N-(4-Aminobenzoyl)-β-alanine/β-Alanine, N-(4-aminobenzoyl)-/3-[(4-aminobenzoyl)amino]propanoic acid
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To analyze the psychosocial factors associated with central serous chorioretinopathy (CSC) according to its phases and subtypes and to correlate the factors with the extent of choroidal hyperpermeability.
Age- and sex-matched CSC patients and controls (n = 37 in each group) were enrolled, and their psychosocial factors were compared. CSC was divided into two phases (active and inactive), and active CSC was further divided into two subtypes (acute and chronic). The correlations between the size of the hyperpermeable choroidal lesion identified on indocyanine green angiography and psychosocial factors were examined.
Active CSC patients experienced more stressful events (p = 0.030), were more depressive (p = 0.037), and felt less emotional (p = 0.014) and informational (p = 0.014) support than the matched controls, whereas inactive CSC patients were comparable to the matched controls in all psychosocial factors. Among the active CSC patients, acute patients were more depressive (p = 0.029), while chronic patients experienced more stressful events (p = 0.024) than their matched controls. The size of the hyperpermeable choroidal lesion was correlated with the severity of depression in acute patients.
Association of CSC with psychosocial factors was dependent on the phase and subtype of CSC. Psychosocial factors were associated with CSC in the active phase, and severity of depression was correlated with the size of the choroidal pathology in acute active CSC. Further prospective studies to investigate if psychosocial factors can trigger CSC are warranted.
Anxiety, Central serous chorioretinopathy, Choroid, Depression, Psychological stress
Association of Central Serous Chorioretinopathy with Psychosocial Factors is Dependent on Its Phase and Subtype
Yong-Kyu Kim,1,2 Se Joon Woo,corresponding author1 Kyu Hyung Park,1 Yeon Kyung Chi,3 Ji Won Han,3 and Ki Woong Kimcorresponding author3,4,5
Increased expression of the Tribbles pseudokinase 1 gene (TRIB1) is associated with lower plasma levels of LDL cholesterol and triglycerides, higher levels of HDL cholesterol and decreased risk of coronary artery disease and myocardial infarction. We identified a class of tricyclic glycal core-based compounds that upregulate TRIB1 expression in human HepG2 cells and phenocopy the effects of genetic TRIB1 overexpression as they inhibit expression of triglyceride synthesis genes and ApoB secretion in cells. In addition to predicted effects related to downregulation of VLDL assembly and secretion these compounds also have unexpected effects as they upregulate expression of LDLR and stimulate LDL uptake. This activity profile is unique and favorably differs from profiles produced by statins or other lipoprotein targeting therapies. BRD8518, the initial lead compound from the tricyclic glycal class, exhibited stereochemically dependent activity and the potency far exceeding previously described benzofuran BRD0418. Gene expression profiling of cells treated with BRD8518 demonstrated the anticipated changes in lipid metabolic genes and revealed a broad stimulation of early response genes. Consistently, we found that BRD8518 activity is MEK1/2 dependent and the treatment of HepG2 cells with BRD8518 stimulates ERK1/2 phosphorylation. In agreement with down-regulation of genes controlling triglyceride synthesis and assembly of lipoprotein particles, the mass spectrometry analysis of cell extracts showed reduced rate of incorporation of stable isotope labeled glycerol into triglycerides in BRD8518 treated cells. Furthermore, we describe medicinal chemistry efforts that led to identification of BRD8518 analogs with enhanced potency and pharmacokinetic properties suitable for in vivo studies.
Novel tricyclic glycal-based TRIB1 inducers that reprogram LDL metabolism in hepatic cells
Marek M. Nagiec,corresponding authora Jeremy R. Duvall,a Adam P. Skepner,a Eleanor A. Howe,a Jessica Bastien,a Eamon Comer,a Jean-Charles Marie,a Stephen E. Johnston,a Joseph Negri,a Michelle Eichhorn,a Julien Vantourout,a Clary Clish,b Kiran Musunuru,c Michael Foley,a Jose R. Perez,a and Michelle A. J. Palmera
2018 Nov 1
Background: It is well known that diabetes mellitus impairs immunity and therefore is an independent risk factor for tuberculosis. However, the influence of associated metabolic factors, such as hypertension, dyslipidemia and gout has yet to be confirmed. This study aimed to investigate whether the strong association between tuberculosis and diabetes mellitus is independent from the influence of hypertension and dyslipidemia, and its treatment in elderly Taiwanese patients. Methods: A total of 27,958 patients aged more than 65 years were identified from the National Health Insurance Research Database (NIHRD) in 1997 and were followed from 1998 to 2009. The demographic characteristics between the patients with and without diabetes were analyzed using the χ2 test. A total of 13,981 patients with type 2 diabetes were included in this study. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risk of tuberculosis. Results: After adjusting for age, sex, other co-morbidities and medications, calcium channel blocker, beta blocker and statin users had a lower independent association, with risk ratios of 0.76 (95% CI, 0.58-0.98), 0.72 (95% CI, 0.58-0.91) and 0.76 (95% CI, 0.60-0.97), respectively. Conclusion: Calcium channel blocker, beta blocker and statin therapy may decrease the incidence of tuberculosis infection in elderly Taiwanese patients with type 2 diabetes.
statin, beta blocker, calcium channel blocker, tuberculosis, elderly, diabetes
Statin, Calcium Channel Blocker and Beta Blocker Therapy May Decrease the Incidence of Tuberculosis Infection in Elderly Taiwanese Patients with Type 2 Diabetes
Mei-Yueh Lee,1,2 Kun-Der Lin,2 Wei-Hao Hsu,1,2 Hsiu-Ling Chang,3 Yi-Hsin Yang,4 Pi-Jung Hsiao,2,†* and Shyi-Jang Shin2,5,†*