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81.
Shan B Morris CA Zhuo Y Shelby BD Levy DR Lasky JA 《Journal of molecular and cellular cardiology》2007,42(3):517-525
Idiopathic pulmonary arterial hypertension (iPAH) is associated with human herpesvirus 8 (HHV8) infection and demonstrates pathological angiogenesis similar to that observed with another HHV8-linked disease, namely Kaposi Sarcoma (KS). Importantly, the HHV8 encoded viral G-protein-coupled receptor (vGPCR) induces KS lesions in a murine model. Investigating the impact of vGPCR expression on the angiogenic activity of human pulmonary arterial endothelial cells (HPAEC) can yield insight into the pathobiology of HHV8-associated vascular disorders, particularly PAH. Cultured HPAECs were transduced with retroviral vectors carrying either control or vGPCR coding regions. vGPCR expression selectively activated matrix metalloproteinase (MMP)-2, a pivotal matrix modulating enzyme during angiogenesis. A membrane type 1 MMP (MT1-MMP) neutralizing antibody and the tissue inhibitor of metalloproteinases-2 (TIMP-2) independently blocked vGPCR-induced MMP-2 activation. vGPCR expression concordantly promoted MMP-2 activation by increasing MT1-MMP expression while decreasing TIMP-2 expression. vGPCR activated Src kinase as demonstrated by phosphorylation of Src and its substrate focal adhesion kinase (FAK). vGPCR promoted angiogenesis of HPAECs as demonstrated by a substantial increase in tubulogenesis in vitro. The Src inhibitors PP2 and SU6656 significantly diminished vGPCR-induced MMP-2 activation and tubulogenesis. Our findings indicate that vGPCR induces MMP-2 activation in HPAECs through regulation of MT1-MMP and TIMP-2 expression. vGPCR activates Src and inhibition of such activation abrogates proMMP-2 activation and in vitro angiogenesis induced by vGCPR. The current study implicates vGPCR as an etiological agent in iPAH and identifies Src and MMP-2 as potential therapeutic targets in HHV8 associated KS and iPAH. 相似文献
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Yuan Li Xiaojuan Chao Li Yang Qian Lu Tiangang Li Wen-Xing Ding Hong-Min Ni 《The American journal of pathology》2018,188(8):1833-1846
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IntroductionHaemostasis is a critical component of ear surgeries, which can be achieved by topical methods including simple manual pressure with gauze or cotton balls soaked with adrenaline, administration of haemostatic agents or vasoconstrictive materials.ObjectiveTo compare efficacy of haemocoagulase and adrenaline in attaining middle ear haemostasis in type - 1 tympanoplasty with or without cortical mastoidectomy. To study the effect of haemocoagulase in middle ear.Materials and methodThis is a prospective comparative study conducted in a tertiary care hospital from January 2013 to June 2014. Patients undergoing type 1 tympanoplasty with or without cortical mastoidectomy were divided into two groups. In group A (50 cases), cotton balls soaked in 2 ml Haemocoagulase was used and in group B (50 cases) cotton balls soaked in 2 ml Adrenaline (1:1000 dilution) was used for middle ear haemostasis. The efficacy of haemocoagulase and adrenaline was compared.ResultsThe mean number of cotton balls used in haemocoagulase group in cases with congested middle ear mucosa was more than those used in the adrenaline group. Duration of surgery was more in haemocoagulase group (65 min) with congested mucosa, compared to adrenaline group (50 min). The mean blood pressure was significantly higher in adrenaline group compared to haemocoagulase group. Postoperative hearing improvement in both groups showed no significant difference with p value 0.694.ConclusionsAdrenaline is a better middle ear haemostatic than haemocoagulase. However, haemocoagulase can safely be used in patients with hypertension. 相似文献
87.
Neila Hannachi Yousri El Kissi Samar Samoud Jaafar Nakhli Leila Letaief Samia Gaabout Bechir Ben Hadj Ali Jalel Boukadida 《Psychiatry research》2014
Many studies have reported an association between Herpes family viruses and an increased risk of schizophrenia, but the role of Human Herpesvirus 8 (HHV8) has never been investigated. This study aimed to assess HHV8 prevalence in schizophrenic patients as well as the possible association between HHV8 infection and schizophrenia clinical features. We consecutively enrolled 108 patients meeting fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria of schizophrenia and 108 age and sex matched controls. Data about a number of demographic characteristics and potential HHV8 risk factors of infection were collected. Standardized psychopathology measures, disease severity and functioning level were obtained using Positive and Negative Syndrome Scale (PANSS), Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Negative Symptoms (SANS), Scale for the Assessment of Positive Symptoms (SAPS), Clinical Global Impressions (CGI) and Global Assessment of functioning (GAF). The presence of anti-HHV8 antibodies was analyzed using an indirect immunofluorescence assay. A higher prevalence of HHV8 infection in schizophrenic patients than in controls was found. Marital status, having children, sexual behavior and risk factors of blood transmission were not associated with HHV8 prevalence. However, among schizophrenic patients, HHV8 prevalence was statically associated with positive symptoms. To our knowledge, this would be the first report of a possible role of HHV8 in the pathogenesis of schizophrenia. To prove this hypothesis, further investigation of HHV8 in schizophrenia with larger samples is needed. 相似文献
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Swashti Agarwal Aditi Khokhar Salvador Castells Albara Marwa Dawn Hagerty Laura Dunkley Jamila Cooper Vivian Chin Vatcharapan Umpaichitra Sheila Perez-Colon 《Journal of the National Medical Association》2019,111(1):37-45
Objective
With the rising incidence of Type 1 diabetes (T1DM), it is important to recognize deficiencies in care and areas of improvement to provide better access to resources and education for T1DM patients. The objective of this study was to recognize social factors and compliance barriers affecting glycated hemoglobin (A1c) level in T1D patients among the minority population.Methods
A total of 84 T1DM patients, ages 3 to 21 years, 49% males, 87% African American participated in the study. Study questionnaires assessing patient knowledge and other variables were distributed and patient charts were reviewed retrospectively to obtain relevant clinical data. T-tests, one-way ANOVA and spearman correlation were used for analysis.Results
Mean A1c in our study was 10.5% and mean knowledge score was 10.1 out of 14. There was no significant correlation (r = 0.12, p = 0.26) between A1c and patients’ knowledge scores. Patients with more frequent blood sugar (BS) monitoring (3-4 times/day) had 2 points lower A1c (9.6 vs 11.6 %, 95% CI 0.2–3.7, p = 0.03) than those with 2 or less times/day. No significant difference in A1c between 3–4 checks/day vs >4 checks/day BS checks. Most patients reported ‘forgetfulness’ (19%) followed by ‘too time consuming’ (17.9%) as barriers to daily BS monitoring. There was no significant difference in A1c between pen or pump users (10.5 vs 10.2 %, p = 0.55). Surprisingly, those with home supervision had higher A1c than those without (10.7 vs 9.6 %, p = 0.04) while there was no significant difference between those with or without nurse supervision at school (10.6 vs 9.8 %, p = 0.33). Those reporting happy mood interestingly had higher A1c than those with sad/depressed mood (10.7 vs 9.4 %, p = 0.04). On multiple linear regression analysis, frequency of BS checks, home supervision and mood were the most significant predictors of A1c and altogether explained 20% of the variability in A1c.Conclusion
Frequent BS monitoring is associated with lower A1c. Supervision at home and school did not improve A1c, but it was self-reported information. Mood did not affect A1c contrary to that reported in other studies. 相似文献89.
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Penketh PG Baumann RP Shyam K Williamson HS Ishiguro K Zhu R Eriksson ES Eriksson LA Sartorelli AC 《Chemical biology & drug design》2011,78(4):513-526
The anticancer prodrug 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119) selectively releases a short-lived cytotoxin following enzymatic reduction in hypoxic environments found in solid tumors. KS119, in addition to two enantiomers, has two stable atropisomers (conformers differing in structure owing to hindered bond rotation) that interconvert at 37 °C in aqueous solution by first-order kinetics with t(1/2) values of ~50 and ~64 h. The atropisomers differ in physical properties such as partition coefficients that allow their chromatographic separation on non-chiral columns. A striking difference in the rate of metabolism of the two atropisomers occurs in intact EMT6 murine mammary carcinoma cells under oxygen-deficient conditions. A structurally related molecule, 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[[1-(3-hydroxy-4-nitrophenyl)ethoxy]carbonyl]hydrazine (KS119WOH), was also found to exist in similar stable atropisomers. The ratio of the atropisomers of KS119 and structurally related agents has the potential to impact the bioavailability, activation, and therapeutic activity. Thus, thermally stable atropisomers/conformers in small molecules can result in chemically and enantiomerically pure compounds having differences in biological activities. 相似文献