Assessment of dexmedetomidine effects on left ventricular function using pressure-volume loops in rats.

PURPOSE: The role of dexmedetomidine on left ventricular function is ambiguous. We analyzed pressure-volume loops to investigate whether dexmedetomidine has a myocardial depressive effect. METHODS: Thirty-two Sprague-Dawley rats were anesthetized and a pressure-volume loop catheter was advanced into the left ventricle. Rats were divided into four groups (n = 8 each). The control group received a 10-min infusion of 0.1 ml of normal saline, and the other three groups received 1.0 (Dex1.0 group) , 2.5 (Dex2.5 group), and 5.0 µg/kg (Dex5.0 group) dexmedetomidine in a similar fashion to the control group. Steady-state hemodynamic parameters were recorded. The inferior vena cava was occluded intermittently to assess preload-independent indices. RESULTS: Compared with the control group, changes in the Dex1.0 group were insignificant. In the Dex2.5 group, only the systolic blood pressure was higher (vs control, P = 0.03), and other parameters were insignificant. The Dex5.0 group exhibited a lower heart rate, higher systolic blood pressure, higher arterial elastance (vs control, all P < 0.001), and unaltered cardiac output. The Dex5.0 group showed steeper slopes of end-systolic pressure increment and end-systolic pressure-volume relationship than the control, Dex1.0, and Dex2.5 groups (all P < 0.001). Slopes of end-diastolic pressure decrement and end-diastolic pressure-volume relationship did not differ among groups. CONCLUSION: Dexmedetomidine had no direct myocardial depressant effect in the rat heart in doses that are similar to those encountered under clinical conditions. Dexmedetomidine did not significantly alter the ability of the heart to cope with bradycardia and greatly increased afterload. Their potentially negative impact on cardiac output was effectively attenuated by improved myocardial contractility and preserved diastolic function in healthy subjects.

[The Structural Equation Model on Resilience of Breast Cancer Patients Receiving Chemotherapy].

PURPOSE: The purpose of this study was to construct and test a structural equation model on resilience of breast cancer patients receiving chemotherapy. METHODS: Participants were 204 patients with breast cancer who received chemotherapy treatment. They participated in a structured interview, which included social support, depression, symptom experience, self-efficacy, hope, resilience, and infection prevention behaviors. Data were analyzed using SPSS/WIN 20.0 and AMOS 18.0. RESULTS: Lower depression (γ=-.33, p=.020) and symptom experience (γ=-.31, p=.012) and higher self-efficacy (γ=.32, p=.005) and hope (γ=.48, p=.016) were influenced by higher social support. Greater resilience was influenced by lower symptom experience (ß=-.18, p=.016), higher self-efficacy (ß=.49, p=.023), and higher hope (ß=.46, p=.012), and these predictors explained 66.7% of variance in resilience. Greater resilience (ß=.54, p=.009) made an impact on greater infection prevention behaviors. Resilience mediated the relations of symptom experience (ß=-.10 p=.013), self-efficacy (ß=.27, p=.006) and hope (ß=.25, p=.009) with infection prevention behaviors. These predictors explained 24.9% of variance in infection prevention behaviors. CONCLUSION: The findings of the study suggest that breast cancer patientsw ith greater resilience who are receiving chemotherapy participate in increased infection prevention behaviors. Further research should be conducted to seek intervention strategies that improve breast cancer patients' resilience.

Effect of Pneumoperitoneum on Oxidative Stress and Inflammation via the Arginase Pathway in Rats.

PURPOSE: Oxidative stress during CO2 pneumoperitoneum is reported to be associated with decreased bioactivity of nitric oxide (NO). However, the changes in endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and arginase during CO2 pneumoperitoneum have not been elucidated. MATERIALS AND METHODS: Thirty male Sprague-Dawley rats were randomized into three groups. After anesthesia induction, the abdominal cavities of the rats of groups intra-abdominal pressure (IAP)-10 and IAP-20 were insufflated with CO2 at pressures of 10 mm Hg and 20 mm Hg, respectively, for 2 hours. The rats of group IAP-0 were not insufflated. After deflation, plasma NO was measured, while protein expression levels and activity of eNOS, iNOS, arginase (Arg) I, and Arg II were analyzed with aorta and lung tissue samples. RESULTS: Plasma nitrite concentration and eNOS expression were significantly suppressed in groups IAP-10 and IAP-20 compared to IAP-0. While expression of iNOS and Arg I were comparable between the three groups, Arg II expression was significantly greater in group IAP-20 than in group IAP-0. Activity of eNOS was significantly lower in groups IAP-10 and IAP-20 than in group IAP-0, while iNOS activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. Arginase activity was significantly greater in group IAP-20 than in groups IAP-0 and IAP-10. CONCLUSION: The activity of eNOS decreases during CO2 pneumoperitoneum, while iNOS activity is significantly increased, a change that contributes to increased oxidative stress and inflammation. Moreover, arginase expression and activity is increased during CO2 pneumoperitoneum, which seems to act inversely to the NO system.

The effects of arginase inhibitor on lung oxidative stress and inflammation caused by pneumoperitoneum in rats.

BACKGROUND: Pneumoperitoneum-induced oxidative stress and organ injury are known to be associated with nitric oxide (NO) inactivation. Because arginase competes with NO synthase (NOS) for a common substrate, L-arginine, arginase inhibition may increase NO bioavailability. Therefore, we evaluated the ability of the arginase inhibitor, 2 (S)-amino-6-boronohexanoic acid (ABH), to attenuate pneumoperitoneum-induced decrease of NO bioavailability and lung injury. METHODS: Thirty rats were randomly divided into the following groups: 1) the PP-ABH group received a subcutaneous injection of ABH (5 mg/kg) 1 h before induction of pneumoperitoneum (insufflation to intraperitoneal pressure of 15 mmHg for 60 min); 2) the PP group received saline by subcutaneous injection 1 h before induction of pneumoperitoneum; and 3) the control group received saline by subcutaneous injection before a sham procedure with no gas insufflation. After desufflation, blood was collected to determine levels of plasma nitrite, NOS, inflammatory cytokines, and malondialdehyde, a marker of oxidative stress. Lung tissue was obtained for histological evaluation. RESULTS: We found that plasma nitrite levels were lower in the PP group and higher in the PP-ABH group, compared with controls (P <0.01 and P <0.05, respectively). In the PP group, endothelial NOS activity was decreased and inducible NOS activity was increased compared with the PP-ABH and control groups. Malondialdehyde levels increased 3-fold in the PP group and 2-fold in the PP-ABH group compared with controls. Tumor necrosis factor-α, interleukin-6, and interleukin-1ß levels were elevated in the PP group compared to the control group, but the increase in cytokine production was attenuated or blocked in the PP-ABH group. Lung injury scores were 4.8-fold higher in the PP group and 2-fold higher in the PP-ABH group compared with controls (P <0.001 and P <0.01, respectively). DISCUSSION: Pneumoperitoneum decreases NO bioavailability and increases the inflammation cytokines, resulting in organ injuries. Inhibition of arginase activity could maintain NO bioavailability by attenuating pneumoperitoneum-induced changes in NOS activity. In addition, arginase inhibition attenuated the oxidative stress and inflammation and decreased the severity of lung injury caused by pneumoperitoneum. CONCLUSIONS: By increasing NO bioavailability and suppressing oxidative stress and inflammation, pretreatment with an arginase inhibitor may protect against lung injury caused by pneumoperitoneum.

Characteristics and Factors Associated with Problem Drinking in Male Workers.

PURPOSE: This study aimed to identify the characteristics and factors related to problem drinking in male workers. METHODS: This study was conducted using a cross-sectional survey and 232 male workers, who completed self-reported questionnaires addressing alcohol consumption, drinking motives, job stress, supervisor/coworker support, and family support. Multivariate analysis was used to uncover factors associated with problem drinking. RESULTS: As compared with normal alcohol users, problem drinkers were more likely to smoke and had greater family support and coping motivations, and fewer confirmatory motives. Problem drinking was found to be related to perceived health status (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] [0.64, 0.95]), current smoking (adjusted OR = 2.79, 95% CI [1.26, 6.18]), family support (adjusted OR = 2.04, 95% CI [1.23, 3.39]), confirmatory motivation (adjusted OR = 0.60, 95% CI [0.37, 0.96]), and coping (adjusted OR = 1.79, 95% CI [1.04, 3.07]). CONCLUSIONS: Our findings suggest that any interventions targeting problem drinking among male workers must address smoking cessation, control of stress, and the improvement of drinking subculture in the workplace.

Lithium chloride suppresses LPS-mediated matrix metalloproteinase-9 expression in macrophages through phosphorylation of GSK-3ß.

Abnormal degradation of matrix components due to dysregulated expression of matrix metalloproteinase (MMP)-9 in macrophages has been linked to progression of acute cerebral ischemia and atherosclerosis. We report that lithium chloride (LiCl) or CHIR99021, inhibitors of Wnt signaling pathway, enhance phosphorylation of glycogen synthase kinase-3beta and suppress lipopolysaccharide-mediated upregulation of MMP-9 expression in murine macrophage RAW264.7 cells in a dose-dependent manner. Suppression of MMP-9 expression by LiCl or CHIR99021 did not result after inhibition of kinases involved in NFκB or AP-1 family proteins, but from changes in the activity of histone deacetylases. Beneficial effects on atherosclerosis or cerebral ischemia in animal studies caused by LiCl may be in part explained by the suppression of MMP-9 gene expression.

Cervical ganglion block attenuates the progression of pulmonary hypertension via nitric oxide and arginase pathways.

It has been recognized that the sympathetic nervous system is activated in pulmonary arterial hypertension (PAH), and abnormal sympathetic hyperactivity leads to worsening of PAH via endothelial dysfunction. The purpose of this study was to examine whether sympathetic ganglion block (SGB) can treat PAH by increasing the availability of nitric oxide (NO). PAH was induced in rats by 50 mg/kg of subcutaneous monocrotaline. After 2 weeks, daily injections of ropivacaine into the left superior cervical ganglion were repeated for 14 days (monocrotaline-SGB group). Monocrotaline group received sham SGB with saline, whereas control group received saline instead of monocrotaline. PAH was evident in monocrotaline group, with right ventricular systolic pressures (47±4 mm Hg) that were higher than those of controls (17±2 mm Hg), whereas SGB significantly attenuated monocrotaline-induced PAH (35±4 mm Hg). The right/left ventricular mass ratios exhibited similar changes to those seen with right ventricular pressures. Heart rate variability showed significantly higher sympathetic activity in the monocrotaline group. Microscopy revealed a higher proportion of muscular arteries with thicker medial walls in the monocrotaline group, which was attenuated by SGB. Monocrotaline induced arginase hyperactivity, which was in turn decreased by SGB-induced endothelial NO synthase activation. SGB restored monocrotaline-induced hypoactivity of superoxide dismutase. In conclusion, SGB could suppress PAH and the remodeling of pulmonary arteries via inactivation of arginase and reciprocal elevation of NO bioavailability, thus attenuating disproportionate hyperactivation of the sympathetic nervous system.

Activation of the GDNF-inducible transcription factor (GIF) gene promoter by glucocorticoid and progesterone.

Steroid hormones, especially glucocorticoids, exert physiologic effects on dopaminergic neurotransmission and have been implicated in several dopamine-mediated neuropsychiatric conditions. D(2) dopamine receptor gene expression is regulated by the zinc finger-type nuclear protein GDNF-inducible transcription factor (GIF). In this study, we sought to investigate if steroids could regulate transcription of the GIF gene itself. Transient co-transfection of the D(2) expressing neuroblastoma cell line NB41A3 with GIF promoter-luciferase constructs along with expression vectors for steroid hormone receptors showed that activation of glucocorticoid receptors but not estrogen receptors up-regulates transcription from the GIF promoter 5.0-fold. Progesterone receptors, which share the same consensus DNA recognition sequence as glucocorticoid receptors, also activated the GIF promoter. Serial 5'-deletion mutants of the GIF gene upstream region localized the glucocorticoid-responsive segment between nucleotides -128 and -66 relative to the transcription start site. This region contains a putative glucocorticoid-responsive element/progesterone-responsive element (GRE/PRE). Additionally, this fragment of the GIF gene 5'-upstream region activated the heterologous herpes simplex virus thymidine kinase (TK) promoter, which is known to be glucocorticoid and progesterone responsive. Furthermore, glucocorticoid receptor activation up-regulated endogenous GIF gene mRNA expression in NB41A3 cells. These observations demonstrate a molecular basis for glucocorticoid and progesterone-induced up-regulation of GIF gene transcription and provide a mechanism for the modulation of dopamine-mediated behaviors by these hormones.

Transcriptional auto-regulation of the dopamine receptor regulating factor (DRRF) gene.

The murine dopamine receptor regulating factor (DRRF) gene is transcribed from a TATA-less promoter that has several putative Sp1 binding sites. The present investigation identifies functional transcription factors that modulate the expression of this gene. In the D2-dopamine receptor expressing NB41A3 cells, Sp1 potently activates transcription from the DRRF promoter in pCAT-DRRF-1153/+17, while DRRF itself effectively inhibits it. Sp1 also activates this promoter in pCAT-DRRF-310/+17. In competitive co-transfection experiments, DRRF represses the transcriptional activation induced by Sp1, while Sp1 de-represses the inhibitory effect of DRRF. Deletion of the 31 bp fragment between -1153 and -1122 decreased basal transcription down to about 60%. This fragment contains a functional AP1 binding site. In addition, deletion of the 129 bp region between -901 and -772 further decreased transcription. The latter region has a functional AP2 binding site. The present observations suggest that DRRF auto-regulates its own promoter by competing with Sp1 and that both AP1 and AP2 modulate expression of this gene.

Standardization of Korean nursing terminology.

Korean nursing terminology was standardized to improve sharing and exchange of nursing data and information. English nursing terms were collected from existing nursing terminology, journal articles, nursing records, text books, and nursing/medical dictionaries, translated into Korean and were tested for their validity. More than 9000 terms were standardized and published on a website for further feedback from the users. This study will contribute to communication within the nursing community and with other health care professionals.

Symptom experience in Korean patients with liver cirrhosis.

This study was done to examine the level of symptom experience, and symptom variation in relation to demographic and clinical variables, in Korean patients with liver cirrhosis (LC). Symptom experience was measured using a scale developed by the researchers through a literature review on LC. Participants were 129 patients whose mean age was 53.6 (standard deviation [SD] = 9.28) years. The results indicated that (1) overall symptom experience was relatively low (mean 41.67, SD 24.71); (2) the main symptoms needing a management were fatigue, abdominal distension and/or peripheral edema, and muscle cramps; and (3) among the study variables, the severity of LC (P < 0.001) and the number of hospitalizations (P = 0.014) showed a significant relationship with overall symptom experience. These results suggest that symptom assessment requires a multidimensional approach and that it is imperative to consider disease severity in developing tailored symptom management programs for Korean patients with LC.

[Influencing factors on HRQOL of physically disabled persons].

PURPOSE: The purpose of this study was to investigate the influencing factors on health-related quality of life of physically disabled persons. METHOD: Data was collected from 96 persons with a physical disability in three cities in Korea from June to September, 2003. Social support and depression were measured by a Social Support Questionnaire 6 (SSQ6) and Center for Epidemiologic Studies Depression questionnaire (CES-D). The Rosenberg Self-esteem Scale was used to measure self-esteem. Health-related quality of life (HRQOL) was measured using Smith Kline Beecham Quality of Life Scale (SBQOL). The SPSS WIN 11.0 version program was used for data analysis. RESULT: There were significant differences of HRQOL according to monthly income and economic status. All subjects had a high level of depression and low self-esteem. CONCLUSION: The findings of this study show that self-esteem and the size of the social support network are significant influencing variables on HRQOL in physically disabled persons. Nursing intervention and counseling programs which improve self-esteem and increase the size of a social support network are needed to promote HRQOL in physically disabled persons.

[Dependency, abuse, and depression by gender in widowed elderly].

PURPOSE: The purpose of this study was to investigate the effects of dependency and abuse on depression according to gender in widowed elderly. METHOD: A convenient sample consisted of 246 widowed elderly who were more than 65 years old in four cities. Data was collected using a structured questionnaire from August to September, 2002. A dependency Scale developed by Ahn (1999) was used to measure the level of dependency. Emotional abuse and physical abuse were measured by 10 items for emotional abuse and 7 items for physical abuse selected out of the Conditions Scale of Elder Abuse. The level of depression was measured by the Geriatric Depression Scale (GDS). The SPSS WIN 11.0 version program was used for data analysis. RESULT: In male widowed elderly, dependency affected depression indirectly through emotional abuse. While in female widowed elderly, dependency affected depression directly and affected emotional abuse indirectly. CONCLUSION: The study showed that dependency was the most explainable variable on depression in widowed female elderly. Therefore, it dependency should be assessed first in nursing intervention to relieve depression of widowed elderly.

[Influencing factors that affect the psychological well-being in family caregivers of stroke patients].

PURPOSE: The purpose of this study was to investigate the factors that affect the psychological well-being in family caregivers of stroke patients. METHOD: The General Health Perception, short form 36, Health Survey Questionaire was used to measure health perception. The Caregiving Mastery Scale was used to assess the mastery, while the Psychological General Well-Being Index was used to examine the level of well-being. RESULT: Subjective health, caregiving mastery, patient's ADL and caregiving duration influenced on caregiver's psychological well-being. Subjective health had effect on psychological well-being both directly and indirectly. Caregiving duration and patient's ADL had indirect effect on psychological well-being through caregiving mastery. CONCLUSION: It is need to develop a health program for the caregivers of stroke patient's and to provide nursing intervention to improve the caregiver's ability, thereby improving the well-being of the family caregivers.

Establishment of in vitro test system for the evaluation of the estrogenic activities of natural products.

In order to evaluate estrogenic compounds in natural products, an in vitro detection system was established. For this system, the human breast cancer cell line MCF7 was stably transfected using an estrogen responsive chloramphenicol acetyltransferase (CAT) reporter plasmid yielding MCF7/pDsCAT-ERE119-Ad2MLP cells. To test the estrogenic responsiveness of this in vitro assay system, MCF7/pDsCAT-ERE119-Ad2MLP cells were treated with various concentrations of 17beta-estradiol. Treatments of 10(-8) to 10(-12) M 17beta-estradiol revealed significant concentration dependent estrogenic activities compared with ethanol. We used in vitro assay system to detect estrogenic effects in Puerariae radix and Ginseng radix Rubra extracts. Treatment of 500 and 50 microg/ml of Puerariae radix extracts increased the transcriptional activity approximately 4- and 1.5-fold, respectively, compared with the ethanol treatment. Treatment of 500, 50, and 5 microg/ml of Ginseng radix Rubra extracts increased the transcriptional activity approximately 3.2-, 2.7-, and 1.4-fold, respectively, compared with the ethanol treatment. These observations suggest that Puerariae radix and Ginseng radix Rubra extracts have effective estrogenic actions and that they could be developed as estrogenic supplements.

Human act and AR1 sequences differentially regulate murine and human D1A dopamine receptor promoters.

The D1A dopamine receptor gene underlies complex transcriptional regulation in order to achieve the tissue-specific expression. Transcription in the D1A genes proceeds from two distinct promoters utilized for the tissue-specific regulation of these genes. Furthermore, analysis of the human D1A dopamine receptor gene has revealed that the region between nucleotides -1173 and -1136 (ActAR1) of the gene might be important for its neural cell-specific expression. To investigate the function of D1A dopamine receptor promoters in the brain cell-specific expression of transgenes, we analyzed the regulatory patterns of two distinct protein-binding regions of ActAR1, i.e., an Act sequence (-1174/-1154) and an AR1 sequence (-1154/-1136), toward murine and human D1A promoters. Transient expression analyses using various chloramphenicol acetyltransferase constructs revealed that Act could not activate murine or human D1A promoters, and that AR1 could effectively stimulate these promoters in a cell type-non-specific manner. Only ActAR1, a combination of Act and AR1, could activate murine and human D1A promoters in a prominent cell type-specific manner. Abundant protein binding to Act was detected by gel mobility shift assay using nuclear extracts from SK-N-MC, NS20Y, OK, and C6 but faint protein binding using nuclear extracts from HepG2. Furthermore, strong protein binding to AR1 was detected using nuclear extracts from SK-N-MC, NS20Y, HepG2 but faint protein binding from C6 extracts and no detectable protein binding from OK extracts. These observations suggest that the tissue-specific expression of the D1A gene is due, at least in part, to the differential expression of these activator proteins that bind to Act and AR1.

Genomic organization and promoter characterization of the murine dopamine receptor regulating factor (DRRF) gene.

To study the transcriptional mechanisms by which expression of the dopamine receptor regulating factor (DRRF) gene is regulated, a murine genomic clone was isolated using a DRRF cDNA as probe. A 24 kb genomic fragment which comprises 13 kb upstream of the transcription initiation site was sequenced. The promoter region lacks a TATA box and CAAT box, is rich in G+C content, and has multiple putative binding sites for the transcription factor Sp1. The DRRF gene also has consensus sequences for AP1 and AP2 binding sites. The transcriptional activity of five deletion mutants of a 1.5 kb fragment was analyzed by modulating transcription of the heterologous chloramphenicol acetyltransferase (CAT) gene in the promoterless plasmid pCAT-Basic. All mutants showed significant transcriptional activity in the murine neuroblastoma cell line NB41A3, except the construct stretching from -901 to +17. These transient expression assays suggested the presence of positive regulators between -1153 and -901 and between -118 and -93 while a negative regulator was found in the region between -901 and -118. Comparison among cell types revealed strong transcriptional activity of the DRRF promoter in neuronal NB41A3 cells and moderate activity in hepatic HepG2 and renal OK cells, but none in skeletal muscle C2C12 or glial C6 cells. These findings confirm the tissue-specific activity of the DRRF promoter and suggest that this gene shares structural and functional similarities with the dopamine receptor genes that it regulates.

[The relationships among loneliness, social support, and family function in elderly Korean].

PURPOSE: To examine the relationships among loneliness, social support, and family function in elderly Korean. METHOD: The sample for this study were 290 elderly Korean who were at least 60 years of age. Data were collected by interview using the translated Korean versions of the Revised University of California Los Angels Loneliness Scale(RULS), Family APGAR, and Social Support Questionnaire 6. RESULT: Subjects were moderately lonely and had moderately functional families. Means for social support were 1.42 for network size and 4.09 for satisfaction. Subjects who lived with their spouses had a larger number of network members than who did not live with spouses. However, living with spouses was not associated with social support satisfaction. The level of loneliness was related negatively to the level of social support network, social support satisfaction and family function in this study. Social support satisfaction and Family function were the significant predictor of loneliness. CONCLUSION: The number of social supporter and satisfaction and family function should be considered in nursing intervention to decrease the level of loneliness in older adults. Further studies and efforts will be needed to reduce the level of loneliness in older adults.