Melatonin modulates nitric oxide-regulated WNK-SPAK/OSR1-NKCC1 signaling in dorsal raphe nucleus of rats

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

Melatonin modulates nitric oxide-regulated WNK-SPAK/OSR1-NKCC1 signaling in dorsal raphe nucleus of rats

The sleep-wake cycle is regulated by the alternating activity of sleep- and wake-promoting neurons. The dorsal raphe nucleus (DRN) secretes 5-hydroxytryptamine (5-HT, serotonin), promoting wakefulness. Melatonin secreted from the pineal gland also promotes wakefulness in rats. Our laboratory recently demonstrated that daily changes in nitric oxide (NO) production regulates a signaling pathway involving with-no-lysine kinase (WNK), Ste20-related proline alanine rich kinase (SPAK)/oxidative stress response kinase 1 (OSR1), and cation-chloride co-transporters (CCC) in rat DRN serotonergic neurons. This study was designed to investigate the effect of melatonin on NO-regulated WNK-SPAK/OSR1-CCC signaling in wake-inducing DRN neurons to elucidate the mechanism underlying melatonin’s wake-promoting actions in rats. Ex vivo treatment of DRN slices with melatonin suppressed neuronal nitric oxide synthase (nNOS) expression and increased WNK4 expression without altering WNK1, 2, or 3. Melatonin increased phosphorylation of OSR1 and the expression of sodium-potassium-chloride co-transporter 1 (NKCC1), while potassium-chloride cotransporter 2 (KCC2) remained unchanged. Melatonin increased the expression of tryptophan hydroxylase 2 (TPH2, serotonin-synthesizing enzyme). The present study suggests that melatonin may promote its wakefulness by modulating NO-regulated WNK-SPAK/OSR1-KNCC1 signaling in rat DRN serotonergic neurons.

Acer tegmentosum Maxim Prevents Bone Loss by Inhibiting Osteoclastogenesis and Promoting Osteoblast Mineralization in Ovariectomized Mice

Osteoporosis is a worldwide disease leading to significant economic and societal burdens globally. Osteoporosis is caused by unbalanced bone remodeling between the rate of osteoclast bone resorption and osteoblast bone formation. Acer tegmentosum Maxim (AT) is a traditional herbal medicine containing multiple biological activities such as anti-oxidant and anti-inflammatory purposes. However, its role in osteoporosis has not been fully studied. Therefore, we investigated whether AT has a potent inhibitory effect on osteoporosis and its mechanism through a systemic evaluation in ovariectomized (OVX) mice. OVX mice were orally administrated with the AT at doses of 50, 100, and 200 mg/kg for 10 weeks. Histological images and histomorphometry analyses were performed by H&E and Toluidine blue satin, and the expression levels of receptor activator for nuclear factor-kB ligand (RANKL), nuclear factor of activated T cells cytoplasm 1 (NFATc1), c-Fos, and matrix metalloproteinase 9 (MMP9) related to the osteoclast differentiation were investigated using immunohistochemical analysis. Administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Further, administration of AT increased periosteal bone formation in a dose-dependent manner. Meanwhile, AT inhibited not only the expression of NFATc1 and c-Fos, which are two major regulators of osteoclastogenesis but also reduced bone resorbed encoding expression of MMP9 and RANKL. Our results indicated that administration of AT prevented bone loss and the alternations of osteoporotic bone parameters at the distinct regions of the distal femur and spongiosa region in OVX mice. Also AT has the bone protective effect through the suppression of osteoclast and promotion of osteoblast, suggesting that it could be a preventive and therapeutic candidate for anti-osteoporosis.

Carotid Wall Imaging with Routine Brain MRI to Facilitate Early Detection of Carotid Plaque and Intraplaque Hemorrhage / 대한뇌졸중학회지

No abstract available.

Uterine artery pulsatility index in hypertensive pregnancies: When does the index normalize in the puerperium?

OBJECTIVE: To investigate whether the uterine artery pulsatility index (UtA PI) of hypertensive pregnancies is higher than that of normal pregnancies in the puerperium, as well as in the antepartum period. METHODS: The UtA PI was measured in hypertensive (group 1) and normal pregnancies (group 2) during antepartum, immediate postpartum or late postpartum periods. Using the transvaginal approach, the bilateral uterine artery indices were measured. RESULTS: One hundred twenty-two women were enrolled: group 1, hypertensive disease in pregnancy (11 cases in antepartum, 13 cases in immediate postpartum and 10 cases in late postpartum period); group 2, normal pregnancies (32 cases in antepartum, 29 cases in immediate postpartum and 27 cases in late postpartum). In antepartum and immediate postpartum periods, the mean UtA PI and the proportion of cases with an early diastolic notch were higher in group 1 than in group 2 (antepartum mean UtA PI, 1.14 in group 1 vs. 0.68 in group 2, P<0.001; early diastolic notch, 46% vs. 9%, P<0.05; immediate postpartum mean UtA PI, 1.30 vs. 1.08, P<0.05; early diastolic notch, 85% vs. 48%, P<0.05). In late postpartum period, the mean value of UtA PI of group 1 was still higher than that of group 2, although the proportion of cases with an early diastolic notch was not different (mean UtA PI, 1.43 vs. 1.20, P<0.05; early diastolic notch, 60% vs. 52%, P=0.73). CONCLUSION: The UtA PI in hypertensive pregnancies was still higher than normal pregnancies in puerperal periods, suggesting that more than several weeks are required to resolve increased uterine artery vascular impedance.

Job Stress, Job Satisfaction, and Organizational Commitment according to Life Organization (LIFO) Behavior Type of Novice Nurses / 간호행정학회지

PURPOSE: This study was done to provide data that would contribute to effective task performance in clinical nursing and development of nursing professional by understanding job stress, job satisfaction and organizational commitment according to Life Organization (LIFO) behavior types of novice nurses. METHODS: This study was a cross-sectional survey and the participants were 313 novice nurses who worked in one university hospital located in the city of Gwangju. Data were collected through the structured questionnaires that included general characteristics, job stress, job satisfaction, and organizational commitment scales. Collected data were analyzed using descriptive statistics, and ANOVA with SPSS/WIN 19.0. RESULTS: Regarding job stress according to LIFO behavior types of novice nurses, there were statistically significant differences between the favorable situation and the unfavorable situation. There were also statistically significant differences regarding the organizational commitment according to LIFO behavior types. CONCLUSION: The results indicate a difference in behavior patterns of novice nurses that suggest a need for education in order to reduce stress from the job and enhance organizational commitment by developing each nurse's preferred pattern and compensating for unfavorable patterns, as well. There also needs to be nursing resources that take into consideration behavior patterns of novice nurses.

Expression and Activity of the Na-K ATPase in Ischemic Injury of Primary Cultured Astrocytes

Astrocytes are reported to have critical functions in ischemic brain injury including protective effects against ischemia-induced neuronal dysfunction. Na-K ATPase maintains ionic gradients in astrocytes and is suggested as an indicator of ischemic injury in glial cells. Here, we examined the role of the Na-K ATPase in the pathologic process of ischemic injury of primary cultured astrocytes. Chemical ischemia was induced by sodium azide and glucose deprivation. Lactate dehydrogenase assays showed that the cytotoxic effect of chemical ischemia on astrocytes began to appear at 2 h of ischemia. The expression of Na-K ATPase alpha1 subunit protein was increased at 2 h of chemical ischemia and was decreased at 6 h of ischemia, whereas the expression of alpha1 subunit mRNA was not changed by chemical ischemia. Na-K ATPase activity was time-dependently decreased at 1, 3, and 6 h of chemical ischemia, whereas the enzyme activity was temporarily recovered to the control value at 2 h of chemical ischemia. Cytotoxicity at 2 h of chemical ischemia was significantly blocked by reoxygenation for 24 h following ischemia. Reoxygenation following chemical ischemia for 1 h significantly increased the activity of the Na-K ATPase, while reoxygenation following ischemia for 2 h slightly decreased the enzyme activity. These results suggest that the critical time for ischemia-induced cytotoxicity of astrocytes might be 2 h after the initiation of ischemic insult and that the increase in the expression and activity of the Na-K ATPase might play a protective role during ischemic injury of astrocytes.

Proportion of Multidrug-Resistant Tuberculosis in Human Immunodeficiency Virus/Mycobacterium tuberculosis Co-Infected Patients in Korea

Much controversy surrounds the issue of whether HIV infection is a risk factor for developing multidrug-resistant tuberculosis (MDR-TB). In this study, we evaluated the prevalence of and risk factors for MDR-TB in HIV-infected patients at the National Medical Center of Korea. We reviewed the medical records of HIV/TB co-infected patients from January 2005 to May 2011; the drug susceptibility profiles were available for 55 patients. Of these, 32.7% had MDR-TB, which was approximately 3.6 times higher than the prevalence among the general population. Additionally, there were more additional AIDS-defining clinical illnesses in the MDR-TB group than in the non-MDR-TB group (27.8% vs 5.4%, P = 0.032). These results suggest that HIV infection and HIV-related immunosuppresion may contribute to the development of MDR-TB.

Rapidly Aggravated Dissecting Flap by Angiography during Percutaneous Stent Placement for Acute Isolated Superior Mesenteric Artery Dissection

Acutely aggravated dissecting flap and consequent occlusion of the superior mesenteric artery (SMA) by simple contrast passage during initial angiography for percutaneous stent placement is a uncommon event, which usually is not reported. After analysis of many factors that underlie development of such complications, we present herein one case of successful treatment of isolated SMA dissection and its complications with favorable outcomes during 25 months follow-up after percutaneous stent placement.

Degree of Disease Progression in Homeless HIV/AIDS Patients during the First Medical Visit / 감염과화학요법

BACKGROUND: In the Korean healthcare system, medical care for HIV patients was provided by a few university affiliated hospitals. Access to these tertiary hospitals by homeless people living with HIV was difficult due to socioeconomic reasons. Consequently, proper treatment for homeless subjects living with HIV was not delivered in a timely manner. This study compares the degree of disease progression of HIV infection/AIDS between homeless and non-homeless patient groups. MATERIALS AND METHODS: Out of 605 HIV/AIDS patients who visited the Center for Infectious Disease, National Medical Center, Seoul, Korea from August 2003 to May 2010, 295 subjects were included for this study. Referred cases (n=310) were excluded. The study subjects were further classified into three socioeconomic groups: National Health Insurance beneficiaries, Medical Aids beneficiaries, and the homeless. Status of HIV/AIDS disease progress was evaluated by peripheral blood CD4 cell count and the presence of AIDS defining illnesses at the first visit. RESULTS: There were 220 National Health Insurance beneficiaries (male 94.1%), 45 Medical Aids beneficiaries (male 88.9%), and 30 homeless people (male 96.7%). CD4 cell counts of the homeless (median: 119/microL, interquartile range: 44-383/microL) were significantly lower than those of the National Health Insurance beneficiaries (median: 267/microL, interquartile range: 159-397/microL; P=0.024). In addition, the proportion of patients whose CD4 cell counts <200/microL was significantly higher in homeless subjects (53.3%) compared to those in the National Health Insurance beneficiaries (27.3%) and the Medical Aids beneficiaries (28.9%) (P=0.004; P=0.033 respectively). Also, the frequency of AIDS defining illnesses was higher in the homeless (73.3%) than for those in other groups (the Health Insurance beneficiaries: 24.5%; the Medical Aids beneficiaries: 40.0%) (P<0.001; P<0.005 respectively). CONCLUSIONS: Homeless people living with HIV tend to seek medical care in far advanced stage, which may attribute to poor prognoses. More organized and strategic interventions are necessary to find and treat homeless people living with HIV at the early stage.

A prospective multicenter randomized study on prophylactic antibiotics use in cesarean section performed at tertiary center / 대한산부인과학회지

OBJECTIVE: To determine whether the duration and timing of prophylactic antibiotics influence maternal postoperative infectious morbidity in cesarean section performed at tertiary center. METHODS: This study was a prospective, randomized trial. Pregnant women who underwent cesarean section between December 2008 and September 2009 at tertiary center were enrolled and divided into two groups: Group A, antibiotic prophylaxis was applied for 24 hours and Group B, antibiotic prophylaxis was applied for 48 hours. First generation of cephalosporin was administrated within 30 minutes prior skin incision or after cord clamping. The occurrence of postoperative infectious morbidity such as febrile morbidity, wound infection, endometritis, urinary track infection, pneumonia, sepsis and pelvic abscess and hospital stays were compared. RESULTS: There were 413 pregnant women enrolled and then randomized into 220 for group A and 197 for group B. No demographic differences were observed between two groups. The infectious morbidity was 1.9% (8/413) and wound infection was the most common postoperative infections morbidity. No significant difference was found between the groups for infectious morbidity and hospital stays. Also timing of prophylactic antibiotics did not result in significant difference for infectious morbidity. CONCLUSION: Short course of prophylactic antibiotics has been shown to be as efficacious as multidose of prophylactic antibiotics for preventing infectious morbidity in cesarean section and timing did not influence on infections morbidity. Further studies focusing on duration and timing of prophylactic antibiotics for cesarean section are needed.

Three cases of delivery in pregnant women with spinal cord injury / 대한산부인과학회지

Effective rehabilitation and assisted reproductive technology may increase the number of women considering pregnancy who have spinal cord injuries. It is important that obstetricians caring for these patients are aware of the specific problems related to spinal cord injuries. Autonomic dysreflexia is the most significant medical complication found in women with spinal cord injuries, and precautions should be taken to avoid stimuli that can lead to this potentially fatal complication. Women with spinal cord injuries may give birth vaginally, but when cesarean delivery is indicated, adequate anesthesia is needed. We report three cases of delivery in patients with spinal cord injury.

Prenatal diagnosis of the vein of Galen aneurysm: A case report / 대한산부인과학회지

The vein of Galen aneurysm is a rare vascular malformation but it can be detected by using conventional ultrasonography and diagnosed by using power Doppler ultrasonography. The prognosis of the vein of Galen aneurysm depends on congestive heart failure caused by cerebral shunt. Embolization at proper times can provide good outcome. We report a case of spontaneous delivery at 41 weeks of gestation by a 35-year-old woman presenting with a fetal vein of Galen aneurysm is described. The vein of Galen aneurysm was prenatally diagnosed by power Doppler ultrasonography and treated postnatally by embolization. This case is a report of successful prenatal diagnosis and postnatal management of the vein of Galen aneurysm.

Pregnancy outcomes of antenatally diagnosed congenital cystic adenomatoid malformation of lung / 대한산부인과학회지

OBJECTIVE: To determine the accuracy of antenatal diagnosis, pregnancy outcome and the predictors for adverse outcome in antenatally diagnosed congenital cystic adenomatoid malformation (CCAM). METHODS: A retrospective review was performed on a total of 32 patients with antenatally diagnosed CCAM between January, 1999 and June, 2008. RESULTS: Of 32 cases with antenatally diagnosed CCAM, 8 patients were lost to follow-up. In remaining 24 patients, postnatal histologic examination and/or radiologic study showed definitive diagnostic features of CCAM (n=20), pulmonary sequestration (n=3) and congenital lobar emphysema (n=1). The accuracy of antenatal diagnosis was 83.3% (20/24). The rate of presence of hydrops and/or ascites was 10% (2/20) in those with CCAM confirmed postnatally. Of the 2 patients with ascites and/or hydrops, thoraco-amniotic (TA) shunt was performed in one case with hydrops and termination was done in the other case. All of the 15 cases with ongoing pregnancy were delivered at term, except one with TA-shunt who was born at 33(+3) weeks of gestation (mean gestational age at birth+/-standard deviation; 39.6+/-2.2 weeks, mean birth weight; 3,200+/-500 gram). All 15 neonates were discharged alive without any complication. Antenatal sonographic microcystic lesion was associated with postnatal histologic type III lesion [5 type III lesions in 7 microcystitc cases (71.4%) vs. no type III lesion in 13 macrocystic cases (0%), P<0.01]. CONCLUSION: The incidence of ascites and/or hydrops was 10% (2/20) in fetuses with CCAM. Antenatally diagnosed CCAM has an excellent prognosis in the absence of signs of ascites and/or hydrops.

Efficacy of saline infusion sonography for the evaluation of the uterine cavity pathologies / 대한산부인과학회지

OBJECTIVE: To evaluate the efficacy of saline infusion sonography (SIS) for the evaluation of uterine cavity pathologies. METHODS: A total of 107 patients underwent hysteroscopy from June 2003 to October 2005 was included in this retrospective study. The mean age of the patients was 42.0+/-8.8 (range 28-62 years old). Two-dimensional ultrasonography (2D-USG) and SIS was performed in all patients prior to hysteroscopy. The findings obtained by 2D-USG and SIS were compared with the final diagnosis from hysteroscopy. RESULTS: The sensitivity and specificity of SIS were 70.0% and 96.1% for submucosal myomas, and 88.3% and 63.8% for endometrial polyps, respectively. In contrast, the sensitivity and specificity of 2D-USG were 53.3% and 93.5% for submucosal myomas, and 35.0% and 83.0% for endometrial polyps, respectively. The overall diagnostic accuracy of SIS was 88.8% for submucosal myomas and 77.6% for endometrial polyps. The corresponding figures for 2D-USG was 82.2% (p=0.9437) and 56.1% (p=0.9934), respectively. The diagnostic accuracy of 2D-USG and SIS for uterine cavity pathologies was 36.4% and 71.0% respectively. CONCLUSION: SIS raised the diagnostic accuracy for uterine cavity pathologies compared with 2D-USG only. SIS seems to be an acceptable and safe method to evaluate uterine cavity pathologies.

Genotoxicity and toxicological effects of acrylamide on reproductive system in male rats

The toxicity of acrylamide was evaluated through mutagenicity of Salmonella, chromosome aberration of Chinese hamster lung fibroblasts, micronucleus formation in mice and reproductive toxicity in rats. Based on Ames test, acrylamide showed mutagenic potency for strains TA98 and TA100. Moreover, both chromosomal aberration assay and micronucleus assay indicated that acrylamide might have genotoxic potency; the chromosomal aberration frequencies were observed to be proportional to acrylamide concentrations of 5-50 mM, and acrylamide significantly increased micronuclei in peripheral blood cells of mice at doses of higher than 72.5 mg/kg. Male rats were treated with acrylamide at doses of 0, 5, 15, 30, 45, or 60 mg/kg/day for 5 consecutive days, and the toxicity of acrylamide was observed. In the group treated with the highest dose of acrylamide (60 mg/kg/day), the loss of body weight and reduced testis weight were observed. Also the epididymides weights were reduced significantly in all the groups treated with acrylamide. The number of sperms in cauda epididymidis decreased significantly in an acrylamide dose-dependent manner. Rats treated with 60 mg/kg/day of acrylamide showed several histopathological lesions in the seminiferous tubules. There were thickening and multiple layering of the tubular endothelium, and the formation of many multinucleated giant cells in seminiferous tubules. Taken together, acrylamide not only causes the genotoxicity of eukaryotic cells and mice but also shows the toxicological effects on reproductive system in male rats.

A Case of Reconstruction of Utero-neovaginal Continuity / 대한산부인과학회잡지

Vaginal and cervical agenesis is an uncommon Mullerian anomaly. Total hysterectomy and vaginoplasty remains the classical treatment of this malformation. We present a case of reconstruction of utero-neovaginal continuity in the patient with normal functioning uterus and previously constructed neovagina by McIndoe method. She experienced two episodes of withdrawal bleeding during 2 months after surgery and fully satisfied with the results.

Identification of IgE-reacting Clonorchis sinensis antigens

Clonorchis sinensis is a liver fluke and it is the most prevalent human parasite in Korea at present. The parasite infection induces immune responses, characteristically an increased production of parasite-specific IgE in the host. Major IgE-reacting C. sinensis antigens in infected humans have been protein bands with MWs of 15, 28, 37, 45, 51, 56, 62, 66, 74, 97 and 160 KD identified by immunoblot analysis. Individual variations of the IgE binding pattern to C. sinensis antigens have also been documented. Using immune BALB/c mouse sera, IgE-reacting protein bands have been visualized with MWs of 28, 74, 86, 160 and several > 200 KD. One of the most strongly reacted C. sinensis antigenic proteins with a molecular weight of 28 KD was purified by gel filtration and preparative electrophoresis. Using a monoclonal antibody produced against the antigenic protein, the protein was localized in the parasite's intestine, and also found to be contained in excretory-secretory antigens.