Inhibitory effect of mangosteen peel and propolis ethanol extracts on alveolar bone loss against increased treatment amount of Porphyromonas gingivalis lipopolysaccharide in rat / 대한치과재료학회지

In previous studies, we introduced that mangosteen extract complex (MEC; ethanol extracts of Garcinia mangostana L. peel and propolis) had inhibitory effects on inflammation and alveolar bone loss in silk-ligature applied and Porphyromonas gingivalis lipopolysaccharide (LPS) induced periodontitis model in rats. This study was conducted to evaluate whether MEC had inhibitory effect of alveolar bone loss when a higher inflammatory state was induced by increasing the injection amount of P. gingivalis LPS by 20 times and increasing the treatment dose of MEC by twice the amount or maintaining MEC dose that used in the previous study. The data showed that alveolar bone loss was significantly reduced in the Lig+L+MEC 1:34 group (treated with mixture of 16 µg mangosteen peel extract powder and 544 µg propolis extract powder) and in the Lig+L+MEC 2:68 group (treated with mixture of 32 µg mangosteen peel extract powder and 1,088 µg propolis extract powder) by 24.3% and 28.9%, respectively. This result reveals that the mixture of MEC 1:34 could be useful in improving periodontal tissue health and may be able to be used as a therapeutic adjuvant for periodontitis.

Inhibitory effect of mangosteen peel and propolis ethanol extracts on alveolar bone loss against increased treatment amount of Porphyromonas gingivalis lipopolysaccharide in rat / 대한치과재료학회지

In previous studies, we introduced that mangosteen extract complex (MEC; ethanol extracts of Garcinia mangostana L. peel and propolis) had inhibitory effects on inflammation and alveolar bone loss in silk-ligature applied and Porphyromonas gingivalis lipopolysaccharide (LPS) induced periodontitis model in rats. This study was conducted to evaluate whether MEC had inhibitory effect of alveolar bone loss when a higher inflammatory state was induced by increasing the injection amount of P. gingivalis LPS by 20 times and increasing the treatment dose of MEC by twice the amount or maintaining MEC dose that used in the previous study. The data showed that alveolar bone loss was significantly reduced in the Lig+L+MEC 1:34 group (treated with mixture of 16 µg mangosteen peel extract powder and 544 µg propolis extract powder) and in the Lig+L+MEC 2:68 group (treated with mixture of 32 µg mangosteen peel extract powder and 1,088 µg propolis extract powder) by 24.3% and 28.9%, respectively. This result reveals that the mixture of MEC 1:34 could be useful in improving periodontal tissue health and may be able to be used as a therapeutic adjuvant for periodontitis.

Immunogenicity of a new, inactivated canine adenovirus type 2 vaccine for dogs

0.05). Dogs inoculated with the former vaccine developed a significantly higher immune titer than non-vaccinated dogs.CONCLUSION: The Cabopol-adjuvanted, inactivated CAV-2 vaccine was safe and induced a high VNA titer in dogs.

Clinical Manifestations and Risk Factors of Anaphylaxis in Pollen-Food Allergy Syndrome

PURPOSE: Many studies have reported that pollen-food allergy syndrome (PFAS) can cause anaphylaxis. No comprehensive investigations into anaphylaxis in PFAS have been conducted, however. In this study, we investigated the clinical manifestations and risk factors for anaphylaxis in PFAS in Korean patients with pollinosis. MATERIALS AND METHODS: Data were obtained from a nationwide cross-sectional study that previously reported on PFAS in Korean patients with pollinosis. Data from 273 patients with PFAS were collected, including demographics, list of culprit fruits and vegetables, and clinical manifestations of food allergy. We analyzed 27 anaphylaxis patients and compared them with patients with PFAS with oropharyngeal symptoms only (n=130). RESULTS: The most common cause of anaphylaxis in PFAS was peanut (33.3%), apple (22.2%), walnut (22.2%), pine nut (18.5%), peach (14.8%), and ginseng (14.8%). Anaphylaxis was significantly associated with the strength of sensitization to alder, hazel, willow, poplar, timothy, and ragweed (p<0.05, respectively). Multivariable analysis revealed that the presence of atopic dermatitis [odds ratio (OR), 3.58; 95% confidence interval (CI), 1.25–10.23; p=0.017]; sensitization to hazel (OR, 5.27; 95% CI, 1.79–15.53; p=0.003), timothy (OR, 11.8; 95% CI, 2.70–51.64; p=0.001), or ragweed (OR, 3.18; 95% CI, 1.03–9.87; p=0.045); and the number of culprit foods (OR, 1.25; 95% CI, 1.15–1.37; p<0.001) were related to the development of anaphylaxis in PFAS. CONCLUSION: The most common culprit foods causing anaphylaxis in PFAS were peanut and apple. The presence of atopic dermatitis; sensitization to hazel, timothy, or ragweed; and a greater number of culprit foods were risk factors for anaphylaxis in PFAS.

Pollen-Food Allergy Syndrome in Korean Pollinosis Patients: A Nationwide Survey

PURPOSE: Pollen-food allergy syndrome (PFAS) is an immunoglobulin E (IgE)-mediated allergy in pollinosis patients caused by raw fruits and vegetables and is the most common food allergy in adults. However, there has been no nationwide study on PFAS in Korea. In this study, we investigated the prevalence and clinical characteristics of PFAS in Korea. METHODS: Twenty-two investigators participated in this study, in which patients with allergic rhinoconjunctivitis and/or bronchial asthma with pollen allergy were enrolled. The questionnaires included demographic characteristics, a list of fruits and vegetables, and clinical manifestations of food allergy. Pollen allergy was diagnosed by skin prick test and/or measurement of the serum level of specific IgE. RESULTS: A total of 648 pollinosis patients were enrolled. The prevalence of PFAS was 41.7% (n = 270). PFAS patients exhibited cutaneous (43.0%), respiratory (20.0%), cardiovascular (3.7%) or neurologic symptoms (4.8%) in addition to oropharyngeal symptoms. Anaphylaxis was noted in 8.9% of the PFAS patients. Seventy types of foods were linked to PFAS; e.g., peach (48.5%), apple (46.7%), kiwi (30.4%), peanut (17.4%), plum (16.3%), chestnut (14.8%), pineapple (13.7%), walnut (14.1%), Korean melon (12.6%), tomato (11.9%), melon (11.5%) and apricot (10.7%). Korean foods such as taro/taro stem (8.9%), ginseong (8.2%), perilla leaf (4.4%), bellflower root (4.4%), crown daisy (3.0%), deodeok (3.3%), kudzu root (3.0%) and lotus root (2.6%) were also linked to PFAS. CONCLUSIONS: This was the first nationwide study of PFAS in Korea. The prevalence of PFAS was 41.7%, and 8.9% of the PFAS patients had anaphylaxis. These results will provide clinically useful information to physicians.

Influence of electrocautery-induced electromagnetic interference on quantitative electroencephalographic monitoring of hypnosis during general anesthesia: comparison between the ADMS® and the BIS VISTATM / 대한마취과학회지

BACKGROUND: Hypnosis monitors analyze small-amplitude electrical signals transmitted from the brain that could be exposed to the electromagnetic field that occurs around the body during electrocautery (ECT). We investigated the influence of ECT on hypnosis monitoring during anesthesia. METHODS: We simultaneously monitored BIS and uCON during 50 gynecologic oncology surgeries. During the episodes of ECT, we compared the absolute difference (a-Diff) between the baseline index and the most deviated index after ECT over either 30–60 s (ECT30–60) or more than 60 s (ECT > 60) between the monitors. We also investigated the bias and the limits of agreement between the monitors. RESULTS: Between the two monitors, the a-Diff of ECT30–60 was 1.4 ± 1.1 for the BIS, which was significantly greater than 0.6 ± 0.9 for the uCON (P = 0.003), and the a-Diff of ECT > 60 was 16.5 ± 8.2 for the BIS, which was also significantly greater than 1.4 ± 1.3 for uCON (P 60 was significantly greater than that during ECT30–60 (P 60 (P = 0.056). The estimated bias between the monitors was 6.3 ± 9.8 and 95% limits agreement was –12.3 to 25.0. CONCLUSIONS: Prolonged ECT intervention might lead to spurious estimations of quantitative EEG indexes. Therefore, hypnosis should be clinically assessed in combination with scrutinized judgment of relevant clinical symptoms and signs for hypnosis.

Long-term outcome of delayed neuropsychiatric sequelae after carbon monoxide poisoning

OBJECTIVE: Delayed neuropsychiatric sequelae (DNS) following carbon monoxide (CO) poisoning, which may result from a demyelinating leukoencephalopathy, is a disease with a poor prognosis. This study examined the factors affecting the long-term prognosis of DNS and the efficacy of hyperbaric oxygen therapy (HBOT) in patients with DNS. METHODS: This retrospective study included 84 patients with DNS following CO poisoning from January 2013 to June 2016. HBOT was given to 24 patients. The patients were divided into an improvement group and non-improvement group based on their clinical condition on a telephone interview at intervals between 3 months and 3 years after the onset of DNS. The improvement group was defined as having Cerebral Performance Category (CPC) scores in their daily life that improve to 1 or 2 grade. RESULTS: Of the 594 patients, DNS were found in 18.2%, and 70.2% (59 of 84) of the patients with DNS improved. The prognostic factors for the improvement of DNS were an age of 45 years or less (odds ratio [OR], 12.068; 95% confidence interval [CI], 2.393–60.858; P 0.1). CONCLUSION: Patients aged less than 45 years, low grade CPC score of 1 and 2, and lucid interval longer than 20 days are more likely to have a good prognosis. On the other hand, HBOT failed to produce a benefit for DNS patients.

Bacopa monnieri extract improves novel object recognition, cell proliferation, neuroblast differentiation, brain-derived neurotrophic factor, and phosphorylation of cAMP response element-binding protein in the dentate gyrus / 한국실험동물학회지

Bacopa monnieri is a medicinal plant with a long history of use in Ayurveda, especially in the treatment of poor memory and cognitive deficits. In the present study, we hypothesized that Bacopa monnieri extract (BME) can improve memory via increased cell proliferation and neuroblast differentiation in the dentate gyrus. BME was administered to 7-week-old mice once a day for 4 weeks and a novel object recognition memory test was performed. Thereafter, the mice were euthanized followed by immunohistochemistry analysis for Ki67, doublecortin (DCX), and phosphorylated cAMP response element-binding protein (CREB), and western blot analysis of brain-derived neurotrophic factor (BDNF). BME-treated mice showed moderate increases in the exploration of new objects when compared with that of familiar objects, leading to a significant higher discrimination index compared with vehicle-treated mice. Ki67 and DCX immunohistochemistry showed a facilitation of cell proliferation and neuroblast differentiation following the administration of BME in the dentate gyrus. In addition, administration of BME significantly elevated the BDNF protein expression in the hippocampal dentate gyrus, and increased CREB phosphorylation in the dentate gyrus. These data suggest that BME improves novel object recognition by increasing the cell proliferation and neuroblast differentiation in the dentate gyrus, and this may be closely related to elevated levels of BDNF and CREB phosphorylation in the dentate gyrus.

Biphasic augmentation of alpha-adrenergic contraction by plumbagin in rat systemic arteries

Plumbagin, a hydroxy 1,4-naphthoquinone compound from plant metabolites, exhibits anticancer, antibacterial, and antifungal activities via modulating various signaling molecules. However, its effects on vascular functions are rarely studied except in pulmonary and coronary arteries where NADPH oxidase (NOX) inhibition was suggested as a mechanism. Here we investigate the effects of plumbagin on the contractility of skeletal artery (deep femoral artery, DFA), mesenteric artery (MA) and renal artery (RA) in rats. Although plumbagin alone had no effect on the isometric tone of DFA, 1 µM phenylephrine (PhE)-induced partial contraction was largely augmented by plumbagin (ΔT(Plum), 125% of 80 mM KCl-induced contraction at 1 µM). With relatively higher concentrations (>5 µM), plumbagin induced a transient contraction followed by tonic relaxation of DFA. Similar biphasic augmentation of the PhE-induced contraction was observed in MA and RA. VAS2870 and GKT137831, specific NOX4 inhibitors, neither mimicked nor inhibited ΔT(Plum) in DFA. Also, pretreatment with tiron or catalase did not affect ΔT(Plum) of DFA. Under the inhibition of PhE-contraction with L-type Ca²⁺ channel blocker (nifedipine, 1 µM), plumbagin still induced tonic contraction, suggesting Ca²⁺-sensitization mechanism of smooth muscle. Although ΔT(Plum) was consistently observed under pretreatment with Rho A-kinase inhibitor (Y27632, 1 µM), a PKC inhibitor (GF 109203X, 10 µM) largely suppressed ΔT(Plum). Taken together, it is suggested that plumbagin facilitates the PKC activation in the presence of vasoactive agonists in skeletal arteries. The biphasic contractile effects on the systemic arteries should be considered in the pharmacological studies of plumbagin and 1,4-naphthoquinones.

Development and Evaluation of an Integrative Palliative Care Scale for Cancer Patients / 한국간호교육학회지

PURPOSE: This study was done to develop and to evaluate an integrative palliative care scale for cancer patients. METHODS: The process included construction of a conceptual framework, generation of initial items, verification of content validity, selection of secondary items, preliminary study, and extraction of final items. The participants were 173 cancer patients in Daegu and Gyeongbuk. Item analysis, factor analysis, criterion related validity, and internal consistency were used to analyze the data. RESULTS: Eighteen items were selected for the final scale, and categorized into 3 factors explaining 58.3% of total variance. The factors were labeled as social/environmental palliative care (9 items), psychological palliative care (4 items), and physical palliative care (3 items), and spiritually palliative care (2 items). The scores for the scale were significantly correlated with the quality of life of cancer patients. Cronbach's alpha coefficient for the 18 items was .88. CONCLUSION: The above findings indicate that the integrative palliative care scale has good validity and reliability when used for cancer patients.

Association Between Sensitization to Mold and Impaired Pulmonary Function in Children With Asthma

PURPOSE: Recent data indicate that sensitization to mold contributes to the severity and persistence of asthma. In this study, we investigated the relationships between sensitization to mold and lung function parameters in children with asthma. METHODS: We retrospectively reviewed clinical data from 551 asthmatic subjects. We selected subjects who met clinical diagnostic criteria of asthma. Their spirometry, methacholine challenge tests, and measurements of blood eosinophils, serum IgE, eosinophil cationic protein (ECP) and fractional exhaled nitric oxide (FeNO) results were included. Skin prick testing (SPT) results with 13 common aeroallergens in Korea including house dust mites, animal dander, pollen, cockroach and mold were reviewed. Subjects were divided into 3 groups according to their SPT results. Subjects who showed no positive result to any aeroallergen were designated as group 1 (non-sensitized). Group 2 represented subjects who were sensitized to aeroallergens other than mold (other allergen-sensitized) and group 3 included subjects who were sensitized to mold allergens (mold-sensitized). RESULTS: Among the 551 asthmatic subjects, 67 (12.2%) were sensitized to mold and 366 (66.4%) were sensitized to other aeroallergens. The log mean IgE levels were higher in groups 2 (5.96±1.14 IU/mL) and 3 (5.81±0.97 IU/mL) compared to group 1 (3.88±1.68 IU/mL). Blood eosinophils, ECP and FeNO concentrations were significantly higher in groups 2 and 3, but no significant difference was found between the 2 groups. The mean FEV1 value was significantly lower in group 3 (86.9±12.1%pred) than in groups 2 (92.0±14.8%pred) and 1 (93.4±15.4%pred). The log mean methacholine PC20 was significantly lower in group 3 (0.08±1.91 mg/mL) than in groups 2 (1.31±1.69 mg/mL) and 1 (2.29±1.66 mg/mL). CONCLUSIONS: We observed a differential association between mold and other aeroallergen sensitization, and severity of asthma. Sensitization to mold is associated with lower lung function and increased airway hyper-responsiveness in children with asthma. Mold sensitization could be an important factor determining asthma severity particularly airflow limitation in children.

Severe Endobronchial Inflammation Induced by Aspiration of a Ferrous Sulfate Tablet / 결핵및호흡기질환

Iron supplements such as ferrous sulfate tablets are usually used to treat iron-deficiency anemia in some elderly patients with primary neurologic disorders or decreased gag reflexes due to stroke, senile dementia, or parkinsonism. While the aspiration of ferrous sulfate is rarely reported, it is a potentially life-threatening condition that can lead to airway necrosis and bronchial stenosis. A detailed history and high suspicion of aspiration are required to avoid delays in diagnosis and treatment. The diagnosis can be confirmed by bronchoscopic examination and a tissue biopsy. Early removal of the aspirated tablet prevents acute complications, such as bronchial necrosis, hemoptysis, and lobar consolidation. Tablet removal is also necessary to prevent late bronchial stenosis. We presented the first case in Korea of a ferrous sulfate tablet aspiration that induced severe endobronchial inflammation.

H2 Receptor-Mediated Relaxation of Circular Smooth Muscle in Human Gastric Corpus: the Role of Nitric Oxide (NO)

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, K+ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, N(G)-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the H2 receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through H2 receptor and NO/sGC pathways.

An Integrative Review on Nursing Studies Related to Humor

PURPOSE: The purpose of this paper was to describe the attributes of nursing with humor based on an integrative review and to present basic information for developing humor intervention programs for children. METHODS: Using combinations of the terms 'nursing' and 'humor' as key words, the researchers searched four electronic databases to relevant identify studies. Thirteen studies were selected through full text screening of related research published in academic journals from January 1993 to April 2013. RESULTS: Through in-depth discussion and investigation of the relevant literature, three components emerged; 1) using instruments of coping for stress relief, 2) symptoms relief through pleasant feeling, and 3) job satisfaction and work improvement of nurse using humor. CONCLUSION: The results of this study suggest that humor is valuable as a nursing intervention for children and the possibility of bringing about positive results in nursing care if nurses utilize the sense of humor as fully as they can. Therefore, it is critical for nurses to develop a diversity of humor interventions for children as well as measurements to test quality and quantity of humor used in clinical pediatric settings.

Relationships Between Exhaled Nitric Oxide and Atopy Profiles in Children With Asthma

PURPOSE: We examined whether fractional exhaled nitric oxide (FeNO) levels are associated with atopy profiles in terms of mono-sensitization and poly-sensitization in asthmatic children. METHODS: A total of 119 children underwent an assessment that included FeNO measurements, spirometry, methacholine challenge, and measurement of blood eosinophil count, serum total IgE, and serum eosinophil cationic protein (ECP). We also examined sensitization to five classes of aeroallergens (house dust mites, animal danders, pollens, molds, and cockroach) using skin prick testing. The children were divided into three groups according to their sensitization profiles to these aeroallergens (non-sensitized, mono-sensitized, and poly-sensitized). RESULTS: The geometric means (range of 1 SD) of FeNO were significantly different between the three groups (non-sensitized, 18.6 ppb [10.0-34.7 ppb]; mono-sensitized, 28.8 ppb [16.6-50.1 ppb]; and poly-sensitized, 44.7 ppb [24.5-81.3 ppb], P=0.001). FeNO levels were correlated with serum total IgE concentrations, peripheral blood eosinophilia, and serum ECP levels to different degrees. CONCLUSIONS: FeNO levels vary according to the profile of atopy, as determined by positive skin prick test results to various classes of aeroallergens. FeNO is also moderately correlated with serum total IgE, blood eosinophilia, and serum ECP. These results suggest that poly-sensitized asthmatic children may have the highest risk of airway inflammation.

High K(+)-Induced Relaxation by Nitric Oxide in Human Gastric Fundus

This study was designed to elucidate high K(+)-induced relaxation in the human gastric fundus. Circular smooth muscle from the human gastric fundus greater curvature showed stretch-dependent high K+ (50 mM)-induced contractions. However, longitudinal smooth muscle produced stretch-dependent high K(+)-induced relaxation. We investigated several relaxation mechanisms to understand the reason for the discrepancy. Protein kinase inhibitors such as KT 5823 (1 microM) and KT 5720 (1 microM) which block protein kinases (PKG and PKA) had no effect on high K(+)-induced relaxation. K+ channel blockers except 4-aminopyridine (4-AP), a voltage-dependent K+ channel (KV) blocker, did not affect high K(+)-induced relaxation. However, N(G)-nitro-L-arginine and 1H-(1,2,4)oxadiazolo (4,3-A)quinoxalin-1-one, an inhibitors of soluble guanylate cyclase (sGC) and 4-AP inhibited relaxation and reversed relaxation to contraction. High K(+)-induced relaxation of the human gastric fundus was observed only in the longitudinal muscles from the greater curvature. These data suggest that the longitudinal muscle of the human gastric fundus greater curvature produced high K(+)-induced relaxation that was activated by the nitric oxide/sGC pathway through a KV channel-dependent mechanism.

Effect of an abdominal obesity management program on dietary intake, stress index, and waist to hip ratio in abdominally obese women: Focus on comparison of the WHR decrease and WHR increase groups

This study was conducted to evaluate the effects of an abdominal obesity management program on dietary intake, stress index, and waist to hip ratio (WHR) in abdominally obese women. The subjects were 195 adult abdominally obese women (WHR > or = 0.80) who had been participating in a nutrition education (total of nine times) and dietary habits and life style modification programs (total of six times) for 12 weeks. The abdominal obesity management program focused on the nutrition provided by breakfast, lunch, and dinner, proper dietary habits, and practices to improve life style. The subjects were divided into a WHR decrease group and a WHR increase group according to changes in the WHR. Daily nutrient intake was assessed with a 3-day food record, body measurements and blood vessel age, stress index, and a health index that were measured at baseline and after 12 weeks. After the intervention, weight, waist circumference, hip circumference, WHR, and body mass index (BMI) decreased significantly in the WHR decrease group. Energy intake increased from 1486.2 kcal to 1541.4 kcal with a significant improvement in nutrient density for animal protein, total fat, animal fat, fiber, calcium, phosphorus, zinc, vitamin B6, vitamin C, vitamin E, and saturated fatty acids in the WHR decrease group. Additionally, dietary diversity increased significantly in the WHR decrease group compared to that in the WHR increase group. The WHR decrease group showed a significant improvement in the stress and health indices. Changes in WHR were correlated with changes in nutrient intake (animal protein, total fat, animal fat, plant fat, fiber, calcium, iron, potassium, vitamin A, vitamin B2, vitamin B6, vitamin C, and folate) and medical index profiles (stress and indices) adjusted for age, birth status, baseline BMI, and baseline WHR. These results show that an abdominal obesity management program was effective not only for reducing the WHR but also to improve dietary intake and the stress index in abdominally obese women.

Requirement of Pretone by Thromboxane A2 for Hypoxic Pulmonary Vasoconstriction in Precision-cut Lung Slices of Rat

Hypoxic pulmonary vasoconstriction (HPV) is physiologically important response for preventing mismatching between ventilation and perfusion in lungs. The HPV of isolated pulmonary arteries (HPV-PA) usually require a partial pretone by thromboxane agonist (U46619). Because the HPV of ventilated/perfused lungs (HPV-lung) can be triggered without pretone conditioning, we suspected that a putative tissue factor might be responsible for the pretone of HPV. Here we investigated whether HPV can be also observed in precision-cut lung slices (PCLS) from rats. The HPV in PCLS also required partial contraction by U46619. In addition, K+ channel blockers (4AP and TEA) required U46619-pretone to induce significant contraction of PA in PCLS. In contrast, the airways in PCLS showed reversible contraction in response to the K+ channel blockers without pretone conditioning. Also, the airways showed no hypoxic constriction but a relaxation under the partial pretone by U46619. The airways in PCLS showed reliable, concentration-dependent contraction by metacholine (EC50, ~210 nM). In summary, the HPV in PCLS is more similar to isolated PA than V/P lungs. The metacholine-induced constriction of bronchioles suggested that the PLCS might be also useful for studying airway physiology in situ.

Ginkgo biloba extract (GbE) enhances the anti-atherogenic effect of cilostazol by inhibiting ROS generation

In this study, the synergistic effect of 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3,4-dihydro-2(1H)-quinolinone (cilostazol) and Ginkgo biloba extract (GbE) was examined in apolipoprotein E (ApoE) null mice. Co-treatment with GbE and cilostazol synergistically decreased reactive oxygen species (ROS) production in ApoE null mice fed a high-fat diet. Co-treatment resulted in a significantly decreased atherosclerotic lesion area compared to untreated ApoE mice. The inflammatory cytokines and adhesion molecules such as monocyte chemoattractant-1 (MCP-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and VCAM-1 which can initiate atherosclerosis were significantly reduced by the co-treatment of cilostazol with GbE. Further, the infiltration of macrophages into the intima was decreased by co-treatment. These results suggest that co-treatment of GbE with cilostazol has a more potent anti-atherosclerotic effect than treatment with cilostazol alone in hyperlipidemic ApoE null mice and could be a valuable therapeutic strategy for the treatment of atherosclerosis.

Nitric Oxide-mediated Relaxation by High K+ in Human Gastric Longitudinal Smooth Muscle

This study was designed to elucidate high-K+induced response of circular and longitudinal smooth muscle from human gastric corpus using isometric contraction. Contraction from circular and longitudinal muscle stripes of gastric corpus greater curvature and lesser curvature were compared. Circular smooth muscle from corpus greater curvature showed high K+ (50 mM)-induced tonic contraction. On the contrary, however, longitudinal smooth muscle strips showed high K+ (50 mM)-induced sustained relaxation. To find out the reason for the discrepancy we tested several relaxation mechanisms. Protein kinase blockers like KT5720, PKA inhibitor, and KT5823, PKG inhibitor, did not affect high K+-induced relaxation. K+ channel blockers like tetraethylammonium (TEA), apamin (APA), glibenclamide (Glib) and barium (Ba2+) also had no effect. However, N(G)-nitro-L-arginine (L-NNA) and 1H-(1,2,4) oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC) and 4-AP (4-aminopyridine), voltage-dependent K+ channel (KV) blocker, inhibited high K+-induced relaxation, hence reversing to tonic contraction. High K+-induced relaxation was observed in gastric corpus of human stomach, but only in the longitudinal muscles from greater curvature not lesser curvature. L-NNA, ODQ and KV channel blocker sensitive high K+-induced relaxation in longitudinal muscle of higher portion of corpus was also observed. These results suggest that longitudinal smooth muscle from greater curvature of gastric corpus produced high K+-induced relaxation which was activated by NO/sGC pathway and by KV channel dependent mechanism.