• Title/Summary/Keyword: Dose-response

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Study of the immunosuppressive activity of methanolic extract of Madhuca longifolia (Koenig)

  • V., Chitra;Ganesh, Dhawle;Shrinivas, Sharma
    • Advances in Traditional Medicine
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    • v.10 no.3
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    • pp.150-154
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    • 2010
  • The immunosuppressive activity of the Methanol extract of bark of Madhuca longifolia (Koenig) consisting of a mixture of saponins, flavonoids, tannins, steroids, phenol and glycosides was studied on the immune responses in mice. Methanol extract of Madhuca longifolia (MLL) was administered orally at doses of 50, 100 and 150 mg/kg/day to healthy mice divided into four groups consisting of six animals each. The assessment of immunomodulatory activity was carried out by testing the humoral (antibody titre) and cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs. Furthermore, the effect on hematological parameters as well as relative organ weight was determined. On oral administration MML showed a significant decrease delayed type hypersensitivity (DTH) response whereas the humoral response to sheep RBCs was unaffected. Thus MLL significantly suppressed the cellular immunity by decreasing the footpad thickness response to sheep RBCs in sensitized mice. With a dose of 100 and 150 mg/kg/day the DTH response was $7.66{\pm}2.75$ and $6.41{\pm}1.21$ respectively in comparison to corresponding value of $14.50{\pm}2.38$ for untreated control group. These differences in DTH response were statistically significant (P < 0.05). The study demonstrates that MLL shows preferential suppression of the components of cell-mediated immunity and shows no effect on the humoral immunity.

Evaluation the Output Dose of Linear Accelerator Photon Beams by Blind Test with Dose Characteristics of LiF:Mg,Cu,P TLD (LiF:Mg,Cu,P 열형광선량계의 선량특성을 이용한 눈가림법에 의한 출력선량 평가)

  • Choi, Tae-Jin;Lee, Ho-Joon;Yie, Ji-Won;Oh, Young-Gi;Kim, Jin-Hee;Kim, Ok-Bae
    • Progress in Medical Physics
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    • v.20 no.4
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    • pp.308-316
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    • 2009
  • To achieve the accurate evaluation of given absorbed dose from output dose of linear accelerator photon beam through investigate the characteristics of LiF:Mg,Cu,P TLD powder. This experimental TL phosphor is performed with a commercial LiF:Mg,Cu,P powder (Supplied by PTW) and TL reader (LTM, France). The TLD was exposed to 6 MV X rays of linear accelerator photon beam with range 15 to 800 cGy in blind dose at two hospitals. The dose evaluation of TLD was through the experimental algorithms which were dose dependency, dose rate dependency, fading and powder weight dependency. The glow curve has shown the three peaks which are 110, 183 and 232 degrees of heating temperature and the main dosimetric peak showed highest TL response at 232 high temperature. In this experiments, the LiF:Mg,Cu,P phosphor has shown the 2.5 eV of electron trap energy with a second order. This experiments guided the dose evaluation accuracy is within 1% +2.58% of discrepancy. The TLD powder of LiF:Mg,Cu,P was analyzed to dosimetric characterists of electron captured energy and order by glow shape, and dose-TL response curve guided the accuracy within 1.0+2.58% of output dose discrepancy.

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A Feasibility Study on the Lens of Eye Dose Assessment Using the System of Multi-Element TLD (다중소자 열형광선량계에 의한 수정체 등가선량 평가의 적정성 연구)

  • Lee, Na-Rae;Han, Seung-Jae;Lee, Byung-Il;Cho, Kun-Woo
    • Journal of Radiation Protection and Research
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    • v.37 no.2
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    • pp.96-102
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    • 2012
  • International Commission on Radiological Protection (ICRP) has revised its recommendations concerning the tissue reaction to ionizing radiation in accordance with consideration of the detriment arising from non-cancer effects of radiation on health based on recent epidemiological basis. Particularly, for the lens of the eye, the threshold in absorbed dose revised to be 0.5 Gy, for occupational exposure in planned exposure situation the commission recommended "An equivalent dose limit for the lens of the eye of 20 mSv in a year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv." To monitor the radiation exposure of radiation worker, TLD is typically provided and the lens of eye dose can be assessed by run of dose calculation algorithm with TL element response data. This study is to assess equivalent dose of the lens of eye using the Harshaw TLD system and its two different dose calculation algorithms. The result provides the Harshaw TLD system showed the assessment of the lens of eye dose with 48.84% error range.

Risperidone as a Janus in Mood Disorder (기분장애에서 risperidone의 양면성)

  • Yoon, Doh Joon
    • Korean Journal of Biological Psychiatry
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    • v.4 no.2
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    • pp.198-210
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    • 1997
  • To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

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Persistence and Anamnestic Response of Antibody to HBsAg Induced by Natural Immunization or Vaccine Treatment (자연발생 또는 백신접종후 생긴 HBsAg에 대한 항체의 지속성과 Anamnestic Response)

  • Chung, Whan-Kook;Sun, Hee-Sik;Chung, Kyu-Won;Ro, Jae-Chul;Kim, Boo-Sung
    • Journal of Preventive Medicine and Public Health
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    • v.20 no.2 s.22
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    • pp.280-286
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    • 1987
  • For evaluating the boosting (anamnestic) effects of the most recent commercially produced plasma derived heat-inactivated hepatitis B vaccine (A. Co.), 117 adults with naturally acquired antibody to hepatitis B surface antigen (anti-HBs) were selected at random. In addition, out of case immunized at zero and 1 month, and boosted at 6 months (primary boosting) by conventional vaccine (B. Co), inactivated by pepsin digestion and formalin treatment, 11 cases who showed elevated titer after primary boosting were also submitted to the study. The results were as follows: 1) Out of the 117 subjects with naturally acquired anti-HBs, 6(5.1%) showed isolated anti-HBs and the titers were below 10 ratio units (RU). Negative seroconversion was seen in 4(3.4%) of the 117 cases at 12 months after the screening and, of these cases, 3 showed isolated anti-HBs and the titers were below 10 RU. 2) Eighty-three percent of the cases with naturally acquired isolated anti-HBs below 10 RU did not respond to a booster injection with 3 us dose of A. Co. vaccine at all, but 90% of the other subjects responded. 3) The anti-HBs titers of all the 11 cases who showed a rise of more than 10 RU (increased GMT, 28.04) at one month after primary booster injection by $20{\mu}g$ dose of B. Co. vaccine decreased at 19 months after the primary booster. And 3 subjects (27.3%) of the 11 reached negative seroconversion. All of the 11 cases, who had secondary booster injection with $3{\mu}g$ dose of A. Co. vaccine at 19 months after primary boosting, showed increased anti-HBs titer at least 20 RU or more (increased GMT, 57. 72) at one month after the boosting. According to the above results in the anti-HBs screening survey for the purpose of immunization with hepatitis B vaccine, subjects with isolated anti-HBs below 10 RU should be regarded as being in an unimmunized state. In cases who are in risk circumstances, immunized primarily with a $20{\mu}g$ dose of B. Co. vaccine, a secondary booster injection should be given within 2 years after initiation of primary immunization and a $3{\mu}g$ booster dose of A. Co. vaccine can be reliably used.

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Impact of Treatment Time on Chemoradiotherapy in Locally Advanced Cervical Carcinoma

  • Pathy, Sushmita;Kumar, Lalit;Pandey, Ravindra Mohan;Upadhyay, Ashish;Roy, Soumyajit;Dadhwal, Vatsla;Madan, Renu;Chander, Subhash
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.12
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    • pp.5075-5079
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    • 2015
  • Background: Adverse effects of treatment prolongation beyond 8 weeks with radiotherapy for cervical cancer have been established. Clinical data also show that cisplatin increases the biologically effective dose of radiotherapy. However, there are no data on the effect of overall treatment time in patients with locally advanced cervical cancer treated with concomitant chemo-radiotherapy (CCRT) in an Indian population. The present study concerned the feasibility of concurrent chemotherapy and interspacing brachytherapy during the course of external radiotherapy to reduce the overall treatment time and compare the normal tissue toxicity and loco-regional control with a conventional schedule. Materials and Methods: Between January 2009 and March 2012 fifty patients registered in the Gynaecologic Oncology Clinic of Institute Rotary Cancer Hospital with locally advanced cervical cancer (FIGO stage IIB-IIIB) were enrolled. The patients were randomly allocated to treatment arms based on a computer generated random number. Arm I (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions, and weekly cisplatin $40mg/m^2$. High dose rate intra-cavitary brachytherapy (HDR-ICBT) was performed after one week of completion of external beam radiotherapy (EBRT). The prescribed dose for each session was 7Gy to point A for three insertions at one week intervals. Arm II (n=25) treatment consisted of irradiation of the whole pelvis to a dose of 50 Gy in 27 fractions. Mention HDR-ICBT ICRT was performed after 40Gy and 7Gy was delivered to point A for three insertions (days 23, 30, 37) at one week intervals. Cisplatin $20mg/m^2/day$ was administered from D1-5 and D24-28. Overall treatment time was taken from first day of EBRT to last day of HDR brachytherapy. The overall loco-regional response rate (ORR) was determined at 3 and 6 months. Results: A total of 46 patients completed the planned treatment. The overall treatment times in arm I and arm II were $65{\pm}12$ and $48{\pm}4$ days, respectively (p=0.001). At three and six months of follow-up the ORR for arm I was 96% while that for arm II was 88%. No statistically significant difference was apparent between the two arms. The overall rate of grade ${\geq}3$ toxicity was numerically higher in arm I (n=7) than in arm II (n=4) though statistical significance was not reached. None of the predefined prognostic factors like age, performance status, baseline haemoglobin level, tumour size, lymph node involvement, stage or histopathological subtype showed any impact on outcome. Conclusions: In the setting of concurrent chemoradiotherapy a shorter treatment schedule of 48 days may be feasible by interspacing brachytherapy during external irradiation. The response rates and toxicities were comparable.

Pharmacological Profile of KR-31125, an Orally Active AT1 Receptor Antagonist (안지오텐신 수용체 리간드 KR-31125의 생체 내 활성에 관한 연구)

  • Lee, Sung-Hou
    • Journal of Life Science
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    • v.20 no.7
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    • pp.969-976
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    • 2010
  • In vivo studies of KR-31125 (2-butyl-5-dimethoxymethyl-6-phenyl-7-methyl-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b]pyridine) were performed in pithed rats, conscious angiotensin II (AII) challenged normotensive rats, renal hypertensive rats (RHRs) and furosemide-treated beagle dogs. KR-31125 induced a non-parallel right shift in the dose-pressor response curve to AII ($ID_{50}$: 0.095 mg/kg) with a dose-dependent reduction in the maximum responses in pithed rats. Compared to losartan, this antagonistic effect was about 18 times more potent, presenting competitive antagonism. Other agonists such as norepinephrine and vasopressin did not alter the responses induced by KR-31125. Orally administered KR-31125 had no agonistic effect and dose-dependently inhibited the pressor response to AII with a slightly weaker potency ($ID_{50}$: 0.25 and 0.47 mg/kg, respectively) in the AII-challenged normotensive rat model, but with a more rapid onset of action than losartan (time to $E_{max}$: 30 min for KR-31125 and 6 hr for losartan). KR-31125 produced a dose-dependent antihypertensive effect with a higher potency than losartan in RHRs, and these effects were confirmed in furosemide-treated dogs where they presented a dose-dependent and long-lasting (>8 hr) antihypertensive effect with a rapid onset of action (time to $E_{max}$: 2-4 hr), as well as a 20-fold greater potency than losartan. These results suggest that KR-31125 is a potent, orally active $AT_1$ receptor antagonist that can be applied to the development of new diagnostic and research tools as an added exploratory potential of $AT_1$ receptor antagonist.

Exocrine Secretory Responsiveness of Dispersed Pancreatic Acini to Secretagogues in Camostat-treated Rats (Camostat 투여 흰쥐 이자 외분비선의 분비자극물질에 대한 반응성)

  • Kim, Chul;Kim, Dong-Goo;Kim, Kyung-Hwan
    • The Korean Journal of Pharmacology
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    • v.30 no.2
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    • pp.205-215
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    • 1994
  • It is well known that chronic stimulation with CCK gives rise to growth of exocrine pancreas and to increased content of enzyme proteins in pancreas. However, littls Is known about changes of the secretory function of exocrine pancreas which has been chronically stimulated with CCK, especially about the responsiveness to secretagogues such as CCK, caerulein and carbachol. The present study was performed to investigate the effect of camostat on secretory profiles and the responsiveness to secretagogues of exocrine pancreas by observing in vitro amylase release stimulated by cholecystokinin-octapeptide(CCK-8) and carbachol in dispersed isolated pancreatic acini from camostat-treated rats for 4 or 10 days. The results summarized as follows : 1) The maximal effective concentration of CCK-8 in amylase release in the camostat treated group was greater than control group, but that of carbachol was not different between groups. 2) Analysis of the stimulated amylase release as the percentage of the maximal response revealed that camostat treatment caused right-shift of the dose-response curve of CCK-8. Camostat did not cause significant changes in the dose-response curve of carbachol. 3) There were considerable increases in the amylase release in the camostat-treated group, compared to the control when acini were stimulated with CCK-8 $10^{-9}\;M$ and carbaochol $10^{-6}\;M$, and higher concentrations. 4) There was a reverse correlation between the tissue content and the maximal release(percent of the total content) of amylase. These results suggest that chronic exposure of exocrine pancreas to increased endogenous CCK can enhance the responsiveness of exocrine enzyme secretion to secretagogues, especially at higher concentrations of CCK and carbachol.

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The Role of Radiotherapy in Esophageal Cancer (식도암에 있어서 방사선치료의 역할)

  • Choi, Eun-Kyung;Kim, Jung-Soo;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.3 no.2
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    • pp.123-129
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    • 1985
  • A retrospective analysis was undertaken of 46 patients who were referred with squamous cell carcinoma of the esophagus during the period of March 1979 through October 1982, and who were treated by curative radiotherapy in the Department of Therapeutic Radiology Seoul National University Hospital. The overall two-year actuarial survival rate was $20\%$ Survival was analyzed with respect to the site of the cancer, its size, radiation dose, and degree of response. Patients with the best two-year survival rate are the ones who had the tumor no of more than 5cm in length $(39.3\%)$ or confined to the upper third of the esophagus $(29.5\%)$. An optimum radiation dose ranged from 1600 to 1700 rets. Patients to complete response had $42.4\%$ of two-year actuarial survival, but those to no response had $0\%$ of survival.

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Early treatment volume reduction rate as a prognostic factor in patients treated with chemoradiotherapy for limited stage small cell lung cancer

  • Lee, Joohwan;Lee, Jeongshim;Choi, Jinhyun;Kim, Jun Won;Cho, Jaeho;Lee, Chang Geol
    • Radiation Oncology Journal
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    • v.33 no.2
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    • pp.117-125
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    • 2015
  • Purpose: To investigate the relationship between early treatment response to definitive chemoradiotherapy (CRT) and survival outcome in patients with limited stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively reviewed 47 patients with LS-SCLC who received definitive CRT between January 2009 and December 2012. Patients were treated with systemic chemotherapy regimen of etoposide/carboplatin (n = 15) or etoposide/cisplatin (n = 32) and concurrent thoracic radiotherapy at a median dose of 54 Gy (range, 46 to 64 Gy). Early treatment volume reduction rate (ETVRR) was defined as the percentage change in gross tumor volume between diagnostic computed tomography (CT) and simulation CT for adaptive RT planning and was used as a parameter for early treatment response. The median dose at adaptive RT planning was 36 Gy (range, 30 to 43 Gy), and adaptive CT was performed in 30 patients (63.8%). Results: With a median follow-up of 27.7 months (range, 5.9 to 75.8 months), the 2-year locoregional progression-free survival (LRPFS) and overall survival (OS) rates were 74.2% and 56.5%, respectively. The mean diagnostic and adaptive gross tumor volumes were 117.9 mL (range, 5.9 to 447 mL) and 36.8 mL (range, 0.3 to 230.6 mL), respectively. The median ETVRR was 71.4% (range, 30 to 97.6%) and the ETVRR >45% group showed significantly better OS (p < 0.0001) and LRPFS (p = 0.009) than the other group. Conclusion: ETVRR as a parameter for early treatment response may be a useful prognostic factor to predict treatment outcome in LS-SCLC patients treated with CRT.