ABSTRACT
We herein report a rare case presenting with severe hypercholesterolemia, massive Achilles tendon xanthomas, and multi-vessel coronary artery disease. Initially, the patient was misdiagnosed with familial hypercholesterolemia. However, a genetic analysis using our custom sequencing panel covering genes associated with Mendelian lipid disorders revealed him to have a genetic basis of sitosterolemia with compound heterozygous mutations in the adenosine triphosphate binding cassette subfamily G5 (ABCG5) gene. A comprehensive genetic analysis can be particularly useful for diagnosing cases with severe phenotypes, leading to appropriate and medical therapies. Our patient was refractory to statins, whereas ezetimibe and PCSK9 inhibitor with a low-plant-sterol diet successfully reduced his serum levels of low-density lipoprotein cholesterol.
Subject(s)
ATP Binding Cassette Transporter, Subfamily G, Member 5/genetics , Antibodies, Monoclonal, Humanized/therapeutic use , Ezetimibe/therapeutic use , Hypercholesterolemia/drug therapy , Intestinal Diseases/drug therapy , Intestinal Diseases/genetics , Lipid Metabolism, Inborn Errors/drug therapy , Lipid Metabolism, Inborn Errors/genetics , Phytosterols/adverse effects , Xanthomatosis/drug therapy , Achilles Tendon/physiopathology , Anticholesteremic Agents/therapeutic use , Cholesterol, LDL/blood , Cholesterol, LDL/drug effects , Humans , Hypercholesterolemia/complications , Hypercholesterolemia/diagnosis , Hypercholesterolemia/etiology , Hypercholesterolemia/genetics , Intestinal Diseases/complications , Intestinal Diseases/diagnosis , Lipid Metabolism, Inborn Errors/complications , Lipid Metabolism, Inborn Errors/diagnosis , Male , Middle Aged , Mutation , Phytosterols/genetics , Treatment Outcome , Xanthomatosis/etiology , Xanthomatosis/physiopathologyABSTRACT
A 78-year-old man with mild coronary arteriosclerosis on coronary CT angiography underwent MRI of the prostate with the administration of Gadolinium-based contrast agent (GBCA) (gadopentetate dimeglumine). He developed acute coronary syndrome immediately after the intravenous injection of GBCA, and recovered after the administration of nitroglycerine, atropine sulfate, and hydrocortisone. He was discharged on the ninth day of hospitalization without recurrent chest symptoms. This is the second reported case of Kounis syndrome caused by GBCA. Kounis syndrome caused by MR contrast media is rare, but we should recognize that all contrast agents have the potential to cause Kounis syndrome.
Subject(s)
Acute Coronary Syndrome/chemically induced , Arrhythmias, Cardiac/chemically induced , Contrast Media/adverse effects , Gadolinium DTPA/adverse effects , Kounis Syndrome/etiology , Magnetic Resonance Imaging/methods , Acute Coronary Syndrome/physiopathology , Aged , Coronary Angiography , Coronary Artery Disease/complications , Coronary Artery Disease/diagnostic imaging , Electrocardiography , Humans , Injections, Intravenous , Kounis Syndrome/physiopathology , Magnetic Resonance Imaging/adverse effects , Male , Prostate/diagnostic imagingABSTRACT
Left ventricular (LV) adrenomedullin (AM) gene expression differs between pressure overload (POL) and volume overload (VOL) and angiotensin II could be a critical stimulator of AM gene expression in POL and VOL models. Calcitonin receptor-like receptor (CRLR) co-expressed with receptor activity modifying protein 2 (RAMP2) or RAMP3 functions as an AM receptor. Levels of CRLR, RAMP2 and RAMP3 mRNA that were significantly increased within 24 h returned to the basal level at 5 days after the imposition of POL in the present study. In contrast, mRNA levels of CRLR and RAMP2 gradually increased over 6 weeks after the imposition of VOL. Continuous infusion of angiotensin II stimulated LV AM gene and AM receptor gene expression independently of LV peak-systolic and LV end-diastolic pressure. The gene expression of LV AM receptors increased in different types of cardiac overload. The present study revealed an intimate association between the AM signaling system and angiotensin II.
Subject(s)
Angiotensin II/metabolism , Gene Expression Regulation , Heart/physiopathology , Receptors, Peptide/metabolism , Animals , Calcitonin Receptor-Like Protein , Disease Models, Animal , Hemodynamics , Intracellular Signaling Peptides and Proteins , Male , Membrane Proteins/genetics , Nuclear Proteins/genetics , Pressure , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Rats, Wistar , Receptor Activity-Modifying Protein 2 , Receptor Activity-Modifying Protein 3 , Receptor Activity-Modifying Proteins , Receptors, Adrenomedullin , Receptors, Calcitonin/genetics , Receptors, Peptide/genetics , Ubiquitin-Protein LigasesABSTRACT
Aliphatic and aromatic sulfonamides were alkynylated with 1-bromo-1-alkynes in the catalytic presence of CuI to give N-(1-alkynyl)sulfonamides in good to excellent yields. The acetylene-titanium complexes generated from N-(1-alkynyl)benzosultams underwent diastereoselective addition to aldehydes. [reaction: see text]
ABSTRACT
Ynamide-titanium alkoxide complexes underwent hydrolysis or addition to aldehydes and ketones to give single, stereodefined di- or trisubstituted enamides in good yields. Alternatively, coupling of a variety of alkyne-titanium alkoxide complexes with terminal ynamides generated amino-substituted titanacyclopentadienes, hydrolysis or aldehyde addition of which afforded stereodefined dienamides. [reaction--see text]
ABSTRACT
To determine whether acute pressure overload (POL) can stimulate adrenomedullin (AM) production, the response of ventricular AM gene expression and plasma AM concentration to aortic banding was investigated in the rat. Furthermore, any link between AM expression and the renin-angiotensin system (RAS) enhanced by acute POL was examined using: a Ca channel blocker (manidipine), an angiotensin II type 1 receptor antagonist (candesartan), and an angiotensin-converting enzyme inhibitor (quinapril). Rats with acute POL produced by suprarenal aortic banding were studied 1, 5 and 14 days after surgery. Plasma AM concentrations in banded rats at day 1 increased 1.49-fold (p<0.01), then gradually declined to near the control level at day 14. Plasma AM concentrations correlated with plasma renin activity (PRA) (p<0.001). Adrenomedullin mRNA expression in the left ventricle (LV) increased 1.35-fold (p<0.05) at day 1. This increase was not significant at either 5 or 14 days after surgery. Adrenomedullin mRNA expression in the right ventricle on days 1 and 5 increased by 1.46-fold (p<0.05) and 1.52-fold (p<0.05), respectively. Candesartan, quinapril and manidipine reduced systolic blood pressure equally and activated PRA at day 1. However, augmented LV AM gene expression was suppressed completely by candesartan and quinapril, but remained unaffected by manidipine. In conclusion, POL induces a rapid increase in cardiac AM gene expression and in plasma AM concentrations. Cardiac AM transcription could therefore be partly regulated by RAS in suprarenal aortic banding rats.
