ADAM10 inhibits the interaction between IL-17 and HMGB1 in Buerger's disease.

OBJECTIVE: Buerger's disease is a rare disease that causes critical limb ischemia; however, the underlying pathophysiological mechanism remains unclear. Therefore, we investigated the interaction between interleukin (IL)-17 and high-mobility group protein B 1 (HMGB1) and determined whether A disintegrin and metalloproteinase 10 (ADAM10) inhibit this interaction. PATIENTS AND METHODS: The study population included 15 patients with Buerger's disease and 10 healthy donors without a history of giving peripheral blood samples. Cytokine levels were measured using a luminex multiplex assay in plasma. Flow cytometry was used to analyze the subtypes of helper T (Th) cells among peripheral blood mononuclear cells (PBMCs). The effect of ADAM10 on PBMCs was analyzed in vitro. RESULTS: The levels of inflammatory cytokines and production of pathogenic Th cells were found to be higher in Korean patients with Buerger's disease. IL-17 treatment induced HMGB1 associated molecules. HMGB1 also induced IL-17 and Th17 associated transcription factors in Buerger's patients. We observed that ADAM10 regulates the interaction between IL-17 and HMGB1 via advanced glycation end products (RAGE)/nuclear factor-kappa B (NF-kB) pathway in patients with Buerger's disease. CONCLUSIONS: This study suggests that IL-17 and HMGB1 cytokines contribute to the pathogenesis of Buerger's disease. These results indicate that ADAM10 alleviates inflammation in Buerger's disease via the HMGB1 and RAGE/NF-κB signaling pathway and provides insights into the molecular basis of and a potential therapeutic strategy for Buerger's disease.

Association of hypertension with small, dense low-density lipoprotein in patients without metabolic syndrome.

A higher proportion of small, dense low-density lipoprotein (sdLDL) is known to be associated with a high prevalence of cardiovascular disease in association with metabolic syndrome (MS). Hypertension (HTN) is one of the known risk factors for MS. However, whether HTN is associated with sdLDL in patients without MS is not yet clear. The lipid profiles, including low-density-lipoprotein (LDL) subfractions, of 383 consecutive subjects were evaluated. The patients without MS consisted of 198 hypertensive patients (non-MS/HTN group) and 108 normotensive subjects (non-MS/non-HTN group). The peak and mean particle diameter of LDL were measured by gradient gel electrophoresis. Plasma total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride (TG), HDL cholesterol/Apo A1, LDL-C/ApoB and Apo(A1, B, CII and E) levels did not differ between the non-MS/non-HTN and non-MS/HTN groups. When analyzing LDL subfraction, the absolute amount of patterns A and B was not different between the non-MS/non-HTN and non-MS/HTN groups. Compared with the non-MS/non-HTN groups, the proportion of sdLDL was higher in the non-MS/HTN group (37.7% versus 39.9%, P=0.046), but not significant after adjustment of waist circumference, serum TG, age and statin usage. The proportion of sdLDL to total LDL was higher in hypertensive subjects, even those without MS, than in normotensive subjects. However, this difference of LDL subfraction in hypertensive patients is associated with higher waist circumference, higher serum TG, older age and more statin usage. This result suggests that HTN may contribute to atherosclerosis and endothelial dysfunction with associated risk factors that influence LDL size.

Prevalence of hepatic parasites in Korean wild rats (Rattus norvegicus) and their association with pulmonary arteriolar medial hypertrophy.

C hepatica, an important zoonotic parasite, and C fasciolaris are common parasites in rodents. In rodent livers, C hepatica causes sequential morphologic changes that are designated as early, intermediate, or late phase, and C fasciolaris forms cysts surrounded by fibroplasia and granulomatous inflammation. The present study describes the prevalence of these parasites and associated liver and lung lesions in wild rats (Rattus norvegicus) living around pig farms in South Korea. Selected parenchymal organs, including liver and lung, of 89 wild rats were examined. Of 89 rats, 28 (31.5%) were infected with either C hepatica or C fasciolaris or with both parasites. Severe medial hypertrophy of small arterioles was observed in the lungs of 11 of the 28 parasite-infected rats (P < .01). The pulmonary arteriolar hypertrophy in the rats infected with C hepatica was strongly associated with early and/or intermediate phases (88.8%) of morphologic change in the livers (P < .01). As such, this report is the first to suggest a significant association between parasite-induced hepatitis and pulmonary arteriolar hypertrophy in rodents. Further studies are warranted for the use of C hepatica-infected rats as an animal model to explore the underlying mechanisms of portopulmonary hypertension in humans.

Impact of hypertension on coronary artery spasm as assessed with intracoronary acetylcholine provocation test.

Both hypertension and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS is expected in hypertensive patients. We evaluated the impact of hypertension on CAS with intracoronary acetylcholine (ACh) provocation test. A total of 986 patients (685 hypertensive patients vs 301 normotensive patients) who underwent coronary angiography with ACh provocation test were enrolled. ACh was injected into the left coronary artery in incremental doses of 20, 50 and 100 microg min(-1). Significant CAS was defined as a transient >70% luminal narrowing with concurrent chest pain and/or ST-segment changes. Although the incidences of significant ACh-induced CAS were similar between hypertensive and normotensive patients (35.8 vs 39.2%, P=0.303), multivariate logistic analysis showed that hypertension was negatively associated with ACh-induced CAS (odds ratio: 0.70, 95% confidence interval: 0.51-0.94, P=0.020). The angiographic characteristics of ACh-induced CAS were similar between these two groups. Subgroup analysis regarding the impact of the status of blood pressure control on CAS showed that hypertensive patients with controlled blood pressure had a significantly higher incidence of CAS than those with uncontrolled blood pressure (45.2 vs 27.9%, P<0.001), and that uncontrolled blood pressure was negatively associated with ACh-induced CAS (odds ratio: 0.56, 95% confidence interval: 0.40-0.79, P=0.001). In conclusion, despite the expected endothelial dysfunction, hypertension and uncontrolled blood pressure are negatively associated with CAS, suggesting that the mechanisms and risk factors of CAS may be significantly different from those of coronary artery disease.

Probability of stroke in Korean hypertensive patients visiting community-based hospitals: using a risk profile from the Framingham study.

Hypertension is the most important single modifiable risk factor of stroke. The purpose of this study was to investigate the distribution patterns of risk factors of stroke and 10-year probability of stroke in hypertensive patients visiting community-based hospitals. A total of 1088 hypertensive patients who visited 61 community-based hospitals nationwide were enrolled. Risk factors of stroke were evaluated using a series of laboratory tests and physical examinations, and the 10-year probability of stroke was determined by applying the Framingham stroke risk equation. The proportion of patients who have uncontrolled hypertension despite the use of antihypertensives was 63.3% (59.6% women, 68.7% men; P=0.006). The average 10-year probability of stroke in hypertensive patients was 16.05% (14.68% women, 17.99% men; P<0.001). The 10-year probability of stroke in patients with hypertension gradually increased in proportion to age. In patients treated with antihypertensives, 10-year probability of stroke gradually increased in proportion to blood pressure. The 10-year risk of stroke in hypertensive patients was approximately 4.6 times higher than that of stroke in the general population. In conclusion, as the 10-year risk of stroke in hypertensive patients was approximately 4.6 times higher than that of stroke in the general population, more aggressive interventions are needed to reduce blood pressure and stroke risk in hypertensive patients.

Myocardial bridging is related to endothelial dysfunction but not to plaque as assessed by intracoronary ultrasound.

BACKGROUND: Myocardial bridge (MB) is characterised by focal compression of a coronary artery in systole by an overlying band of myocardium. Chronic compression and relaxation of the MB may produce endothelial dysfunction by direct stress. OBJECTIVE: To determine whether MB alters endothelial function, thus influencing the plaque formation. METHODS: 128 patients (mean (SD) age 54.7 (10.9) years, 56 men) with typical angiographic systolic milking effects and >30% reduction in diameter of the coronary artery during systole after intracoronary nitrate (glyceryl trinitrate, 200 mug) infusion were studied. 231 control patients (mean (SD) age 52.9 (12.1) years, 111 men) without overt coronary artery disease including MB were also studied. Endothelial function was estimated by incremental acetylcholine (Ach) infusion into the left coronary ostium. Intracoronary ultrasound assessments were obtained in 74/128 patients with MB and 81/231 controls. RESULTS: The mean (SD) vasoconstrictive response to maximal Ach was more pronounced at the bridging segments than at matched segments in controls (-71.9 (14.9) vs -30.3 (22.6), p = 0.009). Coronary vasoconstriction (>50%) to Ach was seen more often in the MB group than in controls (114/128 (89.1%) vs 81/231 (35.1%), p = 0.007). No significant correlation was found between the severity of MB and vasoconstriction in response to Ach. A typical half-moon phenomenon was seen in 71/74 (95.9%) cases of the MB group, but not in controls (p<0.001). Plaques at the bridging segments were absent in 67/74 (90.5%) and mild in 7/74 (9.5%) cases, as compared with those of matched segments of the left anterior descending coronary artery in controls (plaque burden 5.91 (1.37)% vs 24.71 (24.21)%, p = 0.002). CONCLUSION: Despite the prominent relationship between MB and endothelial dysfunction, bridging segments are spared from atherosclerotic plaque formation.

Relationship between blood pressure parameters and pulse wave velocity in normotensive and hypertensive subjects: invasive study.

Blood pressure (BP) is one of the most important contributing factors to pulse wave velocity (PWV), a classic measure of arterial stiffness. Although there have been many non-invasive studies to show the relation between arterial stiffness and BP, the results are controversial. The aim of this study is to evaluate the role of BP as an influencing factor on PWV using invasive method. We observed 174 normotensive and untreated hypertensive subjects using coronary angiography. Arterial stiffness was assessed through aorto-femoral PWV by foot-to-foot velocity method using fluid-filled system. And BP was measured by pressure wave at the right common femoral artery. From univariate analysis, age, diabetes mellitus (DM), hypertension, waist, waist-to-hip ratio, total cholesterol-to-high-density lipoprotein cholesterol ratio, systolic BP (SBP), pulse pressure (PP) and mean arterial pressure (MAP) showed significant association with PWV. To avoid multiple colinearity among SBP, PP and MAP, we performed multiple regression analysis predicting PWV thrice. Age, DM and each BP were significantly and consistently correlated to PWV. In the first and third modules, compared to age, SBP and MAP were less strong predictors, respectively. However, PP was the stronger predictor than age and DM in the second module. Lastly, we simultaneously forced MAP and PP with other variables in the fourth multivariate analysis. Age, DM and PP remained significantly correlated with PWV, but the significance of MAP was lost. This is the first invasive study to suggest that PP has the strongest correlation with PWV among a variety of BP parameters.

A study of NH3-N and P refixation by struvite formation in hybrid anaerobic reactor.

This research is concerned with the removal of ammonia nitrogen and phosphorus in foodwaste by crystallization. Reductions have been achieved by struvite formation after the addition of magnesium ions (Mg2+). Magnesium ions used in this study were from magnesium salts of MgCl2. The results of our analysis using scanning electron microscopy and energy dispersive X-ray analysis showed that the amount of struvite in precipitated sludge grew enough to be seen with the naked eye (600-700 microm). EDX analysis also showed that the main components of the struvite were magnesium and phosphorus. NH3-N removal efficiency using MgCl2 was 67% while PO4-P removal efficiency was 73%. It was confirmed that nitrogen and phosphorus could be stabilized and removal simultaneously through anaerobic digestion by Mg, NH3 and PO4-P, which were necessary for struvite formation.

Adjuvanted subunit vaccines for the control of Salmonella enteritidis infection in turkeys.

Liposomes and immunostimulating complexes (ISCOM) are adjuvants that have been known to potentiate the immune response to membrane proteins. Adjuvanted outer membrane proteins (OMP) from Salmonella enteritidis were evaluated for their protective efficacy against S enteritidis infection in turkeys. The adjuvanted vaccines prepared for evaluation were: positive or negatively charged liposomes, lipid-conjugated ISCOM, and mineral oil vaccines. These preparations were compared with that of a whole cell bacterin and protein alone. After vaccination, turkeys were challenge-exposed with a nalidixic acid-resistant strain of S enteritidis. They were monitored for clinical signs of disease, antibody response, bacterial shedding pattern, and clearance of the challenge S enteritidis from internal organs. Results indicated a significantly (P < 0.05) higher antibody response to the positively charged liposomal OMP vaccine, compared with the whole cell bacterin. The antibody response to positively charged liposomal OMP vaccine was greater when a booster dose of this preparation was given. Shedding of S enteritidis was decreased in all vaccinated and challenge-exposed turkeys (P < 0.001). The tissues from a high percentage (90 to 100%) of birds that received a booster vaccination of the liposomal (+ or -) and ISCOM vaccine were culture-negative for S enteritidis.

Pathogenesis of hemorrhagic enteritis virus infection in turkeys.

The pathogenesis of hemorrhagic enteritis was investigated in 4-week-old specific-pathogen-free (SPF) turkeys after oral administration of hemorrhagic enteritis virus. The virus antigen was detected and quantified in tissues at various days post-infection (DPI) by an avidin-biotin-enhanced enzyme immunoassay and was located by a monoclonal antibody-based immunoperoxidase (IP) staining technique. In the intestinal tract, low levels of viral antigen were detected from 1 to 3 and 9 to 15 DPI, whereas high antigen levels were found from 4 to 7 DPI. The bursa had viral antigen from 2 to 7 DPI. The plasma fraction of blood was positive for the antigen at day 1 PI and the cellular fraction of blood on day 3 PI. Antigen was first detected in the spleen at 2 DPI and reached a peak on day 6 PI. Initially, the viral antigen was present in a few reticular cells of the spleen and an increase in IP positive cells occurred with time. The maximum number of inclusion bodies in the spleen were found on day 6 PI. Following splenomegaly, viremia resulted in high levels of the virus appearing in the lamina propria of the small intestine. The lamina propria had numerous lymphoreticular cells positive for intranuclear viral inclusions from 5-7 DPI. It was at this time that intestinal congestion and hemorrhage were seen. The results suggest that HEV replicates first in the lymphoid cells of intestinal tract including the bursa, and then in those of the spleen with consequent HEV antigen widely distributed in the body. The time course of the high levels of HEV (mainly 4-7 DPI) in the lymphoid organs (cells), and occurrence of hemorrhagic enteritis (congestion, hyperemia) from 5 to 7 DPI and intestinal hemorrhage (5-8 DPI) appear to suggest that the intestinal lesion may be an immune-mediated response.