Purpose: Coronary artery spasm (CAS) and diabetes mellitus (DM) are implicated in endothelial dysfunction, and insulin resistance (IR) is a major etiological cause of type 2 DM. However, the association between CAS and IR in non-diabetic individuals has not been elucidated. The aim of the present study was to evaluate the impact of IR on CAS in patients without DM. Materials and Methods: A total of 330 eligible patients without DM and coronary artery disease who underwent acetylcholine (Ach) provocation test were enrolled in this study. Inclusion criteria included both hemoglobin A1c <6.0% and fasting glucose level <110 mg/dL without type 2 DM. Patients were divided into quartile groups according the level of homeostasis model assessment of insulin resistance (HOMA-IR): 1Q (n=82; HOMA-IR<1.35), 2Q (n=82; $1.35{\leq}HOMA-IR<1.93$), 3Q (n=83; $1.93{\leq}HOMA-IR<2.73$), and 4Q (n=83; $HOMA-IR{\geq}2.73$). Results: In the present study, the higher HOMA-IR group (3Q and 4Q) was older and had higher body mass index, fasting blood glucose, serum insulin, hemoglobin A1c, total cholesterol, and triglyceride levels than the lower HOMA-IR group (1Q). Also, poor IR (3Q and 4Q) was considerably associated with frequent CAS. Compared with Q1, the hazard ratios for Q3 and Q4 were 3.55 (95% CI: 1.79-7.03, p<0.001) and 2.12 (95% CI: 1.07-4.21, p=0.031), respectively, after adjustment of baseline risk confounders. Also, diffuse spasm and accompanying chest pain during Ach test were more strongly associated with IR patients with CAS. Conclusion: HOMA-IR was significantly negatively correlated with reference diameter measured after nitroglycerin and significantly positively correlated with diffuse spasm and chest pain.
[Purpose] The purpose of this study was to assess changes in blood glucose level, blood pressure, and arterial stiffness after a 75 g oral glucose tolerance test (OGTT) in elderly women aged over 65 years with hypertension and either normal glycemic control, impaired fasting glucose tolerance, or diabetes mellitus. We also wished to investigate the relationship between stages of diabetes and physical fitness. [Methods] A total of 24 elderly women with hypertension were assigned to a control group (CON; n=7), impaired fasting glucose group (IFG; n=9), and diabetes mellitus group (DM; n=8). In each group, blood glucose level, brachial ankle pulse wave velocity (PWV), and blood pressure were measured at baseline as well as 60 and 120 minutes after a 75 g OGTT. Physical fitness factors such as hand grip strength, balance test, 4 m gait speed test, chair stand test, short physical performance battery, and 6-minute walking test were subsequently assessed. [Results] In all three groups, blood glucose levels were significantly increased at 60 and 120 minutes after a 75 g OGTT. In the DM group, blood glucose levels were significantly higher before and after a 75 g OGTT than in the CON group. In the CON group, PWV was significantly increased at 60 minutes after a 75 g OGTT; however, there were no changes in other groups after glucose ingestion. In the CON group, systolic and diastolic blood pressures were significantly decreased at 60 and 120 minutes after a 75 g OGTT compared to baseline. However, there was no change in blood pressure after ingestion in the DM group. The IFG group had greater grip strength than the CON group; however, there were no differences in other variables between the groups. [Conclusion] After a 75 g OGTT, elderly women with hypertension and diabetes maintain higher blood glucose levels compared to those with hypertension alone. Unlike elderly women with hypertension alone, those with hypertension and diabetes did not show changes in arterial stiffness and blood pressure after a 75 g OGTT. Therefore, elderly women with hypertension and diabetes may not be able to control their blood vessels following a 75 g OGTT due to impaired vascular endothelial function. Moreover, there was no association between diabetes stage and physical fitness in elderly women with hypertension.
Polymorphonuclear leukocytes(PMN) are the predominant inflammatory cells recruited in acute lung injury such as adult respiratory distress syndrome, pneumonia and also chronic lung disease such as idiopathic pulmonary fibrosis and pulmonary emphysema. Interleukin-8(IL-8) is an 8,000 D protein produced by many cells and has potent neutrophil chemoattractant and activating properties. The GRO, also called melanoma growth-stimulatory activity(MGSA), referring to a peptide of 73 amino acids, was reported to be mitogenic for cultured human melanoma cells. Mature GRO/MGSA has marked sequence similarity to IL-8. In view of the structural similarities to IL-8, it was of particular interest to test GRO for neutrophil activating and chemotactic properties. We found a significant release of IL-8 and GRO/MGSA from the cultured human umbilical vein endothelial cell(HUVEC) which was stimulated either with TNF$\alpha$ or IL-1$\beta$ and also found the expression of IL-8 and GRO/MGSA mRNA. Neutrophil chemotactic activity was enhanced in accordance with the increased IL-8 and GRO/MGSA. Our study also suggest that the IL-8 is more important in the increased neutrophil chemotactic activity than GRO/MGSA when endothelial cell is stimulated with TNF$\alpha$ or IL-1$\beta$ in vitro.
Objective: To explore the inhibiting effect and mechanism of Endostar injection concomitant with cryoablation on lung adenocarcinoma A549 xenografts in nude mice. Materials and Methods: A total of 24 nude mice with subcutaneous xenografts of the A549 cell line were established and divided into 4 groups when the maximal diameters of tumors became 1 cm: control group, Endostar group, cryoablation group and combination group (Endostar concomitant with cryoablation). The nude mice were sacrificed after 21-days treatment, tumour tissues were removed to measure their volume, in situ test of TdT-mediated dUTP nick end labeling (TUNEL) was adopted to determine the cellular apoptosis around freezing injury zones, and immunohistochemical SP test was applied for the detection of micro-vessel density (MVD) and vascular endothelial growth factor (VEGF) expression levels. Results: At 21-days after treatment, the growth velocities of control group, Endostar group, cryoablation group and combination group were $236.7{\pm}51.2%$, $220.0{\pm}30.6%$, $159.5{\pm}29.3%$ and $103.3{\pm}25.5%$ (P<0.01), while cellular apoptosis rates of tumors were $21.7{\pm}2.34%$, ($22.17{\pm}1.47$)%, $38.3{\pm}1.37%$ and $49.2{\pm}1.72%$, (P<0.01), respectively, according to the immunohistochemical test. MVD and VEGF expression levels in the combination group were both lower than in other groups (P<0.01), also being positively related (r=0.925, P<0.01). Conclusions: Endostar can significantly improve the inhibitory effects of cryoablation on xenografts of lung adenocarcinoma A549, and the mechanism is probably associated with its function as an inhibitor of tumour neo-angiogenesis through down-regulating VEGF expression.
Recent studies have revealed that Nitric oxide(NO) was one of the demonstration for the physiological regulator, endothelial derived relaxing factor(EDRF) and that NO was produced by ultraviolet irradiation in human. Thus, the present author have carried out a experimental study on the change of hematological, histological value of ultraviolet irradiation in sprague-dawley rats. The subjects were divided into four groups of ten rats each selected at random. There were 4 groups: 1. no irradiation control; 2. ultraviolet $75mJ/cm^2$ irradiation group; 3. ultraviolet $150mJ/cm^2$ irradiation group; 4. ultraviolet $225mJ/cm^2$ group. After a irradiation, hematological and histological tests were performed to observe erythrocyte, hemoglobin, hematocrit, MCH, MCHC, MCV, $O_2$ saturation, pH, $PO_2,\;PCO_2$ value and to observe histological changes. In hematological tests, erythrocyte, hemoglobin, hematocrit significantly increased in $75mJ/cm^2$ than control group and more $150mJ/cm^2$ ultraviolet irradiation group respectively. Also In blood gas tests, $PO_2$ significantly increased in $75mJ/cm^2$ and more $150mJ/cm^2$ group than control group. Whereas $PCO_2$ significantly decreased in $75mJ/cm^2$ and more $150mJ/cm^2$ group than control group (Duncan-Tukey test, P<0.05). In histological tests, control and $75mJ/cm^2$ group unchanged, but more $150mJ/cm^2$ group changed that it was cytolysis, cytotoxic effect, acanthosis, proliferation of keratinocyte, appearance of amorphous cell and pyknotic nucleus, production of sunburn cell. In conclusion, the present author results support the importance of the relation between NO effect and hematological, histological value by ultraviolet B irradiation.
The advanced glycation endproducts receptor (AGE-R) is a signal transduction receptor for multiligand such as S100b and AGEs. S100b has been demonstrated to activate various cells with important links to atherosclerosis initiation and progression including endothelial cells, and smooth muscle cells via AGE-R, triggering activation of multiple signaling cascades through its cytoplasmic domain. Many studies have suggested AGE-R might even participate in the cardiovascular complications involved in the pathogenesis of type I diabetes. Recently, Small Ubiquitin-Related Modifier 1 (SURM-1 also known as SUMO-1) has been recognized as a protein that plays an important role in cellular post-translational modifications in a variety of cellular processes, such as transport, transcriptional, apoptosis and stability. Computer Database search with SUMOplot Analysis program identified the five potential SURMylation sites in human AGE-R: K43, K44, K123, and K273 reside within the extracellular domain of AGE-R, and lastly K374 resides with the cytosolic domain of AGE-R. The presence of the consensus yKXE motif in the AGE-R strongly suggests that AGE-R may be regulated by SURMylation process. To test this, we decided to determine if AGE-R is SURMylated in living vascular cell system. S100b-stimulated murine aortic vascular smooth muscle cells were used for western blot analysis with relevant antibodies. Taken together, bioinformatics database search and molecular biological approaches suggested AGE-R is SURMylated in living cardiovascular cell system. Whilst SURMylation and AGE-R undoubtedly plays an important role in the cardiovascular biology, it remains unclear as to the exact nature of this contribution under both physiological and pathological conditions.
Park, Chan Young;Chang, Hak;Chung, Jin Haeng;Heo, Eun Ju;Minn, Kyung Won;Yoo, Moon Won;Yang, Han Kwang
Archives of Plastic Surgery
/
v.35
no.5
/
pp.626-629
/
2008
Purpose: We investigate the possibility of vessel preservation with glycerol and evaluate the potential of preserved gastroepiploic artery as a tool for the microsurgical practice. Methods: In 5 early gastric cancer patients, IRB(No. C-0603-040-170), we gained gastroepiploic artery specimens(5 segments, about 10 cm) after gastrectomy. Each segment was rinsed in a normal saline and subsequently placed in a bottle, containing 50 mL anhydrous glycerol (87%). The bottles were refrigerated at $4^{\circ}C$, the longest preservation time being 5 months. Results: At first glance, no fragmentation was detected and the surface of vessel seemed mild sclerotic. In histological examination, vascular structures remained intact though preservation with glycerol led to a mild atrophy of the smooth muscle in the tunica media. Especially, we found out the elastic fibers and endothelial lining of the intima were preserved until 5 months. Adequate status for using microsurgical practice was also maintained and leakage test was performed successfully with gentian violet ink. Conclusion: Based on the results obtained in this study, the gastroepiploic artery preservation with glycerol as a training model for microvascular anastomosis is a technically very simple procedure and useful for the novice microsurgeon.
Considerable research has been conducted concerning galectin-9 and carcinomas, but little information is available about any relation with the hepatocellular carcinoma. In this study, we employed a small interfering RNA (siRNA) targeting galectin-9 to down-regulate the expression in HepG2 cells. As a result, after galectin-9 expression was reduced, cell aggregation was suppressed, while other behaviour such as the proliferation, adhesion and invasion to ECM, cell-endothelial adhesion and transendothelial invasion of the cells were markedly enhanced. When tumors of 200 patients with hepatocellular carcinoma were tested for galectin-9 expression by immunohistochemistry, binding levels demonstrated intimate correlations with the histopathologic grade, lymph node metastasis, vascular invasion and intrahepatic metastasis (P<0.05). Moreover, survival analysis indicated that patients with galectin-9 expression had much longer survival time than those with negative lesions, and the Log-rank test indicated that this difference was statistical significant (P<0.0001). The Cox proportional hazards model suggested that negative galectin-9 expression in hepatocellular carcinoma represented a significant risk factor for patient survival. We propose that galectin-9 might be a new prognostic factor with antimetastatic potential in patients with hepatocellular carcinoma.
Objective : Milk fat globule-epidermal growth factor VIII (MFG-E8) may play a key role in inflammatory responses and has the potential to function as a neuroprotective agent for ameliorating brain injury in cerebral infarction. This study aimed to determine the role of MFG-E8 in brain injury in the subacute phase of cerebral ischemia in a rat model. Methods : Focal cerebral ischemia was induced in rats by occluding the middle cerebral artery with the modified intraluminal filament technique. Twenty-four hours after ischemia induction, rats were randomly assigned to two groups and treated with either recombinant human MFG-E8 or saline. Functional outcomes were assessed using the modified Neurological Severity Score (mNSS), and infarct volumes were evaluated using histology. Anti-inflammation, angiogenesis, and neurogenesis were assessed using immunohistochemistry with antibodies against ionized calcium-binding adapter molecule 1 (Iba-1), rat endothelial cell antigen-1 (RECA-1), and bromodeoxyuridine (BrdU)/doublecortin (DCX), respectively. Results : Our results showed that intravenous MFG-E8 treatment did not reduce the infarct volume; however, the mNSS test revealed that neurobehavioral deficits were significantly improved in the MFG-E8-treated group than in the vehicle group. Immunofluorescence staining revealed a significantly lower number of Iba-1-positive cells and higher number of RECA-1 in the periinfarcted brain region, and significantly higher numbers of BrdU- and DCX-positive cells in the subventricular zone in the MFG-E8-treated group than in the vehicle group. Conclusion : Our findings suggest that MFG-E8 improves neurological function by suppressing inflammation and enhancing angiogenesis and neuronal proliferation in the subacute phase of cerebral infarction.
Purpose: The purpose of this study was to examine the effects of the ulmus root-bark dressing on tissue regeneration in experimentally-induced pressure ulcers in rats. Method: A randomized pretest/post-test control group time-series study design was used. Thirty-three male Sprague-Dawley rats were used in this study. The rats were anesthetized with 100mg/kg of ketamine. Pressure ulcers were induced at 140mmHg for three hours using a personally-designed pressing apparatus. For four weeks, the ulmus root-bark dressing was applied every other day in the experimental group (n=18) and a wet gauze dressing in the control group (n=15). For data analysis, the statistical program SPSS WIN 12 was used. The wounds were examined by light microscopy andelectron microscopy. Result: There were significant statistical differences in the size of the pressure ulcers as time went by(p=0.006). It should be noted that there were no significant statistical differences in the number of capillaries. Using light microscopy the inflammatory infiltration and neovascularization in the dermis in the experimental group emerged densely in the early stages, but recovered rapidly at the latter stages. In addition, the reepithelization of the epidermis occurred earlier than in the control group. By electron microscopy, the cell organelles of the capillary endothelial cells and the basal lamina of capillaries in the experimental group showed a more rapid maturation during the latter stages, compared with the control group. Conclusion: According to this study, it can be concluded that the ulmus root-bark dressing is effective regarding the healing of pressure ulcers.
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