• 제목/요약/키워드: Uterine smooth muscle

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우심실로 전이된 내장 외 연부조직 평활근육종: 증례 보고 및 문헌 고찰 (Unusual Cardiac Metastasis of Nonvisceral Soft Tissue Leiomyosarcoma in the Right Ventricle: A Case Report and Literature Review)

  • 박상민;김희경
    • 대한영상의학회지
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    • 제82권1호
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    • pp.219-224
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    • 2021
  • 평활근육종은 평활근육세포에서 기원하는 연부조직 육종이다. 평활근육종은 자궁에 흔하게 발생하지만 후복막강, 복강 그리고 혈관조직에도 발생할 수 있다. 자궁 또는 혈관에서 기원하는 평활근육종이 심장에 전이된 증례는 많이 보고되었으나, 내장 외 연부조직에서 생긴 평활근육종은 매우 드물게 발생하며 심장으로의 전이는 더욱 드문 것으로 알려져 있다. 이에 좌측 측복부에서 우심실로 전이된 평활근육종의 심초음파 소견과 조영증강 컴퓨터단층촬영소견을 경험하여 보고하고자 한다.

Role of T-type $Ca^{2+}$ Channels in the Spontaneous Phasic Contraction of Pregnant Rat Uterine Smooth Muscle

  • Lee, Si-Eun;Ahn, Duck-Sun;Lee, Young-Ho
    • The Korean Journal of Physiology and Pharmacology
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    • 제13권3호
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    • pp.241-249
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    • 2009
  • Although extracellular $Ca^{2+}$ entry through the voltage-dependent $Ca^{2+}$ channels plays an important role in the spontaneous phasic contractions of the pregnant rat myometrium, the role of the T-type $Ca^{2+}$ channels has yet to be fully identified. The aim of this study was to investigate the role of the T-type $Ca^{2+}$ channel in the spontaneous phasic contractions of the rat myometrium. Spontaneous phasic contractions and $[Ca^{2+}]_i$ were measured simultaneously in the longitudinal strips of female Sprague-Dawley rats late in their pregnancy (on day 18 ${\sim}$ 20 of gestation: term=22 days). The expression of T-type $Ca^{2+}$ channel mRNAs or protein levels was measured. Cumulative addition of low concentrations (< 1 ${\mu}M$) of nifedipine, a L-type $Ca^{2+}$ channel blocker, produced a decrease in the amplitude of the spontaneous $Ca^{2+}$ transients and contractions with no significant change in frequency. The mRNAs and proteins encoding two subunits (${\alpha}$ 1G, ${\alpha}$ 1H) of the T-type $Ca^{2+}$ channels were expressed in longitudinal muscle layer of rat myometrium. Cumulative addition of mibefradil, NNC 55-0396 or nickel induced a concentration-dependent inhibition of the amplitude and frequency of the spontaneous $Ca^{2+}$ transients and contractions. Mibefradil, NNC 55-0396 or nickel also attenuated the slope of rising phase of spontaneous $Ca^{2+}$ transients consistent with the reduction of the frequency. It is concluded that T-type $Ca^{2+}$ channels are expressed in the pregnant rat myometrium and may play a key role for the regulation of the frequency of spontaneous phasic contractions.

폐로 전이된 양성 전이성 근종 (Benign Metastasizing Leiomyoma of Lung)

  • 조석기;류경민;성숙환;정진행;이재호;김용범;전상훈
    • Journal of Chest Surgery
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    • 제39권4호
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    • pp.335-339
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    • 2006
  • 양성 전이성 근종은 조직학적으로는 양성 종양의 소견을 보이는 자궁근종에서 폐로 전이되어, 임상적으로는 악성 종양의 성질을 지닌 매우 드문 질환이다. 저자들은 자궁근종으로 자궁 절제술을 계획하고 있는 환자에서 다발성 폐 결절이 발견되어, 폐절제술과 자궁절제술을 동시에 시행하였다. 수술후 조직병리 검사에서 폐 결절에서 호르몬 수용체 존재를 확인하여 양성 전이성 근종으로 확진할 수 있었으며, 환자는 수술 후 특별한 치료 없이 외래 추적 관찰 중이다.

Acetylcholine및 Oxytocin에 의하여 야기되는 렛드 자궁수축에 미치는 Verapamil 및 Tetracaine의 영향 (Effects of Verapamil and Tetracaine on Acetylcholine-and Oxytocin-induced Uterine Contraction Pattern)

  • 이만기;김중영
    • 대한약리학회지
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    • 제23권2호
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    • pp.133-141
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    • 1987
  • Acetylcholine및 oxytocin에 의하여 야기되는 흰쥐의 적출자궁수축을 $Ca^{2+}$ 길항제의 일종인 verapamil및 tetracaine 존재하에서 acetylcholine및 oxytocin에 의한 자궁수축곡선을 4개의 요소 (trough tension, T: peak tension, P; contraction frequency, F: duration, D)로 나누어 비교분석하여 다음과 같은 결과를 얻었다. Verapamil $(0.25\;{\mu}M)$은 자발수축을 억제시켰으나 tetracaine$(42\;{\mu}M)$은 자발수축을 억제시키지 못하였다. 이들 길항제의 존재하에서 acetylcholine및 oxytocin에 의하여 야기되는 자궁수축의 각 구성요소에 변화를 관찰하였다. 즉 acetylcholine에 의한 수축에서 verapamil은 P와 D를 감소시켰고 tetracaine은 F를 감소시키고 D를 증가시켰다. oxytocin에 의한 수축에서 verapamil은 P와 D를 감소시켰으나 tetracaine은 oxytocin농도에 따라 차이가 있었는데, 저농도의 oxytocin에 의한 수축에서는 F를 감소시키고 D를 증가시켰으나 고농도의 oxytocin에 의한 수축에서 는 F와 D에는 영향을 주지 않고 P만 감소시켰다. 이상의 결과로 미루어 acetylcholine및 oxytocin에 의하여 야기되는 수축곡선은 시각적으로 큰 차이가 없었으나 작용기전이 다른 $Ca^{2+}$ 길항제에 의하여 acetylcholine및 oxytocin의 수축의 구성요소에 다르게 영향을 미칠 수 있었다는 것은 수축곡선의 구성요소의 변화를 면밀히 검토하면 자궁수축제의 수축작용기전이 다름을 예측할 수 있을 뿐만 아니라 수축억제제에 의한 억제 기전의 차이점도 예측할 수 있을 것으로 생각되어 진다.

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여뀌섭취가 반추수에 비치는 임상병리학적 영향 (Clinicopathological Effects of Waterpepper (Persicaria hydropiper) on Ruminants)

  • 조명래;한홍율
    • 한국임상수의학회지
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    • 제6권2호
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    • pp.227-259
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    • 1989
  • Waterpepper is a weed which grows on damp soil. especially near swamps, and in shallow water of ponds and ditches. It Is widespread throughout the country In abundant colonies. In the present experiments, possible toxic effects of waterpepper were investigated in ruminants. Pour cows were fed waterpepper ad libitum or by force in the from of green forage, hay and/or powder, 8 goats were administered in the form of methanol extract, and 4 goats, crude juice, into the lumen. Clinical signs were examined as well as urinalysis, hematology, serum chemical analysis, pH/blood gas analysis and chclinesterase activities following administration of waterpepper. Six goats which were administered the methanol extract or crude juice were sacrificed for pathological examinations., In addition to the clini copathological examinations, the chemical constituents of waterpepper were qualitively analyzed from the methanol extract and the Effects of the waterpepper crude juice were examined on the motility of rabbit duodenum and uterus. It is revealed that waterpepper contains steroids, terpenoids, flavonoids, tannin and essential oils in the methanol extract and nitrates in the crude juice. The crude juice of waterpepper relaxed the rabbit uterine and duodenal smooth muscles. The constraction of duodenum by acetylcholine or BaCl$_2$ were partially inhibited by pretreatment of the crude juice. However, the relaxation of duodenum by the crude juice was not blocked by the pretreatments of phenoxybenzamlne, propranolol, cocaine, reserpine and tetrodotoxin. The constituents of waterpepper to evoke elaxation of duodenal smooth muscle were stable to heat. The cows administered waterpepper showed common clinical symptoms such as acrid expression, restlessness, dullness, inappetence, anorexia, severe diarrhea, mild bloat and left displacement of abomasum, while bloody feces was shown in a cow. The goats administered the mothanol extract showed common clinical signs such as acrid expression, restlessness, dullness, inappetence and soft feces, while bloody feces was shown in a goat, A goat adminstered the crude juice showde bloody feces and diarrhea. Respiratory rates and heart beats were increased along with diarrhea in the experimental cows. The erythrocyte counts and MCHC were decreased whereas PCV, MCV and neutrophils were increased in the cows administered waterpepper. In goats administered methanol extract, there were decreases in erythrocytes, PCV and hemoglobin content, and an increase in MCHC. The goats ingester with the crude juice showed negligible changes in hematologic values compared with control group which was administered the same amount of water instead of the crude juice. The contents of serum calcium, Inorganic phosphorus, magnesium, Iron, glucose, cholesterol, total protein, triglycerides and phospholipids were tended to decrease in cows. In goats serum iron, glucose, triglycerides, cholesterol, BUN and phospholipids content were decreased while the content of sodium and chloride were increased after administration of the methamol extract The goats ingested with the crude juice did not show significant changes in serum chemical analysis. Even though there were some pathological findings such as hyperemia in the small intestines and kidneys and swelling of liver parenchymal cells, the values of serum AST, ALT, LDH, alkaline phosphatase, total bilirubin and creatinine did not change significantly. While proteins, hemoglobin and blood were detected in the urine of cows, urine pH, ketone bodies, glucose, bilirubin and urobilinogen content were normal or undetected. There were no significant changes in pH/bolld gas analysis data of cows and cholinesterase activities of plasma and erythrocytes of cows and goats ingested with waterpepper or the methanol extract. It is concluded that waterpepper irritates the gatrointestinal system, causes abdominal pain, relaxes the gastrointestinal smooth muscle and dilatates blood vessels supplied to the system. The irritation and relaxation may lead to abnormal fermentation, maldigestion and malabsorption of nutrients and result in diarrhea, body feces, mild bloat and left displacement of abomasum.

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포유동물 생식세포 및 생식기관에서 발현되는 Two-Pore Domain 칼륨 통로 (Two-Pore Domain $K^+$ Channels Expressed in Mammalian Reproductive Cells and Organs)

  • 이효진;한재희;강다원
    • 한국수정란이식학회지
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    • 제24권3호
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    • pp.189-197
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    • 2009
  • Two-pore domain 칼륨($K_{2P}$) 통로는 흥분세포 및 비흥분세포의 안정막 전압을 일정하게 유지하는데 관여한다. 그러나 생식세포 및 생식기관에서 발현되는 $K_{2P}$ 통로의 분포영역 및 그 기능에 대해서는 연구자들에 의해 아직 정리되지 못하였다. 본 종설에서는 $K_{2P}$ 통로의 생식세포 및 생식기관에서 발현, 분포 및 생리학적 의의를 논하였다. $K_{2P}$ 통로는 인간 영양막세포, 자궁근층, 태반혈관계, 자궁평활근조직, 태반융모조직 및 임신자궁조직에서 발현되어 임신에 있어서 관련성을 제시되었다. 또한, $K_{2P}$ 통로는 마우스 전핵배, 원숭이 정자 및 한우의 난소, 정소, 난자, 정자 및 수정란에서 발현 변화를 보였다. 특히, $K_{2P}$ 통로는 체외배양 시 변화되는 온도, 산소분압과 같은 배양조건에 의해 조절되는 특징을 보임으로써 수정 및 배 발달에 영향을 줄 수 있는 인자로 제시되었다. 그리고 $K_{2P}$ 통로는 과산화수소에 의해 유도된 마우스 전핵배의 세포 사멸에 있어서 칼륨 이온의 유출에 관여함이 확인되었다. $K_{2P}$ 통로의 생식세포 및 생식기관 내 발현 형태와 생리학적 특징은 생식생리학에 있어서 이온 통로 관련 기능들을 이해하는데 도움이 될 것이다.

원발성 기관지내 평활근종 1예 (A Case of Primary Endobronchial Leiomyoma)

  • 이희경;이재형;김상헌;김태형;손장원;윤호주;신동호;박성수;민경환;백승삼;강정호
    • Tuberculosis and Respiratory Diseases
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    • 제61권3호
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    • pp.273-278
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    • 2006
  • 기관지 평활근종은 기관지에 발생하는 양성 종양으로 드문 질환이다. 기도를 폐쇄하여 호흡기계 증상을 유발할 수 있고, 원위부의 비가역적인 폐실질의 손상을 초래할 수 있으므로, 본 증례처럼 비교적 젊은 나이에서 만성 기침이나 반복되는 폐렴 등의 기관지 폐쇄의 징후가 있을 시에는, 드물지만 평활근종이 다른 기관지내의 종양과의 감별진단에 고려되어야 하고, 기관지경검사에 의한 조기 진단으로 이차적인 폐실질의 손상을 막는 것이 중요하다고 여겨진다. 이에 기관지 평활근종 1예를 경험하였기에 문헌 고찰과 함께 보고하는 바이다.

Myometrial relaxation of mice via expression of two pore domain acid sensitive K+ (TASK-2) channels

  • Kyeong, Kyu-Sang;Hong, Seung Hwa;Kim, Young Chul;Choi, Woong;Myung, Sun Chul;Lee, Moo Yeol;You, Ra Young;Kim, Chan Hyung;Kwon, So Yeon;Suzuki, Hikaru;Park, Yeon Jin;Jeong, Eun-Hwan;Kim, Hak Soon;Kim, Heon;Lim, Seung Woon;Xu, Wen-Xie;Lee, Sang Jin;Ji, Il Woon
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권5호
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    • pp.547-556
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    • 2016
  • Myometrial relaxation of mouse via expression of two-pore domain acid sensitive (TASK) channels was studied. In our previous report, we suggested that two-pore domain acid-sensing $K^+$ channels (TASK-2) might be one of the candidates for the regulation of uterine circular smooth muscles in mice. In this study, we tried to show the mechanisms of relaxation via TASK-2 channels in marine myometrium. Isometric contraction measurements and patch clamp technique were used to verify TASK conductance in murine myometrium. Western blot and immunehistochemical study under confocal microscopy were used to investigate molecular identity of TASK channel. In this study, we showed that TEA and 4-AP insensitive non-inactivating outward $K^+$ current (NIOK) may be responsible for the quiescence of murine pregnant longitudinal myometrium. The characteristics of NIOK coincided with two-pore domain acid-sensing $K^+$ channels (TASK-2). NIOK in the presence of $K^+$ channel blockers was inhibited further by TASK inhibitors such as quinidine, bupivacaine, lidocaine, and extracellular acidosis. Furthermore, oxytocin and estrogen inhibited NIOK in pregnant myometrium. When compared to non-pregnant myometrium, pregnant myometrium showed stronger inhibition of NIOK by quinidine and increased immunohistochemical expression of TASK-2. Finally, TASK-2 inhibitors induced strong myometrial contraction even in the presence of L-methionine, a known inhibitor of stretch-activated channels in the longitudinal myometrium of mouse. Activation of TASK-2 channels seems to play an essential role for relaxing uterus during pregnancy and it might be one of the alternatives for preventing preterm delivery.

Effects of zearalenone on the localization and expression of the growth hormone receptor gene in the uteri of post-weaning piglets

  • Zhou, Min;Yang, Li Jie;Yang, Wei Ren;Huang, Li Bo;Zhou, Xue Mei;Jiang, Shu Zhen;Yang, Zai Bin
    • Asian-Australasian Journal of Animal Sciences
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    • 제31권1호
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    • pp.32-39
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    • 2018
  • Objective: In this study, we investigated the adverse effects of dietary zearalenone (ZEA) (0.5 to 1.5 mg/kg diet) on the localization and expression of the growth hormone receptor (GHR) in the uteri of post-weaning gilts and explored alternative mechanism of the reproductive toxicity of ZEA on piglets. Methods: A total of forty healthy piglets (Duroc${\times}$Landrace${\times}$Large White) aged 28 d were selected for study. Piglets were transferred to single cages after 10 days' adaptation on an obstetric table. The animals were allocated to one of four treatments: a normal basal diet supplemented with 0 (Control), 0.5 (ZEA0.5), 1.0 (ZEA1.0), or 1.5 (ZEA1.5) mg/kg purified ZEA, and fed for 35 d after the 10-d adaptation. Analyzed ZEA concentrations in the diets were 0, $0.52{\pm}0.07$, $1.04{\pm}0.03$, and $1.51{\pm}0.13mg/kg$, respectively. At the end of the feeding trial, piglets were euthanized after being fasted for 12 h. Two samples of uterine tissue from each pig were rapidly collected, one of which was stored at $-80^{\circ}C$ for analysis of the relative mRNA and protein expression of GHR, and the second was promptly fixed in Bouin's solution for immunohistochemical analysis. Results: The relative weight of the uteri and thickness of the myometrium and endometrium increased linearly (p<0.001) and quadratically (p<0.001) with an increasing level of ZEA. The results of immunohistochemical analysis indicated that GHR immunoreactive substance was mainly localizated in the cytoplasm of uterine smooth muscle, glandular epithelial, luminal epithelial, stromal, and vascular endothelial cells. In contrast, nuclear staining was rarely observed. The immunoreactive integrated optic density of GHR in the myometrium, luminal epithelium, glandular epithelium, and whole uteri of weaning gilts increased linearly (p<0.001) and quadratically (p<0.05) with an increasing level of ZEA. The mRNA and protein expression of GHR in the uteri of weaning gilts increased linearly (p<0.001) and quadratically (p<0.05) with an increasing level of ZEA. Conclusion: In conclusion, ZEA at a concentration of 0.5 mg/kg was sufficient to significantly thicken the myometrium and endometrium, and at a concentration of 1.0 mg/kg induced a high level of GHR expression to promote growth and development of the uteri. This revealed an alternative molecular mechanism whereby ZEA induces growth and development of the uteri and provides a theoretical basis for the revision of Chinese feed hygiene standards.

Cefoperazone(T-1551)의 약리학적 연구 (Pharmacological Studies of Cefoperazone(T-1551))

  • 임정규;홍사악;박찬웅;김명석;서유헌;신상구;김용식;김혜원;이정수;장기철;이상국;장우현;김익상
    • 대한약리학회지
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    • 제16권2호
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    • pp.55-70
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    • 1980
  • The pharmacological and microbiological studies of Cefoperazone (T-1551, Toyama Chemical Co., Japan) were conducted in vitro and in vivo. The studies included stability and physicochemical characteristics, antimicrobial activity, animal and human pharmacokinetics, animal pharmacodynamics and safety evaluation of Cefoperazone sodium for injection. 1) Stability and physicochemical characteristics. Sodium salt of cefoperazone for injection had a general appearance of white crystalline powder which contained 0.5% water, and of which melting point was $187.2^{\circ}C$. The pH's of 10% and 25% aqueous solutions were 5.03 ana 5.16 at $25^{\circ}C$. The preparations of cefoperazone did not contain any pyrogenic substances and did not liberate histamine in cats. The drug was highly compatible with common infusion solutions including 5% Dextrose solution and no significant potency decrease was observed in 5 hours after mixing. Powdered cefoperazone sodium contained in hermetically sealed and ligt-shielded container was highly stable at $4^circ}C{\sim}37^{\circ}C$ for 12 weeks. When stored at $4^{\circ}C$ the potency was retained almost completely for up to one year. 2) Antimicrobial activity against clinical isolates. Among the 230 clinical isolates included, Salmonella typhi was the most susceptible to cefoperazone, with 100% inhibition at MIC of ${\leq}0.5{\mu}g/ml$. Cefoperazone was also highly active against Streptococcus pyogenes(group A), Kletsiella pneumoniae, Staphylococcus aureus and Shigella flexneri, with 100% inhibition at $16{\mu}g/ml$ or less. More than 80% of Escherichia coli, Enterobacter aerogenes and Salmonella paratyphi was inhibited at ${\leq}16{\mu}/ml$, while Enterobacter cloaceae, Serratia marcescens and Pseudomonas aerogenosa were somewhat less sensitive to cefoperagone, with inhibitions of 60%, 55% and 35% respectively at the same MIC. 3) Animal pharmacokinetics Serum concentration, organ distritution and excretion of cefoperazone in rats were observed after single intramuscular injections at doses of 20 mg/kg and 50 mg/kg. The extent of protein binding to human plasma protein was also measured in vitro br equilibrium dialysis method. The mean Peak serum concentrations of $7.4{\mu}g/ml$ and $16.4{\mu}/ml$ were obtained at 30 min. after administration of cefoperazone at doses of 20 mg/kg and 50 mg/kg respectively. The tissue concentrations of cefoperazone measured at 30 and 60 min. were highest in kidney. And the concentrations of the drug in kidney, liver and small intestine were much higher than in blood. Urinary and fecal excretion over 24 hours after injetcion ranged form 12.5% to 15.0% in urine and from 19.6% to 25.0% in feces, indicating that the gastrointestinal system is more important than renal system for the excretion of cefoperazone. The extent of binding to human plasma protein measured by equilibrium dialysis was $76.3%{\sim}76.9%$, which was somewhat lower than the others utilizing centrifugal ultrafiltration method. 4) Animal pharmacodynamics Central nervous system : Effects of cefoperazone on the spontaneous movement and general behavioral patterns of rats, the pentobarbital sleeping time in mice and the body temperature in rabbits were observed. Single intraperitoneal injections at doses of $500{\sim}2,000mg/kg$ in rats did not affect the spontaneous movement ana the general behavioral patterns of the animal. Doses of $125{\sim}500mg/kg$ of cefoperazone injected intraperitonealy in mice neither increased nor decreased the pentobarbital-induced sleeping time. In rabbits the normal body temperature was maintained following the single intravenous injections of $125{\sim}2,000mg/kg$ dose. Respiratory and circulatory system: Respiration rate, blood pressure, heart rate and ECG of anesthetized rabbits were monitored for 3 hours following single intravenous injections of cefoperazone at doses of $125{\sim}2,000mg/kg$. The respiration rate decreased by $3{\sim}l7%$ at all the doses of cefoperazone administered. Blood pressure did not show any changes but slight decrease from 130/113 to 125/107 by the highest dose(2,000 mg/kg) injected in this experiment. The dosages of 1,000 and 2,000 mg/kg seemed to slightly decrease the heart rate, but it was not significantly different from the normal control. All the doses of cefoperazone injected were not associated with any abnormal changes in ECG findings throughout the monitering period. Autonomic nervous system and smooth muscle: Effects of cefoperazone on the automatic movement of rabbit isolated small intestine, large intestine, stomach and uterus were observed in vitro. The autonomic movement and tonus of intestinal smooth muscle increased at dose of $40{\mu}g/ml$ in small intestine and at 0.4 mg/ml in large intestine. However, in stomach and uterine smooth muscle the autonomic movement was slightly increased by the much higher doses of 5-10 mg/ml. Blood: In vitro osmotic fragility of rabbit RBC suspension was not affected by cefoperazone of $1{\sim}10mg/ml$. Doses of 7.5 and 10 mg/ml were associated with 11.8% and 15.3% prolongation of whole blood coagulation time. Liver and kidney function: When measured at 3 hours after single intravenous injections of cefoperaonze in rabbits, the values of serum GOT, GPT, Bilirubin, TTT, BUN and creatine were not significantly different from the normal control. 5) Safety evaluation Acute toxicity: The acute toxicity of cefoperazone was studied following intraperitoneal and intravenous injections to mice(A strain, 4 week old) and rats(Sprague-Dawler, 6 week old). The LD_(50)'s of intraperitonealy injected cefoperazone were 9.7g/kg in male mice, 9.6g/kg in female mice and over 15g/kg in both male and female rats. And when administered intravenously in rats, LD_(50)'s were 5.1g/kg in male and 5.0g/kg in female. Administrations of the high doses of the drug were associated with slight inhibition of spontaneous movement and convulsion. Atdominal transudate and intestinal hyperemia were observed in animals administered intraperitonealy. In rats receiving high doses of the drug intravenously rhinorrhea and pulmonary congestion and edema were also observed. Renal proximal tubular epithelial degeneration was found in animals dosing in high concentrations of cefoperazone. Subacute toxicity: Rats(Sprague-Dawley, 6 week old) dosing 0.5, 1.0 and 2.0 g/kg/day of cefoperazone intraperitonealy were observed for one month and sacrificed at 24 hours after the last dose. In animals with a high dose, slight inhibition of spontaneous movement was observed during the experimental period. Soft stool or diarrhea appeared at first or second week of the administration in rats receiving 2.0g/kg. Daily food consumption and weekly weight gain were similar to control during the administration. Urinalysis, blood chemistry and hematology after one month administration were not different from control either. Cecal enlargement, which is an expected effect of broad spectrum antibiotic altering the normal intestinal microbial flora, was observed. Intestinal or peritoneal congestion and peritonitis were found. These findings seemed to be attributed to the local irritation following prolonged intraperitoneal injections of hypertonic and acidic cefoperazone solution. Among the histopathologic findings renal proximal tubular epithelial degeneration was characteristic in rats receiving 1 and 2g/kg/day, which were 10 and 20 times higher than the maximal clinical dose (100 mg/kg) of the drug. 6) Human pharmacokinetics Serum concentrations and urinary excretion were determined following a single intravenous injection of 1g cefoperazone in eight healthy, male volunteers. Mean serum concentrations of 89.3, 61.3, 26.6, 12.3, 2.3, and $1.8{\mu}g/ml$ occured at 1,2,4,6,8 and 12 hours after injection respectively, and the biological half-life was 108 minutes. Urinary excretion over 24 hours after injection was up to 43.5% of administered dose.

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