L. Previato

Pro-inflammatory monocyte-macrophage polarization imbalance in human hypercholesterolemia and atherosclerosis

Monocyte-macrophages (MoMas) play a major role in atherosclerosis. In mice, hypercholesterolemia increases pro-inflammatory monocytes that promote plaque growth, but whether this is true also in humans in unknown. We herein analyzed monocyte subsets and MoMa phenotypes in familiar (FH, n = 22) and non-familiar (NFH, n = 20) hypercholesterolemic compared with normocholesterolemic (CTRL, n = 20) patients. We found that FH and NFH had higher circulating pro-inflammatory CD68(+)CCR2(+) M1 MoMas than CTRL, while anti-inflammatory CX3CR1(+)CD163(+)/CD206(+) M2 MoMas were reduced only in NFH. As a result, the M1/M2 polarization balance was increased in FH and, more markedly in NFH. M1 MoMas and the M1/M2 polarization ratio were directly correlated to pre-treatment LDL cholesterol levels and strongly associated with the presence of atherosclerotic plaques. In conclusion, we show for the first time that human hypercholesterolemia is associated with a pro-inflammatory imbalance of circulating monocytic cells, which can predispose to the development of atherosclerosis.

Selection of diagnostic tests for clinical decision making and translation to a problem oriented medical record

The leading function of the physician is the clinical reasoning, which involves appropriate investigation of the problems of the patient, formulation of a diagnostic suspect based on the patients symptoms and signs, gathering of additional relevant information, to select necessary tests and administration of the most suitable therapy. The problems of the patient are expressed by symptoms or signs or abnormal test results, requested for a variety of reasons. The entire scientific, as well as diagnostic approach, is based on three steps: to stumble in a problem; to try a solution through a hypothesis; to disprove or to prove the hypothesis by a process of criticism. Clinicians use the information obtained from the history and physical examination to estimate initial (or pre-test) probability and then use the results from tests and other diagnostic procedures to modify this probability until the post-test probability is such that the suspected diagnosis is either confirmed or ruled out. When the pre-test probability of disease is high, tests characterized by high specificity will be preferred, in order to confirm the diagnostic suspect. When the pre-test probability of disease is low, a test with high sensitivity is advisable to exclude the hypothetical disease. The above mentioned process of decision making has been transferred to a problem oriented medical record that is currently employed in our Clinic.

Apolipoprotein C-II Deficiency Syndrome: New Insights into the Molecular Mechanism Leading to the Disease in the Apo C-II Padova Kindred

Human apolipoprotein C-II (apo C-II) is a 79 amino acid protein secreted primarily by the liver and present in plasma associated with triglyceride-rich lipoproteins and high density lipoproteins (HDL)1. As a cofactor for lipoprotein lipase, the enzyme that catalyzes the hydrolysis of triglycerides on lipoproteins, the presence of normal apo C-II is crucial for normal lipoprotein metabolism2,3.

Apo C-IIPadova: A New Apoprotein Variant in Two Patients with Apo C-II Deficiency Syndrome

Apoprotein C-II, present in chylomicrons, VLDL, and HDL is the co-factor of lipoprotein lipase, the enzyme responsible for trigly-ceride-rich lipoproteins catabolism1.