Medical Research

Expression of Upa and Microvessel Density Correlate with Invasion and Metasasis of Hypoharyngeal Squamous Cell Carcinmoma

Medical — Fri, 18 May 2012 03:52:07 +0000

Objective To explore the difference between the expressions of urokinase-type plasminogen activator (uPA) and microvessel density (MVD) in affected tissue and adjacent normal tissue of hypopharyngeal squamous cell carcinoma (HSCC) and to study their correlation with invasion and metastasis of HSCC.Methods The expressions of uPA and MVD of 60 patients with HSCC and 20 cases of paraneoplastic tissues were detected with the SP immunohistochemical staining. The relations between the expressions of uPA and MVD and the clinicopathological parameters of HSCC were analyzed by statistical methods. The correlation between MVD and uPA in patients with HSCC was analyzed by Spearman correlation analysis. The level of significance was set at P<0.05.Results The positive expression rates of uPA in patients with HSCC were 78.33%, which was significantly higher than that in paraneoplastic tissues(.P<0.01). The uPA positive expression was closely correlated with the clinical stage, pathological differentiation and lymph node metastases of hypopharyngeal carcinoma (P<0.05). MVD counting was also correlated with the clinical stage, pathological differentiation and lymph node metastases of hypopharyngeal carcinoma (P<0.05 or 0.01). Neither was significantly correlated with the patient age and the primary anatomic area of HSCC. Expression of uPA had a positive correlation with MVD(r=0.561, P<0.01) in patients with HSCC. The cervical lymph node metastatic rate in patients with uPA positive-expression and high MVD value was 90.91% (20/22), which was significantly higher than that in patients with uPA positive-expression but low MVD value (52.00%), and that in patients with uPA negative-expression and low MVD value (30.77%) (x2=9.538, P<0.05).Conclusion1. The positive expression rates of uPA and MVD counting in patients with HSCC were significantly higher than that in paraneoplastic tissues. The uPA positive expression and MVD counting were closely correlated with the clinical stage, pathological differentiation and lymph node metastases of hypopharyngeal carcinoma. Expression of uPA had a positive correlation with MVD in patients with HSCC.2. The active angiogenesis and uPA positive-expression are closely correlated with the invasion and metastasis of HSCC. HSCC with uPA positive-expression and high MVD value are susceptible to invasion and cervical lymphatic metastasis. Therefore, uPA and MVD counting may be used as effective indices to evaluate the possibility of invasion and metastasis of HSCC.3. The expression of uPA and MVD counting can be used as an important index for the capacity of growth,invasion and metastasis in the hypopharyngeal squamous cell carcinomas.

Effects of Smart Plug Lacrimal Plug in the Treatment of Dry Eye

Medical — Fri, 18 May 2012 03:50:05 +0000

BACKGROUND AND OBJECTIVE:With the development of the economy, more and more people pay close attention to dry eye. The uncomfortable symptom of dry eye is followed with interest. The cause of dry eye is very complicated. At present, the clinical application of artificial tears still mostly to treatment. This paper applied Smart Plug lacrimal plug to treat dry eye, Smart Plug lacrimal plug to prevent tear outflow, make normal tear secretion reserves in the eye, thereby improving dry eye symptoms. So to evaluate the clinical efficacy of Smart Plug lacrimal plug in the treatment of dry eye.METHODS:A total of 42 patients were screened for dry eye from January 2009 to May 2010.42 patients (84 eyes) were inserted Smart Plug lacrimal plug to treat dry eye. All patients were follow up after 5- 15mouths (average 8.3 mouths). SchirmerⅠtest (SIT), Tear break-up time (TBUT) and Fluorescent of cornea (FL), were used for evaluation of the clinical efficacy.RESULTS:1. pre-and post-treatment, SchirmerⅠtest (SIT) respectively was 3.41±0.60mm and 5.75±0.44mm (P<0.05); 2. pre-and post-treatment, Tear break-up time (TBUT) respectively was 3.75±1.26 seconds and 6.46±1.47seconds (P<0.05); 3. Fluorescent of cornea (FL) respectively was 2.45±0.06fen and 0.04±0.02fen (P<0.05); 4. the subject symptoms were improved in most patients.CONCLUSIONS:Application Smart Plug lacrimal plug treatment dry eye, closed patients part lacrimal plug to prevent the tear outflow, make normal tear secretion reserves in the eye, thus improve symptoms, obtain good effect. So the conclusion: the Smart Plug lacrimal plug treatment effect, have clear dry eye clinically as a treatment method for dry eye can one. It is significantly simplified procedures and difficulty, also significantly reduces the actual autologous exclude rate, plug and lacrimal duct secondary infection. Improved dry eye the patient’s eye table physiological micro environment, improve the patient’s quality of life. Deserves further clinical research and promotion.

Prospective Study of Weight Loss during Radiotherapy in Nasopharyngeal Carcinoma

Medical — Fri, 18 May 2012 03:47:26 +0000

[Background]:Weight loss and malnutrition are common among cancer patients, especially the patients with head and neck (H&N) cancer. They are due mainly to tumor effects and the adverse effects of the treatments. Several studies shown that patients with critical weight loss had associated with lower quality-of-life scores and poorer treatment tolerance, further with delayed recovery, prolonged hospital stay and unfavorable prognosis. Recently, the positive influence of an early and intensive nutritional support on quality of life and outcome were demonstrated in patients with HN cancer undergoing RT. The early nutritional management may lead to less weight loss, fewer radiotherapy breaks for toxicity and better prognosis, so it would be wise to have a better knowledge of the factors predicting weight loss to intervene early. Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with a remarkable geographic and racial distribution worldwide. The incidence of NPC is extremely high in Southern China and Northern Africa. Although all Chinese possess increased risk of NPC, rates generally decline as one travels from south to north China. At present, radiotherapy (RT) alone or in combination with chemotherapy is the main therapy for NPC. Most studies on prognostic risk factors in HN cancer include oral cavity, oropharynx, hypopharynx and larynx, few data is available to estimate the extent of weight loss in nasopharyngeal carcinoma patients, because NPC is a rare malignancy in most parts of the world, with an incidence under 1 per 100 000 person-years, adequately screening NPC patients at higher risk for weight loss is still a challenge.[Objectives]:Little is known about nutritional status in patients treated for nasopharyngeal carcinoma. The objective of this explorative study was to measure weight loss during radiotherapy and to select predictive factors for early identification of malnourished patients. [Methods]:This is a prospective study of 159 consecutive initial diagnosed nasopharyngeal carcinoma patients attending the Oncology Center at Qilu Hospital of Shandong University in the period from March 2007 to March 2010. Patients younger than 18 years old, pregnant, with distant metastases or a history of other malignancies were excluded. At baseline, sociodemographic and tumor-related patient characteristics were recorded, i.e. sex, age, TNM classification, albumin (ALB) hemoglobin (Hb) level, Karnofsky performance status (KPS), radiation techniques, concurrent chemotherapy, body mass index (BMI), pre-treatment weight loss and nutrition-related symptoms. Patients’ weights were measured at the baseline visit and at the end of radiotherapy.Bivariate analyses of categorical variables were done by Student’s t-test and analysis of variance. The continuous variables, such as quality-of-life dimensions, age and the level of albumin were examined by Pearson’s correlation analysis. One-way analysis of variance was used to compare the amount of weight loss between groups divided by the radiation techniques. Stepwise linear regression analyses were used to select possible independent predictors of weight loss. The weight loss during radiotherapy was used as the dependent variable, the general and tumor-related patient characteristics and QOL nutrition-related items at the start of radiotherapy were used as the independent variables. The significance level was established at 0.05 and the P value is two-tailed.[Results]:1、At baseline,5% weight loss at the last three month was observed in 89 patients (56%), after the treatment, the median weight loss was 6.9 (range,2.1-12.6) kg, representing a proportional weight loss of 3.5% to 16.4%2、The bivariate analysis showed that most of the clinical factors were positively associated with weight loss, i.e. tumor stage, node stage, albumin, hemoglobin level, Karnofsky performance status, radiation techniques, concurrent chemotherapy and number of comorbidities. Among the patients’ general characteristics, age, education level of 12 or more, Body mass index and pre-treatment weight loss were associated with weight loss. There was no statistically significant difference in patients with respect to differences in sex, smoking habit and marital status. In the quality-of-life dimensions, most items were significantly correlated with weight loss, the greatest correlation was with the Global QOL (r=-.637; P<.001), while the items as nausea/vomiting, social eating, sticky saliva and use of painkillers were not observed significant relationship with weight loss.3、The ANOVA between the radiation techniques and weight loss during RT shows that there is a statistically significant difference in the radiation techniques (P<.001). The multiple comparisons found that the patients who received conventional RT lost more weight during radiotherapy compared with the patients received 3D-CRT (P=.019) or IMRT (P<.001), while no statistically significant difference was observed between the 3D-RT and IMRT groups (P=.112).4、In the stepwise linear regression,8 factors were associated with a greater weight loss:Global QOL, Body mass index, N stage, insomnia, radiation schedule, Karnofsky performance status, concurrent chemotherapy and fatigue. In this example, the variance inflation factor are all smaller than 3 indicates that there is little multicollinearity. The histogram of the Residuals shows that the deviation is normally distributed. The R2 value tells us that about 70% of the total variation about the Y mean is explained by the linear regression model.[Conclusions]:Severe weight loss during radiotherapy for nasopharyngeal carcinoma is common, which is not only from treatment but also from tumor cachexia. A combination of clinical factors may lead to malnutrition for nasopharyngeal carcinoma during radiotherapy, the clinical predictors would be useful for screening NPC patients at high malnutrition risk and suggest to give professional nutritional counseling at the very beginning.

Miniscrews for Maxillary Incisor Intrusion in Adult

Medical — Fri, 18 May 2012 03:44:58 +0000

Correction of a deep-bite malocclusion often confuses orthodontists. Generally, there are 3 ways to correct overbite:intrusion of the incisors, extrusion of the posterior teeth and the combination. However, almost all the conventional methods accompany extrusion of the anchorage tooth as counteracting force, diminishing their clinical effectiveness. Extrusion of the anchorage posterior teeth may increase lower facial height, in turn lead to posterior rotation of the mandible and, as a result, mandibular plane angle increases. This bite opening may be desirable in brachyfacial patients who have a low mandibular plane angle, but is not desirable in some patients with dolichofacial skeletal patterns. Furthermore, an adult patient will have a different skeletodental response to orthodontic bite opening than a growing patient. With minimal extrusion of the molars, the adults increase the original mandibular plane angle. While adolescent patients maintain a stable mandibular plane angle even with a significantly greater amount of molar extrusion attributed to the greater amount of posterior mandibular development.Besides the conventional mechanics, the increasing use of mini-implants have found their way, also in this type of tooth movement, providing maximum anchorage control and requiring minimal compliance, playing important part in several aspects of orthodontic. Several articles have focus on the mini-implants in the intrusion of maxillary incisors, however, no detailed research about the clinical evaluation and periodontal change is present.Objective:To investigate the clinical effects of miniscrews in the maxillary incisors intrusion of adults, estimate the change of the maxillary incisor in 3 dimensions, lip-mouth relationship and the periodontal supporting tissue. And then, comparing the effect between minisrews and conventional utility arch, to evaluate the difference and provide information for the clinical maxillary incisor intrusion.Methods:40 adult patients, withⅢ°deep bite, overgrowth of maxillary anterior alveolar and partly uncoordinated relationship between maxillary lip and maxillary anterior teeth after levering were chosen and divided into two groups randomly:miniscrew group and conventional utility arch group. Miniscrews were inserted into the labial alveolar bone between the roots of maxillary lateral incisors and canines in the miniscrew group, and then 50g force in each side was imposed by nickel titanium closed-coil springs,Ωbends were used 1mm before the medial of maxillary first molar brackets and connected together. In the conventional utility arch group, typical 0.016×0.016 inch stainless steel wires were used. The cephalometric films, intraoral periapical radiographies with metal guide bars, facial photos and periodontium review were taken before and after the intrusion. The major measurement items are the alteration of the maxillary first molar in vertical dimension, torque and length of maxillary central incisors, overbite, clinical crown of maxillary central incisors, probing depth (PD), gingival index (GI), plaque index (PI) and so on. PASW statistics 18.0 was used for the Statistical analysis.Results1. In the miniscrew group, there is no change of U1-SN, U6-PP distance, U6-SN or root length of the maxillary incisor was observed. Significant reductions in overbite, maxillary incisor intrusion(3.42±1.17mm), and maxillary incisor to upper lip were observed after intrusion of the incisors. Smile arc improved significantly. The maxillary central incisors’ width-length ratio performed normal after the treatment. What’s more, probing depth (PD), increased, and the width of keratinized gingiva(WKG) decreased.2. In the conventional utility arch group, significant increases of U1-SN, U6-PP distance were observed. Similar change in overbite, maxillary incisor intrusion(2.95±0.78mm), and root resorption presented after the intrusion. Improved lip-tooth relationships, normal maxillary central incisors’width-length ratio, slightly increase of the PD can also be seen after the treatment. WKG decreased similarly.3.There were significantly greater reductions in maxillary incisor to palatal plane and U1-Stm in the miniscrew group than in the conventional utility arch group (P<0.05). More improvement of smile arc in the miniscrew group. No significant difference of U6-PP distance, root resorption or periodontal supporting tissue between the two groups after intrusion was observed (P>0.05). Furthermore, the utility arch group took significantly more treatment time than the miniscrew group and showed increase of Ul-SN and U6-PP.Conclusion1. As relatively stable anchorage, miniscrew can intrude upper incisors significantly by simply controlling the force moment, improving the aesthetic.2. No meaningful change of U6-PP distance or madibular plane angle can be found in the miniscrew group.3. Comparing to the the minisrew group, conventional utility arch group shows the shortcoming in intruding upper incisors. More treating period is needed and increase of U6-SN and U1-SN can be observed in the utility arch group. No additional root resorption or periodontal supporting tissue was observed between the two.

Comparison of Cleaning Effect of Different Methods on Complete Denture

Medical — Fri, 18 May 2012 03:42:37 +0000

OBJECTIVE:This aim of this study was to evaluate effect of different methods on cleaning pigment and Candida albicans on heat curing acrylic resin using in denture base in vitro.METHODS:Sixty specimens(10×10×l.3mm) were dyed by coffee, tea and other pigmant from normal food. Then they were contaminated (37℃for 48 hours) by Candida albicans inoculum with 106 colony-forming units (CFU)/ml. Then, specimens were classed into 6 groups randomly and cleaned by the following methods respectively: (1) mechanical:brushing for 20 seconds; (2) chemical:immersion in an alkaline peroxide solution (Sushuang Denture Cleaning Tablets) for 10 minutes; (3) a combination of (1) and (2); (4) after ultrasonical cleaning, a combination of (1) and (2);(5) a combination of ultrasonical cleaning and brushing; (6) just washing by steriled distilled water. Afterward, the specimens were incubated in Yeast Extract Peptone Dextrose Medium (YPD) at 37℃for 24 hours. Then the concentration of Candida albicans inoculum in 1ml YPD was tested by spectrophotometer, and the effect of color removal was tested by Shade-Eye NCC (Shofu Dental Inc.) RESULTS:1、Removal of Candida albicans:Comparing with method (6),method(1),(2),(3),(4) and (5) had significant greater effect(p<0.01). There was no statistic difference between cleaning effect of method (2)and(5).The other methods have statistic differences between each other(p<0.01).2、Removal of pigment: Comparing with method (6), method(1),(2),(3),(4) and (5)had significantly greater cleaning effect(p<0.01). There are no significant differences between results of method (1)and method(4).So as (2) and (4). The other methods have statistic differences between each other(p<0.01).CONCLUSIONS:A combination of brushing, chemical cleanser and ultrasonic cleaning is the best method to clean Candida albicans as well as pigment. Ultrasonic cleaning is advised to be used regularly among persons with RPD.

The Research and Clinical Meaning of the Serum Leves of Matrixtalloproteinase-2 of Patients with Acute Cerebral Infarction

Medical — Fri, 18 May 2012 03:40:14 +0000

Objictive: High incidence,high morbidity and mortality of cerebral infarction brought a heavy burden to the socity and the family, this study was to investigate the relationship between the serum level of matrixtalloproteinase-2, the volum size of infarction, degree of neurofunction impairment as well as prognosis in patients with acute cerebral infarction. We expect new intervention targets for clinical prevention and treatment of cerebral infarction.Methods:All cases were persons with health check and patients with acute ischemic stroke admitted to the medical department of Neurology of Heze Municipal Hospital since December 1,2009-September 30,2010.All cases were divided into A, cerebral infarction group:56 patients with acute ischemic strok treated in our hospital,aged from 35 years to 80 years,average.All were in line with the Fourth National Conference revised diagnostic criteria of cerebral infarction, and confirmed by brain CT or MRI. Hospital treatment closely follows the “china guideline to Cerebral Vascular Disease”. According to the head CT or MRI lesion size, infarct volume by Pullicino formula (length×width×number of layers÷2) calculation, the cerebral infarction patients were divided into large groups (LI) 20 cases, lesion volume> 10cm3;middle infarction group (MI) 18 patients, lesion size (5-10cm3); small infarct group (SI) 18 cases, lesion size<5cm3. All cases were rated by the clinical neurological deficit scoring (CNFDS), developed based on the 1995 Fourth National Conference on cerebrovascular disease,then divided into severe group (31-45 points),17 cases, medium group(16-30 points),20 cases, light group (0-15 points), 19 cases. According to the National Institutes of Health Stroke Scale (NIHSS), the emerging infarction,which score at 7 days after admission compared with the time of admission increased by at least 2 points, parallel head CT excluded hemorrhagic infarction and other vascular diseases caused by is defined as the early neural function deterioration. The cerebral infarction group was divided into the early neurological deterioration in 26 patients, the non-early neurological deterioration group of 30 patients,which rate reduced at day 7 after admission compared with the admission; B control group:Select the normal healthy subjects, at the same period,as control group,30 cases, aged 42-70 years, mean 52.1±13.4 years. Fasting venous blood were taken 4ml,for two samples, cerebral infarction group were taken after the onset of 24h and 7d,contral group were taken at the first day and the 7d.The serum were collected afterone blood sample at room temperature to be solidified,and centrifugated for 10 minutes at 2000 r/min,then detected the MMP-2 concentration,the other sample was send to our biochemistry laboratory to tested the indicators of blood glucose, cholesterol, triglycerides, low density lipoprotein and lipoprotein a. Experimental data analyzed by statistical software SPSS11.5. Comparison between two groups were the number of samples t test, multiple samples mean comparision used to single-factor analysis of variance.Results:1. Compared with the control group, the systolic pressure, diastolic pressure, blood glucose, cholesterol,and lipoproteins of infarction group(onset 24-48h) were significantly different (P<0.01); Other indicators, including age, gender, coronary heart disease, cerebrovascular disease, family history, smoking, alcohol consumption, triglycerides were not significantly different between the two groups.2. Compared with the control group, cerebral infarction serum levels of MMP-2-in the course of 24h, at 7d were significantly higher (P<0.01);it was more higher at 7d than that of 24h(P<0.01).3. Of patients with cerebral infarcton,the MMP-2 level was positively correlated with the size of the infarction volum(P<0.05), the larger the infarction volum,the higer the serum level of mmp-2.4. Of patients with cerebral infarction,the MMP-2 level was positively correlated with neurologic dificit extent(P<0.01);i.e., the more severe neurologic impairment the higher the serum levels of MMP-2.5. The mmp-2 levels in patients with cerebral infarction correlated with different recent prognosis,i.e.,the higher the level of serum mmp-2, the worse the prognosis of patients with cerebral infarction.Conclusion: The results showed that the increased levels of MMP-2 of patients with cerebral infarction was positively correlated with the lesion size and severity, also closely correlated with prognosis.sugesting MMP-2 play an important role in the pathegenesis and development of acute ischemic cerebrovascular disease.earl detection of serum levels of MMP-2 could be a reliable indicator to determined the infarction size, severity and prognosis of patients. To reduce the level of MMP-2 may be effective for the treatment of cerebral infarction.

Primary Study of Carotid Plaque Biomechanics with Strain and Strain Rate Imaging in Patients with Acute Cerebral Infarction

Medical — Fri, 18 May 2012 03:37:42 +0000

1. IntroductionMore than half of ischemic strokes are related to extra cranial athermanous disease in the developed world. In present clinical practice, selection for surgery or revascularization is based on the degree of luminal stenosis as measured by angiography such as ultrasound or magnetic resonance angiography (MRI). Carotid endarterectomy is well known to be beneficial in patients with symptomatic and asymptomatic severe carotid stenosis [1-4]. However, increasing evidences suggested that the severely luminal stenosis alone might not be sufficient to detect patients at high risk to develop ischemic stroke [5 6]. Instead, the identification of plaque factors other than degree of stenosis may improve risk stratification and help to decrease the opportunity of stroke in the carotid territory [7]“Vulnerable plaque” has been used to describe rupture-prone plaques. Histological data suggests that vulnerable plaque is characterized by a large necrotic lipid pool(>40% of the plaque’s total volume), a thin overlying fibrous cap<100um, and inflammatory infiltrate within the plaque [8-11]. Thus, to evaluate plaque vulnerability, an ideal approach would provide information containing both plaques’anatomic characteristics (morphology) and its functional properties (activity) [8 9 12 13]Once atherosclerotic plaques are formed, there should be a great change of the distribution of stress and strain in the wall [14 15].It has been hypothesized that mechanics play an important role in plaque rupture and should be considered in an incorporated way with plaque morphology and composition for possible improvement of plaque assessment schemes [16]. Several studies was carried out to analyze stress in atherosclerotic wall [14 15 17]. They primarily focused on the biomechanical properties in atherosclerotic plaques. Previously, such biomechanical profiling has been based on finite element analyses that use ex vivo histology or imaging data to create stress maps of vessel wall [9-13], which may alter the morphology and geometric relationships, that calling into question of the simulation validity.In recent years, the advent of high-resolution imaging techniques such as intravascular ultrasound has allowed detailed morphologic and structural characterization of carotid plaques to be performed in vivo, which can avoid the problem of possible structural alterations in the vessel wall. MRI technique has shown its ability to non-invasively quantify plaque size, shape and component [18-20]. Attempts of using ultrasound and IVUS techniques have been made to determine vessel motion, mechanical properties and vessel wall structure, even to predict rupture locations [21 22]Two-dimensional (2D) strain, which is based on speckle tracking in gray-scale B-mode images, has been implemented in numerous experimental and clinical studies for exploration of cardiac function different clinical setting [23 24]. This method enables simultaneous evaluation of radial, longitudinal and circumferential myocardial deformation. However, little data has been reported for its usability in plaque biomechanics assessment.In this study, we examined carotid plaque morphology and biomechanics properties by high-resolution B-mode ultrasonography combined with strain and strain rate imaging, for evaluated carotid plaque elasticity and investigated the association between ACI and carotid plaque biomechanics.2. Materials and Methods2.1. SubjectsOne hundred patients(Ages between 34-89 years, male and female) were enrolled for this cross-sectional study in the Department of Neurology at Qilu hospital. Fifty patients with ACI of anterior circulation according to the result of CT or MRI within 24 hours of the onset of symptoms were selected as ACI group. In addition, Age and gender matched fifty patients without ACI, were taken as control group. The following patients were excluded from the study:(1) patients with lacuna infarcts, silence infarcts, or posterior circulation infarcts; (2) patients with aerial fibrillation, cardiac valve abnormalities, recent myocardial infarction, or heart failure; (3) patients with concurrent diseases which influence the expression of inflammatory mediators, such as ischemic events, trauma, or surgery during the previous 3 months, sever liver disease, renal failure, hematologic, or malignant diseases, chronic inflammatory diseases, autoimmune diseases, as well as fever or infectious conditions. General data including age, sex, hypertension, coronary heart disease, smoking state were derived. And venous blood was obtained between 7 and 8 am after 12 hours of fasting. Laboratory parameters contained red blood cell count, plasma fibrinogen, serum levels of total cholesterol, triglycerides, high density cholesterol, low density cholesterol, apolipoprotein A1, apolipoprotein B, cystatin-C (Cys-C), fasting blood glucose (GLU) were acquired.2.2. Carotid artery ultrasound examinationUltrasound images of the carotid artery were achieved with a high-resolution ultrasound scanner, Mylab90 equipped with a linear array 5-8MHZ transducer. Patients with ACI were underwent the examination within 24 hours after onset of symptoms. All ultrasound examinations were performed by the same experienced ultrasonographer who was unaware of history and physical signs of the patient. Patients were examined in the supine position. Each carotid artery scan started above the clavicle, and the transducer moved along the common carotid, internal and outer carotid arteries in order. Transverse views and three different longitudinal views (anterior, posterior and lateral) were scanned for the presence of atherosclerotic plaques. The intimae-media thickness (IMT) and blood flow index were all evaluated in the position 1-1.5 centimeters (cm) distal to the common carotid artery proximal to the bifurcation. The intimae-media thickness (IMT) was measured with quality intimae-media thickness (QIMT), software in the ultrasound scanner, automatically. And blood flow index including blood flow velocity integral, end-diastolic velocity, resistance index, systolic and diastolic end speed ratios were all measured automatically. Dynamic state images in three cardiac cycles of the longitude and transverse views in the plaques’position were saved. Left and right carotid arteries were all examined by turns for each patient. In arteries with multiple plaques, only the thickest plaque was selected.2.3. Carotid plaque analysisThe plaque biomechanics parameters were analyzed by strain and strain rate imaging software within the ultrasound scanner. The saved dynamic state images were imported into strain and train rate imaging mode. All the analyses were done in systolic phase monitored by electrocardiogram. In the transverse views, the outer members were traced. However, the fibrous cap and outer member were traced in the longitude view. Eight regions of interest (ROT) of plaque longitude axis were separated:the half part near the heart(na),the half part far away the heart(fa), shoulder near the heart(ns), middle near the heart(nm), top (t), shoulder far away the heart(fs),middle far away the heart(fm). Data was exported into computer, positive peak of circ strain (Sc) and negative peak of radial displacement (Dr) in the outer member of plaque short axis images, as well as positive peak of fibrous cap long strain (Si1), negative peak of fibrous cap long strain (Si2), positive peak of outer member long strain (Se1), negative peak of outer member long strain (Se2) were measured correspondingly. Positive peak of shear stress (SS1), negative peak of shear stress (SS2) were calculated with fibrous cap and outer member long strains. Then difference of sheer stress and fibrous cap strain between two regions of interest was calculated one by one.Plaque morphology in terms of echogenicity was divided into fibrous type and lipid type. The plaque thickest position (PT) and the thinnest IMT beyond the plaque were measured, and then the eccentric index (EI) was calculated. A second observer reviewed each plaque to determine the reproducibility of ultrasonic characterization of plaque morphology.2.4. Statistical analysisData were analyzed with SPSS software version 17.0. Continuous variables were demonstrated as means±standard error (SEM). Measurement features between patients with ACI and control group were evaluated with Independent-samples t test, while Chi-square test was used for the categorical comparisons. Independent-samples t test was also used for the comparisons of plaque biochemists parameters between fibrous type plaques and lipid type plaques. The comparisons of biomechanics parameters between the different regions of interest were evaluated with One-way ANOVA. Binary logistic regression was performed to assess the association between ACI and plaque biomechanics index or morphology data or carotid artery parameters. Model 1 included the general variables with age and sex adjusted. Then variables with significant association were added into model 1 subsequently to determine the final regression model. For each model, a receiver operating characteristic curve was plotted to describe the sensitivity and specificity according to the area under the curve (AUC) and 95% confidence interval (CI). For p<0.05, results were considered as statistically significant.3. ResultsAs illustrated from the general and laboratory data, there is no statistical significant difference between patients with ACI and control group in terms of age, gender, Hypertension, CHD and smoking state. Blood parameters included red blood cell count, plasma fibrinogen, serum levels of total cholesterol, triglycerides, high density cholesterol, low density cholesterol, apolipoprotein A1, apolipoprotein B, cystatin-C (Cys-C), fasting blood glucose (GLU) did not differ between the two groups.For carotid artery, the two groups differed significantly in carotid blood flow velocity integral, end-diastolic velocity (p=0.001 and p=0.018 respectively). As well intimae-media thickness, resistance index, systolic and diastolic end velocity did not differ between the two groups.The ratio of fibrous plaque in patients with ACI and control group were 62% and 55% respectively (p=0.291). Eccentric index (EI) in patients with ACI was lower than control group (p=0.057). The plaque thickness (PT) in longitudinal view in ACIs was significantly higher than patients without ACI (p=0.012).3.1. Plaque biomechanics between the two groupsCompared with control group, negative peak of sheer stress(SS2) in the half part far away the heart (fa) and middle far away the heart (fm) were significantly higher (p=0.044, p=0.020 respectively) in ACIs. And, negative peak of fibrous cap strain(Si2) and sheer stress(SS2) in the regions of interest contained half part near heart, top and shoulder far away heart with ACIs were no significantly higher than NACIs. However in ACIs, other plaque biomechanics indexes contained positive peak of fibrous cap strain (Si1) and sheer stress (SS1) in the half part near heart, top and shoulder far away heart were on significantly lower than patients without ACI. Other biomechanics parameters were all no significantly different between two groups.3.2. Plaque biomechanics distribution in ACIsIn one way ANOVA, plaque biomechanics contained positive and negative peak of fibrous cap strain (Sil and Si2) among regions of interest in patients with ACI were all significant different (p=0.020 and p=0.009 respectively). And the concentrated region for positive peak of strain and sheer stress was in shoulder near away heart (ns), while the concentrated region for negative peak of strain and sheer stress was in shoulder far away heart (FS). However plaque biomechanics index among different regions in control group all had insignificant differences. The next pairwise comparison was performed among different regions in ACIs. Figure 2 shows plaque strain and sheer stress distribution in ACIs.3.3. Plaque biomechanics difference among regions of interestDifference of plaque fibrous cap strain and sheer stress between two regions of interest was collected by turn. Compared with NACIs, strain difference between fm and shoulder far away heart (d10-Si1) was significantly lower (p=0.03) in ACIs. And strain difference between top and middle far away heart (d6-Si1) was significantly lower (p=0.021) too. Meanwhile in patients with ACI, sheer stress difference between top and far away shoulder (d9-SS1) were significantly lower (p=0.034) than patients without ACI.3.4. Correlation between acute cerebral infarction events and plaque biomechanicsBinary logistic regression model was used to choose the significant correlation between ACI and the carotid artery data, plaque morphology and biomechanics index. General data included age, sex, hypertension, coronary heart disease, smoking state, serum level of total cholesterol and triglycerides, high density cholesterol, low density cholesterol, fasting blood glucose were added into the model firstly. Then index with significant differ was added into the model independently by turn. Strain difference (d6-Si1) and sheer stress (SS2-fa and SS2-fm) were all significantly associated with ACI.General data included age, sex, hypertension, coronary heart disease, smoking state, serum level of total cholesterol and triglycerides, high density cholesterol, low density cholesterol, fasting blood glucose were constituted Model 1, which the receiver operating characteristic (ROC) AUC was 0.825 (95%CI= 0.687-0.962, P=0.002). And indexes with significantly associated with ACI in logistic analysis were added into model 1 respectively. The AUC with peak positive strain difference between top and middle far away heart (d6-Si1) added into Model 1 was 0.890 (95%CI= 0.777-1.000, P=0.000). And when added negative peak of sheer stress of half part far away heart (SS2-fa) into Model 1, the AUC was 0.870 (95%CI=0.743-0.997,P＝0.000). Similarly, the AUC with peak negative sheer stress of middle far away heart (SS2-fm) added into Model 1 was 0.903 (95%CI=0.797-1.000, P=0.000).4. ConclusionsThe peak values of shear stress and long strain in plaque different regions were significant different in patients with ACI. High sheer stress of middle far away heart(SS2-fm) and half part far away heart(SS2-fa) in plaque longitudinal views were significantly associated with ACI. Plaque biomechanics in the longitudinal view could be calculated by strain and strain rate imaging, which may provide a more useful quantitative assessment of plaque biomechanics. Therefore, the reliability and clinical importance of these quantitative parameters will be specified by further investigations.

Synthesis and Evaluation on Anticonvulsant and Antidepressant Activities of 5-Alkoxy (Phenoxy)-tetrazolo [1,5-a] Quinazolines

Medical — Fri, 18 May 2012 03:34:05 +0000

In order to find more safe and effective new anti-epileptic drugs, a series of 5-alkoxy (phenoxy) tetrazolo[1,5-a]quinazoline derivatives was synthesized using 2,4-dichloroquinazoline as the starting material. Their anticonvulsant activities were evaluated by the maximal electroshock test (MES). Results demonstrated that most of the test compounds exhibited weak anticonvulsant activity. Taking into account that depression is often the complication of epilepsy, research also shows that epilepsy and depression may have a common pathogenesis, and while some drugs have been clinically used for the treatment of these two diseases. Therefore, the antidepressant activity of this series of compounds were also measured by forced swimming test in mice (FST). The results showed that most of the compounds had strong antidepressant activity. Two compounds, namely 5-(hexyloxy)tetrazolo[1,5-a]quinazoline and 5-(4-methoxyphenoxy)tetrazolo[1,5-a] quinazoline, showed significant antidepressant activity, which decreased the immobility time by 62.2% and 51.7% at 100 mg/kg dose level (i.p).

Synthesis and Anti-inflammatory Activity Evaluation of Some Novel 3-amine-6-Alkoxy (Phenoxy)-[1,2,4] Triazolo [3,4,-α] Phthalazine Derivatives

Medical — Fri, 18 May 2012 03:32:01 +0000

Starting from phthalic anhydride, several new 3-amine-6-alkoxy(phenoxy)-[1,2,4]triazo-lo[3,4-a]phthalazine derivatives were synthesized as potent anti-inflammatory agent. Their anti-inflammatory activities were studied via the method of the xylene-induced ear edema in mice. The study showed that most of the synthsised compounds exhibited anti-inflammatory activity to a certain extent. Especially, the compounds 6h (3-amine-6-(2-chlorophenoxy)-[1,2, 4]triazolo[3,4-a]phthalazine) and 6s (3-amine6-(4-aminophenoxy)-[1,2,4]triazolo[3,4-a]phth-alazine) showed the highest anti-inflammatory activity (81% and 83% inhibition, respectively, at 0.5 h after i.p. administration) which were slightly more potent than the reference drug Ibuprofen (61%). Furthermore, the structure-activity relationship of these 1,2,4-triazole phthalazines was demonstrated.

Application of New Reagent Tbfmoc-Met-OH for the Solid Phase Synthesis and Purification of Ubiquitin and Chemical Synthesis of Azabicyclo Drug Intermediates

Medical — Fri, 18 May 2012 03:29:38 +0000

This thesis consists of two projects:one is chemical synthesis of new reagent Tbfinoc-Met-OH and using it as building block of ubiquitin in solid phase synthesis as well as the product purification helper; another is chemical synthesis of azabicyclo drug intermediates.In the first project, the new reagent Tbfmoc-Met-OH is synthesized in five steps, and then it is used as building block for the solid phase peptide synthesis (SPPS) of ubiquitin (Ub), a protein containing 76 amino acids and the N-terminal is methioine (Met), to introduce the Tbfmoc group into the N-terminal of ubiquitin. The synthetic Tbfinoc-Ub can show strong absorbance at 365 nm, be separated from the impurities efficiently due to its short retention time in gel filtration chromatography. The Tbfinoc group in the separated Tbfmoc-Ub can be removed under pH 8.5 condition, and the synthetic ubiquitin can be obtained with high efficiency and purity. The established purification strategy and the synthetic Tbfmoc-Met-OH will have important application value for other synthetic peptides and proteins.The second project concentrates on the chemical synthesis of azabicyclo conpounds including 6,7-dihydro-5H-pyrrolo (3,4-b) pyridine and 2,8-diazabicyclo (4,3,0) nonane, which are important structural units in various drugs and bioactive compounds, and play significant roles in the research fields of structure activity relationship and new drug discovery. By exploring, comparing and optimizing different methods and reaction conditions, the synthetic routes with mild reaction conditions and easy operation are established to synthesize the azabicyclo conpounds as well as their derivatives efficiently. The established routes in this project can overcome the weak points such as harsh reaction conditions, low yields and long reaction time in the present methods, and will become important basis for future research in this direction.