The aim of this study is to develop a physiologically based pharmacokinetic (PBPK) model in intra-abdominal infected rats, and extrapolate it to human to predict moxifloxacin pharmacokinetics profiles in various tissues in intra-abdominal infected human. 12 male rats with intra- abdominal infections, induced by Escherichia coli, received a single dose of 40 mg/kg body weight of moxifloxacin. Blood plasma was collected at 5, 10, 20, 30, 60, 120, 240, 480, 1440 min after drug injection. A PBPK model was developed in rats and extrapolated to human using GastroPlus software. The predictions were assessed by comparing predictions and observations. In the plasma concentration versus time profile of moxifloxcinin rats, $C_{max}$ was $11.151{\mu}g/mL$ at 5 min after the intravenous injection and $t_{1/2}$ was 2.936 h. Plasma concentration and kinetics in human were predicted and compared with observed datas. Moxifloxacin penetrated and accumulated with high concentrations in redmarrow, lung, skin, heart, liver, kidney, spleen, muscle tissues in human with intra-abdominal infection. The predicted tissue to plasma concentration ratios in abdominal viscera were between 1.1 and 2.2. When rat plasma concentrations were known, extrapolation of a PBPK model was a method to predict drug pharmacokinetics and penetration in human. Moxifloxacin has a good penetration into liver, kidney, spleen, as well as other tissues in intra-abdominal infected human. Close monitoring are necessary when using moxifloxacin due to its high concentration distribution. This pathological model extrapolation may provide reference to the PK/PD study of antibacterial agents.
The present study was undertaken to investigate the role of endogenous nitric oxide in renin release under different physiological conditions. In the first series of experiments, renin release was either inhibited by acute volume-expansion (VE) or stimulated by clipping one renal artery in the rat. VE was induced by intravenous infusion of saline (0.9% NaCl) up to 5% of the body weight over 45 min under thiopental (50 mg/kg, IP) anesthesia. VE caused a decrease of plasma renin concentration (PRC). With $N^G-nitro-L-arginine$ methyl ester $(L-NAME,\;5\;{\mu}g/kg\;per\;min)$ superadded to VE, PRC decreased further. The magnitude of increase in plasma atrial natriuretic peptide levels following VE was not affected by the L-NAME. In two-kidney, one clip rats, L-NAME-supplementation resulted in a decrease, and L-arginine-supplementation an increase of PRC. Plasma atrial natriuretic peptide levels were significantly lower in the L-arginine group than in the control. Blood pressure did not differ among the L-NAME, L-arginine, and control groups. In another series of experiments, the renin response to a blockade of NO synthesis was examined using in vitro preparations from isolated renal cortex. L-NAME significantly increased basal renin release, although it was without effect on the isoproterenol-stimulated release. These findings suggest that endogenous nitric oxide significantly contributes to the renin release. Since many factors may affect the renin release in vivo, an interaction between NO and renin under various pathophysiological states is to be further defined.
Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications including nephropathy. However, the role of AGE in the activation of mesangial cells cultured under high glucose has not been elucidated. The effects of aminoguanidine, which prevents formation of AGE and protein cross-linking, on the synthesis of $TGF-{\beta}1$ and fibronectin by rat mesangial cells cultured under high glucose for 2 weeks were examined and compared with the effects of $N^G$-nitro-L-arginine methyl ester (NAME), a selective nitric oxide synthase inhibitor, because aminoguanidine also inhibits the inducible nitric oxide synthase. Culture of mesangial cells in 30 mM (high) glucose for 2 weeks induced 1.5-fold (ELISA) and 1.9-fold (Western blot analysis) increase in AGE in the culture media compared to 5.6 mM (control) glucose. Northern blot analysis revealed 1.5-fold increase in $TGF-{\beta}1$ and 1.7-fold increase in fibronectin mRNA expression in cells cultured under high glucose compared to control glucose. Increases in mRNA expression were followed by increased protein synthesis. Mink lung epithelial cell growth inhibition assay revealed 1.4-fold increase in $TGF-{\beta}1$ protein in high glucose media compared to control. Fibronectin protein also increased 2.1-fold that of control glucose by Western blot analysis. Administration of aminoguanidine suppressed AGE formation in a dose dependent manner and at the same time suppressed $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells cultured in both control and high glucose. In contrast, NAME did not affect high glucose-induced changes. These findings support a role for AGE in high glucose-induced upregulation of $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells.
Kim, In-Su;Kim, Joo-Wan;Kim, Hong-Tae;Lee, Sung-Dong;Ku, Sae-Kwang;Do, Yoon-Jung;Lee, Keun-Woo
Journal of Veterinary Clinics
/
v.28
no.4
/
pp.357-364
/
2011
To evaluate hepatoprotective effect of Epimedium Koreanum nakai (EKN) on liver-damaged animal model, rats were intoxicated with carbon tetrachloride (1 ml/kg) for 9 weeks orally. Liver-damaged rats were divided into 2 groups: liver-damaged control (LDC) group and EKN group were administered vehicle (saline), EKN extract per os for 4 weeks respectively. Normal control (NC) group was administered saline as the same process of LDC group. The weights of prostate (absolute), testis (relative), epididymis (relative) and packed cell volume (PCV), mean corpuscular volume (MCV) of EKN group significantly (P < 0.05) increased compared with LDC group. But Mean corpuscular hemoglobin (MCH), mean corpusulcar hemoglobin concentration (MCHC) and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) were significantly (P < 0.01, P < 0.05) decreased. Fibrotic regions in hepatic parenchyma of EKN group significantly (P < 0.01) decreased compared with LDC group and mean diameters of hepatic lobules significantly (P < 0.01) increased. Percentages of degenerative kidney regions and number of degenerative kidney tubules, number of vasodilated atrophic glomerulus of EKN group was significantly (P < 0.01, P < 0.05) decreased compared with LDC group. Number of atrophic seminiferous tubules and epididymal tubules showing oligospermatozoa of EKN group were significantly (P < 0.01) decreased compared with LDC group. In conclusion, EKN extract has a favorable effect on the $CCl_4$-induced liver damage.
The aim of this study was to determine the changes of body weight, organ weight, hematological values and biochemical parameters by testosterone (Testos) on the orchidectomized (Orch) rats. The animals were divided into 4 groups. Intact group (n=10) received no treatment and operation. Sham group (n=10) received only sham operation and no treatment. Orch group received operation and no treatment. Orch+Testos received operation and testosterone. The body weights of each group increased, but that of Orch+Testos group was significantly lower in Orch+Testos group than in all the other groups. There were significant differences (P<0.05, P<0.001) of body weights between Orch+Testos group and all the other groups. Also, organ weights such as heart, liver, spleen and kidney were measured. The heart weights were significantly lower (P<0.001) in the Orch+Testos group than in all the other groups. The liver weights in the Orch+Testos group were significantly differences in comparison with those in the Sham (P<0.001) and Orch group (P<0.05). On the other hand, there were no significantly differences in the organ weights of spleen and kidney between the Orch+Testos group and the any other groups. The hematological values of white blood cell (WBC), red blood cell (RBC), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC) were no significant differences in any other groups. The concentrations of serum total protein and albumin increased significantly (P<0.05) in the Orch+Testos group as compared to that in the Orch group. However, there were no significant differences in Ca, IP and Mg in any other groups. We conclude that testosterone was significantly decreased the body weight in the orchidectomized rats. Our findings suggest that testosterone may influence the process of lipid packaging and absorption in the orchidectomized rats.
This study was performed to investigate the effect of different levels of protein and iron in the diet upon Fe, Cu and Zn metabolism in rat during four weeks of growing period. Forty-five male weanling rats of Sprague-Dawley strain weighing $68.5{\pm}1.1g$ were divided into 9 groups and each group was given with one of the 9 different kinds of diets for four weeks. The three dietary protein levels used were 5, 20 and 40% and Fe levels 0, 35, and 350 ppms. The results obtained were summarized as following ; 1) Food intake and body weight gain in 20%(SP) and 40%(HP) dietary protein groups tended to be significantly higher than 5%(LP) protein groups. Protein efficiency ratio (PER) was higher in LP groups than in HP and SP groups. With dietary Fe levels, there were no significant differences among groups in food intake, body weight gain, and PER. 2) In LP groups, the Fe concentrations in liver, kidney, and hind limb muscle were higher than in SP and HP groups. Regarding with dietary protein levels, the liver Cu concentrations in LP groups were slightly higher, but the liver Zn concentrations were lower in LP groups. The Fe concentrations in liver and kidney tended to decrease with decrease in dietary Fe levels, but Cu and Zn concentrations showed no consistent tendency with dietary Fe levels. 3) The Fe, Cu and Zn concentrations in serum were not different from dietary treatments except that the serum Fe concentrations increased slightly in LP groups. 4) The Fe and Cu concentrations in urine tended to be higher in HP groups. Fecal Cu and Zn concentrations showed no significant differences in dietary protein or Fe levels, but the Fe concentrations tended to increase with increase in dietary Fe levels.
The renin-angiotensin system plays an important role in the regulation of blood pressure and in body fluid homeostasis. There is increasing evidence for generation of endogenous angiotensin II in many organs and for its role in paracrine functions. Studies were designed to investigate whether hemorrhage produces rapid changes in the gene expression of angiotensinogen in peripheral and brain tissues. Wistar rats received saline drinking water for 7 days, were bled at a rate of $3\;ml\;kg^{-1}\;min^{-1}$ for 7 min, and then decapitated 0, 2, 4, 8, or 24 hr after hemorrhage. Hemorrhage produced a produced hypotension with tachycardia at $2{\pm}8\;hr$, but blood pressure and heart rate had not fully recovered to the basal level at 24 hr. Plasma renin concentration was significantly increased at 2, 4, and 8 hr (maximum sixfold increase at 4 hr) and had returned to the basal level at 24 hr. Renal renin content was significantly increased only at 4 hr after hemorrhage. Angiotensinogen mRNA in both the kidney and liver were stimulated at 2 to 8 hrs, but recovered to the basal level at 24 hr. On the other hand, angiotensinogen mRNA levels il the hypothalamus and brainstem were continuously increased from 2 to 24 hrs. The present study demonstrates the presence of angiotensinogen mRNA in both hepatic and extrahepatic tissues, and more importantly, their up-regulation after hemorrhage. These results suggest that the angiotensinogen-generating systems in the liver, kideny and brain are, at least in part, under independent control and play a local physiological role.
This study was conducted to investigated the short-term effects of early weaning and protein intake on organ and cell growth, nitrogen metabolism and physiological functions of rats. Five groups of early weaned rats separated from the dam on the 15th day postpartum were each given one five diets consisting of either one of the three levels of casein-low(8%), -normal (16%), and -high(32%), or a normal level (16%) of isolated soy protein(ISP) or egg yolk protein, for 7 days. The normal weaned rats were fed maternal breast milk for three weeks from birth. On the 22nd day postpartum , all the rats were sacrificed . The weight gain of the early weaned rats, especially the ones fed high protein, was observed to be significantly lower than that of the normal weaned rats. By the 15th day, of early weaning and especially in the ISP-fed rats, the total DNA contents of liver and kidney, which may be said to represent an index of cell numbers, significantly decreased, but their fresh and dry weight and protein/DNA ratio, allegedly representing an index of cell size, significantly increased , not affecting the cell number and cell size of brain. There were no differences in total serum protein and albumin concentrations between early and normal weaned rats. In the early weaned rats observed , the serum urea N and $\alpha$-amino N concentrations significantly increased in high protein-fed rats, and decreased in low protein-fed rats. Another observation was that no significant difference was noticed as regards to serum GOT activity, total bilirubin, uric acid, and creatinine concentration, which may represent indices of liver and kidney functions, among rat groups, GPT activity was an exception . These results suggest that premature weaning and the quality and quantity of dietary protein significantly affect organ and cell growth and nitrogen metabolism but does not seriously affect physiological functions in the neonatal development of rats.
Effect of the ingestion of porphyran extracted from Porphyra yezoensis on calcium, magnesium and potassium contents in serum and tissue was investigated using hyperlipidemic and hypercholesterolemic rats. The contents of calcium magnesium and potassium in serum of rats fed porphyran for four weeks were higher than those of the control group. The contents of calcium and potassium were decreased with increasing a porphyran level while magnesium content was increased. Liver calcium contents in an $1\%$ porphyran group were significantly (p<0.05) higher than those in the control group, and magnesium contents in a $10\%$ porphyran group were higher than those in the control group. Kidney calcium and magnesium contents in rats fed porphyran were significantly (p<0.05) high compared with the control group. However, potassium content in kidney was Increased as a porphyran level was increased in diet. Spleen calcium and potassium contents were significantly lower in the porphyran groups than those in the control group. Rats fed the $5\%$ porphyran diet had higher magnesium content in spleen than any other diets. The results showed that diets supplemented with several porphyran levels had variable effects on the contents of calcium, magnesium and potassium in serum and tissue of hyperlipidemic rats.
Objectives This study was performed to investigate the effects of Saengkanggamchotang (SKT) on the monosodium iodoacetate (MIA) induced osteoarthritis in rats. Methods Osteoarthritis was induced by injection of MIA (50 ul, 60 mg/ml) into knee joints of rats. Rats are divided into a total of 4 groups (normal, control, positive comparison group, SKT treated group, each n=6). Normal group are not treated at all without inducing osteoarthritis whereas control group were induced for osteoarthritis by MIA and oral medicated with 20 ml of distilled water per day. Positive comparison group was injected with MIA and after 7 days, that was taken indomethacin (30 mg/kg/mouse). SKT treated group was injected with MIA and after 7 days that was taken SKT (30 mg/kg/mouse). Positive comparison group and SKT treated group were oral medicated for each substance a total of 4 weeks with one time per day. After experiments (from 1 week after injection of papain to 4 weeks elapsed), the functions of liver and kidney, Prostaglandin E2, inflammatory cytokine (IL-$1{\beta}$, IL-6, TNF-${\alpha}$), osteocalcin, TIMP-1, MMP-9 within serum. Knee joint structures were observed by H&E, safranin-O staining method, and amount of cartilage were measured by ${\mu}CT$-arthrography. Results 1) Hind paw weight bearing ability was significantly improved. 2) Functions of liver and kidney were not affected. 3) Prostaglandin E2, osteocalcin, TIMP-1, MMP-9 in serum were significantly decreased. 4) Inflammatory cytokine IL-$1{\beta}$ was significantly decreased, and IL-6, TNF-${\alpha}$ were decreased but had not significant. 5) In terms of histopathology, significantly reduced subsidence of cartilage and bone in H&E staining. And in Safranin O staining, proteoglycan content in synovial membrane was significantly increased compared with control group. 6) Destruction of cartilage on ${\mu}CT$-arthrography was significantly reduced. Conclusions Based on all results mentioned above, Saengkanggamchotang (SKT) is believed to be meaningful for suppressing the progress of osteoarthritis and its treatments.
본 웹사이트에 게시된 이메일 주소가 전자우편 수집 프로그램이나
그 밖의 기술적 장치를 이용하여 무단으로 수집되는 것을 거부하며,
이를 위반시 정보통신망법에 의해 형사 처벌됨을 유념하시기 바랍니다.
[게시일 2004년 10월 1일]
이용약관
제 1 장 총칙
제 1 조 (목적)
이 이용약관은 KoreaScience 홈페이지(이하 “당 사이트”)에서 제공하는 인터넷 서비스(이하 '서비스')의 가입조건 및 이용에 관한 제반 사항과 기타 필요한 사항을 구체적으로 규정함을 목적으로 합니다.
제 2 조 (용어의 정의)
① "이용자"라 함은 당 사이트에 접속하여 이 약관에 따라 당 사이트가 제공하는 서비스를 받는 회원 및 비회원을
말합니다.
② "회원"이라 함은 서비스를 이용하기 위하여 당 사이트에 개인정보를 제공하여 아이디(ID)와 비밀번호를 부여
받은 자를 말합니다.
③ "회원 아이디(ID)"라 함은 회원의 식별 및 서비스 이용을 위하여 자신이 선정한 문자 및 숫자의 조합을
말합니다.
④ "비밀번호(패스워드)"라 함은 회원이 자신의 비밀보호를 위하여 선정한 문자 및 숫자의 조합을 말합니다.
제 3 조 (이용약관의 효력 및 변경)
① 이 약관은 당 사이트에 게시하거나 기타의 방법으로 회원에게 공지함으로써 효력이 발생합니다.
② 당 사이트는 이 약관을 개정할 경우에 적용일자 및 개정사유를 명시하여 현행 약관과 함께 당 사이트의
초기화면에 그 적용일자 7일 이전부터 적용일자 전일까지 공지합니다. 다만, 회원에게 불리하게 약관내용을
변경하는 경우에는 최소한 30일 이상의 사전 유예기간을 두고 공지합니다. 이 경우 당 사이트는 개정 전
내용과 개정 후 내용을 명확하게 비교하여 이용자가 알기 쉽도록 표시합니다.
제 4 조(약관 외 준칙)
① 이 약관은 당 사이트가 제공하는 서비스에 관한 이용안내와 함께 적용됩니다.
② 이 약관에 명시되지 아니한 사항은 관계법령의 규정이 적용됩니다.
제 2 장 이용계약의 체결
제 5 조 (이용계약의 성립 등)
① 이용계약은 이용고객이 당 사이트가 정한 약관에 「동의합니다」를 선택하고, 당 사이트가 정한
온라인신청양식을 작성하여 서비스 이용을 신청한 후, 당 사이트가 이를 승낙함으로써 성립합니다.
② 제1항의 승낙은 당 사이트가 제공하는 과학기술정보검색, 맞춤정보, 서지정보 등 다른 서비스의 이용승낙을
포함합니다.
제 6 조 (회원가입)
서비스를 이용하고자 하는 고객은 당 사이트에서 정한 회원가입양식에 개인정보를 기재하여 가입을 하여야 합니다.
제 7 조 (개인정보의 보호 및 사용)
당 사이트는 관계법령이 정하는 바에 따라 회원 등록정보를 포함한 회원의 개인정보를 보호하기 위해 노력합니다. 회원 개인정보의 보호 및 사용에 대해서는 관련법령 및 당 사이트의 개인정보 보호정책이 적용됩니다.
제 8 조 (이용 신청의 승낙과 제한)
① 당 사이트는 제6조의 규정에 의한 이용신청고객에 대하여 서비스 이용을 승낙합니다.
② 당 사이트는 아래사항에 해당하는 경우에 대해서 승낙하지 아니 합니다.
- 이용계약 신청서의 내용을 허위로 기재한 경우
- 기타 규정한 제반사항을 위반하며 신청하는 경우
제 9 조 (회원 ID 부여 및 변경 등)
① 당 사이트는 이용고객에 대하여 약관에 정하는 바에 따라 자신이 선정한 회원 ID를 부여합니다.
② 회원 ID는 원칙적으로 변경이 불가하며 부득이한 사유로 인하여 변경 하고자 하는 경우에는 해당 ID를
해지하고 재가입해야 합니다.
③ 기타 회원 개인정보 관리 및 변경 등에 관한 사항은 서비스별 안내에 정하는 바에 의합니다.
제 3 장 계약 당사자의 의무
제 10 조 (KISTI의 의무)
① 당 사이트는 이용고객이 희망한 서비스 제공 개시일에 특별한 사정이 없는 한 서비스를 이용할 수 있도록
하여야 합니다.
② 당 사이트는 개인정보 보호를 위해 보안시스템을 구축하며 개인정보 보호정책을 공시하고 준수합니다.
③ 당 사이트는 회원으로부터 제기되는 의견이나 불만이 정당하다고 객관적으로 인정될 경우에는 적절한 절차를
거쳐 즉시 처리하여야 합니다. 다만, 즉시 처리가 곤란한 경우는 회원에게 그 사유와 처리일정을 통보하여야
합니다.
제 11 조 (회원의 의무)
① 이용자는 회원가입 신청 또는 회원정보 변경 시 실명으로 모든 사항을 사실에 근거하여 작성하여야 하며,
허위 또는 타인의 정보를 등록할 경우 일체의 권리를 주장할 수 없습니다.
② 당 사이트가 관계법령 및 개인정보 보호정책에 의거하여 그 책임을 지는 경우를 제외하고 회원에게 부여된
ID의 비밀번호 관리소홀, 부정사용에 의하여 발생하는 모든 결과에 대한 책임은 회원에게 있습니다.
③ 회원은 당 사이트 및 제 3자의 지적 재산권을 침해해서는 안 됩니다.
제 4 장 서비스의 이용
제 12 조 (서비스 이용 시간)
① 서비스 이용은 당 사이트의 업무상 또는 기술상 특별한 지장이 없는 한 연중무휴, 1일 24시간 운영을
원칙으로 합니다. 단, 당 사이트는 시스템 정기점검, 증설 및 교체를 위해 당 사이트가 정한 날이나 시간에
서비스를 일시 중단할 수 있으며, 예정되어 있는 작업으로 인한 서비스 일시중단은 당 사이트 홈페이지를
통해 사전에 공지합니다.
② 당 사이트는 서비스를 특정범위로 분할하여 각 범위별로 이용가능시간을 별도로 지정할 수 있습니다. 다만
이 경우 그 내용을 공지합니다.
제 13 조 (홈페이지 저작권)
① NDSL에서 제공하는 모든 저작물의 저작권은 원저작자에게 있으며, KISTI는 복제/배포/전송권을 확보하고
있습니다.
② NDSL에서 제공하는 콘텐츠를 상업적 및 기타 영리목적으로 복제/배포/전송할 경우 사전에 KISTI의 허락을
받아야 합니다.
③ NDSL에서 제공하는 콘텐츠를 보도, 비평, 교육, 연구 등을 위하여 정당한 범위 안에서 공정한 관행에
합치되게 인용할 수 있습니다.
④ NDSL에서 제공하는 콘텐츠를 무단 복제, 전송, 배포 기타 저작권법에 위반되는 방법으로 이용할 경우
저작권법 제136조에 따라 5년 이하의 징역 또는 5천만 원 이하의 벌금에 처해질 수 있습니다.
제 14 조 (유료서비스)
① 당 사이트 및 협력기관이 정한 유료서비스(원문복사 등)는 별도로 정해진 바에 따르며, 변경사항은 시행 전에
당 사이트 홈페이지를 통하여 회원에게 공지합니다.
② 유료서비스를 이용하려는 회원은 정해진 요금체계에 따라 요금을 납부해야 합니다.
제 5 장 계약 해지 및 이용 제한
제 15 조 (계약 해지)
회원이 이용계약을 해지하고자 하는 때에는 [가입해지] 메뉴를 이용해 직접 해지해야 합니다.
제 16 조 (서비스 이용제한)
① 당 사이트는 회원이 서비스 이용내용에 있어서 본 약관 제 11조 내용을 위반하거나, 다음 각 호에 해당하는
경우 서비스 이용을 제한할 수 있습니다.
- 2년 이상 서비스를 이용한 적이 없는 경우
- 기타 정상적인 서비스 운영에 방해가 될 경우
② 상기 이용제한 규정에 따라 서비스를 이용하는 회원에게 서비스 이용에 대하여 별도 공지 없이 서비스 이용의
일시정지, 이용계약 해지 할 수 있습니다.
제 17 조 (전자우편주소 수집 금지)
회원은 전자우편주소 추출기 등을 이용하여 전자우편주소를 수집 또는 제3자에게 제공할 수 없습니다.
제 6 장 손해배상 및 기타사항
제 18 조 (손해배상)
당 사이트는 무료로 제공되는 서비스와 관련하여 회원에게 어떠한 손해가 발생하더라도 당 사이트가 고의 또는 과실로 인한 손해발생을 제외하고는 이에 대하여 책임을 부담하지 아니합니다.
제 19 조 (관할 법원)
서비스 이용으로 발생한 분쟁에 대해 소송이 제기되는 경우 민사 소송법상의 관할 법원에 제기합니다.
[부 칙]
1. (시행일) 이 약관은 2016년 9월 5일부터 적용되며, 종전 약관은 본 약관으로 대체되며, 개정된 약관의 적용일 이전 가입자도 개정된 약관의 적용을 받습니다.