• Title/Summary/Keyword: beneficial effects

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Application of a Single-pulsatile Extracorporeal Life Support System for Extracorporeal Membrane Oxygenation -An experimental study - (단일 박동형 생명구조장치의 인공폐 적용 -실험연구-)

  • Kim, Tae-Sik;Sun, Kyung;Lee, Kyu-Baek;Park, Sung-Young;Hwang, Jae-Joon;Son, Ho-Sung;Kim, Kwang-Taik;Kim. Hyoung-Mook
    • Journal of Chest Surgery
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    • v.37 no.3
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    • pp.201-209
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    • 2004
  • Extracorporeal life support (ECLS) system is a device for respiratory and/or heart failure treatment, and there have been many trials for development and clinical application in the world. Currently, a non-pulsatile blood pump is a standard for ECLS system. Although a pulsatile blood pump is advantageous in physiologic aspects, high pressure generated in the circuits and resultant blood cell trauma remain major concerns which make one reluctant to use a pulsatile blood pump in artificial lung circuits containing a membrane oxygenator. The study was designed to evaluate the hypothesis that placement of a pressure-relieving compliance chamber between a pulsatile pump and a membrane oxygenator might reduce the above mentioned side effects while providing physiologic pulsatile blood flow. The study was performed in a canine model of oleic acid induced acute lung injury (N=16). The animals were divided into three groups according to the type of pump used and the presence of the compliance chamber, In group 1, a non-pulsatile centrifugal pump was used as a control (n=6). In group 2 (n=4), a single-pulsatile pump was used. In group 3 (n=6), a single-pulsatile pump equipped with a compliance chamber was used. The experimental model was a partial bypass between the right atrium and the aorta at a pump flow of 1.8∼2 L/min for 2 hours. The observed parameters were focused on hemodynamic changes, intra-circuit pressure, laboratory studies for blood profile, and the effect on blood cell trauma. In hemodynamics, the pulsatile group II & III generated higher arterial pulse pressure (47$\pm$ 10 and 41 $\pm$ 9 mmHg) than the nonpulsatile group 1 (17 $\pm$ 7 mmHg, p<0.001). The intra-circuit pressure at membrane oxygenator were 222 $\pm$ 8 mmHg in group 1, 739 $\pm$ 35 mmHg in group 2, and 470 $\pm$ 17 mmHg in group 3 (p<0.001). At 2 hour bypass, arterial oxygen partial pressures were significantly higher in the pulsatile group 2 & 3 than in the non-pulsatile group 1 (77 $\pm$ 41 mmHg in group 1, 96 $\pm$ 48 mmHg in group 2, and 97 $\pm$ 25 mmHg in group 3: p<0.05). The levels of plasma free hemoglobin which was an indicator of blood cell trauma were lowest in group 1, highest in group 2, and significantly decreased in group 3 (55.7 $\pm$ 43.3, 162.8 $\pm$ 113.6, 82.5 $\pm$ 25.1 mg%, respectively; p<0.05). Other laboratory findings for blood profile were not different. The above results imply that the pulsatile blood pump is beneficial in oxygenation while deleterious in the aspects to high pressure generation in the circuits and blood cell trauma. However, when a pressure-relieving compliance chamber is applied between the pulsatile pump and a membrane oxygenator, it can significantly reduce the high circuit pressure and result in low blood cell trauma.

The Effect of Seminal Plasma on Chilling and Freezing of Canine Spermatozoa (개 정액의 정장이 개정자의 냉각과 동결에 미치는 영향)

  • You, Myung-Jo;Lee, John-Hwa;Kim, In-Shik;Park, Jin-Ho;Kwon, Jung-Kee;Kim, Jong-Hoon;Kim, Bum-Seok;Yu, Il-Jeoung
    • Journal of Veterinary Clinics
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    • v.24 no.4
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    • pp.486-492
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    • 2007
  • Seminal plasma(SP) is usually removed from semen that is to be cryopreserved. However, some reports indicate that SP has beneficial effects on spermatozoa during chilling and freezing. The purpose of this study was to determine the effect of SP on sperm survival by adding SP to the extender before cooling and freezing canine spermatozoa. In replicate experiments, ejaculates obtained from four healthy dogs(1-4 years old) of various breeds were pooled, centrifuged at $300{\times}g$ for 10 min at $25^{\circ}C$, and the supernatant of seminal plasma was decanted. Spermatozoa were suspended in egg yolk-Tris(EYT) buffer. The study comprised two experiments: [Exp 1] Sperm were suspended in EYT extender containing either 0, 20, 40, 80 or 100% SP and were slowly cooled to $4^{\circ}C$ for 2h or held at $25^{\circ}C$ as controls. Sperm concentration was adjusted to $2{\times}10^8/ml$. [Exp II] Sperm samples, each of which contained $1{\times}10^8/ml$, were assigned to nine groups to be frozen. In the first four groups, sperm in EYT containing either 20, 40, 80 or 100% SP were cooled to $4^{\circ}C$, then diluted to contain final concentrations of EYT+0.6M glycerol and then were frozen. The final concentrations of SP were 10, 20, 40 or 50%. In the other four groups, sperm in EYT alone were first cooled slowly to $4^{\circ}C$, then diluted to contain final concentrations of EYT+0.6M glycerol plus 10, 20, 40 or 50% SP and then were frozen. Spermatozoa, which chilled in EYT alone and diluted to contain final concentrations of EYT+0.6M glycerol without seminal plasma, and then frozen, was regarded as control. Spermatozoa were frozen at $25^{\circ}C/min$ of cooling rate in plastic straws that were suspended above liquid nitrogen and thawed in water at $38^{\circ}C$ for 1 min. Sperm survival was assayed by determining progressive motility and integrity of plasma and acrosome membranes. Progressive motility was determined by microscopic examination at $200{\times}$ magnification. Membrane integrity was assessed by use of a double fluorescent dye, and acrosome integrity by staining sperm with Pisum sativum agglutinin. The results of the first experiment showed that adding SP did not improve motility of spermatozoa compared to those incubated without SP regardless of temperature. The results of the second experiment showed that spermatozoa suspended in EYT+0.6M glycerol containing SP exhibited the higher progressive motility before being frozen(P<0.05). However, frozen-thawed spermatozoa that had suspended in EYT+0.6M glycerol containing SP showed the similar or lower viability(P<0.05). In summary, although seminal plasma did not affect spermatozoa that were chilled in EYT without cryoprotectant(CPA), addition of seminal plasma to EYT containing CPA did significantly improved progressive motility of canine spermatozoa that were chilled.

Effects of Dietary Salt Restriction on the Development of Renal Failure in the Excision Remnant Kidney Model (식이 sodium 제한 및 식이 sodium 제한에 따른 항고혈압제의 투여가 만성신부전증의 진행에 미치는 영향에 관한 실험적 연구)

  • Kim Kee-Hyuk;Kim Sang-Yun;Kang Yong-Joo;Maeng Won-Jae;Kim Kyo-Sun
    • Childhood Kidney Diseases
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    • v.3 no.2
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    • pp.170-179
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    • 1999
  • Purpose: To evaluate whether or not sodium restriction had its own beneficial effect and increased the efficiency of the anti-hypertensive drugs on the progression of renal failure. Methods: We studied using the excision remnant kidney model. Treatment groups were as follows: 5/6 nephrectomy and a 0.49% (normal-high) sodium diet (NN); 5/6 nephrectomy and a 0.25% (normal-low) sodium diet (LN); 5/6 nephrectomy, a 0.49% sodium diet and enalapril (NNE); 5/6 nephrectomy, a 0.49% sodium diet and nicardipine (NNN); 5/6 nephrectomy, a 0.25% sodium diet and enalapril (LNE); 5/6 nephrectomy, a 0.25% sodium diet and nicardipine (LNN). Both diets were isocaloric and had the same content of protein, phosphorus and calcium. Proteinuria, remnant kidney weight, mesangial expansion scores, and glomerular volume were assessed. Results: Blood pressure tended to be lower in LN compared to NN (P<0.05). NN developed progressive hypertension. LNE, LU, NNE, and NNN reduced blood pressure. LNE, LNN, NNE, NNN, and LN had significantly less proteinuria than NN at 16 weeks (P<0.05). At 24 weeks, LN developed proteinuria (82 mg/day), which were lessened in LNE (54 mg/day) and not lessened in LNN (76 mg/day). Mesangial expansion scores were significantly less in LN rats compared to those in NN rats. Glomerular volumes at 24 weeks in LN rats were significantly less compared to those at 16 weeks in NN rats. Mesangial expansion scores and glomerular volumes at 4, weeks, 12 weeks, and 24 weeks were not different among LN, LNE, and LNN groups. Conclusion: Dietary salt restriction lessens renal damage, at least in part, by inhibiting compensatory renal growth and reducing blood pressure. Enalapril was particularly successful in reducing proteinuria and glomerular injury when combined with dietary salt restriction.

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The Role of Control Transparency and Outcome Feedback on Security Protection in Online Banking (계좌 이용 과정과 결과의 투명성이 온라인 뱅킹 이용자의 보안 인식에 미치는 영향)

  • Lee, Un-Kon;Choi, Ji Eun;Lee, Ho Geun
    • Information Systems Review
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    • v.14 no.3
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    • pp.75-97
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    • 2012
  • Fostering trusting belief in financial transactions is a challenging task in Internet banking services. Authenticated Certificate had been regarded as an effective method to guarantee the trusting belief for online transactions. However, previous research claimed that this method has some loopholes for such abusers as hackers, who intend to attack the financial accounts of innocent transactors in Internet. Two types of methods have been suggested as alternatives for securing user identification and activity in online financial services. Control transparency uses information over the transaction process to verify and to control the transactions. Outcome feedback, which refers to the specific information about exchange outcomes, provides information over final transaction results. By using these two methods, financial service providers can send signals to involved parties about the robustness of their security mechanisms. These two methods-control transparency and outcome feedback-have been widely used in the IS field to enhance the quality of IS services. In this research, we intend to verify that these two methods can also be used to reduce risks and to increase the security protections in online banking services. The purpose of this paper is to empirically test the effects of the control transparency and the outcome feedback on the risk perceptions in Internet banking services. Our assumption is that these two methods-control transparency and outcome feedback-can reduce perceived risks involved with online financial transactions, while increasing perceived trust over financial service providers. These changes in user attitudes can increase the level of user satisfactions, which may lead to the increased user loyalty as well as users' willingness to pay for the financial transactions. Previous research in IS suggested that the increased level of transparency on the process and the result of transactions can enhance the information quality and decision quality of IS users. Transparency helps IS users to acquire the information needed to control the transaction counterpart and thus to complete transaction successfully. It is also argued that transparency can reduce the perceived transaction risks in IS usage. Many IS researchers also argued that the trust can be generated by the institutional mechanisms. Trusting belief refers to the truster's belief for the trustee to have attributes for being beneficial to the truster. Institution-based trust plays an important role to enhance the probability of achieving a successful outcome. When a transactor regards the conditions crucial for the transaction success, he or she considers the condition providers as trustful, and thus eventually trust the others involved with such condition providers. In this process, transparency helps the transactor complete the transaction successfully. Through the investigation of these studies, we expect that the control transparency and outcome feedback can reduce the risk perception on transaction and enhance the trust with the service provider. Based on a theoretical framework of transparency and institution-based trust, we propose and test a research model by evaluating research hypotheses. We have conducted a laboratory experiment in order to validate our research model. Since the transparency artifact(control transparency and outcome feedback) is not yet adopted in online banking services, the general survey method could not be employed to verify our research model. We collected data from 138 experiment subjects who had experiences with online banking services. PLS is used to analyze the experiment data. The measurement model confirms that our data set has appropriate convergent and discriminant validity. The results of testing the structural model indicate that control transparency significantly enhances the trust and significantly reduces the risk perception of online banking users. The result also suggested that the outcome feedback significantly enhances the trust of users. We have found that the reduced risk and the increased trust level significantly improve the level of service satisfaction. The increased satisfaction finally leads to the increased loyalty and willingness to pay for the financial services.

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Clinical Efficacy of Clomiphene Citrate and Letrozole Combined with Gonadotropins for Superovulation in Patients with Clomiphene-Induced Thin Endometrium (클로미펜에 얇은 자궁내막을 보이는 환자에서 성선자극호르몬 병합 과배란유도시 클로미펜과 레트로졸의 임상적 효용성)

  • Lee, Eun-Joo;Park, Hyun-Jong;Yang, Hyo-In;Lee, Kyung-Eun;Seo, Seok-Kyo;Kim, Hye-Yeon;Cho, Si-Hyun;Choi, Young-Sik;Lee, Byung-Seok;Park, Ki-Hyun;Cho, Dong-Jae
    • Clinical and Experimental Reproductive Medicine
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    • v.36 no.2
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    • pp.111-119
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    • 2009
  • Objective: The aim of this study was to compare the clinical efficacy of clomiphene citrate (CC) and letrozole combined with gonadotropins for controlled ovarian stimulation (COS) in patients with CC-induced thin endometrium Methods: Fifty-one intrauterine insemination cycles performed in patients who previously had a thin endometrium (<8 mm) to ovulation induction using CC were included in this study. A CC 100 mg/day (CC+gonadotropin group, n=26) or letrozole 2.5 or 5 mg/day (letrozole+gonadotropin group, n=25) was administered on day 3~7 of the menstrual cycle, combined with gonadotropins at dose 75~150 IU every other day starting on day 5~7. We compared total dose of gonadotropin used, endometrial thickness, endometrial pattern, number of follicles ${\geq}14\;mm$ on hCG day, pregnancy rate and multiple pregnancy rate between the two groups, which were statistically analyzed using Mann-Whitney U test or Fisher's exact test, where appropriate. Results: There were no significant differences in clinical characteristics such as age, duration of infertility, number of previous IUI cycles, basal serum hormone levels and cause of infertility between the two groups. In both groups, the endometrium was significantly thicker than that of previous ovulation induction cycles using CC. No significant differences were found in the total dose of gonadotropin used, day of hCG administration, the rate of triple endometrium and pregnancy rate. The number of follicles ${\geq}14\;mm$ was significantly lower ($3.7{\pm}1.7$ vs. $2.8{\pm}1.7$, p=0.03) and the endometrium on hCG day was significantly thicker ($7.7{\pm}1.5$ vs. $9.1{\pm}1.7$, p=0.001) in letrozole+gonadotropin group compared to CC+gonadotropin group. Conclusion: The clomiphene citrate and letrozole combined with gonadotropins appear to avoid the undesirable effects on the endometrium frequently seen with CC for ovulation induction. However, in terms of adequate endometrial development or optimal follicular growth, letrozole may be more beneficial than CC for gonadotropin-combined COS in patients with CC-induced thin endometrium. Further prospective randomized controlled studies in a larger scale will be necessary to confirm our findings.

Research and Development Trends on Omega-3 Fatty Acid Fortified Foodstuffs (오메가 3계 지방산 강화 식품류의 연구개발 동향)

  • 이희애;유익종;이복희
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.26 no.1
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    • pp.161-174
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    • 1997
  • Omega-3 fatty acids have been major research interests in medical and nutritional science relating to life sciences since after the epidemiologic data on Green3and Eskimos reported by several researchers clearly showed fewer per capita deaths from heart diseases and a lower incidence of adult diseases. Linolenic acid(LNA) is an essential fatty acid for human beings as well as linoleic acid(LA) due to the fact that vertebrates lack an enzyme required to incorporate a double bond beyond carbon 9 in the chain. In addition the ratio of omega-6 and 3 fatty acids seems to be important in terms of alleviation of heart diseases since LA and LNA competes for the metabolic pathways of eicosanoids synthesis. High consumption of omega-3 fatty acids in seafoods may control heart diseases by reducing blood cholesterol, triglyceride, VLDL, LDL and increasing HDL and by inhibiting plaque development through the formation of antiaggregatory substances like PGI$_2$, PGI$_3$ and TXA$_3$ metabolized from LNA. Omega 3 fatty acids also play an important role in neuronal developments and visual functioning, in turn influence learning behaviors. Current dietary sources of omega-3 fatty acids are limited mostly to seafoods, leafy vegetables, marine and some seed oils and the most appropriate way to provide omega-3 fatty acids is as a part of the normal dietary regimen. The efforts to enhance the intake of omega-3 fatty acids due to several beneficial effects have been made nowadays by way of food processing technology. Two different ways can be applied: one is add Purified and concentrated omega-3 fatty acids into foods and the other is to produce foods with high amounts of omega-3 fatty acids by raising animals with specially formulated feed best for the transfer of omega-3 fatty acids. Recently, items of manufactured and marketed omega-3 fatty acids fortified foodstuffs are pork, milk, cheese, egg, formula milk and ham. In domestic food market, many of them are distributed already, but problem is that nutritional informations on the amounts of omega-3 fatty acids are not presented on the labeling, which might cause distrust of consumers on those products, result in lower sales volumes. It would be very much wise if we consume natural products, result in lower sales volumes. It would be very much wise if we consume natural products high in omega-3 fatty acids to Promote health related to many types of adult diseases rather than processed foods fortified with omega-3 fatty acids.

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The Recovery of Left Ventricular Function after Coronary Artery Bypass Grafting in Patients with Severe Ischemic Left Ventricular Dysfunction: Off-pump Versus On-pump (심한 허혈성 좌심실 기능부전 환자에서 관상동맥우회술시 체외순환 여부에 따른 좌심실 기능 회복력 비교)

  • Kim Jae Hyun;Kim Gun Gyk;Baek Man Jong;Oh Sam Sae;Kim Chong Whan;Na Chan-Young
    • Journal of Chest Surgery
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    • v.38 no.2 s.247
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    • pp.116-122
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    • 2005
  • Background: Adverse effects of cardiopulmonary bypass can be avoided by 'Off-pump' coronary artery bypass (OPCAB) surgery. Recent studies have reported that OPCAB had the most beneficial impact on patients at highest risk by reducing bypass-related complications. The purpose of this study is to compare the outcome of OPCAB and conventional coronary artery bypass grafting (CCAB) in patients with poor left ventricular (LV) function. Material and Method: From March 1997 to February 2004, seventy five patients with left ventricular ejection fraction (LVEF) of $35\%$ or less underwent isolated coronary artery bypass grafting at our institute. Of these patients, 33 patients underwent OPCAB and 42 underwent CCAB. Preoperative risk factors, operative and postoperative outcomes, including LV functional change, were compared and analysed. Result: Patients undergoing CCAB were more likely to have unstable angina, three vessel disease and acute myocardial infarction among the preoperative factors. OPCAB group had significantly lower mean operation time, less numbers of total distal anastomoses per patient and less numbers of distal anastomoses per patient in the circumflex territory than the CCAB group. There was no difference between the groups in regard to in-hospital mortality $(OPCAB\; 9.1\%\;(n=3)\;Vs.\;CCAB\;9.5\%\;(n=4)),$ intubation time, the length of stay in intensive care unit and in hospital postoperatively. Postoperative complication occurred more in CCAB group but did not show statistical difference. On follow-up echocardiography, OPCAB group showed $9.1\%$ improvement in mean LVEF, 4.3 mm decrease in mean left ventricular end-diastolic dimension (LVEDD) and 4.2 mm decrease in mean left ventricular end-systolic dimension (LVESD). CCAB group showed $11.0\%$ improvement in mean LVEF, 5.1 mm decrease in mean LVEDD and 5.5 mm decrease in mean LVESD. But there was no statistically significant difference between the two groups. Conclusion: This study showed that LV function improves postoperatively in patients with severe ischemic LV dysfunction, but failed to show any difference in the degree of improvement between OPCAB and CCAB. In terms of operative mortality rate and LV functional recovery, the results of OPCAB were as good as those of CCAB in patients with poor LV function. But, OPCAB procedure was advantageous in shortening of operative time and in decrease of complications. We recommend OPCAB as the first surgical option for patients with severe LV dysfunction.

Comparison of Serum Cytokines($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) between Terminal Cancer Patients Treated with Vitamin C and Them without Vitamin C Therapy (Anorexia-Cachexia Syndrome을 가진 말기 암 환자에서 비타민 C 사용여부에 따른 사이토카인 변화 비교)

  • Yeom, Chang-Hwan;Suh, Sang-Youn;Cho, Kyung-Hee;Sun, Young-Gyu;Park, Yong-Gyu;Lee, Hye-Ree
    • Journal of Hospice and Palliative Care
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    • v.6 no.1
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    • pp.51-57
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    • 2003
  • Purpose : Anorexia-cachexia syndrome is one of the most common symptoms and main cause of death in terminal cancer patients. This symptom is due to the enlarged cancer mass as well as tumor released cytokines. Some doctors have suggested that vitamin C was preferentially toxic to tumor cells in vitro and in vivo, and improved clinical symptoms in terminal cancer patients. Therefore, we measured cytokines in serum of terminal cancer patients to determine whether vitamin C treatment improved the anorexia-cachexia syndrome. Methods : We investigated that 49 terminal cancer patients admitted to the department of family medicine, National Health Insurance Corporation Ilsan hospital from March 1, 2002 to August 31, 2002. The study was done on 22 patients who were given 10 g/day of vitamin C infusions during 1 week and 27 patients who were not infused. We measured the cytokines levels ($IL-1{\beta}$, IL-6, and $TNF-{\alpha}$) before and after 1 week between terminal cancer patients treated vitamin C and without vitamin C. Results : Out of 49 patients, patents treated with vitamin C infusions were 22 (12 male, 10 female), and these without vitamin C were 27 (18 male, 9 female). In patients treated with vitamin C, $IL-1{\beta}\;were\;6.19{\pm}5.17$ before day and $8.76{\pm}5.72$ after 1 week, IL-6 were $3.07{\pm}8.09$ before day and $1.31{\pm}2.36$ after 1 week, and $TNF-{\alpha}\;were\;2.74{\pm}14.24$ before day and $0.50{\pm}2.00$ after 1 week. In patients treated without vitamin C, $IL-1{\beta}\;were\;2.50{\pm}3.58$ before day and $6.49{\pm}12.01$ after 1 week, IL-6 were $1.00{\pm}2.19$ before day and $17.16{\pm}81.55$ after 1 week, and $TNF-{\alpha}\;were\;1.19{\pm}2.98$ before day and $1.27{\pm}1.52$ after 1 week. The level of cytokines in patients treated with vitamin C decreased more than those without vitamin C. However, this represented no statistical value (P=0.0598 in $IL-1{\beta}$, P=0.1664 in IL-6, and P=0.5395 in $TNF-{\alpha}$). Conclusion : In terminal cancer, even if there was no statistical difference in the cytokines levels between patients treated with vitamin C and those not treated, those who were treated had a decrease all cytokines levels. Vitamin C is very safe with almost no side effects. Therefore, vitamin C treatment in terminal cancer patients can be seen as beneficial and helpful for clinical symptoms.

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Combined Effect of Ganciclovir and Vidarabine on the Replication, DNA Synthesis, and Gene Expression of Acyclovir-resistant Herpes Simplex Virus (Acyclovir저항성 Herpes Simplex Virus의 복제, DNA합성 및 형질 발현에 미치는 Ganciclovir 및 Vidarabine의 병용효과에 관한 연구)

  • Yang, Young-Tai;Cheong, Dong-Kyun;Mori, Masakazu
    • The Korean Journal of Pharmacology
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    • v.25 no.1
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    • pp.115-134
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    • 1989
  • Combined effects of ganciclovir (GCV) and vidarabine (ara-A) on the replication, DNA synthesis, and gene expression of wild type-1 herpes simplex virus (HSV-1) and three acyclovir (ACV)-resistant HSV-1 mutants were studied. These mutants include a virus expressing no thymidine kinase $(ACV^r)$, a virus expressing thymidine kinase with altered substrate specificity $(IUdR^r)$, and a mutant expressing altered DNA polymerase $(PAA^r5)$. GCV, an agent activated by herpesvirus specific thymidine kinase, showed potent antiviral activity against the wild type HSV-1(KOS) and DNA polymerase mutant $(PAA^r5)$. The ACV-resistant mutants with thymidine kinase gene $(ACV^r\;and\;IUdR^r)$ were resistant to GCV. All tested wild type HSV-1 or ACV-resistant HSV-1 mutants did not display resistance to vidarabine (are-A). Combined GCV and ara-A showed potentiating synergistic antiviral activity against wild type KOS and $PAA^r5$, and showed subadditive combnined ativiral activity against thymidine kinase mutants. Combined GCV and ara-A more significantly inhibited the viral DNA synthesis in wild type KOS and $PAA^r5-infected$ cells to a greater extent than either agent alone, but the synergism was not determined in $ACV^r$ or $IUdR^r-infected$ cells. These data clearly indicate that combined GCV and ara-A therapy might be useful for the treatment of infections caused by wild type HSV-1 or ACV-resistant HSV-1 with DNA polymerase mutation. ACV-resistant viruses with the mutation in thymidine kinase gene are also, resistant to GCV, but susecptible to ara-A, indicating that ara-A would the drug of choice for the treatment of ACV-resistant HSV-1 which does not express thymidine kinase or expresses thymidine kinase with altered substrate specificity. While the synthesis of viral ${\alpha}-proteins$ of wild type HSV-1 was not affected by ACV, GCV, ara-A, or combined GCV and ara-A, the synthesis of ${\beta}-proteins$ was slightly but significantly increased at the later stage of viral infection by the antiviral agents. The synthesis of ${\gamma}-proteins$ of wild type HSV- 1 was significantly inhibited by ACV, GCV, ara-A, and combined GCV and ara-A. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ also significantly altered the expression of viral ${\beta}-and$ ${\gamma}-proteins$, of which efffct was similar to that of GCV $(10-{\mu}M)$ alone. Although ACV at the concentration of $10-{\mu}M$ did not alter the expression of ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ of ACV-resistant $PAA^r5$, GCV and ara-A significantly alter the epression of ${\beta}-and$ ${\gamma}-proteins$, not ${\alpha}-protein$, as same manner as they altered the expression of those proteins in cells inffcted with wild type HSV-1. Combined GCV $(5-{\mu}M)$ and ara-A $(100-{\mu}M)$ altered the expression ${\beta}-and$ ${\gamma}-proteins$ in $PAA^r5$ infected cells, and the effect of combined regimen was comparable of that of GCV $(10-{\mu}M)$. These data indicate that the alteration in the expression of ${\beta}-and$ ${\gamma}-proteins$ in wild type HSV-1 or $PAA^r5$ infected cells could be more significantly affected by combined GCV and are-A than individual GCV or ara-A. In view of the fact that (a) viral ${\alpha}-$, ${\beta}-$, and ${\gamma}-proteins$ are synthesized in a cascade manner; (b) ${\beta}-proteins$ are essential for the synthesis of viral DNA; (c) the synthesis of ${\beta}-proteins$ are inhibited by ${\gamma}-proteins$; and (d) most ${\gamma}-proteins$ are made from the newly synthesized progeny virus, it is suggested that GCV and ara-A, alone or in combination, primarily inhibit the synthesis of viral DNA, and by doing so might exhibit their antiherpetic activity. The alteration in viral protein synthesis in the presence of tested antiviral agents could result from the alteration in viral DNA synthesis. From the present study, it can be concluded that (a) combined GCV and ara-A therapy would be beneficial for the control of inffctions caused by wild type HSV-1 or ACV-resistant DNA polymerase mutants; (b) the combined synergistic activity of GCV and ara-A is due to further decrease in the viral DNA by the combined regimen; (c) ara-A is the drug of choice for the infection caused by ACV-resistant HSV-1 with thymidine kinase mutation; and (d) the alteration in viral protein synthesis by GCV and ars-A, alone or in combination, is mostly due to the decreased synthesis of viral DAN.

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Comparison of Effects of Normothermic and Hypothermic Cardiopulmonary Bypass on Cerebral Metabolism During Cardiac Surgery (체외순환 시 뇌 대사에 대한 정상 체온 체외순환과 저 체온 체외순환의 임상적 영향에 관한 비교연구)

  • 조광현;박경택;김경현;최석철;최국렬;황윤호
    • Journal of Chest Surgery
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    • v.35 no.6
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    • pp.420-429
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    • 2002
  • Moderate hypothermic cardiopulmonary bypass (CPB) has commonly been used in cardiac surgery. Several cardiac centers recently practice normothermic CPB in cardiac surgery, However, the clinical effect and safety of normothermic CPB on cerebral metabolism are not established and not fully understood. This study was prospectively designed to evaluate the clinical influence of normothermic CPB on brain metabolism and to compare it with that of moderate hypothermic CPB. Material and Method: Thirty-six adult patients scheduled for elective cardiac surgery were randomized to receive normothermic (nasopharyngeal temperature >34.5 $^{\circ}C$, n=18) or hypothermic (nasopharyngeal temperature 29~3$0^{\circ}C$, n=18) CPB with nonpulsatile pump. Middle cerebral artery blood flow velocity (VMCA), cerebral arteriovenous oxygen content difference (CAVO$_{2}$), cerebral oxygen extraction (COE), modified cerebral metabolic rate for oxygen (MCMRO$_{2}$), cerebral oxygen transport (TEO$_{2}$), cerebral venous desaturation (oxygen saturation in internal jugular bulb blood$\leq$50 %), and arterial and internal jugular bulb blood gas analysis were measured during six phases of the operation: Pre-CPB (control), CPB-10 min, Rewarm-1 (nasopharyngeal temperature 34 $^{\circ}C$ in the hypothermic group), Rewarm-2 (nasopharyngeal temperature 37 $^{\circ}C$ in the both groups), CPB-off and Post-CPB (skin closure after CPB-off). Postoperaitve neuropsychologic complications were observed in all patients. All variables were compared between the two groups. Result: VMCA at Rewarm-2 was higher in the hypothermic group (153.11$\pm$8.98%) than in the normothermic group (131.18$\pm$6.94%) (p<0.05). CAVO$_{2}$ (3.47$\pm$0.21 vs 4.28$\pm$0.29 mL/dL, p<0.05), COE (0.30$\pm$0.02 vs 0.39$\pm$0.02, p<0.05) and MCMRO$_{2}$ (4.71 $\pm$0.42 vs 5.36$\pm$0.45, p<0.05) at CPB-10 min were lower in the hypothermic group than in the normothermic group. The hypothermic group had higher TEO$_{2}$ than the normothermic group at CPB-10 (1,527.60$\pm$25.84 vs 1,368.74$\pm$20.03, p<0.05), Rewarm-2 (1,757.50$\pm$32.30 vs 1,478.60$\pm$27.41, p<0.05) and Post-CPB (1,734.37$\pm$41.45 vs 1,597.68$\pm$27.50, p<0.05). Internal jugular bulb oxygen tension (40.96$\pm$1.16 vs 34.79$\pm$2.18 mmHg, p<0.05), saturation (72.63$\pm$2.68 vs 64.76$\pm$2.49 %, p<0.05) and content (8.08$\pm$0.34 vs 6.78$\pm$0.43 mL/dL, p<0.05) at CPB-10 were higher in the hypothermic group than in the normothermic group. The hypothermic group had less incidence of postoperative neurologic complication (delirium) than the normothermic group (2 vs 4 patients, p<0.05). Lasting periods of postoperative delirium were shorter in the hypothermic group than in the normothermic group (60 vs 160 hrs, p<0.01). Conclusion: These results indicate that normothermic CPB should not be routinely applied in all cardiac surgery, especially advanced age or the clinical situations that require prolonged operative time. Moderate hypothermic CPB may have beneficial influences relatively on brain metabolism and postoperative neuropsychologic outcomes when compared with normothermic CPB.