• Title/Summary/Keyword: 랫드

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항균제 임상시험 Guideline

  • 우준희
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.11a
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    • pp.27-30
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    • 1994
  • 잠재적으로 항감염 약제로 사용될 가능성이 있는 약제들의 초기 연구과정에서 주된 관심사는 이들이 미생물(세균, 바이러스, 기타 기생충)에 대한 작용들이 있는가 하는 점이다. 이러한 작용들이 실험적으로 충분히 연구가 된 후에야 실험동물에서 그 효과를 연구한다. 항 바이러스 제제의 경우에는 세포배양을 통한 연구가 그 약제의 독성과 효용성을 나타내는데 필수적인 것이 된다. 여러 종류의 동물을 이용한 생체실험에서 약제의 일반적인 흡수와 배설, 분포 등에 관한 정보와 약제 자체와 동물 내에서의 대사적 변화에 대한 정보가 제공된다. 여러 가지 미생물로 감염을 시킨 적합한 동물과 여러 가지 용량으로 치료하는 실험을 통하여 약제의 항 감염 능력이 알려지게 된다. 동물에서의 생체실험과 실험관내에서 실험을 하고 나서야 사람에서의 연구가 이루어지게 된다. 소위 전임상시험에서 대표적 병원성 미생물에 대한 생물학적효과, 약리학적 효과와 독성 그리고 동물실험모델에서의 가능한 효과가 결정된 후에 임상시험에 들어가기 마련이다. 항균제의 임상시험에는 각각의 감염질환에 대한 진단 및 치료기준을 반영하는 것이 기본이다. 새로운 항균제의 임상시험에서는 안전성과 효과가 반드시 밝혀져야 한다. 1상에서는 인체에서의 약리효과, 안전성이 주목적이며, 2상과 3상은 겹쳐지는 점도 있으나 하나 또는 그 이상의 적응증에 대한 항균제의 효과와 단기간의 부작용은 2상에서 관찰하여야하며, 다수의 환자에서 제안된 적응질환의 무작위임상시험과 다수에서의 안전성도 3상에서 관찰하여야 한다. 4상에서는 이상에서의 자료로 시판된 후에도 계속해서 감시하는 것으로 지속적으로 안전성을 관찰하는 것이다. 이러한 기본사항외에도 소아, 임산부, 고령자등에서의 임상시험도 넓은 의미에서 포함되어야 할 것이며 또한 질적인 면에서 조절하는 Quality Assurance도 중요하다.양상은 세 용량군 간 차이가 없었으나, 시험기에서 발열의 발현율이 낮았으며, 발열일 수와 항생제 사용일 수가 짧았다. 결론: 골수억제 조절 효과는 용량에 따른 혈액소견에 미치는 영향, 부작용, 감염의 빈도, 감염발생에 따른 항생제 사용기간 등을 고려하여 그 임상 유효성 평가시, 제 3상 시험에 사용할 권장량 (recommended dose) 은 250 ug/$m^2$/d $\times$ 10d 으로 관찰되었다.5주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 모든 처리군들이 대조군에 비하여 높게 발현되는. 것이 관찰되었으나 시험개시후 26주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 대조군에 비하여 차이가 거의 없었다. 따라서 랫드에서 화학적으로 유도한 간암발생 과정에서 NK 세포활성이 현저하게 억제되는 것으로 생각되며, c-myc 종양단백의 발현은 시험개시후 15주에 그 발현이 확실한 것으로 사료되어 진다.에 영향을 주는 성분이 있음을 제시하였다.1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.바와 같이 MCl에서 작은 Dv 값을 갖는데, 이것은 CdCl$_{4}$$^{2-}$ 착이온을 형성하거나 ZnCl$_{4}$$^{2-}$ , ZnCl$_{3}$$^{-}$같은 이온과 MgCl$^{+}$, MgCl$_{2}$같은 이온종을 형성하기 때문인것 같다. 한편 어떠한 용리액에서던지 NH$_{4}$$^{+}$의 경우 Dv값이 제일 작았다. 바. 본 연구의 목적중의 하나인 인체유

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Protective effects of Jijang-kimchi extracts on diabetes mellitus and alcoholic liver injury in laboratory rats (랫드에서 김치가 당뇨병 및 알코올성 간 손상 예방에 미치는 효과)

  • Kim, Chang-Hyu;Park, Byung-Sung;Um, Kyung-Hwan
    • Journal of the Korean Applied Science and Technology
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    • v.37 no.5
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    • pp.1078-1087
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    • 2020
  • The current study was carried out to investigate the effect of oral administration for 30 days of the Jijang kimchi extracts on prevention of diabetes, alcoholic liver injury and reduction of blood lipids in laboratory rats with alcoholic liver injury and diabetes induced by streptozotocin. In a diabetic model animals, the blood lipid profile, ALT, and AST levels were lower in kimchi extract groups compared to DC (diabetes control) group, and blood glucose level of DCJK (DC+oral administration with Jijang kimchi extracts) group was lower than that of DCCK (DC+oral administration with commercial kimchi extracts) group. Insulin levels were increased in order of NC (normal control), DCJK > DCCK > DC groups. In alcoholic liver injury model animals, ALT, AST and bilirubin were lowed in order of AC (alcohol group received 1 bottle of soju) > ACCK (1 bottle of soju plus oral administration with commercial kimchi extracts) ACJK (AC plus oral administration with Jijang kimchi extracts) > NC groups. In the clinical pathologic findings of liver tissue, AC group was severely injured, and tended to be improved in groups eating a 1 bottle of soju plus oral administration with kimchi extracts, especially Jijang kimchi extract group. The results suggest that eating Jijang kimchi can improve insulin secretion ability while lowering blood lipid profile, blood sugar and ALT, AST, and bilirubin levles in diabetic and alcoholic liver injury model animals.

EffeCt of tricalcium phosphate (TCP) as a scaffold during bone grafting using cultured periosteum-derived cells in a rat calvarial defect model (두개결손부 모델에서 배양된 골막유래세포를 이용한 골이식 시 지지체로서 TCP의 효과)

  • Shim, Kyung-Mi;Kim, Se-Eun;Kim, Jong-Choon;Bae, Chun-Sik;Choi, Seok-Hwa;Kang, Seong-Soo
    • Journal of the Korean Society of Radiology
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    • v.5 no.1
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    • pp.11-18
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    • 2011
  • The periosteum contains multipotent cells that can differentiate into osteoblasts and chondrocytes. Cultured periosteum-derived cells (PDCs) have an osteogenic capacity. The purpose of this study was to evaluate the interaction of PDCs with bone graft biomaterial. After cell isolation from the calvarial periosteum of Sprague-Dawley rats, cultured PDCs were placed in critical-sized calvarial defects with beta-tricalcium phosphate (${\beta}$-TCP). All rats were sacrificed 8 weeks after bone graft surgery, and the bone regenerative ability of bone grafting sides was evaluated by plain radiography, micro-computed tomography (CT), and histological examination. PDCs grafted with ${\beta}$-TCP displayed enhanced calcification in the defect site, density of regenerated bone and new bone formation within the defect and its boundaries. Furthermore, these PDCs more efficiently regenerated new bone as compared to grafted ${\beta}$-TCP only. The results suggest that cultured PDCs have the potential to promote osteogenesis in bone defects.

The effect of Allium sativum L. extract on hepatic function in rats with CCl4-induced (hepatic) injury (마늘 열수추출물의 CCl4 유발된 간 손상 랫드에서 기능학적 변화에 관한 연구)

  • Lee, Tae-Jong;Min, Kyung-Jin
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.11 no.5
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    • pp.1936-1942
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    • 2010
  • To examine the effect of overdosed functional food in liver-injured patients, we tried to investigate the dose effect of Allium sativum L. (also called garlic) extract on rats with CCl4-induced liver damage, by comparatively examinating the hepatic function of each group. 42 male Sprague-Dawley rats were selected and divided equally (n=7) into normal, control, positive control, and three experimental subgroups (E1, E2 and E3), respectively. For each kg of body weight, hepatic injury was induced by intraperitoneal administration of $0.5\;m{\ell}$ (0.20 g/kg/day) $CCl_4$, which was diluted in equal amount of olive oil, once a day on every other day for total 5 times. Hot water extraction was performed using domestically cultivated organic garlics, and the obtained extract was injected by sonde, once daily during 4 weeks, to each experimental subgroups by different dosage of 0.35 g/kg(E1), 0.70 g/kg(E2), 1.40 g/kg(E3), respectively. Results showed that the injection of garlic extract positively influenced the physiological activation which lowered the oxidative stress, changed the toxicity, and functionally improved the hepatic condition. Comparing the dose effect between the three experimental subgroups (E1, E2, E3), results of the maximal-dosed subgroup (E3) showed less significance compared with the lower-dosed subgroups(E1 and E2), which seems to resulted from the (increased) toxicity of garlic.

Studies on Early Detection of the Chemical Hepatocarcinogenesis in Newborn Rats (신생랫드를 이용한 화학적 간암발생의 조기진단에 관한 연구)

  • 장민열;김형진;이영순
    • Journal of Food Hygiene and Safety
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    • v.6 no.1
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    • pp.13-26
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    • 1991
  • This study was performed for searching for non-hepatectomy medium-term bioassay model by using newborn female rats. Newborn female Sprague-Dawley rats (1 day old) were given an intraperitoneal injection of 150 mg/kg of diethylnitrosamine (DENA). After three weeks, all rats were weaned and divided into three groups. Group 1 were fed on diets containing 0.01% 2-acetylaminofluorene (2-AAF) as a promoter for three weeks. Group 2 were given 0.05% phenobarbital (PB) in drinking water as a promoter for 8 weeks. Group 3 was control group. The autopsy was carried out at 4 weeks and 8 weeks after weaning. Preneoplastic lesions were indentified with immunohistochemical staining for glutathione S-transferase placental form (GST-P). In liver weight to body weight ratios, group 2 showed significant difference from group 1 (p<0.001) at 4 weeks after weaning. Group 1 and group 2 showed significant difference from group 3 at 8 weeks after weaning (p<0.0I, p<0.001), respectively. In quantitative analysis for GST-P positive lesion area by using Image Analyzer, group 1 and group 2 represented significant difference in comparison with group 3 at early 4 weeks after weaning (p

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Development Toxicity Evaluation (랫드에서 표준 및 사료제한 시험에 의한 fluoroquinolone 항균제 DW-116의 발생독성평가)

  • 김종춘;윤효인;이희복;한상섭;정문구
    • Journal of Life Science
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    • v.11 no.5
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    • pp.447-456
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    • 2001
  • We have recently demonstrated that the fluoroquinolone antibacterial DW-116 caused a significant developmental toxicity in rats. The present study was conducted to determine whether the development toxicity induced by DW-116 treatment was the result of malnutrition fro reduced food intake or the direct effects of test chemical on conceptuses. The test chemical was administered by gavage to pregnant rats from gestational days 6 through 16 at dose levels of 0 and 500 mg/kg/day. A pair-feeding study was also performed in which the pregnant rats received the same amount of diet consumed by the DW-116-treated pregnant rats. All dams were subjected to caesarean section on day 20 of gestation and their fetuses were examined for examined for external, visceral, and skeletal abnormalities. In this treatment group, the maternal toxicities included increased abnormal clinical signs, decreased maternal body weight, suppressed body weight gain during treatment and posttreatment periods, and reduced food intake. The significant developmental toxicities included increased fetal deaths, decreased live fetuses, reduced fetal body weight and placental weight, increased incidence of fetal abnormalities, and increased fetal ossification delay. In this pair-fed group, however, slight maternal toxicities including decreased body weight and suppressed body weight gain during treatment period were observed in comparison with the control group, and minimal development toxicities including reduced fetal and placental weights and increased fetal ossification delay were found. The number of fetal deaths and live fetuses, and the incidences of malformed fetuses and litters with affected fetuses were comparable to the control values. Based on the results, it could be concluded that the development toxicity observed in the treatment group is attributable to the direct effects of Dw-116 treatment, but not to the maternal malnutrition from reduced food consumption during pregnancy.

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Chondroprotective Effects of Cinnamomum cassia Blume in a Rat Model of Osteoarthritis (골관절염 랫드 모델에서 계피의 연골보호 효과)

  • Kim, Myoung Hwan;Kang, Seong Soo;Kim, Gonhyung;Choi, Seok Hwa
    • Journal of Veterinary Clinics
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    • v.30 no.3
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    • pp.159-165
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    • 2013
  • The present study was conducted to evaluate the efficacy of Cinnamomum cassia Blume (CC) extract on the repair of damaged cartilage in a rat model of osteoarthritis (OA) by anterior cruciate ligament transection (ACLT) and medial meniscus resection (MMx). Forty-eight rats were assigned to six groups (n = 8 per group): sham as negative control (NC), positive control (PC), diclofenac sodium (DS, 2 mg/kg), CC 25 mg/kg, CC 50 mg/kg and CC 100 mg/kg groups. Treatments were 12 weeks from 7 days after ACLT + MMx. Loss of cartilage and joint instability were significantly reduced in response to treatment with CC or DS compared to the PC (p < 0.05). CC significantly ameliorated cartilage degradation in a dose-dependent manner as assessed by histological findings (p < 0.01). A reduction in the severity of structural changes and a dose-dependent increase in Safranin-O staining intensity were observed in CC treatments, indicating that cartilage degradation was inhibited. Although DS did not affect the increase in active caspase-3 and cleaved poly(ADP-ribose) polymerase-induced apoptosis during the progression of OA, cells reactive to these apoptotic markers were decreased significantly by CC (p < 0.05). However, treatments with CC or DS did not influence the uptake of 5-bromo-2'-deoxyuridine. The findings suggest that CC can exert a chondroprotective action on OA through anti-inflammatory and anti-apoptotic properties.

Effect of an Improving Agent for the Intestinal Function, a Poly Herbal Formulation (KTG075) on Secretion of Mucus (장기능개선제(KTG075)의 대장관내 점액(Mucus)분비에 미치는 영향)

  • Baik, Soon-Ok;Lee, You-Hui;Kim, Hyun-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.34 no.3
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    • pp.356-360
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    • 2005
  • The maintenance of intestinal health is complex and relies on a delicate balance between the diet, the normal microflora and mucosa, including the digestive epithelium and overlying mucus layer. The colorectal mucosa is protected by a visco-elastic mucus gel formed by high molecular mass glycoproteins referred to as mucins. Abnormality of mucin have been identified with colorectal disease. Constipation increases with age, and is more common among women than men in all age groups, e.g. 10% of men and 20% of women in the USA. The aim of the present study was conducted to investigate that the effects of formulation KTG075 from edible plants on intestinal function on mucus secretion, were examined by loperamide-induced constipation method using Sprague Dawley male rats. Epithelial cells of colonic crypt contained more mucus in the KTG075 group compared with those of the control group and the thickness of the mucus layer stained with alcian blue was significantly thicker in KTG075 treated rats compared with in control rats. Mucus production of epithelial cells of crypt and mucus contents at fecal and mucosa surfaces were reduced by loperamide-induced constipation. These results indicates that a poly herbal formulation KTG075 accelerates evacuation and activated intestines.

Characteristics of Alcohol Metabolism of Hahyangju in Rats (하향주의 랫드에 대한 알코올 대사 특성)

  • Jung, Hee-Kyoung;Park, Chi-Duck;Hwang, Mi-Hyun;Park, Seung-Chun;Kim, Dae-Ik;Hong, Joo-Heon
    • Food Science and Preservation
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    • v.15 no.1
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    • pp.155-160
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    • 2008
  • This study was conducted to examine the volatile flavor compounds of Hahyangju, a traditional Korean liquor, and to evaluate the effect of the beverage on alcohol metabolism in rats. By GC/MS analysis, 17 volatile flavor compounds including iso-butyl alcohol and iso-amyl alcohol were detected in Hahyangju. The concentrations of acetaldehyde and ethylacetate in Hahyangju were decreased by filtration. Alcohol (0.035 mg/dL) and acetaldehyde (0.29 mg/dL) levels in the blood of rats given Hahyangju (HT animals) were lower than in rats given 17% (v/v) alcohol (AT rats). Also, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH) activities in HT rats were $24.63{\pm}1.8{\mu}$moles/mg protein and $9.8{\pm}1.3{\mu}$moles/mg protein, respectively, and were higher than in AT animals. The increases in ADH and ALDH activity in HT animals resulted in decreases in alcohol and acetaldehyde concentrations in blood, compared to the levels seen in rats given 17% (v/v) alcohol. These results suggest that Hahyangju may increase alcohol metabolizing activity, and consumption of Hahyangju may result in less of a hangover than follows ingestion of beverages (such as wine) containing about 17% (v/v) alcohol.

Degenerative Changes of the Rat Dorsal Root Ganglion (DRG) Cells Following a Tight Spinal Nerve Ligation (랫드 척수신경 결찰에 따른 척수신경절세포의 퇴행성변화)

  • Kim, Yi-Suk;Jo, Seung-Mook
    • Applied Microscopy
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    • v.39 no.3
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    • pp.261-266
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    • 2009
  • This study aim to disclose a possible mechanism for the neuronal cell death induced by peripheral nerve injury following a spinal nerve ligation (SNL) as a neuropathic pain model. Male Sprague-Dawley rats (270~290 g) were used for this study. Pain threshold was evaluated for their response to mechanical (von Frey hairs) stimuli 1, 3, and 7 days after a tight ligation of L5 ventral ramus. In control group, the small ganglion cells were strongly stained with routine toluidine blue (TB), whereas the large ganglion cells showed a little bit weak stainity. Each large ganglion cell is surrounded by perineuronal satellite cells. In experimental groups, small ganglion cells showing apparent degenerative changes increased on 1 day, and showed a peak in degenerative cell number at 3 days group, and decreased gradually at 7 days group. We also found a small number of large-sized ganglion cells showing mild degenerative changes. However their satellite cells ware relatively intact with no typical findings throughout this experiment. Under the electron microscope, small ganglion cells showed various stage and typical features of the dark degeneration including mitochondrial swelling.