• Biomolecules & Therapeutics
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• v.32 no.4
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• pp.467-473
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• 2024

In this study, we investigated the potential protective effects of (+)-afzelechin (AZC), a natural compound that is derived from Bergenia ligulata, on lipopolysaccharide (LPS)-induced inflammatory responses. AZC is known to have antioxidant, anticancer, antimicrobial, and cardiovascular protective properties. However, knowledge regarding the therapeutic potential of AZC against LPS-induced inflammatory responses is limited. Thus, we investigated the protective attributes of AZC against inflammatory damage caused by LPS exposure. We examined the effects of AZC on heme oxygenase (HO)-1, cyclooxygenase (COX)-2, and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs). In addition, the effects of AZC on the expression of iNOS, tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were analyzed in the lung tissues of LPS-injected mice. Data revealed that AZC promoted the production of HO-1, inhibited the interaction between luciferase and nuclear factor (NF)-κB, and reduced the levels of COX-2/PGE2 and iNOS/NO, thereby leading to a decrease in the signal transducer and activator of transcription (STAT)-1 phosphorylation. Moreover, AZC facilitated the nuclear translocation of Nrf2, increased the binding activity between Nrf2 and the antioxidant response elements (AREs), and lowered the expression of IL-1β in the LPS-treated HUVECs. In the animal model, AZC significantly reduced the expression of iNOS in the lung tissue structure and the TNF-α level in the bronchoalveolar lavage fluid. These findings demonstrate that AZC possesses anti-inflammatory properties that regulate iNOS through the inhibition of both NF-κB expression and p-STAT-1. Consequently, AZC has potential as a future candidate for the development of new clinical substances for the treatment of pathological inflammation.

• Journal of Chest Surgery
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• v.33 no.5
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• pp.407-418
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• 2000

Background: With open heart surgery(OHS), it has been recognized that many postoperative complications and postperfusion syndrome are associated with the activations of complements and leulocytes. Recently, some investigators also demonstrated that interlukin-6(IL-6) linked highly with postperfusion syndrome. The puropose of this study was to investigate the sequential changes of the IL-6 and to clarify each IL-6 relationship to the complements(C3, C4) and inflammatory response following cardiopulmonary bypass(CPB). Material and Method: To determine serum levels of IL-6, complements, leukocytes, and biochemistric markers of liver and renal function, blood samples were taken from th radial artery in 30 adult patients undergoing OHS with CPB. Result: Serum IL-6 levels incrased significantly at 10 minutes after CPB-on(CPB-10) in comparison with the control levels and reached the peak at CPB-off(p<0.05). Serum complement levels declined rapidly at CPB-10 and remained at the lower levels during CPB(p<0.01). Sequential changes of IL-6 levels had positive correlations with the changes of total leukocytes and neutrophil fractions(p<0.05), but had negative correlations with lymphocyte fractions(p<0.05). Changes of C3 related postively to monocyte fractions(p<0.05). Postoperative levels of total protein and albumin, decreased significantly in comparison with the control levels(p<0.01), while the postoperative levels of AST(aspartate transaminase) and bilirubin increased (p<0.01). At CPB-off, IL-6 levels had negative correlations with total protein and albumin levels(r=-0.60, -0.47 respectively, p<0.05), whereas C3 levels had positive correlations with albumin levels(r=0.40, p<0.05). IL-6 levels, as well as neutrophil fractions, had positive correlations with aortic clamp time(ACT) and total bypass time(TBT) (IL-6; r=0.82, 0.79 respectively, neutrophil fractions; r=0.50, 0.56 respectively, p<0.05), wheres lymphocyte frations and albumin levels had negative correlations whith ACT and TBT(lymphocyte fractions; r=-0.52, -0.58 respectively, albumin; r=-0.58, -0.55 respectively, p<0.05). Conclusion: These data showed that elevated production of serum IL-6 during CPB may play a pivotal role in systemic inflammatory responses and prologed CPB period may be assosiated with more sever postperfusion syndromes.

• Radiation Oncology Journal
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• v.33 no.1
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• pp.12-20
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• 2015

Purpose: To evaluate treatment outcomes and determine prognostic factors in patients with esophageal cancer treated with esophagectomy after neoadjuvant chemoradiotherapy (NCRT) Materials and Methods: We retrospectively evaluated 39 patients with esophageal cancer who underwent concurrent chemoradiotherapy followed by esophagectomy between 2002 and 2012. Initial clinical stages of patients were stage IB in 1 patient (2.6%), stage II in 5 patients (12.9%), and stage III in 33 patients (84.6%). Results: The median age of all the patients was 62 years, and the median follow-up period was 17 months. The 3-year overall survival (OS) rate was 33.6% in all the patients. The 3-year locoregional recurrence-free survival (LRFS) rate was 33.7%. In multivariate analysis with covariates of age, the Eastern Cooperative Oncology Group performance status, hypertension, diabetes mellitus, tumor length, clinical response, clinical stage, pathological response, pathological stage, lymphovascular invasion, surgical type, and radiotherapy to surgery interval, only pathological stage was an independent significant prognostic factor affecting both OS and LRFS. The complications in postoperative day 90 were pneumonia in 9 patients, anastomotic site leakage in 3 patients, and anastomotic site stricture in 2 patients. Postoperative 30-day mortality rate was 10.3% (4/39); the cause of death among these 4 patients was respiratory failure in 3 patients and myocardial infarction in one patient. Conclusion: Only pathological stage was an independent prognostic factor for both OS and LRFS in patients with esophageal cancer treated with esophagectomy after NCRT. We could confirm the significant role of NCRT in downstaging the initial tumor bulk and thus resulting in better survival of patients who gained earlier pathological stage after NCRT.

• Environmental Mutagens and Carcinogens
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• v.22 no.2
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• pp.112-124
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• 2002

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to exert detrimental toxicities on various organ systems including reproductive, cardiovascular, nervous, or dermal system. Immunomodulatory effects of TCDD is thymic atrophy, downregulation of cytotoxic T or B lymphocyte differentiation and activation, which were demonstrated using experimental animals, whereas immunotoxicity in human has not been investigated well. This study was proceeded to evaluate general immunologic spectrum of the Korean Vietnam War veterans exposed to TCDD during their operation, and compare with that of the non-exposed control subjects with similar age. Regarding composition and quantity, immune cells in peripheral blood collected from the TCDD-exposed was not much different from those of the control except decreased red blood cell, hemoglobin and hematocrit level. Furthermore, plasma IgG2, G3, and G4 isotype distribution was similar between two groups, but IgG1 level was significantly lowered in the TCDD-exposed, indicating a TCDD-mediated functional alteration of B cells. Significantly enhanced level of IgE in plasma, a hallmark of dermal or respiratory allergic response, was also observed in the TCDD-exposed compared with that of the control. Elevated generation of IL-4 and IL-10 was resulted from in vitro stimulation of T cells with PMA plus ionomycin or PHA, respectively, from the TCDD-exposed in comparison to those of the control, suggesting a skewed type-2 response. In addition, the level of IFN${\gamma}$, a multifunctional cytokine for T cell-mediated immunity, was lowered in the TCDD-exposed with upregulation of tumor necrosis factor $\alpha$. The present study suggests that TCDD exposure disturbs immunohomeostasis in humans observed as an aberrant plasma IgE and IgG1 levels and dysregulation of T cell activities.

• Journal of Chest Surgery
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• v.31 no.2
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• pp.102-107
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• 1998

It has not been clear whether L-arginine plays solely a role contributing to vascular nitric oxide (NO) synthesis. To investigate the mechanisms by which L-arginine induces vasorelaxation, effects of L-arginine on the isometric tension, and tissue NOx and cyclic guanosine monophosphate(cGMP) contents were examined in the isolated rat thoracic aorta. L-Arginine induced a dose-dependent relaxation of aortic rings only with intact endothelium only. The vasorelaxation response to low concentrations of L-arginine was abolished by the pretreatment with NG-nitro-L-arginine methyl ester(L-NAME, 10-4 mol/L), whereas the relaxation caused by higher concentrations L-arginine(10-5-10-3 mol/L) was maintained and even more pronounced in the presence of L-NAME. L-Arginine did not affect the vascular tension precontracted with KCl. The vascular tissue contents of NOx/cGMP were not significantly affected by L-arginine, while they were decreased by L-NAME. L-Arginine could not completely recover the NOx/cGMP decreased by L-NAME. Methylene blue only partially antagonized the relaxation response to L-arginine. Indomethacin did not affect the L-arginine-induced vasorelaxation, whereas ouabain markedly attenuated the relaxation. It is suggested that L-arginine induces vasorelaxation not only through its contribution to NO synthesis, but also through enhancing another endothelium-dependent mechanism which is NO/cGMP-independent and cyclooxygenase- independent.

• Journal of Chest Surgery
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• v.16 no.2
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• pp.213-220
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• 1983

Pulmonary function is the determinant of blood gas tension. However, Acid-Base disturbances can also alter partial pressures of oxygen and carbon dioxide in arterial blood. During respiratory acidosis $PO_2$ will be lowered and reverse changes will be produced during respiratory alkalosis. On the other hand, in metabolic acidosis $PO_2$ will be elevated and $PCO_2$ will be lowered by the respiratory compensation, and reverse response will be induced in metabolic alkalosis. Urinary gas tension has many influencing factors than arterial blood and difficult to estimate the tendency of its alterations. Urinary $PO_2$ and $PCO_2$ are not always identical level as venous blood. It is to be altered by blood gas tension, flow rate of urine, metabolic rate of kidney, and Acid-Base status of blood. Particularly countercurrent exchange of oxygen and carbon dioxide in the renal medulla will make larger alteration of gas tension than venous blood. After induction of Acid-Base disturbances [disturbances] arterial and urinary $PCO_2$, $PO_2$, urinary volume, and osmolarity were determined in dogs, and the relationships between arterial and urinary $PCO_2$ , $PO_2$ Acid-Base disturbances, urinary volume, and osmolarity were investigated. 1. During the acute Metabolic and Respiratory disturbances urinary pH did not respond on respiratory origin. However, there were immediate urinary response in pH on metabolic origin. 2. Urinary $PO_2$, $PCO_2$, did not always follow arterial or venous gas tension and Acid-Base disturbance. Urinary $PCO_2$, correlate well with the urinary volume. The larger the urinary volume, $PCO_2$ lowered to the venous level. The smaller the urinary volume, urinary $PCO_2$ tends to be higher. However urinary $PO_2$ did not have any particular correlation with urinary volume. 3. Correlation between urinary $PCO_2$ and $PO_2$ were inversely proportional to arterial blood. Differences of $PCO_2$ between arterial blood and urine also did not have any particular correlation with urinary volume. This may suggest that changes on blood gas tensions can influence on urinary $PCO_2$. 4. There were eminent clear inverse correlation between urinary $PCO_2$ and osmolar concentrations of urine. Above results strongly suggest that partial pressure of gas in urine primarily depend upon counter-current exchanges in renal medullary tissues.

• Journal of Chest Surgery
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• v.34 no.10
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• pp.763-768
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• 2001

Background: The high pressure zone(HPZ) at the gastroesophageal junction is an important barrier for prevention of gastroesophageal reflux. Smooth muscle layers in the lower esophageal sphincter mainly contributes to HPZ at the throacoabdominal junction. The purpose of this study was to investigate the manometric characteristics of the thora-coabdominal junction in patients after surgical removal of the lower esophageal sphincter. Material and Method: Twenty two patients with prior esophagogastrectomy(10 Ivor-Lewis method and 12 left thoracotomy) and 30 normal adults(control group) were studied manometrically. Result: Esophageal manometry showed a HPZ and pressure inversion points distal to the anastomosis in 12 of 22 patients(2 of 10 patients with Ivor-Lewis method and 10 of 12 patients with left thoracotomy) and a HPZ in 30 of 30 normal adults. The location of HPZ front nostril was not significant different between the two groups(42.5$\pm$0.9cm in patients and 43.9$\pm$2.1cm in the control), while the length of HPZ was shorter in patients than in the control(2.13$\pm$0.6cm vs 2.83$\pm$0.59cm). By SPT and RPT, pressures of HPZ at rest were lower in patients(13.78$\pm$1.63mmHg, 28.58$\pm$6.06mmHg) than in control(20.3$\pm$4.95mmHg, 42.80$\pm$15.91mmHg). The HPZ relaxed partially in response to deglutition(84.4% in patient, 90.5% in control group) and contracted in response to increased intra- abdominal pressure induced by leg lifts(HPZ/ Intra-abdominal pressure= 1.81$\pm$0.23 in patient, 2.13$\pm$ 0.58 in control group).

• Biomolecules & Therapeutics
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• v.11 no.4
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• pp.257-264
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• 2003

Carnitine, hydroxycitric acid, and soy peptide have been known to be anti-obesity agents. The purpose of this study was to evaluate the combined effects of carnitine, hydroxycitric acid, and soy peptide mixture as a potential anti-obesity supplement in overweight women. Overweight premenopausal women (n=33; PIBW>110; 20 to 39 years) were randomized into two groups: the placebo group and the functional beverage group (the test group). Functional beverage was composed of 2000 mg soy peptide, 20 mg L-carnitine and 300 mg garcinia(40% hydroxycitric acid). Body weight and 3 day food dimes, biochemical measurements and computerized tomography were measured at baseline and 8-week. After 8-week consumption of functional beverage with usual diet and exercise, body weight fell an average of 1.4 kg (2.1%). Visceral fat area reduced an average of 7.8% at L1($69.6{\pm}8.7\;vs\;64.2{\pm}7.5\;\textrm{cm}^2$) and 5.1% ($60.7{\pm}4.9\;vs\;57.6{\pm}4.8\;\textrm{cm}^2$, p<0.05) at L4level after weight loss in the test group. Calf fat area in the test group showed about 10% reduction ($31.0{\pm}2.7\;vs=\;27.7{\pm}1.7\;\textrm{cm}^2$, p<0.05) after weight loss. These reductions in fat areas were not shown in the placebo group. There were tendencies of increase in serum levels of $\beta-hydroxybutyrate$, acetoacetate, and total ketones in the test group. There were 7% and 17% insignificant increase in fasting free fatty acid (FFA) and response area of FFA during oral glucose tolerance test(OGTT), respectively, in this group. ill addition, little weight loss in the test group showed 8% but not significant reduction in insulin response area during OGTT. In conclusion, this study shows that taking a mixture of carnitine, hydroxycitric acid, and soy peptide as a potential anti-obesity supplement for 8-week produced advantageous changes in the weight and visceral fat accumulation of overweight women.

• Journal of Chest Surgery
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• v.43 no.4
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• pp.345-355
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• 2010

Background: Extracellular and intracellular pH ($pH_o$ and $pH_i$), which can be changed in various pathological conditions such as hypoxia, affects vascular contractility. To elucidate the mechanism to alter vascular contractility by pH, the effects of pH on reactivity to vasocontracting agents, intracellular $Ca^{2+}$ influx, and $Ca^{2+}$ sensitivity in vascular smooth muscle were examined. Material and Method: Isometric contractions in rat superior mesenteric arteries (SMA) were observed. Intracellular $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) was recorded by microfluorometer using Fura-2/acetoxylmethyl ester in muscle cells. $pH_o$ was increased from 7.4 to 7.8 or decreased to 6.9 or 6.4. $pH_i$ was decreased by applying $NH_4^+$ or propionic acid or modulated by changing $pH_o$ after increasing membrane permeability using $\beta$-escin. Result: Decreases in $pH_o$ from 7.4 to 6.9 or 6.4 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the right and significantly increased half maximal effective concentration (EC50) to NE or SE. Increase in $pH_o$ from 7.4 to 7.8 shifted concentration-response curve by norepinephrine (NE) or serotonin (SE) to the left and significantly reduced EC50 to NE or SE. NE increased $[Ca^{2+}]_i$ in cultured smooth muscle cells from SMA and the increased $[Ca^{2+}]_i$ was reduced by decreases in $pH_o$. NE-induced contraction was inhibited by $NH_4^+$, whereas the resting tension was increased by $NH_4^+$ or propionic acid. When the cell membrane of SMA was permeabilized using ${\beta}$-escin, SMA was contracted by increasing extracellular $Ca^{2+}$ concentration from 0 to $10{\mu}M$ and the magnitude of contraction was decreased by a decrease in $pH_o$ and vice versa. Conclusion: From these results, it can be concluded that a decrease in $pH_o$ might inhibit vascular contraction by reducing the reactivity of vascular smooth muscle to vasoactive agents, $Ca^{2+}$ influx and the sensitivity of vascular smooth muscle to $Ca^{2+}$.

• Journal of Korean Biological Nursing Science
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• v.2 no.1
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• pp.1-19
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• 2000

The purpose of this study was to define the content of the requisite knowledge of pathophysiology, clinical microbiology, and mechanisms and effects of drugs needed for clinical knowledge for nursing practice. Contents of knowlege on pathological physiology, clinical microbiology, and mechanisms and effects of drugs were constructed from syllabus of basic nursing subjects in 4 colleges of nursing, and textbooks. The degree of need of 72 items was measured with a 4 point scale. The subjects of this study were college-graduated 136 nurses from seven university hospital in Seoul and three in Chonnam Province, Kyungbook Province, and Inchon. They have been working at internal medicine ward, surgical ward, intensive care unit, obstetrics and gynecology ward, pediatrics ward, opthalmology ward, ear, nose, and throat ward, emergency room, rehabilitation ward, cancer ward, and hospice ward. The results were as follows : 1. The highest scored items of the knowledge of pathophysiology, clinical microbiology, and mechanisms and effects of drugs necessary for nursing practice were side effects of drugs, anticoagulants, mechanisms of drugs, antihypertensive drugs, tolerance and addiction of drugs, interactions among drugs, hospital infection in the order of importance. The lowest scored item was structure of microorganisms. 2. The highest order of need according to unit was repair in tissue injury unit, definition etiology classification of inflammation in inflammation unit, transplantation and immunologic response in alterations in immunity unit, thrombus and thrombosis in disorders of cardiovascular function unit, gene disorders in genetic disorders unit, hospital infection in infection unit, virus in microorganisms unit, side reactions of drugs in introduction unit, anticonvulsants in drugs for central nervous system unit, local anesthesia in anesthesia unit, anticoagulants in drugs for cardiovascular system unit, anti-inflammatory drugs in antibiotics unit, anti-ulcer drugs in drugs for digestive system unit, and bronchodilators in drugs for respiratory system unit. 3. The common content of the knowledge of pathophysiology, clinical microbiology, and mechanisms and effects of drugs needed for all clinical areas in nursing were side effects of drugs, anticoagulants, interactions among drugs, and hospital infection. However, the degree of need of each pathological physiology, clinical microbiology, clinical microbiology, and mechanisms and effects of drugs was different depending on clinical areas. 4. Significant differences in the knowledge of pathophysiology, clinical microbiology, and mechanisms and effects of drugs necessary for nursing practice such as tissue changes due to injurious stimuli, degenerative changes of tissue, alterations in metabolism of carbohydrates, ischemia, hyperemia and congestion, hospital infection, structure of microorganism, classification of microorganism, bacteria, virus, antidepressants, antipsychotic drugs, antiemetic drugs, antiparkinsonism drugs, antianxiety drugs, antibiotics, tuberculostatics, antiviral drugs, antifungal drugs, parasiticides, antiulcer drugs, antidiarrheais, and anti constipation drugs were shown according to the work area. 5. Significant differences in the knowledge of pathophysiology, clinical microbiology, and mechanisms and effects of drugs necessary for nursing practice such as transplantation and immunologic response, alterations in the metabolism of uric acid, structure of microorganism, classification of microorganism, immunosuppressants, drugs for congestive heart failure were demonstrated according to the duration of work. Based on these findings, all the 72 items constructed by Korean Academic Society of Basic Nursing science should be included as contents of the knowledge of pathophysiology, clinical microbiology, and mechanisms and effects of drugs.