Agung;Park, Hee-Juhn
    • Natural Product Sciences
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    • v.14 no.4
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    • pp.260-264
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    • 2008
  • To find the antidiabetic activity of the tripterpenoid-rich fractions of Rubus coreanus (TRF-cor) and R. crataegifolius (TRF-cra) leaves or its main component niga-ichigoside $F_1$ (Niga-$F_1$), anti-hyperglycemic and antihyperlipidemic effects were investigated in the diabetic rat model induced by streptozotocin (STZ). Treatments of rats with 200 mg/kg of the TRF-cor, TRF-cra (each, p.o.) or 20 mg/kg of Niga-$F_1$ significantly inhibited the increase of blood glucose concentration about 44.8%, 28.7% or 20.6%, respectively, in the diabetic rats. In addition, treatments with those fractions inhibited the increase of serum concentrations of triglyceride, total cholesterol or LDL-cholesterol caused by STZ. The inhibitory rate on atherogenic index (AI) values of the TRFcor (200 mg/kg), TRF-cra (200 mg/kg) or Niga-$F_1$ (20 mg/kg)-treated groups were decreased about 55.7%, 36.3% or 22.6%, respectively, comparable to STZ-treated group. In the oral glucose tolerance test, treatment of TRF-cor or TRF-cra inhibited the increase of blood glucose concentration in the STZ-induced rats. Administration of 20 mg/kg of Niga-$F_1$ (p.o.) also exhibited similar effects with the effects of both TRFs at 200 mg/kg dose (p.o.). These results support that the triterpenoids, in particular Niga-$F_1$, are contributed to the antidiabetic effects of R. coreanus or R. crataegifolius.

Dosimetric comparison of axilla and groin radiotherapy techniques for high-risk and locally advanced skin cancer

  • Mattes, Malcolm D.;Zhou, Ying;Berry, Sean L.;Barker, Christopher A.
    • Radiation Oncology Journal
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    • v.34 no.2
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    • pp.145-155
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    • 2016
  • Purpose: Radiation therapy targeting axilla and groin lymph nodes improves regional disease control in locally advanced and high-risk skin cancers. However, trials generally used conventional two-dimensional radiotherapy (2D-RT), contributing towards relatively high rates of side effects from treatment. The goal of this study is to determine if three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), or volumetric-modulated arc therapy (VMAT) may improve radiation delivery to the target while avoiding organs at risk in the clinical context of skin cancer regional nodal irradiation. Materials and Methods: Twenty patients with locally advanced/high-risk skin cancers underwent computed tomography simulation. The relevant axilla or groin planning target volumes and organs at risk were delineated using standard definitions. Paired t-tests were used to compare the mean values of several dose-volumetric parameters for each of the 4 techniques. Results: In the axilla, the largest improvement for 3D-CRT compared to 2D-RT was for homogeneity index (13.9 vs. 54.3), at the expense of higher lung $V_{20}$ (28.0% vs. 12.6%). In the groin, the largest improvements for 3D-CRT compared to 2D-RT were for anorectum $D_{max}$ (13.6 vs. 38.9 Gy), bowel $D_{200cc}$ (7.3 vs. 23.1 Gy), femur $D_{50}$ (34.6 vs. 57.2 Gy), and genitalia $D_{max}$ (37.6 vs. 51.1 Gy). IMRT had further improvements compared to 3D-CRT for humerus $D_{mean}$ (16.9 vs. 22.4 Gy), brachial plexus $D_5$ (57.4 vs. 61.3 Gy), bladder $D_5$ (26.8 vs. 36.5 Gy), and femur $D_{50}$ (18.7 vs. 34.6 Gy). Fewer differences were observed between IMRT and VMAT. Conclusion: Compared to 2D-RT and 3D-CRT, IMRT and VMAT had dosimetric advantages in the treatment of nodal regions of skin cancer patients.

Assessment of Clinical Outcome in Dogs with Naturally Infected with Dirofilaria immitis after American Heartworm Society Protocol vs Slow Kill Method

  • Choi, Miru;Yoon, Won-Kyoung;Suh, Sang-IL;Hyun, Changbaig
    • Journal of Veterinary Clinics
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    • v.34 no.1
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    • pp.1-6
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    • 2017
  • Heartworm disease (HWD) in dogs is a life-threatening mosquito-borne disease resulting in right-sided congestive heart failure and inflammatory pulmonary disease. Due to complications from adulticidal therapy with melarsomine, slow kill protocol either with preventive dose of ivermectin or combined with doxycycline has been proposed for an alternative adultcidal therapy in dogs with HWD. Therefore, this study evaluated the clinical outcome of adultcidal therapy in dogs with class II stage of HWD after treating either American Heartworm Society (AHS) or slow kill protocol for 10 months. Clinical outcome after therapy was evaluated by clinical, radiographic and echocardiographic examination along with hematology before (D0) and after therapy (D300). Although clinical signs associated with HWD were all resolved after therapy in both groups, the infection was not cleared out 67% of dogs treated by slow kill protocol at the end of therapy. Furthermore, pulmonary arterial flow of acceleration time to ejection time ratio (AT/ET) and the right pulmonary artery distensibility index (RPADI) have been firstly used for detecting pulmonary hypertension in this study group. The pulmonary hypertension was more common in dogs with mild clinical signs, although tricuspid and pulmonary regurgitation were not detectable in most dogs in this study. Our study findings suggested that the slow kill protocol might not be efficacious enough to clear out HWD in dogs and more attention on the presence of pulmonary hypertension might be necessary for effective management of HWD in dogs.

Comparison of the Effects of Sufentanil and Fentanyl Intravenous Patient Controlled Analgesia after Lumbar Fusion

  • Kim, Do Keun;Yoon, Seung Hwan;Kim, Ji Yong;Oh, Chang Hyun;Jung, Jong Kwon;Kim, Jin
    • Journal of Korean Neurosurgical Society
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    • v.60 no.1
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    • pp.54-59
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    • 2017
  • Objective : Postoperative pain is one of the major complaints of patients after lumbar fusion surgery. The authors evaluated the effects of intravenous patient controlled analgesia (IV-PCA) using fentanyl or sufentanil on postoperative pain management and pain-related complications. Methods : Forty-two patients that had undergone surgery with lumbar instrumentation and fusion at single or double levels constituted the study cohort. Patients were equally and randomly allocated to a sufentanil group (group S) or a fentanyl group (group F) for patient controlled analgesia (PCA). Group S received sufentanil at a dose of $4{\mu}g/kg$ IV-PCA and group F received fentanyl $24{\mu}g/kg$ IV-PCA. A numeric rating scale (NRS) of postoperative pain was applied before surgery, and immediately and at 1, 6, and 24 hours (hrs) after surgery. Oswestry disability index (ODI) scores were obtained before surgery and one month after surgery. Opioid-related side effects were also evaluated. Results : No significant intergroup difference was observed in NRS or ODI scores at any of the above-mentioned time points. Side effects were more frequent in group F. More specifically, nausea, vomiting rates were significantly higher (p=0.04), but pruritus, hypotension, and headache rates were non-significantly different in the two groups. Conclusion : Sufentanil displayed no analgesic advantage over fentanyl postoperatively. However, sufentanil should be considerable for patients at high risk of GI issues, because it had lower postoperative nausea and vomiting rates than fentanyl.

Mineral Phosphate Solubilization by Wild Type and Radiation Induced Mutants of Pantoea dispersa and Pantoea terrae

  • Murugesan, Senthilkumar;Lee, Young-Keun;Kim, Jung Hun
    • Journal of Radiation Industry
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    • v.3 no.1
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    • pp.39-45
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    • 2009
  • Three mineral phosphate solubilizing (MPS) bacteria where isolated from rhizosphere soil samples of common bean and weed plants. 16S rDNA analysis indicated that the isolate P2 and P3 are closely related to Pantoea dispersa while isolate P4 is closely related to Pantoea terrae. Isolates P2 and P3 recorded $381.60{\mu}g\;ml^{-1}$ and $356.27{\mu}g\;ml^{-1}$ of tricalcium phosphate (TCP) solubilization respectively on 3 days incubation. Isolate P4 recorded the TCP solubilization of $215.85{\mu}g\;ml^{-1}$ and the pH was dropped to 4.44 on 24 h incubation. Further incubation of P4 sharply decreased the available phosphorous to $28.94{\mu}g\;ml^{-1}$ and pH level was raised to 6.32. Gamma radiation induced mutagenesis was carried out at $LD_{99}$ dose of the wild type strains. The total of 14 mutant clones with enhanced MPS activity and 4 clones with decreased activity were selected based on solubilization index (SI) and phosphate solubilization assay. Mutant P2-M1 recorded the highest P-solubilizing potential among any other wild or mutant clones by releasing $504.21{\mu}g\;ml^{-1}$ of phosphorous i.e. 35% higher than its wild type by the end of day 5. A comparative evaluation of TCP solubilization by wild type isolates of Pantoea and their mutants, led to select three MPS mutant clones such as P2-M1, P3-M2 and P3-M4 with a potential to release >$471.67{\mu}g\;ml^{-1}$ of phosphorous from TCP. These over expressing mutant clones are considered as suitable candidates for biofertilization.

Expression of the genes for peroxisome proliferator-activated receptor-γ, cyclooxygenase-2, and proinflammatory cytokines in granulosa cells from women with polycystic ovary syndrome

  • Lee, Joong Yeup;Tae, Jin Cheol;Kim, Chung Hyon;Hwang, Doyeong;Kim, Ki Chul;Suh, Chang Suk;Kim, Seok Hyun
    • Clinical and Experimental Reproductive Medicine
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    • v.44 no.3
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    • pp.146-151
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    • 2017
  • Objective: To identify differences in the expression of the genes for peroxisome proliferator-activated receptor $(PPAR)-{\gamma}$, cyclooxygenase (COX)-2, and the proinflammatory cytokines interleukin (IL)-6 and tumor necrosis factor $(TNF)-{\alpha}$ in granulosa cells (GCs) from polycystic ovary syndrome (PCOS) patients and controls undergoing controlled ovarian stimulation. Methods: Nine patients with PCOS and six controls were enrolled in this study. On the day of oocyte retrieval, GCs were collected from pooled follicular fluid. Total mRNA was extracted from GCs. Reverse transcription was performed and gene expression levels were quantified by realtime quantitative polymerase chain reaction. Results: There were no significant differences in age, body mass index, and total gonadotropin dose, except for the ratio of luteinizing hormone to follicle-stimulating hormone between the PCOS and control groups. $PPAR-{\gamma}$ and COX-2 mRNA was significantly downregulated in the GCs of PCOS women compared with controls (p= 0.034 and p= 0.018, respectively), but the expression of IL-6 and $TNF-{\alpha}$ mRNA did not show significant differences. No significant correlation was detected between the expression of these mRNA sequences and clinical characteristics, including the number of retrieved oocytes, oocyte maturity, cleavage, or the good embryo rate. Positive correlations were found among the $PPAR-{\gamma}$, COX-2, IL-6, and $TNF-{\alpha}$ mRNA levels. Conclusion: Our data may provide novel clues regarding ovarian GC dysfunction in PCOS, and indirectly provide evidence that the effect of $PPAR-{\gamma}$ agonists in PCOS might result from alterations in the ovarian follicular environment. Further studies with a larger sample size are required to confirm these proposals.

Antidiabetic Activity of IH-901 in db/db Mice (db/db 마우스에서 IH-901의 항 당뇨 활성)

  • Choi, Yun-Suk;Han, Gi-Cheol;Han, Eun-Jung;Park, Keum-Joo;Park, Jong-Suk;Sung, Jong-Hwan;Chung, Sung-Hyun
    • YAKHAK HOEJI
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    • v.50 no.6
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    • pp.345-350
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    • 2006
  • The pharmacological properties of ginseng are mainly attributed to ginsenosides, the active constituents that are found in the extracts of different species of ginseng. Lately; the studies on ginsenosides are mainly focused on IH-901, a major intestinal bacterial metabolite of ginsenosides. In this study; we examined the anti-diabetic activity of IH-901 in C57BU61 db/db mice model. IH-901 was administrated orally at a dose of 20 mg/kg for 5 weeks. During the experimental period, body weight and blood glucose levels were measured every week. After 5 weeks, db/db mice were sacrificed and diabetic parameters were analyzed. IH-901 treated group showed a significant decrease in fasting blood glucose levels (from 10.5 mM to 9.4 mM), insulin resistance index (from 163.6 to 100.2) and triglyceride levels (from 115.3 to 70.1) compared to the diabetic control. In Pancreatic islets morphology; IH-901 treated group revealed much less infltrated mononuclear cells, indicating that IH-901 recovered ${\beta}$-cell damage due to hyperglycemia. In addition, IH-901 upregulated expressions of glucose transporter 4 (GLUT4) and PPAR-${\gamma}$ in skeletal muscle and adipose tissue, respectively. Taken together IH-901might be a potential anti-hyperglycemic agent with insulin sensitizing effect.

The Urine Cotinine level and Periodontal Disease among Environmental Tobacco Smoke Exposure on Convergence study (간접흡연자의 요코티닌과 치주질환의 관련성에 관한 융합연구)

  • Kim, Song Sook
    • Journal of the Korea Convergence Society
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    • v.9 no.12
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    • pp.295-299
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    • 2018
  • The aim of this study was to evaluate the association between the level urine cotinine and periodontal diseases in Korea adults. The date from the 2014, 2015 Korean National Health and Nutrition Survey were used, and 5,146 subjects over 30 years were included in the analysis. Periodontal disease was assessed using the Community Periodontal Index. Binary logistic regression model was used to estimate the odds ratio with 95% confidence intervals. There was a 2.08-fold (95% CI; 1.73-2.05) increased in the odds of periodontal disease for those with any ETS exposure compared with those with non-smokers following adjustment for sex, age, education, and income. The level of urine cotinine also showed a dose-dependent increase in extent of periodontal disease. Among persons in the Korea who had never used tobacco, those exposed to ETS were more likely to have periodontal disease than were those not exposed to ETS. In the future, voluntary compliance of smokers to measures to reduce ETS exposure should be encouraged.