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Toxicological Aspects of Carboxylesterases -A Sensitive Biomarker of Organophosphate Toxicity-

  • Satoh, Tetsuo;Suzuki, Satoshi;Hosokawa, Masakiyo
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1998.11a
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    • pp.108-113
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    • 1998
  • Egasyn is accessory protein of ${\beta}$-glucuronidase(${\beta}$-G) in the liver microsomes. Liver microsomal ${\beta}$-G is stabilized within the luminal site of the microsomal vesicles by complexation with egasyn which is one of carboxylesterase isozymes. We investigated the effects of organophosphorus compounds(OPs) such as insecticides on the dissociation of egasyn-${\beta}$-glucuronidase(EG) complex. The EG complex was easily dissociated by administration of OPs, i.e., Fenitrothion, EPN, Phenthionate, and bis-p-nitrophenyl phosphate(BNPP), and resulting ${\beta}$-G dissociated was released into blood, leading to the rapid and transient increase of plasma ${\beta}$-G level with a concomitant decrease of liver microsomal ${\beta}$-G level. In a case of phenthionate treatment, less increase in plasma ${\beta}$-G level was observed, as compared with those of other OPs. This may be explained by a fact that phenthionate was easily hydrolyzed by carboxylesterase. Similarly, carbamate insecticides such as Carbaryl caused rapid increase of plasma ${\beta}$-G level. In contrast, no significant increase of plasma ${\beta}$-G level was observed when pyrethroid insecticides were administered to rats. This is due to a fact that pyrethroids such as Phenthrin and Allethrin were easily hydrolyzed by A-esterase as well as carboxylesterase. On the other hand, addition of OPs to the incubation mixture containing liver microsomes caused the release of ${\beta}$-G from microsomes to the medium. From these in vivo and in vitro data, it is concluded that increase of the plasma ${\beta}$-G level after OPs administration is much more sensitive biomarker than cholinesterase inhibition to acute intoxication of OPs and carbamates.

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Expression, Purification and Functional and structural relationship of pyruvate dehydrogenase phosphatase

  • Kim, Young-Mi;Jung, Ki-Hwa
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2002.07a
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    • pp.236-236
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    • 2002
  • Pyruvate dehydrogenase phosphatase (PDP) is a mitochondrial protein serine/threonine phosphatase that catalyzes the dephosphorylation and concomitant reactivation of the pyruvate dehydrogenase componant of the pyruvate dehydrogenase complex (PDC). PDP consists of a Mg$\^$+2/ -dependent and Ca$\^$+2)-stimulated catalytic subunit (PDPc) of Mr 52,600 and a FAD-containing regulatory subunit (PDPr) of Mr 95.600. Catalytic subunit of pyruvate dehydrogenase phosphatase (PDPc) has been suggested to have three major functional domains such as dihydrolipoamide acetyltransferase(E$_2$)-binding domain, regulatory subunit of PDP(PDPr)-binding domain, and calcium-binding domain. In order to identify functional domains, recombinant catalytic subunit of pyruvate dehydrogenase phosphatase (rPDPc) was expressed in E. coli JM101 and purified to near homogeneity using the unique property of PDPc: PDPm binds to the inner lipoyl domain (L$_2$) of E$_2$ of pyruvate dehydrogenase complex (PDC) in the presence of Ca$\^$+2/, not under EGTA. PDPc was limited-proteolysed by trypsin, chymotrypsin, Arg-C, and elastase at pH7.0 and 30$^{\circ}C$ and N-terminal analysis of the fragment was done. Chymotrypsin, trypsin, and elastase made two major framents: N-terminal large fragment, approx. 50kD and C-terminal small fragment, approx. 0 kDa. Arg-C made three major fragments: N-terminal fragment, approx. 35 kD, and central fragment, approx. 15 kD, and C-terminal fragment, approx. 10 kD. This study strongly suggest that PDPc consists of three major functional domains. However, further study should be necessary to identify the functional role.

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승모판 협착증의 외과적 요법

  • 이영균
    • Journal of Chest Surgery
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    • v.4 no.1
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    • pp.11-24
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    • 1971
  • Eighty-four cases of mitral commissurotomy were done in this department between October 1958 and September 1970. Therc wcre 54 males and 30 females. Six cases were under the age of 20 years. Prcoperativc embolization occurred in 9. 5% of the cases. consisting of 8. 3% cerebral and 1.2% peripheral embolization. Intraoperative and postoperative cmbolization occurred in 4.7% of the cases, with 1. 2% cerebral and 3.5% peripheral embolism. Two out of three postopeative embolism cases expired, one of which was caused by septic cerebral embolism due to valve vegetation nnd the other by mesenteric embolism. Atrial fibrillation was 1loted ill 43% of the case. Seventy closed mitral commissurotomy was done by left appendegeal approach with finger fracture method or Bailey's guillotine valvotome. Fourteen open mitral commissurotomy cases were done either by right side approach or median sternotomy, three of which were reoperation cases after blind mitral commissurotomy. One out of 14 cases were operated on with open mitral commissurotomy and concomitant open aortic valve bicuspidalization, This case expired due to severe serum hepatitis ten days after operation. Thirty-two per cent of valve calcification was noted during operation and one of which had marked vegetation on the valve cusps too. Operative mortality was 1.4% in blind mitral commissurotomy and 14% in open mitral commissurotomy. Over-all mortality in the entire series was 3.5%. One case among the blind commissurotomy cases expired during operation due to left inferior pulmonary vein laceration and death was caused in two open mitral commissurotomy cases by coronary artery airembolism. Three hospital death occurred in blind operation group, one due to coronary embolism, and two by hepatic failures. Three hospital death among open heart surgery cases were caused by hepatic failure in two and cerebral embolism in one cases. ln most of the survivors improved functional capacity and exercise lolerance were noted.

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Usefulness of Cytologic Study of Intraoperative Suction Fluid in Brain Tumors (수술시 뇌종양 흡인액의 세포학적 검사의 유용성)

  • Lee, Hye-Kyung;Lee, Hyung-Jin;Lee, Eun-Hee;Kim, Hee-Jung;Lee, Il-Woo
    • The Korean Journal of Cytopathology
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    • v.13 no.2
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    • pp.66-69
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    • 2002
  • In diagnosing a brain tumor, it is essential to obtain samples from many areas of the tumor. Although there are reports about the suitability of material obtained by cavitron ultrasonic surgical aspirator(CUSA), there is a paucity of reports regarding conventional intraoperative suction. This study was performed to evaluate the usefulness of the suction fluid and the effect of different hemolytic fixatives. Intraoperative suction fluid was obtained from 2 pituitary adenomas and 2 choroid plexus carcinomas. In two cases of mixed astro-oligodendroglioma, one of glioblastoma multiforme and 3 of meningioma, the fluid was collected by CUSA. Each sample was divided into four bottles for the different fixatives such as 0.1N HCI, 10% acetic acid, 95% alcohol, and no additive. All cases were evaluated by the both cytologic smear and cell block preparations, and were reviewed with concomitant histologic diagnosis. The result showed a good correlation between the cytologic study and the histologic diagnosis and 95% alcohol was found to be superior to other fixatives in ceil preservation.

Purification and Crystallization of the Recombinant Catalytic Subunit of Pyruvate Dehydrogenase Phosphatase (Pyruvate Dehydrogenase Phosphatase의 Catalytic Subunit의 분리정제 및 결정화)

  • Kim, Young-Mi
    • Journal of Food Hygiene and Safety
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    • v.18 no.3
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    • pp.146-152
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    • 2003
  • Pyruvate dehydrogenase phosphatase (PDP) is a mitochondrial protein serine/threonine phosphatase that catalyzes the dephosphorylation and concomitant reactivation of the pyruvate dehydrogenase component of the pyruvate dehydrogenase complex (PDC). PDP consists of a catalytic subunit (PDPc, Mr 52,600) and regulatory subunit (PDPr, Mr 95,600). In the presence of $Ca^{2+}$, PDPc binds to the dihydrolipoamide acetyltransferase (E2) component of the pyruvate dehydrogenase complex in proximity to its substrate, the phosphorylated E1 component, thereby increasing the rate of dephosphorylation. PDPc possesses and intrinsic $Ca^{2+}$ binding site and a second $Ca^{2+}$ site is generated in the presence of E2. Using the unique interaction, highly pure PDPc was produced by the GSH-Sepharose-GST-L2 matrix with a specific activity of approx. 1000 U/mg and a yield of about 80%.

Progesterone Effects on Microsomal Epoxide Hydrolase and Glutathione S-transferease mRNA Levels in Rats (랫드 간 Epoxide Hydrolase와 Glutathione S-Transferase 유전자 발현에 미치는 Progesterone의 효과)

  • Cho, Joo-Youn;Kim, Sang-Geon
    • The Korean Journal of Pharmacology
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    • v.32 no.2
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    • pp.233-241
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    • 1996
  • Previous studies have shown that glucocorticoid suppresses microsomal epoxide hydrolase(EH) gene expression and that EH expression is altered during pregnancy. The effects of progesterone on the expression of rat EH and certain glutathione S-transferase(GST) genes were examined in this study. Northern RNA blot analysis revealed that progesterone was effective in increasing hepatic EH mRNA levels at 12 h to 48 h after treatment with a maximal 9-fold increase being noted at 12 h time point. Nonetheless, multiple daily treatment with progesterone rather caused minimal relative increases in EH mRNA levels. GST Ya and Yb1/2 mRNA levels were also transiently elevated at 12 h after progesterone treatment, followed by gradual decreases from the maximal Increases at day 1, 2 and 5 post-treatment. These changes in EH and GST mRNA levels were noted only at a relatively high dose of progesterone. Furthermore, immunoblot analyses showed that rats treated with progesterone for 5 days failed to show EH or GST induction, indicating that progesterone-induced alterations in EH and GST mRNA levels do not reflect bona fide induction of the detoxifying enzymes. Concomitant progesterone treatment of rats with the known EH inducers including ketoconazole and clotrimazole failed to additively nor antagonistically alter EH mRNA levels. In contrast, dexamethasone substantially reduced ketoconazole- or clotrimazole-inducible EH expression. These results showed that progesterone stimulates the EH, GST Ya and Yb1/2 gene expression at early times followed by marked reduction in the RNA levels from the maximum after multiple treatment and that the changes in mRNA do not necessarily reflect induction of the proteins.

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Gracilis Muscle Free Flap Transplantation in the Lower Extremities - 32 Cases Snalysis - (하지에 시행한 박근 유리 판 이식술 - 32예 분석 -)

  • Lee, Jun-Mo;Kim, Hak-Ji;Kim, Yong-Min;Park, Jae-Kyu
    • Archives of Reconstructive Microsurgery
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    • v.13 no.1
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    • pp.58-62
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    • 2004
  • Purpose: To cover the exposed tendons and bones after trauma and cure the concomitant osteomyelitis in the lower extremities, gracilis muscle free flaps are frequently preferred. 32 cases of gracilis muscle free flap we had done were analysed according to the indications, specification of flap length and width, pedicle length, vessels used in the anastomosis and final healing after at least over 1 year follow up. Materials and methods: From August 1995 through November 2002, we have performed 32 cases of gracilis muscle free flap transplantation with the general microsurgical procedures in the lower extremities. Open fracture of the middle and distal tibia were 12, exposed heel 6, crushing injury in the foot 5 cases, open fracture of the ankle 4, chronic osteomyelitis of the tibia 3 and osteomyelitis of the tarsal bones 2. Tailored flap length were ranged from 16 cm to 4 cm, width were from 5cm to 4cm. Pedicle length averaged around 4 cm. Anastomosis of one artery and two veins in both of donor and recipient were performed in 17 cases and one artery and one vein in 15 cases. Results: All flaps were survived, except 2 cases. Final flap healing was satisfactory to both of the patients and microsurgeon. Conclusion: Gracilis muscle free flaps are frequently chosen to cover the exposed components and cure the osteomyelitis in the lower extremities.

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Enhanced Production of hCTLA4Ig by Suppressing Cell Death in Transgenic Rice Cell Suspension Cultures (형질전환 벼 현탁세포 배양에서 세포 사멸 억제를 통한 hCTLA4Ig 생산성 증대)

  • Kim, Myong-Sik;Nam, Hyung-Jin;Kim, Min-Sub;Kwon, Jun-Young;Kim, Dong-Il
    • KSBB Journal
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    • v.28 no.4
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    • pp.260-268
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    • 2013
  • Transgenic plant cell cultures are an attractive expression system for the production of industrial and pharmaceutical proteins because of their advantages in safety and low production cost. Human cytotoxic T-lymphocyte antigen 4-immunoglobulin (hCTLA4Ig) was produced and secreted when sugar was depleted in culture medium by transgenic rice cell lines (Oryza sativa L.) using RAmy3D promoter. Due to the production of the target protein by sugar depletion, concomitant occurrence of cell death is inevitable. For that reason, inhibition of cell death for enhancing productivity was necessary for the production period without energy sources. Supplementation of 0.1 mM sodium nitroprusside improved cell viability by 1.4-fold and maximum hCTLA4Ig production by 1.3-fold compared to those of control. Addition of 1 and 10 mM glutathione, N-acetylcysteine (NAC), and nicotinamide inhibited apoptotic-like programmed cell death by decreasing the activity of reactive oxygen species. Production hCTLA4Ig was enhanced 1.4-, 1.25-, and 1.15-fold with 10 mM NAC, 1 mM NAC, and 1 mM glutathione, respectively. In addition, it was found that the supplementation of NAC enhanced the cell viability.

Recent trend and surgical management for panfacial fracture (범안면골 골절의 최근 경향 및 수술개념)

  • Kim, Jin-Wook
    • The Journal of the Korean dental association
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    • v.54 no.10
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    • pp.811-819
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    • 2016
  • Panfacial fracture is extremely difficult to manage facial injuries but concomitant injuries and severe complications including facial esthetic and functional problems can make it harder. Thorough evaluation and closed co-work with other specialists is needed when reduction and fixation cannot be achieved quickly. Emergency bony support and soft tissue key suture provide the patients with airway integrity, hard and soft tissue vitality. A systemic treatment plan must be made by 3D CT image. This plan include airway management for surgery, sequence of reduction and fixation, approach method, soft tissue resuspension and reconstruction of lost tissue like inferior orbital wall, zygomaic buttress and soft tissue. From known to unknown structures, accurate reduction and fixation will provide proper occlusion, facial projection, width, hight and function. Consideration about facial retaining ligaments must be given to prevent soft tissue sagging.

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Potential mechanism of anti-diabetic activity of Picrorhiza kurroa

  • Husain, Gulam Mohammed;Rai, Richa;Rai, Geeta;Singh, Harikesh Bahadur;Thakur, Ajit Kumar;Kumar, Vikas
    • CELLMED
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    • v.4 no.4
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    • pp.27.1-27.5
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    • 2014
  • Picrorhiza kurroa Royle ex Benth. (Scrophulariaceae) is a traditional Ayurvedic herb known as Kutki. It is used as a remedy for diabetes by tribes of North Eastern Himalayan region of India. Present study was conducted to explore the mechanism of antidiabetic activity of standardized aqueous extract of Picrorhiza kurroa (PkE). PkE (100 and 200 mg/kg/day) was orally administered to streptozotocin induced diabetic rats, for 14 consecutive days. Plasma insulin levels were measured and pancreas of rat was subjected to histopathological investigations. Glucose transporter type 4 (GLUT-4) protein content in the total membrane fractions of soleus muscle was estimated by Western blot analysis. Plasma insulin level was significantly increased along with concomitant increase in GLUT-4 content of total membrane fractions of soleus muscle of diabetic rats treated with extract. There was evidence of regeneration of ${\beta}$-cells of pancreatic islets of PkE treated group in histopathological examinations. PkE increased the insulin-mediated translocation of GLUT-4 from cytosol to plasma membrane or increased GLUT-4 expression, which in turn facilitated glucose uptake by skeletal muscles in diabetic rats.