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Increased Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Levels in the Cerebrospinal Fluid from Children with Aseptic Meningitis (무균성 뇌수막염 소아에서 뇌척수액내 Matrix Metalloproteinase(MMP)-9과 Tissue Inhibitor of Metalloproteinase(TIMP)-1의 증가)

  • Yang, Ju Hee;Park, Min Hyuk;Shim, Jung-Yeon;Jung, Hye Lim;Park, Moon Soo;Keum, Dong Hyuck
    • Clinical and Experimental Pediatrics
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    • v.46 no.6
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    • pp.548-553
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    • 2003
  • Purpose : Matrix metalloproteinase(MMP)-9 is known to breakdown the blood-brain barrier by degrading the extracellular matrix of the subendothelial basement membrane in meningitis. Tissue inhibitor of metalloproteinase(TIMP)-1, a known inhibitor of MMP-9, has been postulated to inhibit the proteolytic activity of MMP-9 by bindng to MMP-9, but their interaction has not been fully understood yet. So far, there have been some reports on the relationship of MMP-9 and TIMP-1 in bacterial meningitis, but few reports in viral meningitis. Furthermore, there has been no report on this in Korea. We investigated the concentrations of MMP-9 and TIMP-1 in cerebrospinal fluid (CSF) and serum of patients with viral meningitis and control subjects, and evaluated their relationship with other clinical parameters of meningitis. Methods : CSF and blood were obtained from 25 subjects with viral meningitis and 14 control subjects. After centrifugation, supernatants were stored at $-20^{\circ}C$ and we assayed concentrations of MMP-9 and TIMP-1 by the sandwich ELISA method. Results : Concentrations of CSF MMP-9 and TIMP-1 were significantly elevated in patients with viral meningitis, when compared with those in control subjects. Their serum levels showed no differences between the two groups. MMP-9 levels were closely correlated with TIMP-1 levels in the CSF($r_s=0.42$, P<0.05). CSF MMP-9/TIMP-1 ratios were significantly higher in patients with viral meningitis than those in the control subjects(P<0.05). Both CSF MMP-9 and TIMP-1 levels positively correlated with CSF total leukocyte counts($r_s=0.43$, P<0.05, $r_s=0.48$, P<0.05). TIMP-1 levels positively correlated with total protein concentrations in the CSF($r_s=0.43$, P<0.05). Conclusion : MMP-9 and TIMP-1 may play an important role in the breakdown and maintenance of BBB in viral meningitis, respectively.

Effect of Pancreatic Polypeptide Family on Cardiovascular Muscle Contractility: 1. Interactions with cyclic nucleotide activators and $K^+$ channel openers in canine cerebral arteries (Pancreatic Polypeptide Family의 심혈관계 근육 수축성에 대한 약리학적 작용: I. 개의 뇌혈관에서 cyclic nucleotide활성제와 칼륨통로개방제와의 상호작용)

  • Kim, Won-Joon;Lee, Kwang-Youn;Ha, Jeoung-Hee;Kwon, Oh-Cheol
    • The Korean Journal of Pharmacology
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    • v.28 no.2
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    • pp.147-162
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    • 1992
  • The objectives of the present experiments were to characterize the effects of the peptides belonging to the pancreatic polypeptide family on the contractility of cerebral arteries and to observe the interactions of these peptides with the cyclic nucleotide activators and the potassium channel openers. Dogs of either sex, $20{\sim}30\;Kg$ in weight, were sacrificed. Basilar and middle cerebral arteries from brain were isolated and prepared for myography in the PSS equilibrated with 95% $O_2$ and 5% $CO_2$ at $37^{\circ}C$. The endothelial cells of the spiral strips were removed by CHAPS solution (0.3% w/v, 15 seconds). 1. PP, PYY and NPY contracted the arterial strips concentration-dependently with a rank order of potency of PYY>NPY>PP. These peptides were 20 to 200 times more potent than norepinephrine, and only PYY showed a greater potency than 5-HT. 2. Cyclic nucleotide activators, forskolin (for cAMP) and sodium nitroprusside (for cGMP) reduced the basal tone and inhibited the PP-, PYY- and NPY- induced contractions by concentration-dependent manners. Forskolin was more potent in reducing basal tone than sodium nitroprusside. 3. Potassium channel openers, RP 49356, P 1060 and BRL 38227 reduced the basal tone concentration-dependently and tended to inhibit the PP-, PYY- and NPY- induced contractions. Notably, BRL 38227 with low concentration $(0.1\;{\mu}M)$ enhanced the contractions induced by those peptides while P 1060 inhibited the contractions concentration-dependently. 4. The combinations of the cyclic nucleotide activators and the potassium channel openers were slightly additive in reducing the basal tone. P 1060 and BRL 38227 enhanced the relaxant effect of sodium nitroprusside significantly. On the PYY-induced contration $(0.1\;{\mu}M)$, $K^+$ channel openers tended to inhibit the inhibitory actions of forskolin and sodium nitroprusside. P 1060 and BRL 38227 antagonized the inhibitory action of sodium nitroprusside significantly. The results of the present study may be summarized that in canine cerebral arteries, not only NPY but also PYY may play a role in a cerebrovascular spasm, and intracellular concentration of either cAMP or cGMP may be involved in the mechanism of vasoconstrictive actions of these peptides, which may be affected either positively or negatively by a $K^+$ channel opener.

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Effect of Ischemic Preconditioning on the Oxygen Free Radical Production in the Post-ischemic Reperfused Heart

  • Park, Jong-Wan;Kim, Young-Hoon;Uhm, Chang-Sub;Bae, Jae-Moon;Park, Chan-Woong;Kim, Myung-Suk
    • The Korean Journal of Pharmacology
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    • v.30 no.3
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    • pp.321-330
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    • 1994
  • The protective effect of 'ischemic preconditioning (PC)' on ischemia-reperfusion injury of heart has been reported in various animal species, but without known mechanisms in detail. In an attempt to investigate the cardioprotective mechanism of PC, we examined the effects of PC on the myocardial oxidative injuries and the oxygen free radical production in the ischemia-reperfusion model of isolated Langendorff preparations of rat hearts. PC was performed with three episodes of 5 min ischemia and 5 min reperfusion before the induction of prolonged ischemia (30 min)-reperfusion(20 min). PC prevented the depression of cardiac function (left ventricular pressure x heart rate) observed in the ischemic-reperfused heart, and reduced the release of lactate dehydrogenase during the reperfusion period. On electron microscopic pictures, myocardial ultrastructures were relatively well preserved in PC hearts as compared with non-PC ischemic-reperfused hearts. In PC hearts, lipid peroxidation of myocardial tissue as estimated from malondialdehyde production was markedly reduced. PC did not affect the activity of xanthine oxidase which is a major source of oxygen radicals in the ischemic rat hearts, but the myocardial content of hypoxanthine (a substrate for xanthine oxidase) was much lower in PC hearts. It is suggested from these results that PC brings about significant myocardial protection in ischemic-reperfused heart and this effect may be related to the suppression of oxygen free radical reactions.

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Anatomical Studies of Major Tree Barks Grown in Korea - II. Anatomy of Quercus Barks (한국산(韓國産) 주요수피(主要樹皮)의 해부학적(解剖學的) 연구(硏究) - 제2보(第二報) 참나무속(屬) 수피(樹皮)의 해부(解剖))

  • Lee, Hwa-Hyoung;Lee, Phil-Woo
    • Journal of the Korean Wood Science and Technology
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    • v.5 no.1
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    • pp.3-8
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    • 1977
  • A bark comprises about 10 to 20 percents of a typical log by volume, and is generally considered as an unwanted residue rather than a potentially valuable resource. As the world has been confronted with decreasing forest resources, natural resources pressure dictate that a bark should be a raw material instead of a waste. The utilization of the largely wasted bark of genus Quercus grown in Korea can be enhanced by learning its anatomical structure and properties. In this paper, bark characteristics of Quercus grown in Korea are described. In bark anatomy, general features such as color of rhytidome, exfoliating form, color of periderm, arrangement of periderm, and thickness of the inner and outer hark. etc., arc discussed. Studies on the microscopic structure include sieve tube, companion cell, parenchyma, pholem fiber, ray, periderm(phelloderm, phelloogen, phellem), sclereid, and crystal, etc. The results may be summarized as follows: 1. In general characteristics of rhytidomes, exfoliating is not easy and sclereids are distint to the naked eye. Inner bark is thicker than that of outer bark except in case of Q. variabilis. 2. It is not clear to distinguish between phelloderm and phellogen in Quercus bark. The phellem is developed conspicuously in Q. variabilis but that of Q. accutissima is composed of thinwalled phellem and thickwalled stone cell. 3. Quercus Bark has sieve tube, companion cell, phloem fiber and sclereid. Sclereids of Quercus bark are the most distinguished characteristics comparing with pinus and populus. The volume percent of sclereids are higher than that of fiber. 4. Rays are 1~3 seriate, and multiseriate ranging with from 15 to 20. 5. Parenchyma cell contains two types, polygonal and druses crystal.

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Early Time Course of Immunopathologic Changes in Coronary Arteries of Heterotopically Transplanted Mouse Heart (이소 생쥐심장이식 모델에서 조기 시간경과에 따른 관상동맥의 면역병리학적인 변화)

  • 이정렬;임홍국;서정욱
    • Journal of Chest Surgery
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    • v.31 no.12
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    • pp.1119-1126
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    • 1998
  • Background: In this study, we investigated the early time course of expression of the major histocompatibility(MHC) antigens, intercellular adhesion molecule-1(ICAM-1), vascular cell adhesion molecule-1(VCAM-1), interleukin-6 and the histopathological changes in the coronary arteries of cardiac allografts exchanged between inbred mice strains that differ in one loci of class I major histocompatibility antigen (B10.BR to B10.A). Material and Method: No immunosuppressive therapy was used. Both allografts and the hearts of the recipients were harvested at 7(group 1, n=6), 15(group 2, n=6), 21(group 3, n=6), and 30(group 4, n=6) days after transplantation. They were examined by immunohistochemistry, microscopy and morphometry. All allografts had contractions at the time of harvest. Result: A strong MHC class I antigen expression was present on the endothelial and medial cells of the coronary arteries in group 1 and remained unchanged in the rest of the groups. However, MHC class II reactivity was none or very little at any time. Mild to moderate ICAM-1 expression was observed on the endothelial cells, but not on the medial cells at any time by 30 days. VCAM-1 expression was strong both on the endothelial and medial cells at any time. Moderate degree expression of interleukin-6 was observed from 7 to 30 day specimens. Histopathologically, percentage of affected vessels(vessels with intimal thickening) was less than 10 % in 7 day group and increased up to 50 % at 30 days. Mean percent narrowing of the lumen of the affected vessels revealed less than 20 % at 7 days and 40 % at 30 days. The area occupied by tropomyosin positive cells in the intimal lesion, graded from 0 to 3, showed gradual increase but remained between grade 0 to 1 by 30 days. Medial integrity was also well preserved at any time. Moderate perivascular mononuclear cell infiltration was observed at 7 days and it was progressively increased upto 30 days. Recipients' heart revealed no positive immunopathologic findings. Conclusion: In this study, the early time course of progression of the transplantation vasculopathy was demonstrated in the murine heterotopic heart transplant model.

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Use of Human Adipose Tissue as a Source of Endothelial Cells (혈관내피세포 채취의 원천으로 인간 지방조직의 활용)

  • Park, Bong-Wook;Hah, Young-Sool;Kim, Jin-Hyun;Cho, Hee-Young;Jung, Myeong-Hee;Kim, Deok-Ryong;Kim, Uk-Kyu;Kim, Jong-Ryoul;Jang, Jung-Hui;Byun, June-Ho
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.4
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    • pp.299-305
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    • 2010
  • Purpose: Adipose tissue is located beneath the skin, around internal organs, and in the bone marrow in humans. Its main role is to store energy in the form of fat, although it also cushions and insulates the body. Adipose tissue also has the ability to dynamically expand and shrink throughout the life of an adult. Recently, it has been shown that adipose tissue contains a population of adult multipotent mesenchymal stem cells and endothelial progenitor cells that, in cell culture conditions, have extensive proliferative capacity and are able to differentiate into several lineages, including, osteogenic, chondrogenic, endothelial cells, and myogenic lineages. Materials and Methods: This study focused on endothelial cell culture from the adipose tissue. Adipose tissues were harvested from buccal fat pad during bilateral sagittal split ramus osteotomy for surgical correction of mandibular prognathism. The tissues were treated with 0.075% type I collagenase. The samples were neutralized with DMEM/and centrifuged for 10 min at 2,400 rpm. The pellet was treated with 3 volume of RBC lysis buffer and filtered through a 100 ${\mu}m$ nylon cell strainer. The filtered cells were centrifuged for 10 min at 2,400 rpm. The cells were further cultured in the endothelial cell culture medium (EGM-2, Cambrex, Walkersville, Md., USA) supplemented with 10% fetal bovine serum, human EGF, human VEGF, human insulin-like growth factor-1, human FGF-$\beta$, heparin, ascorbic acid and hydrocortisone at a density of $1{\times}10^5$ cells/well in a 24-well plate. Low positivity of endothelial cell markers, such as CD31 and CD146, was observed during early passage of cells. Results: Increase of CD146 positivity was observed in passage 5 to 7 adipose tissue-derived cells. However, CD44, representative mesenchymal stem cell marker, was also strongly expressed. CD146 sorted adipose tissue-derived cells was cultured using immuno-magnetic beads. Magnetic labeling with 100 ${\mu}l$ microbeads per 108 cells was performed for 30 minutes at $4^{\circ}C$ a using CD146 direct cell isolation kit. Magnetic separation was carried out and a separator under a biological hood. Aliquous of CD146+ sorted cells were evaluated for purity by flow cytometry. Sorted cells were 96.04% positivity for CD146. And then tube formation was examined. These CD146 sorted adipose tissue-derived cells formed tube-like structures on Matrigel. Conclusion: These results suggest that adipose tissue-derived cells are endothelial cells. With the fabrication of the vascularized scaffold construct, novel approaches could be developed to enhance the engineered scaffold by the addition of adipose tissue-derived endothelial cells and periosteal-derived osteoblastic cells to promote bone growth.

The Effect of Antihistamine on Endotoxin-induced Acute Lung Injury (내독소 유도 급성폐손상에서 항히스타민의 역할)

  • Jung, Bock-Hyun;Koh, Youn-Suck;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.52 no.3
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    • pp.219-229
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    • 2002
  • Background : Sepsis-induced acute lung injury (ALI) is caused by many cellular and humoral mediators induced by an endotoxin. Histamine, which is widely distributed in the lungs and has been considered as an important mediator of sepsis. It increases P-selectin expression on the endothelial cell surfaces and induces IL-8 secretion. Therefore, an endotoxin-induced histamine may be related to neutrophil-mediated ALI by inducing the migration and activation of neutrophils in the lung tissue. However, the role of endogenous histamine in endotoxin ALI has not been clarified. The purpose of this study was to investigate how endotoxin-induced ALI is influenced by endogenous histamine and to identify the possible mechanism of action. Materials and Methods : The study consisted of 4 groups using Sprague-Dawley rats : 1) control group, where the rats were infused intratracheally by normal saline, 2) an endotoxin group, where lipopolysaccharide (LPS) was administered intratracheally 3) the $H_2$ receptor antagonist-treated group ($H_2$ group) and 4) the $H_1$ receptor antagonist-treated group ($H_1$ group), where $H_2$-receptor blocker (ranitidine) and $H_1$-receptor blocker(pyrilamine) were co-treated intravenously with the intratracheal administration of an endotoxin. The lung leak index using $I^{125}$-BSA, the total protein and LDH concentration in the lung lavage fluid, myeloperoxidase(MPO) activity in the lung tissue, the pathologic score and the total number of neutrophils, TNF-$\alpha$, IL-$1{\beta}$ and IL-10 in lung lavage (BAL) fluid were measured in each group as the indices of lung injury. Results : Compared to the control group, the endotoxin group exhibited significant increases in all lung injury indices. Significant reductions in the endotoxin-mediated increases in lung leak index (p<0.05) were observed in both the $H_1$ and $H_2$ groups. In addition the total protein (p<0.05) and LDH concentration (p<0.05) in the BAL fluid were also lower in the $H_2$ group compared to the endotoxin group. However, there was no change in the MPO activity in the lung tissue, the pathologic score and the total number of neutrophils in the BAL fluid in both the $H_2$ and $H_1$ groups compared to the endotoxin group. The increases in TNF-$\alpha$ IL-$1{\beta}$ and IL-10 concentrations in the BAL fluid observed in the endotoxin group were not reduced in the $H_2$ and $H_1$ groups. Conclusion : Antihistamine attenuated the enhanced alveolar-capillary permeability induced by the endotoxin via the $H_2$ receptor. However the attenuating mechanism may not be related to the pathogenesis of neutrophil dependent lung injury.

Prognostic Value of Vascular Endothelial Growth Factor (VEGF) in Resected Non-Small Cell Lung Cancer (비소세포폐암의 예후인자로서 Vascular Endothelial Growth Factor(VEGF)의 의의)

  • Ko, Hyeck-Jae;Park, Jeong-Hyun;Shim, Hyeok;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.6
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    • pp.676-685
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    • 2001
  • Background : Angiogenesis is an essential component of tumor growth and metastasis, and the vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors. Several solid tumors produce substantial amounts of VEGF, which stimulates proliferation and the migration of endothelial cells, thereby inducing neovasculization by a paracrine mechanism. To evaluate the prognostic roles of angiogenesis and VEGF expression in patients with non-small cell lung cancer, the relationship between VEGF expression in tumor tissues, the clinicopathologic features and the overall survival rate were analysed. Methods : Sixty-nine resected primary non-small cell lung cancer specimens were evaluated. The paraffin-embedded tumor tissues were stained by anti-VEGF polyclonal antibodies using an immunohistochemical method to assess VEGF expression. Results : In Forty-one patients (59%), the VEGF antigen was expressed weakly in their tumor tissue, whereas in twenty-eight patients (41%) the VEGF antigen was expressed strongly. The median survival time of the weak VEGF expression group was 24 months, and that of the strong VEGF expression group was 19 months. The three year-survival rates were 35%, 33%, respectively. The survival difference between both groups was not statistically significant. Conclusion : Although results were not statistically significant, the strong expression group tended to poorer prognosis than the weak expression group.

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Studies on the Zanthoxylum piperitum $D_E$ $C_{ANDOLIE}$ - 1. Pungent principles and Essential oil composition - (천초(川椒)에 관(關)한 연구(硏究) - 1. 신미성분(辛味成分)과 정유성분(精油成分) -)

  • Jung, Hyun-Sook
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.16 no.2
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    • pp.123-127
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    • 1987
  • The Pungent principles and Essential oil compositions of Zanthoxylum piperitum $D_E$ $C_{ANDOLIE}$(peel, barb) were analysed by HPLC and GC, respectively. Total Pungent principle contents of peels were about as 12 times as those of barks. The Sanshool I, Sanshool IV, Sanshool III and Sanshoo V were the major Pungent principles in the peels and barks. Besides, several Unknown Pungent principles were discovered in the peels and barks, too. Total Essential oil contents of peels were higher than those of barks at the ratio of 1.8 % to 0.5%. The Cineol+Limonene(37.7%) were the main Essential oil compositions in the peels, while ${\alpha}-Terpineol(16.5%)$ and Pinene(15.5%) were the major portion in the barks. The Essential oil of peels and barks were composed Pinen, Myrcene, Cineol+Limonene, Linalool, Isopulegol, Terpinen-4-ol, ${\alpha}-Terpineol$ and Piperitone. Besides, seven Unknown compositions were discovered, too.

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The Effects of Aminophylline on the Superoxide Anion Generation of Neutrophils from Established Human Sepsis Caused by Acute Pneumonia (급성 폐렴에 의한 패혈증 환자에서 Aminophylline이 혈중 호중구의 과산화물 음이온 유리에 미치는 영향)

  • Kim, Yong-Hoon;Park, Jun-Young;Cha, Mi-Kyong;Lee, Sang-Moo;Kim, Hyeon-Tae;Uh, Soo-Taek;Chung, Yeon-Tae;Park, Choon-Sik
    • Tuberculosis and Respiratory Diseases
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    • v.40 no.1
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    • pp.16-22
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    • 1993
  • Background: The Microbicidal and cytotoxic activities of neutrophils are to a large extent dependent on a burst of oxidative metabolism which generates superoxide anion, hydrogen peroxide, and other reactive products of oxygen. The respiratory burst of PMN is initiated by intracellular calcium mobilization that follows immune or particular stimulation and is very sensitive to modulation by c-AMP or adenosine. Despite its antagonism against adenosine, earlier study has demonstrated potent theophylline inhibition of the PMN respiratory burst at variable ranges of blood concentrations of theophylline in the healthy normal volunteers and in the septic animals pretreated or early post-treated with aminophylline (AMPH) or pentoxifylline. However it is unclear whether theophylline inhibits the superoxide generation or not in the established human sepsis caused by acute pneumonia, as taking into consideration of the fact that full activation of neutrophils have occurred within minutes after the septic insult in the animal experiments. Methods: We measured the $O_2$ generation of peripheral arterial neutrophils obtained from 11 human septic subjects caused by acute pneumonia before and 1 hour after completion of continuous AMPH infusion. Patients were identified and studied within 48 hour of admission. All subjects were administered an intravenous loading and maintenance dose of AMPH. The generation of $O_2$ was measured at a discrete time point (60 min) by the reduction of ferricytochrome c.PMA (10 ${\mu}g/ml$) was used as a stimulating agent. PMNs were isolated at a concentration of $2{\times}10^6$ cells/ml. The arterial oxygen tension, blood pressure and heart rates were also checked to evaluate the systemic effects of AMPH in the acute pneumonia. Results: The mean serum concentration of AMPH at 60 minutes was $8.8{\pm}0.6{\mu}g/ml$. Sixty minutes after AMPH infusion the generatition of $O_2$ was decreased from $0.076{\pm}0.034$ to $0.013{\pm}0.004$(OD) (p<0.05) and from $0.177{\pm}0.044$ to $0.095{\pm}0.042$(OD) (p<0.01) in the resting and stimulated PMNs respectively. $PaO_2$ was not changed after AMPH infusion. Conclusion: AMPH may compromise host defense by significant inhibition of neutrophil release of superoxide anion and it had no effect on improving $PaO_2$ in the acute pneumonia.

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