BACKGROUND: Previous studies indicated that a recently approved synthetic HMG-CoA reductase inhibitor, atorvastatin, reduces LDL cholesterol and triglyceride. To assess the efficacy on the level of serum LDL cholesterol and other lipoprotein fractions and its safety, we investigated 59 patients for lipid and side effect profile. METHOD: In patients with hypercholesterolemia, who showed 12-hours fasting serum LDL cholesterol>145 mg/dl and <250 mg/dl and triglyceride levels<400 mg/dl were enrolled to diet therapy for 4 weeks. After 4 weeks of diet therapy, serum lipid profile were reevaluated and patients with LDL cholesterol > or =130 mg/dl were assigned to receive 10 mg dose of atorvastatin once daily for 4weeks. After 4 weeks of drug therapy, serum lipid profile were rechecked, if showed LDL cholesterol level> or =130 mg/dl, assigned to receive 20 mg dose of atorvastatin once daily until 8 weeks. RESULTS: Of the 59 patients were assigned to receive atorvastatin therapy, 52 patients completed the study. Among lipid profiles, total cholesterol, triglyceride, LDL-cholesterol and apolipoprotein B levels showed significant reduction with mean reduction rate of 28%, 13%, 38%, 32% respectively after 4 weeks and 31%, 13%, 41% and 34% respectively after 8 weeks. HDL-Cholesterol and lipoprotein (a) level did not show significant change after 8 weeks of therapy. Nine patients had mild adverse events, such as elevated ALT, epigastric pain, insomnia, thumb pain. postural hypotension, palpitation and constipation. Only three patients of fifty-nine withdrew from the study due to adverse events related to drug treatment. CONCLUSION: The atorvastatin was highly effective and generally well tolerated with an acceptable safety profile in patients with primary hypercholestelemia.
Apolipoproteins ; Cholesterol ; Cholesterol, LDL ; Constipation ; Diet Therapy ; Drug Therapy ; Fasting ; Humans ; Hypercholesterolemia* ; Hypotension, Orthostatic ; Lipoprotein(a) ; Lipoproteins ; Oxidoreductases ; Sleep Initiation and Maintenance Disorders ; Thumb ; Triglycerides ; Atorvastatin Calcium

Keratinocyte-fibroblast interactions are critical for skin repair after injury. During the proliferative phase of wound healing, proliferation, migration and differentiation of these cells are the major mechanisms leading to tissue remodeling. We have previously reported that glycitin, a major soy isoflavone, stimulates dermal fibroblast proliferation; and the phytochemical, 4′,6,7-trimethoxyisoflavone (TMF), induces migration of HaCaT keratinocyte cells. We therefore investigated whether these compounds display synergistic effects on skin cells during wound healing in vitro and in vivo. Co-treatment with TMF and glycitin synergistically promotes the proliferation and migration of both keratinocytes and dermal fibroblasts, with a 1:1 ratio of these compounds showing the greatest efficacy in our co-culture system. This keratinocyte-fibroblast interaction occurred via the secretion of TGF-β, and the induction of differentiation and proliferation was confirmed in both indirect and direct co-culture assays. In an excisional and burn wound animal model, mice treated with a 1:1 ratio of TMF and glycitin showed faster wound closure, regeneration and scar reduction than even the positive control drug. These data indicate that two isoflavones, TMF and glycitin, act synergistically to promote wound healing and anti-scarring and could potentially be developed together as a bioactive therapeutic for wound treatment.
Animals ; Burns ; Cicatrix ; Coculture Techniques ; Fibroblasts* ; In Vitro Techniques ; Isoflavones ; Keratinocytes* ; Mice ; Models, Animal ; Regeneration ; Skin ; Wound Healing* ; Wounds and Injuries*

Microglial cells are the resident innate immune cells that sense pathogens and tissue injury in the central nervous system (CNS). Microglial activation is critical for neuroinflammatory responses. The synthetic compound 2-hydroxy-3',5,5'-trimethoxychalcone (DK-139) is a novel chalcone-derived compound. In this study, we investigated the effects of DK-139 on Toll-like receptor 4 (TLR4)-mediated inflammatory responses in BV2 microglial cells. DK-139 inhibited lipopolysaccharide (LPS)-induced TLR4 activity, as determined using a cell-based assay. DK-139 blocked LPS-induced phosphorylation of IkappaB and p65/RelA NF-kappaB, resulting in inhibition of the nuclear translocation and trans-acting activity of NF-kappaB in BV2 microglial cells. We also found that DK-139 reduced the expression of NF-kappaB target genes, such as those for COX-2, iNOS, and IL-1beta, in LPS-stimulated BV2 microglial cells. Interestingly, DK-139 blocked LPS-induced Akt phosphorylation. Inhibition of Akt abrogated LPS-induced phosphorylation of p65/RelA, while overexpression of dominant-active p110CAAX enhanced p65/RelA phosphorylation as well as iNOS and COX2 expression. These results suggest that DK-139 exerts an anti-inflammatory effect on microglial cells by inhibiting the Akt/IkappaB kinase (IKK)/NF-kappaB signaling pathway.
Animals ; Binding Sites ; Cell Line ; Chalcones/chemistry/*pharmacology ; Cyclooxygenase 2/metabolism ; I-kappa B Kinase/metabolism ; Inflammation/*drug therapy ; Interleukin-1beta/metabolism ; Lipopolysaccharides/immunology ; Microglia/*drug effects/immunology/metabolism ; Molecular Dynamics Simulation ; NF-kappa B/*antagonists & inhibitors ; Nitric Oxide Synthase Type II/metabolism ; Phosphorylation/drug effects ; Protein Binding ; Proto-Oncogene Proteins c-akt/*antagonists & inhibitors ; Rats ; Signal Transduction ; Toll-Like Receptor 4/*antagonists & inhibitors/metabolism ; Transcription Factor RelA/metabolism

A three-dimensional (3D) segmentation and model reconstruction is a specialized tool to reveal spatial interrelationship between multiple internal organs by generating images without overlapping structures. This technique can also be applicable to mummy studies, but related reports have so far been very rare. In this study, we applied 3D segmentation and model reconstruction to computed tomography images of a Korean mummy with congenital diaphragmatic hernia. As originally revealed by the autopsy in 2013, the current 3D reconstruction reveals that the mummy’s heart is shifted to the left due to the liver pushing up to thoracic cavity thorough diaphragmatic hernial defect. We can generate 3D images by calling up the data exclusively from mummy’s target organs, thus minimizing the confusion of diagnosis that could be caused by overlapping organs.