Background: Synthetic forms of glucocorticoids (GCs; eg, prednisone, prednisolone) are anti-inflammatory drugs that are widely used in clinical practice. The role of GCs in cardiovascular diseases, including atherosclerosis, is highly controversial, and their impact on macrophage foam cell formation is still unknown. We investigated the effects of prednisone and prednisolone on macrophage oxidative stress and lipid metabolism. Methods and Results: C57BL/6 mice were intraperitoneally injected with prednisone or prednisolone (5 mg/kg) for 4 weeks, followed by lipid metabolism analyses in the aorta and peritoneal macrophages. We also analyzed the effect of serum samples obtained from 9 healthy human volunteers before and after oral administration of prednisone (20 mg for 5 days) on J774A.1 macrophage atherogenicity. Finally, J774A.1 macrophages, human monocyte-derived macrophages, and fibroblasts were incubated with increasing concentrations (0-200 ng/mL) of prednisone or prednisolone, followed by determination of cellular oxidative status, and triglyceride and cholesterol metabolism. Prednisone and prednisolone treatment resulted in a significant reduction in triglyceride and cholesterol accumulation in macrophages, as observed in vivo, ex vivo, and in vitro. These effects were associated with GCs’ inhibitory effect on triglyceride- and cholesterol-biosynthesis rates, through downregulation of diacylglycerol acyltransferase 1 and HMG-CoA reductase expression. Glucocorticoid-induced reduction of cellular lipid accumulation was mediated by the GC receptors on the macrophages, because the GC-receptor antagonist (RU486) abolished these effects. In fibroblasts, unlike macrophages, GCs showed no effects. Conclusion: Prednisone and prednisolone exhibit antiatherogenic activity by protecting macrophages from lipid accumulation and foam cell formation.
Objectives To investigate the association between KCNQ1 rs2237892, KLF14 rs972283, ZBED3 rs4457053, COL8A1 rs792837, and FTO rs8050136; gene polymorphisms; and T2DM in the male Palestinian population. Methods In this case-control study, 100 T2DM male patients and 100 control men were examined. The two groups were genotyped for the five gene polymorphisms using restriction fragment length polymorphism–PCR (RFLP-PCR) and allele-specific (AS-PCR) techniques. Body mass index (BMI), glycated hemoglobin (HbA1c), insulin (C-peptide), total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-c), and low-density lipoprotein cholesterol (LDL-c) were measured for all the study participants. The relation between the five gene polymorphisms, T2DM, and the measured clinical parameters were statistically analyzed using appropriate tests. Results Among the tested polymorphisms, significant associations were evident between KLF14 “GG” genotype (P = .014), FTO “CC” genotype (P = .043), and COL8A1 TC genotype (P = .015) and increased risk of T2DM. The KLF14 G-containing genotypes exerted a significant effect on lowering HDL-c (P = .026) and on elevating LDL-c (P = .045) and cholesterol level (P = .042) in the control group. The FTO “CC” genotype showed a significant effect on raising HbA1c level in the patients (P = .007). KCNQ1 (rs2237892 T>C), ZBED3 (rs4457053 A>G), and COL8A1 (rs792837 T>C) genotypes did not reveal significant effects on the tested parameters. Conclusion KLF14 “GG,” FTO “CC,” and COL8A1 C allele and “TC” genotypes are significantly associated with T2DM in the investigated population. KLF14 “GG” and “AG” have an association with the levels of HDL-c, LDL-c, and cholesterol in control subjects. The HbA1c level was significantly higher in patients with the FTO “CC” genotype. The study recommends confirming the obtained results on a larger sample and examining the association of other gene polymorphisms with T2DM in the Palestinian population.
Background: Intravenous levothyroxine (IVT4) is FDA-approved for the treatment of myxedema coma (ME). ATA guidelines also acknowledge other rare situations, mostly such where oral/enteral access is compromised for prolonged periods, in which IVT4 may be appropriate. We noticed that at our hospital, IVT4 is administered more frequently than expected. Aim of study: To assess the extent of IVT4 administration, the indications for such a treatment, and its outcome at a tertiary facility. Study design and Methods: A retrospective study of IVT4 administered to adult inpatients at Tel Aviv-Sourasky Medical Center between January 2017 and July 2020. A list of dispensed T4 vials during the period of interest was generated from the hospital pharmacy computerized database. Patients’ charts were searched for relevant clinical and laboratory data. Results: 107 patients (62 W/45 M), age 62.5±17.3 y (range 20-97) received IV T4, in the course of 113 hospitalizations. 94 subjects had primary hypothyroidism (PH), 10 had central hypothyroidism, while 3 subjects had no documented evidence of hypothyroidism. ME was likely in only 4 cases (3.5%). The leading stated indication for IVT4 was profound hypothyroidism in 57 instances (50.4%), jeopardized enteral route in 11 (9.7%), while no clear or justifiable indication was found in 39 cases (34.5%). An official endocrine consult backed treatment 74 times (65.5%). In subjects with PH, median serum TSH prior to treatment was 36.4 mIU/L (IQR 8-42), while free T4 was 0.4 ng/dl (IRQ 0.22-0.61, normal 0.8-1.7). In subjects with no ME, altered consciousness was present in 19%, bradycardia in 6.3% and 4.5% were hypothermic. The median initial dose of IV-T4 was 150 μg (range 20-500). Repeated administrations ranged from 1 to 29 times, with a median cumulative dose of 250 μg (IQR 150-400, range 20-3300). We could not identify adverse events directly attributable to IV-T4. Of the 113 admissions, 61 ended in patient’s recovery and discharge (54%), 22 (19.5%) in transfer to a rehab or nursing facility, while there were 30 cases of death (26.5%). Only one of the 4 patients with presumed ME died. In a logistic regression model, that also included age, gender, and ICU admission, the only variable that significantly predicted death was a need for artificial ventilation (OR:27.8, CI 3.5-189). In contrast, free T4, TSH, hospitalization length, altered consciousness, and other potential variables, were excluded from the equation. Conclusions: IVT4 administration is a common practice at our hospital. In a small minority of cases (13.2%), it is given for approved clinical conditions, while in all the others it appears to be unjustified. Reports on this practice are all but absent from the literature. Studies from other institutions are needed to determine its global extent, safety, and efficacy. Until it is proven safe and cost-effective, greater caution should be exercised before allowing it.
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