• 대한수의학회지
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• 제34권4호
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• pp.787-799
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• 1994

To elucidate morphologic lesion of porcine exudative epidermitis which is occurred sporadically in Korea, Staphylococcus hyicus subsp. hyicus isolated from the naturally affected pigs was inoculated to suckling pigs. The infected piglets were observed grossly and histopathologically. Although affected piglets were taking acute, subacute, or chronic course, some piglets suffered from chronic disease showed poor prognosis and marked growth depression. Affected peglets had erythematous skin on the face, ear, and abdomen and these localized lesions appear as brownish spots of exudative epidermitis and fromed crust in the early stage. But, after this stage, the skin were covered by viscous greasy exudate and formed blackish brown crust and appeared fissures and hypertrophy. Grossly, there has been hemorrhage with the removal of crust-like materials of epidermis and edematous subcutis. The superficial lymph nodes were edematous and swollen or congested and hemorrhagic. Some piglets had swollen ureters, cysts in the renal cortex, or polyarthritis. A few cases had mild edematous swelling of kidney, intestinal catarrh and congestion of brain. Microscopically, skin lesions had detachment of keralinized layer and parakeratosis of epidermis, hydropic degeneration of epidermal cell, and retrogressive degeneration of hair root sheath. Dermis had edema, and infiltration of neutrophils and mononuclear cells. As the disease was proceeded, there was marked perivasculitis with lots of mononuclear inflammatory cells. More chronic lesions formed granuloma-like bodies(nodules) due to more mononuclear, perivascular inflammatory cell infiltration and proliferation of fibroblast. Lots of plasma cells and eosinophils were also present in dermis. Epidermis was hyperplastic by proliferation of basal cells stratum germinativum and epidermal pegs often extended into the dermis. In secondary infection, lots of neutrophils could be seen in epidermis and derms. Kidney had neutrophilic infiltration, necrotic and cystic glomeruli, and dilation of renal tubules and ureters. Purulent arthritis was sometimes observed in joints. Three days old mice administrated Staphylococcus hyicus subsp hyicus subcutaneously before had focal congestion and hemorrhage, necrosis, and subcutaneous edema of the skin. This observation was also seen in the study of mice administrated exfoliatin toxin of Staphylococcus which evoked human staphylococcal scalded skin syndrome.

• Biomolecules & Therapeutics
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• 제10권1호
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• pp.19-24
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• 2002

The effects of a newly synthesized $H^+/K^+$ ATPase inhibitor,1-(2-methyl-4-methoxypheny)-4-[(3-hy-droxypropyl)amino] -6-methyl-2,3-dihydropyrrolo (3,2-c) quinoline (DBM-819) , on the central nervous system, isolated smooth muscle, cardiovascular and digestive systems and renal function were investigated in various experimental animals. Oral administration of DBM-819 had no effect on the central nervous system except body temperature of mice slightly decreased at doses of 15 and 50 mg／kg. DBM-819 produced a moderate analgesic effect in acetic acid-induced writhing test in mice at 50 mg／kg (p.o.). In conscious rats, DBM-819 (15 and 50 mg／kg, p.o.) showed a slight increase in blood pressure and a small decrease in heart rate. DBM-819 had an significant effect on agonist-induced contraction of guinea pig ileum at $1.5{\times}10^{-5}g/ml.$ No significant effect of DBM-819 (5 and 15 mg／kg, i.p) on urinary volume or urinary excretion of $Na^+,\;K^+$ and Cl- was observed in rats. DBM-819 had no significant effect on intestinal transport of a semisolid meal in mice at 15 and 50 mg／kg (p.o.). These findings suggest that DBM-819 exerts no significant pharmacological effects on the central nervous system and renal function at 15 mg／kg (p.o.), but produces some effects on the smooth muscle and circulatory system.

• 대한수의학회지
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• 제24권2호
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• pp.173-181
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• 1984

This paper dealt with the histopathological observations of the perirenal edema in pigs and rabbits administered with Amaranthus retroflexus, based on the clinical and pathological observations of the porcine perirenal edema naturally occurred in Korea. The results observed are summarized as follows; In the natural case, clinical signs were trembling, weakness and incoordination of the hindquarters, followed by sternal recumbency, coma and death. Death usually occurred within 24 hours after the signs of illness appeared. In gross findings, the grayish yellow fluid in the perirenal area was observed in each case. In some cases, the amount of fluid in the thoracic and abdominal cavities was increased and the yellowish red color of the hydrothorax and ascites was seen. When the renal capsule was incised, the kidneys were enlarged and congested and petechiae on the cortical surface and blood clots on the capsule appeared. In microscopical findings, there were cloudy swelling, hyaline droplets and necrosis of the convoluted tubules containing proteinaceous casts and a few oxalate crystals. In addition, interstitial and perivascular edema, distention of the Bowman's space and the convluted tubules and hemorrhages were recognized. In the weanling pigs and the adult pig fed various weeds, including Amaranthus retroflexus, Euxolus blitum and Portulaca oleracea, the pigs fed Amaranthus retroflexus appeared clinical signs and pathological findings of perirenal edema usually seen in the pigs of natural cases. In the pigs fed Euxolus blitum or fed Portulaca oleracea, neither clinical signs nor pathological changes were seen. It was regarded that this disease was affected with Amaranthus retroflexus, but there was no sensitivity in the adult pigs.

• The Korean Journal of Physiology
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• 제23권1호
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• pp.23-34
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• 1989

Gentamicin (GM) is a polybasic, aminoglycoside antibiotic used frequently for the treatment of serious gram-negative infections. The major limiting factors in the clinical use of GM as well as other aminoglycoside antibiotics are their nephrotoxicity and ototoxicity. The primary mechanism of cell injury in aminoglycoside toxicity appears to be the disruption of normal membrane function and the inhibition of $Na^{+}-K^{+}$ ATPase activity. There are both indirect and direct evidences which suggests that the effect of aminoglycoside antibiotics on $Na^{+}-K^{+}$ ATPase may explain, or contribute to, their toxicity. It has been shown that aminoglycoside reduce total ATPase activity (Kaku et al., 1973) and $Na^{+}-K^{+}$ ATPase activity (linuma et al., 1967) in the stria vascularis and spiral ligament of the guinea-pig cochlea. Lipsky and Lietman (1980) reported that aminoglycoside antibitoics inhibited the activity of $Na^{+}-K^{+}$ ATPase in microsomal fractions of the cortex and medulla of the guinea-pig kidney, isolated rat renal tubule and human erythrocyte ghosts. The present invstigation was undertaken to elucidate the mechanism of GM on human erythrocytes by examining its effect on $Na^{+}-K^{+}$ ATPase activity, actives sodium and potassium transport across red blood cell and $^{3}H-ouabain$ binding to red blood cell membranes. The results obtained are summarized as follows: 1) CM inhibited significantly both the activity of total ATPase and $Na^{+}-K^{+}$ ATPase at all concentrations tested. 2) GM inhibited active $^{22}Na$ efflux across red blood cell. When ouabain is present, the rate of $^{22}Na$ efflux was completely inhibited. When both GM and ouabain were added, the inhibitory effect of active $^{22}Na$ efflux was more pronounced. 3) Active $^{86}Rb$ influx was inhibited significantly by GM. In the presence of ouabain, the rate of $^{86}Rb$ influx is markedly inhibited. But $^{86}Rb$ influx is not appreciably altered by the presence of both GM and ouabain. 4) In the presence of GM, $^{3}H-ouabain$ binding to red blood cell membrane increased. From the above results, it may be concluded that the inhibition of active sodium and potassium transport across red blood cell by gentamicin appears to be due to the inhibition of $Na^{+}-K^{+}$ ATPase activity and an increase in ouabain binding to red blood cell membranes.

• Toxicological Research
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• 제26권3호
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• pp.223-232
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• 2010

Artesunate, a semi-synthetic derivative of artemisinin, is used primarily as a treatment for malaria. Its effects on the central nervous system, general behavior, and cardiovascular, respiratory, and other organ systems were studied using mice, rats, guinea pigs, and dogs. Artesunate was administered orally to mice at doses of 125, 250, and 500 mg/kg and to rats and guinea pigs at 100, 200, and 400 mg/kg. In dogs, test drugs were administered orally in gelatin capsules at doses of 50, 100, and 150 mg/kg. Artesunate induced insignificant changes in general pharmacological studies, including general behavior, motor coordination, body temperature, analgesia, convulsion modulation, blood pressure, heart rate (HR), and electrocardiogram (ECG) in dogs in vivo; respiration in guinea pigs; and gut motility or direct effects on isolated guinea pig ileum, contractile responses, and renal function. On the other hand, artesunate decreased the HR and coronary flow rate (CFR) in the rat in vitro; however, the extent of the changes was small and they were not confirmed in in vivo studies in the dog. Artesunate increased hexobarbital-induced sleeping time in a dose-related manner. Artesunate induced dose-related decreases in the volume of gastric secretions and the total acidity of gastric contents, and induced increases in pH at a dose of 400 mg/kg. However, all of these changes were observed at doses much greater than clinical therapeutic doses (2.4 mg/kg in humans, when used as an anti-malarial). Thus, it can be concluded that artesunate is safe at clinical therapeutic doses.

• Toxicological Research
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• 제16권3호
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• pp.211-219
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• 2000

The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.

• 대한한의학방제학회지
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• 제7권1호
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• pp.167-181
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• 1999

Rhizoma Arisaematis, Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Folium Perillae, Radix Sophorae Subprostratae, Radixi, Radix Ledeboutriellae, Rhizoma Atractylodis, Herba Ephedrae, Radix Puerariae and Radi Aconitx Bupleuri have been used in Korea for many centuries as a treatment for various disease. The purpose of the present study is to determine the effect of several herbs on norepinephrine(NE) induced blood vessel contraction in rabbits and pigs. Rabbit(2 kg, male) were killed by $CO_2$ exposure and a segment (8-10mm) of each rabbit was cut into equal segments and mounted in a tissue bath. Contractile force was measured with force displacement transducers under 2-3 g loading tension. The dose of norepinephrine(NE) which evoked 50% of maximal response $(ED_{50})$ was obtained from cumulative dose response curves for NE $(10^{-6}{\sim}10^{-3}M)$. Contractions evoked by NE $(ED_{50})$ were inhibited significantly by Rhizoma Arisaematis, Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Folium Perillae, Radix Sophorae Subprostratae and Herba Ephedrae in abdominal aorta. Contractions evoked by NE $(ED_{50})$ were inhibited significantly be Lignum Akebiae, Rhizoma Zedoariae, Cortex Eucommiae, Herba Ephedrae, Radix Puerariae and Radix Bupleuri in femoral artery. Contractions evoked by NE $(ED_{50})$ were inhibited significantly by Radix Sophorae Subprostratae, Radix Aconiti and Herba Ephedrae in renal artery. These results indicate that each herb can relax NE induced contraction of rabbit and pig blood vessel selectively, and that this relaxation relates to Gui-Gyung(歸經).

• 대한기관식도과학회:학술대회논문집
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• 대한기관식도과학회 1982년도 제16차 학술대회연제순서 및 초록
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• pp.17.1-17
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• 1982

1965년 Rosenberg등은 platinum electrode가 platinum 복합물을 형성함으로써 E-coli의 세포분열과 성장을 억제할 뿐아니라 항암작용도 갖고 있다는 보고를 하였으며 그 후 Welsch (1971), Speer (1972), Rossof(1972), Hill (1974), 그리고 Wittes등(1975)에 의하여 동물 및 임상실험을 통하여 Cis-platinum이 악성종양 특히 두경부악성종양에 탁월한 효과가 있다는 것이 밝혀짐에 따라서 Cis-platinum은 단독투여제 또는 Bleomyun, MTX등 다른 항암제와 함께 병용투여제로써 각광을 받게 되었다. 그러나 Cis-platinum은 항암효과이외에 때때로 내이에 영향을 미쳐 회화영역이상의 고주파에서 청력장애를 초래할 뿐만아니라 renal tubule에도 불가역적인 병변을 초래 할 수 있다는 보고들이 있어서 우수한 항암효과에 도 불구하고 임상에서 사용제한을 받는 경우가 많다. 특히 청력장애에 대하여는 Kohonen등(1965), Stadnacki등(1974)이 guinea pig에서 Cis-platinum을 투여한 후에 와우각의 기저부에 중독작용을 보고한 이래 많은 연구가 있었으나 사람에서의 이 중독작용은 Piel(1974)과 Hong등(1979)의 보고등을 찾아볼 수 있을 정도이다. 이에 저자들은 1979년 7월부터 1982년 3월까지 2년 6개월간 두경부악성종양으로 이비인후과에 입원하였던 환자중 30례에서 Cis-platinum의 투여전과 투여후의 청력상을 비교해 이중독증의 여부와 그 정도를 규명하고 그 결과를 임상적적응에 이용하고저 본 검사를 시행하여 다음과 같은 결론을 얻었다. 1) Cis-platinum 투여전과 투여후 pure tone average, 4000Hz와 8000Hz의 hearing threshold, speech reception threshold, PB score, SISI를 측정한 결과 변화는 볼 수 없었다. 2)Cis-platinum총 투여량에 따른 청력상에도 변화가 없었다. 3) 투여전에 전음성난청과 감음성난청이 있었던 환자에게 Cis-platinum을 투여한 후의 청력상을 투여전에 청력이 정상이었던 환자와 비교한 결과 차이가 없었다. 4) Cis-platinum투여로 인한 혈색소, 백혈구수, 혈소판수는 변화가 없었다. 5) Creatinine Clearance, Creatinine, Uric acid의 변화를 본 결과 Cis-platinum 투여후에 변화는 없었으나 100mg을 1 회투여하였던 한 환자에게서 creatine clearance가 25ml/min로써 신중독증을 나타냈다. 6) Cis-platinum 투여시 hydration에 따른 전해질 특히 혈청내의 $K^{+}$치를 측정한 결과 투여전과 차이가 없었다. 7) 이상의 결과로 볼때 Cis-platinum 사용으로 인한 이중독증은 신장기능이 정상일때는 충분한 hydration으로써 예방이 가능하며 동시에 금기로 알려져왔던 감음성난청이 있는 두경부악성종양환자에서도 세심한 주의하에 적절히 사용한다면 좋은 결과를 얻을 수 있을 것으로 사려된다.

• Journal of Ginseng Research
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• 제40권2호
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• pp.135-140
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• 2016

Background: Nephrotoxicity is a common side effect of medications. Panax ginseng is one of the best-known herbal medicines, and its individual constituents enhance renal function. Identification of its efficacy and mechanisms of action against drug-induced nephrotoxicity, as well as the specific constituents mediating this effect, have recently emerged as an interesting research area focusing on the kidney protective efficacy of P. ginseng. Methods: The present study investigated the kidney protective effect of fermented black ginseng (FBG) and its active component ginsenoside 20(S)-Rg3 against cisplatin (chemotherapy drug)-induced damage in pig kidney (LLC-PK1) cells. It focused on assessing the role of mitogen-activated protein kinases as important mechanistic elements in kidney protection. Results: The reduced cell viability induced by cisplatin was significantly recovered with FBG extract and ginsenoside 20(S)-Rg3 dose-dependently. The cisplatin-induced elevated protein levels of phosphorylated c-Jun N-terminal kinase (JNK), p53, and cleaved caspase-3 were decreased after cotreatment with FBG extract or ginsenoside 20(S)-Rg3. The elevated percentage of apoptotic LLC-PK1 cells induced by cisplatin treatment was significantly abrogated by cotreatment with FBG and the ginsenoside 20(S)-Rg3. Conclusion: FBG and its major ginsenoside 20(S)-Rg3, ameliorated cisplatin-induced nephrotoxicity in LLC-PK1 cells by blocking the JNKep53ecaspase-3 signaling cascade.

• Animal Bioscience
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• 제36권5호
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• pp.740-752
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• 2023

Objective: Dietary phytase increases bioavailability of phytate-bound phosphorus (P) in pig nutrition affecting dietary calcium (Ca) to P ratio, intestinal uptake, and systemic utilization of both minerals, which may contribute to improper bone mineralization. We used phytase to assess long-term effects of two dietary available P (aP) levels using a one-phase feeding system on gene expression related to Ca and P homeostasis along the intestinal tract and in the kidney, short-chain fatty acids in stomach, cecum, and colon, serum, and bone parameters in growing gilts and barrows. Methods: Growing pigs (37.9±6.2 kg) had either free access to a diet without (Con; 75 gilts and 69 barrows) or with phytase (650 phytase units; n = 72/diet) for 56 days. Samples of blood, duodenal, jejunal, ileal, cecal, and colonic mucosa and digesta, kidney, and metacarpal bones were collected from 24 pigs (6 gilts and 6 barrows per diet). Results: Phytase decreased daily feed intake and average daily gain, whereas aP intake increased with phytase versus Con diet (p<0.05). Gilts had higher colonic expression of TRPV5, CDH1, CLDN4, ZO1, and OCLN and renal expression of TRPV5 and SLC34A3 compared to barrows (p<0.05). Phytase increased duodenal expression of TRPV5, TRPV6, CALB1, PMCA1b, CDH1, CLDN4, ZO1, and OCLN compared to Con diet (p<0.05). Furthermore, phytase increased expression of SCL34A2 in cecum and of FGF23 and CLDN4 in colon compared to Con diet (p<0.05). Alongside, phytase decreased gastric propionate, cecal valerate, and colonic caproate versus Con diet (p<0.05). Phytase reduced cortical wall thickness and index of metacarpal bones (p<0.05). Conclusion: Gene expression results suggested an intestinal adaptation to increased dietary aP amount by increasing duodenal trans- and paracellular Ca absorption to balance the systemically available Ca and P levels, whereas no adaption of relevant gene expression in kidney occurred. Greater average daily gain in barrows related to higher feed intake.