• Title/Summary/Keyword: Dose response relationship

Search Result 241, Processing Time 0.029 seconds

Experimental Studies on Lead Toxicity in Domestic Cats 1. Symptomatology and Diagnostic Laboratory Parameters (고양이의 납중독에 관한 실험적 연구 1. 임상증상 및 실험실적 평가)

  • Hong Soon-Ho;Han Hong-Ryul
    • Journal of Veterinary Clinics
    • /
    • v.10 no.1
    • /
    • pp.111-130
    • /
    • 1993
  • Lead toxicity was evaluated in forty-five cats on a balanced diet, Treated with 0(control), 10, 100(low), 1, 000, 2, 000, and 4, 000(high) ppm of lead acetate orally on a body weight basis. The objectives were to establish toxic dosage level of leaf in cats, to characterize changes in behavior and clinical pathology, and to demonstrate what blood lead concentrations correlate with the known dosages of lead. Some high dose cats showed projectile vomiting, hyperactivity, and seizures. The growth rates did not appear to be altered in any of the dosed groups. Normal blood lead concentration in cats were lower than that of humans, dogs, and cattle. Blood lead concentrations of 3 to 20$\mu\textrm{g}$/100$m\ell$ could be termed a 'subclinical' range in the cat. Clinical lead toxicity in cats may have blood lead concentrations ranging 20 to 120$\mu\textrm{g}$/100$m\ell$. Zinc protoporphyrin concentrations were proportional to lead dosages and a significant ZPP elevation, greater than 50$\mu\textrm{g}$/100$m\ell$, may be indicative of clinical lead toxicity. The enzyme aminolevulinic acid dehydratase showed an inverss dose response relationship for all lead dosages and a significant ZPP elevation, greater than 50$\mu\textrm{g}$/100$m\ell$, may be indicative of clinical lead toxicity. The enzyme aminolevulinic acid dehydratase showed an inverse dose response relationship for all lead dosages and appears to be a good indicator of lead exposure in cats. Urinary aminolevuliruc acid concentrations generally increased with lead dosage, but individual values varied. Hair lead concentrations rose proportionately to lead dosages. Lead at least in high doses appears to inhibit chemotactic activity of polymorphonuclear cells and monocytes. No consistent dose response relationships were observed in hemoglobin, RBC, WBC, neutrophil, lymphocyte, monocyte, and eosinophil counts. There were no consistent dose related changes in total protein, plasma protein, BUN, and ALT values. Reticulocyte counts did not increase significantly in most lead dosage levels, and are probably of little value in diagnosing lead toxicity in cats. The fact that no significant changes were found in nerve conduction velocities may support that there was no segmental demyelination resulting from lead ingestion. The lethal dose in cats appear to range from 60 to 150mg/kg body weight. A reliable diagnosis of lead poisoning can be made utilizing blood lead, ZPP, and ALAD, and hair lead.

  • PDF

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

  • Yoon, Doh Joon
    • Korean Journal of Biological Psychiatry
    • /
    • v.4 no.2
    • /
    • pp.198-210
    • /
    • 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.

  • PDF

Hormesis as a Confounding Factor in Epidemiological Studies of Radiation Carcinogenesis

  • Sanders Charles L.
    • Journal of Radiation Protection and Research
    • /
    • v.31 no.2
    • /
    • pp.69-89
    • /
    • 2006
  • Biological mechanisms for ionizing radiation effects are different at low doses than at high doses. Radiation hormesis involves low-dose-induced protection and high-dose-induced harm. The protective component is associated with a reduction in the incidence of cancer below the spontaneous frequency, brought about by activation of defensive and repair processes. The Linear No-Threshold (LNT) hypothesis advocated by the International Commission on Radiological Protection (ICRP) and the Biological Effects of ionizing Radiation (BEIR) Report VII for cancer risk estimations Ignores hormesis and the presence of a threshold. Cancer incidences significantly less than expected have been found in a large number of epidemiological studies including, airline flight personnel, inhabitants of high radiation backgrounds, shipyard workers, nuclear site workers in scores of locations throughout the world, nuclear power utility workers, plutonium workers, military nuclear test site Participants, Japanese A-bomb survivors, residents contaminated by major nuclear accidents, residents of Taiwan living in $^{60}Co$ contaminated buildings, fluoroscopy and mammography patients, radium dial painters, and those exposed to indoor radon. Significantly increased cancer was not found at doses <200 $mSv^*$. Evidence for radiation hormesis was seen in both sexes for acute or chronic exposures, low or high LET radiations, external whole- or partial body exposures, and for internal radionuclides. The ubiquitous nature of the Healthy Worker Effect (HWE)-like responses in cellular, animal and epidemiological studies negates the HWE as an explanation for radiation hormesis. The LNT hypothesis is wrong and does not represent the true nature of the dose-response relationship, since low doses or dose-rates commonly result in thresholds and reduce cancer incidences below the spontaneous rate. Radiation protection organizations should seriously consider the cost and health implications of radiation hormesis.

A Study on Gamma ray effects on Stress Response and Cellular Toxicity using Bacterial Cells

  • Min, Ji-Ho;Lee, Hyeon-Ju;Lee, Chang-U;Gu, Man-Bok
    • 한국생물공학회:학술대회논문집
    • /
    • 2000.11a
    • /
    • pp.187-190
    • /
    • 2000
  • Effects of gamma ionizing radiation on recombinant Escherichia coli cells containing stress promoters, recA, fabA, grpE, or katG, fused to luxCDABE originated from Vibrio fischeri were characterized by monitoring transcriptional responses reflected by bioluminescent output. Quantification of gamma-ray intensity may be possible using the recA and fabA promoter fusion since a linear enhancement of bioluminescence emission with increasing gamma-ray intensity was observed. Other strains sensitive to either oxidative stress (DPD2511, katG::luxCDABE) or protein-damaging stress (TV1061, grpE::luxCDABE) were also irradiated by gamma-rays, and resulted in no noticeable bioluminescent output while DPD2794 with recA promoter and DPD2540 with fabA promoter irradiated by the same intensities of gamma-rays gave a significant bioluminescent output. This indicates that the main stresses in the recombinant bacteria caused by ionizing radiation are DNA and membrane-damage, not protein- or oxidative-damage. In addition, in this study, to investigate the relationship between the radiation dose rate and bacterial responses, two recombinant Escherichia coli strains, DPD2794 and GC2, containing lac promoter fused to luxCDABE originating from Photorhapdus luminescences, were used for detecting DNA damage and cellular toxicity under various radiation dose rates. Throughout this study, it was found that these bacteria showed quantitative stress responses to DNA damage and general toxicity caused by gamma rays, depending on the radiation dose rates, indicating that the bacterial stress responses and general toxicity were seriously influenced according to radiation dose rates.

  • PDF

Gamma Knife Surgery for Brain Metastasis from Renal Cell Carcinoma : Relationship Between Radiological Characteristics and Initial Tumor Response

  • Kim, Jin-Wook;Han, Jung-Ho;Park, Chul-Kee;Chung, Hyun-Tai;Paek, Sun-Ha;Kim, Dong-Gyu
    • Journal of Korean Neurosurgical Society
    • /
    • v.42 no.2
    • /
    • pp.92-96
    • /
    • 2007
  • Objective : The authors have speculated that metastatic brain lesions from renal cell carcinoma (RCC) show diverse radiological patterns and tumor responses after Gamma knife surgery (GKS), and have hypothesized that these can be predicted from tumor radiological characteristics. The goal of the current study was to identify the radiological characteristics of RCC brain metastases and the predictors of initial radiosurgical response after GKS. Methods : A retrospective analysis was performed on 48 lesions in 18 patients with RCC brain metastasis treated by GKS. The radiological characteristics of these lesions in magnetic resonance images (MRI) were classified into 3 categories according to enhancement patterns in T1-weighted images and signal intensity characteristics in T2-weighted images. Responses to GKS were analyzed according to these categories, and in addition, other potential predictive factors were also evaluated. Results : MRI findings in the three categories were diverse, though numbers of the lesion were comparable. At 2-month MRI follow-ups after GKS, response rate was 54% and the local tumor control rate 83%. T2 signal intensity was found to be the principal predictive factor of response to GKS, namely negative predictive factor. Other variables such as age, sex, tumor volume, dose, duration from initial diagnosis to GKS, and previous systemic therapies failed to show significant relationships with treatment response by multivariate analysis. Conclusion : Careful evaluation of the radiological characteristics of brain metastases from RCC is important prior to GKS because MRI heterogeneity has predictive value in terms of determining initial tumor response.

Leucocyte Promoting Factor of B. Pertussis Vaccine (백일해 예방약의 백혈구 증가 인자에 관한 연구)

  • Choi, Sung-Bae
    • The Journal of the Korean Society for Microbiology
    • /
    • v.20 no.1
    • /
    • pp.109-113
    • /
    • 1985
  • It was well known that B. pertussis cells possess protective antigen, histamine sensitizing factor, heatstable and labile toxin, hemagglutinin, agglutinogen and the others. Previous reports involving above antigenic properties of B. pertussis have been carried out for several years. However, leucocyte promoting property was not yet investigated. In this report, the results of studies on the leucocytosis, particulary the lymphocytosis, produced in mice by injecting pertussis vaccine were presented. Especially leucocyte promoting property and histamine sensitizing property of B. pertussis vaccine treated at various temperatures were compared. The relationship between the leucocyte promoting property and histamine sensitizing property was investigated. Results were as follows. 1. Although leucocytosis was significantly rised in both 0.5ml injection and 0.1ml injection of pertussis vaccine than in control, at the higher dose (0.5ml injection) an elevation in white cell count was more significant. The leucocyte responce to pertussis vaccine was greater following 0.5 ml injection than following 0.1ml injection. 2. Lymphocytosis was significantly rised in both 0.5ml injection and 0.1ml injection of pertussis vaccine than in control. At higher dose (0.5ml injection), an elevation in lymphocyte count was more significant. 3. Order of elevation in differential leucocyte counts was lymphocyte, polymorphonuclear leucocyte and monocyte. 4. The leucocyte response to pertussis vaccine was 2 fold greater following intravenous injection than following subcutaneous injection. 5. Decrease leucocyte promoting activity and histamine sensitizing activity resulted from exposure to temperature above $56^{\circ}C$. Histamine sensitizing activity of pertussis vaccine treated at various temperatures paralleled leucocyte promoting activity.

  • PDF

Influence of Intraventricular Ouabain on the Renal Function of the Rabbit (가토(家兎) 신장기능(腎臟機能)에 미치는 측뇌실내(側腦室內) Ouabain의 영향(影響))

  • Lee, Shin-Woong
    • The Korean Journal of Pharmacology
    • /
    • v.12 no.1
    • /
    • pp.31-44
    • /
    • 1976
  • It has been reported that many of the effects of digitalis glycosides could be mediated partly through the central nervous system. In this study the effects of ouabain given directly into the lateral ventricle of the brain on the renal function of the rabbit were investigated. Intraventricular ouabain elicited antidiuresis in doses ranging from 0.1 to $3\;{\mu}g$, exhibiting a rough dose-response relationship, and decreased the renal plasma flow, glomerular filtration rate and urinary excretion of sodium and potassium, concomitant with the decrease of urine flow. These decreases in urine flow, excretory rate of electrolytes significantly correlated with the decrease in renal plasma flow or glomerular filtration rate, suggesting that the antidiuresis might have been induced by the hemodynamic changes. Intravenous ouabain in a dose of $1\;{\mu}g$ did not affect the renal function. Systemic blood pressure as well as cardiac activity was not affected by the intraventricular ouabain. Effects of the intraventricular ouabain on renal function were abolished by the intravenous phentolamine-pretreatment but not affected by intraventricular phentolamine-pretreatment. Neither vasopressin infusion nor hydration did affect the renal effects of intraventricular ouabain. From these observations, it is suggested that the antidiuresis of intraventricular ouabain is induced by the increased sympathetic influence to the kidney.

  • PDF

Fabrication of a superheated emulsion based on Freon-12 and LiCl suitable for thermal neutrons detection

  • Sara Sadat Madani Kouchak;Dariush Rezaei Ochbelagh;Peiman Rezaeian;Majid Abdouss
    • Nuclear Engineering and Technology
    • /
    • v.56 no.4
    • /
    • pp.1425-1430
    • /
    • 2024
  • This study develops superheated emulsion detectors that are both sensitive to fast neutrons, and thermal neutrons owing to the exergonic 63Li(n, α)31H capture reaction caused by the 6Li-containing compound dispersed throughout the gel-like medium. The experimental research was conducted on two SEDs. One detector was an ordinary Freon-12 detector and the other was a Freon-12 detector containing 3.4 % (by weight) LiCl. In order to investigate the sensitivity of lithium-containing SEDs to thermal neutrons, two types of SEDs were simultaneously exposed to various flux levels of thermal neutrons from 241Am-Be neutron source inside a cylindrical tank filled with water. A Boron-lined proportional counter was used to estimate the thermal neutron flux and the relevant MCNP code was developed for flux and dose calculations in the prepared set-up around 241Am-Be source. The results demonstrate that there is a proportional relationship between the variations of SED response and the change in thermal neutron flux and dose. Also, the sensitivity of SED was estimated.

Effect of Radiation Therapy on Atelectasis from Lung Cancer (무기폐를 동반한 폐암의 방사선 치료)

  • Hong, Seong-Eon;Hong, Young-Ki
    • Radiation Oncology Journal
    • /
    • v.8 no.1
    • /
    • pp.73-77
    • /
    • 1990
  • From January 1981 to December 1989, total 42 patients with atelectasis from lung cancer were treated with radiation therapy at the Department of Therapeutic Radiology in Kyung Hee University Hospital. The reexpansion of atelectasis after radiotherapy of the lung was evaluated retrospectively, utillzing treatment records and follow-up chest radiographs. Of the patients with non-small cell carcinoma of the lung, the response rate was $62\%$ (21/34). Patient with small cell carcinoma showed a $75\%$ (6/8) response rate. There appears to be some evidence of a relationship of total tumor dose versus response of atelectasis; radiation dose over 40 Gy (1337 ret), had a favorable effect on the rate of response compared with that below 40 Gy (1297 ret), $70\%$(21/30) and $50\%$ (6/12), respectively (p<0.01). Total response rate (partial and complete responses) of all patients was $64\%$ (27/42). Franction size was not contributed to the difference of response rates between small fraction ($180\~200$ cGy) and large fraction (300 cGy), $53\%$ (14/22) and $65\%$ (13/20), respectively. The results of this study suggest that radiation therapy has a definite positive role in management of atelectasis caused by lung cancer, especially in inoperable non-small cell carcinoma.

  • PDF

Assessment of Vibration Produced by the Grinder Used in the Shipbuilding Industry and Development of Prospective Prevalence Model of Hand-arm Vibration Syndrome (선박건조업에서 사용되는 그라인더의 진동평가와 수지진동증후군 예측 모델 개발)

  • Yim, Sanghyuk;Lee, Yunkeun;Park, Hee-Sok
    • Journal of Korean Society of Occupational and Environmental Hygiene
    • /
    • v.16 no.4
    • /
    • pp.398-412
    • /
    • 2006
  • The purpose of this study is to investigate the relationship between the acceleration of vibration by the powered hand tools used in the shipbuilding industry, and to develop the prospective prevalence model for the hand-arm vibration syndrome among the shipbuilding workers.The acceleration levels and frequencies of six types of grinder were measured using the ISO5349 method along with the time of exposure to the vibration from the powered hand tools. Medical examination for 114 workers were performed using the cold provocation test. Comparisons were made between the estimated prevalence of hand-arm vibration syndrome from ISO5349 and the observed values from the medical examinations. By multiple regression, we developed the prospective prevalence model of hand-arm vibration syndrome produced by the hand tools used in the shipbuilding industry. 4 hour-energy-equivalent frequency-weighted accelerations were $6.23m/s^2$ in the grinding job done after welding, and $13.39m/s^2$ in the grinding job done before painting. The mean exposure time while holding powered hand tools was 4.64 hours. Prevalence rates of Raynaud's Phenomenon were 12.04% in the grinding after soldering, and 42.9% in the grinding before painting measured using the ISO5349 method. After exposure to vibration for 10.79 years, about a half of the workers in the grinding after welding could developed Raynaud's Phenomenon. For the workers in the grinding before painting, the latency was 5.02 years. The ISO equation for dose response relationship was not significantly correlated with observed recovery rates of finger skin temperatures, blood flows and amplitudes of nerve conduction velocities. A multiple regression model for dose-response relationship was proposed from the results. Recovery rate of the skin temperatures = -0.668+ 0.337 ${\times}$ 4 hour energy equivalent frequency-weighted accelerations + 0.767 ${\times}$ duration of vibration exposure(years) The validity was proved by multiple regression analysis after correlation transformation and regression results based on model-building data and validation data.