• Title/Summary/Keyword: Dose-response Function

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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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IL-6 mRNA Expression in Mouse Peritoneal Macrophages and NIH3T3 Fibroblasts in Response to Candida albicans

  • Lee, Young-Sun;Kim, Hee-Sun;Kim, Sung-Kwang;Kim, Sang-Dal
    • Journal of Microbiology and Biotechnology
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    • v.10 no.1
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    • pp.8-15
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    • 2000
  • Despite extensive investigation, the mechanisms of immune responses to Candida albicans infection remain poorly understood. Using RT-PCR and Northern blot analysis, this study demonstrates the pattern of IL-6 mRNA expression in thioglycollate-elicited mouse peritoneal macrophages and NIH3T3 fibroblasts (NIH3T3) in response to C. albicans. The expression of IL-6 mRNA was detectable in both cell types. However, IL-10 mRNA was only expressed in the macrophages, and IL-4 mRNA was not expressed in neither of the two cell types. Although the phagocytic function of the macrophages was inhibited by Cytochalasin D, these macrophages could still induce the expression of IL-6mRNA. These findings indicated that the phagocytosis of C. albicans is not pivotal in the induction of IL-6 mRNA expression. A Northern blot analysis was used to investigate the dose effects of C. albicans and time-course kinetics of IL-6 mRNA expression at various time points. IL-6 mRNA was expressed in a dose-independent manner, and was detectable as early as 30min after C. albicans stimulation. It was evenly sustained up to 4h. These results can contribute to understanding the mechanism of IL-6 mRNA expression in macrophages and NIH3T3 cells in response to C, albicans.

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Association between Thyroid Dysfunction and Severity, Treatment Response in Schizophrenic Inpatients (조현병 입원 환자에서의 갑상샘 기능이상과 증상 심각도, 치료 반응과의 관계)

  • Jung, Mee-Jool;Hwang, Hyun-Kuk;Seo, Yung-Eun;Choi, Jong-Hyuk
    • Korean Journal of Biological Psychiatry
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    • v.26 no.1
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    • pp.14-21
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    • 2019
  • Objectives Thyroid hormone deficiency during the neurodevelopmental period can impair brain development and induce psychiatric symptoms. This study examined the association between thyroid dysfunction and the severity of symptoms in schizophrenia patients, and the treatment response of patients with schizophrenia. Methods Three hundred thirty-eight schizophrenia patients, with no prior history of thyroid disease or taking medication associated with it, were studied. We assessed the blood thyroid hormone level, the Brief Psychiatric Rating Scale (BPRS) scores on the day of admission and discharge, admission period, dose of administered antipsychotics, and the number of antipsychotic combinations. The collected data were subsequently analyzed using the Kruskal-Wallis test and Pearson's chi-square test. Results The percentage of schizophrenia patients who presented with abnormal thyroid hormone level was 24.6%. High total triiodothyronine (TT3) (p = 0.003), low TT3 (p = 0.001), and high free thyroxine (fT4) (p < 0.001) groups showed a higher BPRS score on admission than did the normal thyroid hormone group, while thyroid stimulating hormone (TSH) levels were not significantly correlated with the severity of symptoms. Furthermore, thyroid hormone was not associated with the treatment response assessed by the rate of BPRS score reduction, admission days, use of clozapine, and dose of antipsychotics. Conclusions The TT3 and fT4 hormone levels were significantly associated with the severity of symptoms in schizophrenia patients. These relations suggested that thyroid dysfunction may be associated with the severity of schizophrenia. And hence, further analysis of the results of the thyroid function test, which is commonly used in cases of psychiatric admission, is required.

Moderate hypofractionated image-guided thoracic radiotherapy for locally advanced node-positive non-small cell lung cancer patients with very limited lung function: a case report

  • Manapov, Farkhad;Roengvoraphoj, Olarn;Li, Minglun;Eze, Chukwuka
    • Radiation Oncology Journal
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    • v.35 no.2
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    • pp.180-184
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    • 2017
  • Patients with locally advanced lung cancer and very limited pulmonary function (forced expiratory volume in 1 second $[FEV1]{\leq}1L$) have dismal prognosis and undergo palliative treatment or best supportive care. We describe two cases of locally advanced node-positive non-small cell lung cancer (NSCLC) patients with very limited lung function treated with induction chemotherapy and moderate hypofractionated image-guided radiotherapy (Hypo-IGRT). Hypo-IGRT was delivered to a total dose of 45 Gy to the primary tumor and involved lymph nodes. Planning was based on positron emission tomography-computed tomography (PET/CT) and four-dimensional computed tomography (4D-CT). Internal target volume (ITV) was defined as the overlap of gross tumor volume delineated on 10 phases of 4D-CT. ITV to planning target volume margin was 5 mm in all directions. Both patients showed good clinical and radiological response. No relevant toxicity was documented. Hypo-IGRT is feasible treatment option in locally advanced node-positive NSCLC patients with very limited lung function ($FEV1{\leq}1L$).

Analytical Consideration of Surface Dose and Kerma for Megavoltage Photon Beams in Clinical Radiation Therapy

  • Birgani, Mohammad Javad Tahmasebi;Behrooz, Mohammad Ali;Razmjoo, Sasan;Zabihzadeh, Mansour;Fatahiasl, Jafar;Maskni, Reza;Abdalvand, Neda;Asgarian, Zeynab;Shamsi, Azin
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.1
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    • pp.153-157
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    • 2016
  • Background: In radiation therapy, estimation of surface doses is clinically important. This study aimed to obtain an analytical relationship to determine the skin surface dose, kerma and the depth of maximum dose, with energies of 6 and 18 megavoltage (MV). Materials and Methods: To obtain the dose on the surface of skin, using the relationship between dose and kerma and solving differential equations governing the two quantities, a general relationship of dose changes relative to the depth was obtained. By dosimetry all the standard square fields of $5cm{\times}5cm$ to $40cm{\times}40cm$, an equation similar to response to differential equations of the dose and kerma were fitted on the measurements for any field size and energy. Applying two conditions: a) equality of the area under dose distribution and kerma changes in versus depth in 6 and 18 MV, b) equality of the kerma and dose at $x=d_{max}$ and using these results, coefficients of the obtained analytical relationship were determined. By putting the depth of zero in the relation, amount of PDD and kerma on the surface of the skin, could be obtained. Results: Using the MATLAB software, an exponential binomial function with R-Square >0.9953 was determined for any field size and depth in two energy modes 6 and 18MV, the surface PDD and kerma was obtained and both of them increase due to the increase of the field, but they reduce due to increased energy and from the obtained relation, depth of maximum dose can be determined. Conclusions: Using this analytical formula, one can find the skin surface dose, kerma and thickness of the buildup region.

Loss of Function in GIGANTEA Gene is Involved in Brassinosteroid Signaling

  • Hwang, Indeok;Park, Jaeyoung;Lee, Beomgi;Cheong, Hyeonsook
    • Journal of Integrative Natural Science
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    • v.4 no.2
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    • pp.113-120
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    • 2011
  • Brassinosteroids (BRs) are plant steroid hormones that play essential roles in growth and development. Mutations in BR-signaling pathways cause defective in growth and development like dwarfism, male sterility, abnormal vascular development and photomorphogenesis. Transition from vegetative to reproductive growth is a critical phase change in the development of a flowering plant. In a screen of activation-tagged Arabidopsis, we identified a mutant named abz126 that displayed longer hypocotyls when grown in the dark on MS media containing brassinazole (Brz), an inhibitor of BRs biosynthesis. We have cloned the mutant locus using adapter ligation PCR walking and identified that a single T-DNA had been integrated into the ninth exon of the GIGANTEA (GI) gene, involved in controling flowering time. This insertion resulted in loss-of-function of the GI gene and caused the following phenotypes: long petioles, tall plant height, many rosette leaves and late flowering. RT-PCR assays on abz126 mutant showed that the T-DNA insertion in GIGANTEA led to the loss of mRNA expression of the GI gene. In the hormone dose response assay, abz126 mutant showed: 1) an insensitivity to paclobutrazole (PAC), 2) an altered response with 6-benzylaminopurine (BAP) and 3) insensitive to Brassinolide (BL). Based on these results, we propose that the late flowering and tall phenotypes displayed by the abz126 mutant are caused by a loss-of-function of the GI gene associated with brassinosteroid hormone signaling.

Increase in the Th1-Cell-Based Immune Response in Healthy Workers Exposed to Low-Dose Radiation - Immune System Status of Radiology Staff

  • Karimi, Gholamreza;Balali-Mood, Mahdi;Alamdaran, Seyed-Ali;Badie-Bostan, Hassan;Mohammadi, Elaheh;Ghorani-Azam, Adel;Sadeghi, Mahmood;Riahi-Zanjani, Bamdad
    • Journal of Pharmacopuncture
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    • v.20 no.2
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    • pp.107-111
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    • 2017
  • Objectives: Radiation is one of the most important sources of free radical (such as reactive oxygen species) production, which plays an essential role in the etiology of over hundred diseases. The aim of the study was to investigate some immune parameters and hematological indices in healthy workers of the Radiology Department, University Hospital of Mashhad, Iran. Methods: The study was performed on 50 healthy workers: 30 radiology staff as the case group and 20 laboratory workers as the control group. The radiation dose received by the radiology staff participating in the study was less than the annual maximum permissible level, 50 millisievert. Hematological parameters, lymphocyte proliferation and cytokine production were studied in both groups. Results: Among healthy radiology workers, the hematological indices did not differ statistically; however, their proliferation indices and $IFN-{\gamma}$ levels showed significant increases in parallel with decreases in the IL-4 levels as compared to controls. The immune system of workers exposed to low-dose ionizing radiation was found to be shifted from a Type 2 to a Type 1 response to promote cellular immunity. Conclusion: Based on our data, exposure to low-dose ionizing radiation may decrease the prevalence, frequency, and recurrence of various cancers and infectious diseases because of an increase in Th1-cell-based response, thus leading to more protection of the human body against tumor cells and foreign agents and possibly increased longevity. However, due to high rate of fluoroscopy use for interventional radiology, we suggest continuing research projects on radiation protection and hazards to prevent irreversible damage. As a recommendation, in future studies, radiology staff with a weakened immunity due to high radiation exposure should be considered as good choices to be treated using acupuncture techniques because acupuncture has been demonstrated to enhance the function and the number of immune cells.

Risk assessment for norovirus foodborne illness by raw oyster (Ostreidae) consumption and economic burden in Korea

  • Yoo, Yoonjeong;Oh, Hyemin;Lee, Yewon;Sung, Miseon;Hwang, Jeongeun;Zhao, Ziwei;Park, Sunho;Choi, Changsun;Yoon, Yohan
    • Fisheries and Aquatic Sciences
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    • v.25 no.5
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    • pp.287-297
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    • 2022
  • The objective of this study was to evaluate the probability of norovirus foodborne illness by raw oyster consumption. One hundred fifty-six oyster samples were collected to examine the norovirus prevalence. The oyster samples were inoculated with murine norovirus and stored at 4℃-25℃. A plaque assay determined norovirus titers. The norovirus titers were fitted with the Baranyi model to calculate shoulder period (h) and death rate (Log PFU/g/h). These kinetic parameters were fitted to a polynomial model as a function of temperature. Distribution temperature and time were surveyed, and consumption data were surveyed. A dose-response model was also searched through literature. The simulation model was prepared with these data in @RISK to estimate the probability of norovirus foodborne. One sample of 156 samples was norovirus positive. Thus, the initial contamination level was estimated by the Beta distribution (2, 156), and the level was -5.3 Log PFU/g. The developed predictive models showed that the norovirus titers decreased in oysters under the storage conditions simulated with the Uniform distribution (0.325, 1.643) for time and the Pert distribution (10, 18, 25) for temperature. Consumption ratio of raw oyster was 0.98%, and average consumption amount was 1.82 g, calculated by the Pert distribution [Pert {1.8200, 1.8200, 335.30, Truncate (0, 236.8)}]. 1F1 hypergeometric dose-response model [1 - (1 + 2.55 × 10-3 × dose)-0.086] was appropriate to evaluate dose-response. The simulation showed that the probability of norovirus foodborne illness by raw oyster consumption was 5.90 × 10-10 per person per day. The annual socioeconomic cost of consuming raw oysters contaminated with norovirus was not very high.

Dose-Response Effects of Epichlorohydrin on Male Reproductive Function in Rats

  • Kim, Kang-Hyeon;Shin, In-Sik;Lim, Jeong-Hyeon;Kim, Sung-Hwan;Park, Na-Hyeong;Moon, Chang-Jong;Kim, Sung-Ho;Shin, Dong-Ho;Kim, Jong-Choon
    • Toxicological Research
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    • v.25 no.4
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    • pp.203-207
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    • 2009
  • Present study was conducted to investigate potential effects of epichlorohydrin on testicular and epididymal function in male rats. The test chemical was administered to adult male rats by gavage at dose levels of 0, 3.125, 12.5, and 50 mg/kg/day for 7 days. Testicular and epididymal function were assessed by measurement of reproductive organ weight, testicular spermatid count, epididymal sperm count, motility and morphology, and histopathology in rats. At 50 mg/kg, a decrease in the sperm motility and an increase in the incidence of sperm abnormalities were observed. Histopathological examinations revealed an increase in the incidence of histopathological changes including cell debris in the ducts, vacuolization of the epithelial cells, oligospermia, and epithelial disruption in the proximal caput epididymidis. At 12.5 mg/kg, an increase in the incidence of histopathological changes of the epididymidis was found. There were no treatment-related effects at 3.125 mg/kg. These results show that 7-day repeated oral administration of epichlorohydrin to male rats results in adverse effects on sperm motility, sperm morphology, and epididymal histology at $\geq$ 12.5 mg/kg/day.

Effects of KH204 on the Relaxation Response of Rabbit Corpus Cavernosum and Reproductive Function in Male Rats (토끼 음경해면체평활근 이완 및 10주간 경구투여한 흰쥐의 생식기능에 미치는 KH204의 효과)

  • Lee, Hyun-Ji;Lee, Eun-Jeong;Kim, Hee-Seok;Kim, Si-Na;Hwang, Sung-Yeoun
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.7
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    • pp.847-852
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    • 2006
  • This study was designed to investigate the effects of KH204 on the relaxation response and reproductive function in male. Strips of rabbit corpus cavernosum were prepared for mounting and isometric tension measurement in an organ bath. On cavernosal strips contracted with $1{\times}10^{-6}$ phenylephrine and KH204 was applied in increasing concentrations from 0, 61, 183 and 549 mg/L, causing dose-dependent relaxation. Male Sprague-Dawley rats were orally administered with 61, 183 and 549 mg/kg/day of KH204 for 10 weeks. We examined organ weights, testicular sperm head counts, epididymal sperm counts, motility and morphology. KH204 relaxed rabbit corpus cavernosal strip contracted by $1{\times}10^{-6}$ phenylephrine in a dose-dependent manner. In the male rat, testicular weight was increased significantly in the KH204 treated groups compared with control group. Also in the testicular sperm head counts, epididymal sperm counts were increased significantly in the KH204-treated rats. In conclusion, the data suggest that KH204 could enhance erectile and reproductive function.