A Novel, Orally Bioavailable, Small-Molecule Inhibitor of PCSK9 With Significant Cholesterol-Lowering Properties In Vivo

Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibits the clearance of low-density lipoprotein (LDL) cholesterol (LDL-C) from plasma by directly binding with the LDL receptor (LDLR) and sending the receptor for lysosomal degradation. As the interaction promotes elevated plasma LDL-C levels, and therefore a predisposition to...

Alirocumab, evinacumab, and atorvastatin triple therapy regresses plaque lesions and improves lesion composition in mice

Atherosclerosis-related cardiovascular disease causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab-monoclonal...

Anacetrapib reduces (V)LDL-cholesterol by inhibition of CETP activity and reduction of plasma PCSK9

Recently, we showed in APOE*3-Leiden.CETP mice that anacetrapib attenuated atherosclerosis development by reducing (V)LDL-C rather than by raising HDL-C. Here, we investigated the mechanism by which anacetrapib reduces (V)LDL-C and whether this effect was dependent on the inhibition of CETP. APOE*3-Leiden.CETP mice were fed a Western type diet...

Cardiovascular risk markers during treatment with estradiol and trimegestone or dydrogesterone

Objective: To study cardiovascular risk markers in women taking estradiol/trimegestone or estradiol/dydrogesterone. Design: Multicenter, randomized, prospective, double-blind study of 184 healthy post-menopausal women randomized to 6 cycles of either estradiol (2 mg) + trimegestone (0.5 mg) (T-group) or estradiol (2 mg) + dydrogesterone (10 mg) ...

Eradication of Helicobacter pylori infection favourably affects altered gastric mucosal MMP-9 levels

Background: Helicobacter pylori gastritis is recognized as an important pathogenetic factor in peptic ulcer disease and gastric carcinogenesis, and is accompanied by strongly enhanced gastric mucosal matrix metalloproteinase-9 (MMP-9) levels. Aim: This study was performed to investigate whether H. pylori-affected gastric mucosal MMP-2 and MMP-9...

Alveolar macrophages suppress non-specific inflammation caused by inhalation challenge with trimellitic anhydride conjugated to albumin

Occupational exposure to low molecular weight chemicals, like trimellitic anhydride (TMA), can result in occupational asthma. Alveolar macrophages (AMs) are among the first cells to encounter these inhaled compounds and were previously shown to affect TMA-induced asthma-like symptoms in the Brown Norway rat (Valstar et al., Toxicol. Appl....

Anti-atherosclerotic effect of amlodipine, alone and in combination with atorvastatin, in APOE*3-Leiden/hCRP transgenic mice

We investigated the pleiotropic effects of a calcium antagonist (amlodipine) on early atherosclerosis development in the presence and absence of an HMG-CoA-reductase inhibitor (atorvastatin) in apolipoprotein E*3-Leiden/human C-reactive protein (E3L/CRP) transgenic mice. Male E3L/CRP transgenic mice were fed a cholesterol-containing diet either...

Systems biology, connectivity and the future of medicine

The concept of systems-based strategies in medicine is emerging, with systems pathology guiding an understanding of the multidimensional aspects of disease system fingerprints and systems pharmacology providing insight into dynamic system responses upon (multiple) drug perturbations. Knowledge of the changes of system characteristics during...

Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by Curosurf and N-acetylcysteine

Airborne exposure to lung-toxic agents may damage the lung surfactant system and epithelial and endothelial cells, resulting in a life-threatening pulmonary edema that is known to be refractory to treatment. The aim of this study was to investigate in rats (1) the respiratory injury caused by nose-only exposure to perfluoroisobutene (PFIB), and ...

Markers for Type II Collagen Breakdown Predict the Effect of Disease-Modifying Treatment on Long-Term Radiographic Progression in Patients with Rheumatoid Arthritis

Objective. To investigate in a randomized clinical trial setting with an aggressive combination-therapy arm and a mild-monotherapy arm, whether therapy-induced changes in urinary C-terminal crosslinking telopeptide of type I collagen (CTX-I) and type II collagen (CTX-II) predict 5-year radiographic progression in patients with rheumatoid...

Differential effects of amlodipine and atorvastatin treatment and their combination on atherosclerosis in ApoE*3-Leiden transgenic mice

This study was designed to investigate the potential antiatherosclerotic effects of the calcium antagonist amlodipine as compared with the HMG-CoA reductase inhibitor atorvastatin and the combination of both in ApoE*3-Leiden transgenic mice. Four groups of 15 ApoE*3-Leiden mice were put on a high-cholesterol diet. One group received 0.002% (wt...

Bone turnover, joint damage and bone mineral density in early rheumatoid arthritis treated with combination therapy including high-dose prednisolone

Objectives. Exploration of bone metabolism changes at different levels of disease activity, both with and without oral corticosteroid therapy, and prediction of changes in joint damage and bone density from the observed changes in markers of bone turnover. Methods. Data analysis from a randomized clinical trial with 155 rheumatoid arthritis (RA)...

Erytromycine bij prematuur gebroken vliezen gunstig voor de gezondheid van het kind [Erythromycin for premature rupture of membranes is beneficial for infant]

In the 'Overview of the role of antibiotics in curtailing labour and early delivery'(ORACLE I)-trial in women with premature rupture of membranes, the use of erythromycin was found to be associated with a decrease in the primary composite outcome (neonatal death, chronic lung disease or major cerebral abnormality on ultrasound; p = 0.08) and in...

The influence of improved glycaemic control with insulin and sulphonylureas on acute phase and endothelial markers in Type II diabetic subjects

Aims/hypothesis. Improved glycaemic control might reduce both microvascular and macrovascular complications of Type II diabetes (non-insulin-dependent) mellitus. To explore such possible mechanisms, we investigated the effects of intensive treatment on markers of endothelial dysfunction and of acute phase activation, using both sulphonylureas...

The potential of Lactobacillus as a carrier for oral immunization: Development and preliminary characterization of vector systems for targeted delivery of antigens

Oral administration of lactobacilli evokes mucosal and systemic immune responses against epitopes associated with these organisms (Gerritse et al., 1990, 1991). The adjuvant function of different Lactobacillus species was investigated under the conditions of intraperitoneal (i.p.) injection or oral administration. After i.p. injection of...

Quality of life: 1. Perspectives

Assessing the value of health care interventions is more and more a concern of governments, clinicians, health insurance companies, policy makers, and the general public. One dimension of the outcomes of such interventions that has received relatively little attention until recently is quality of life. However, during the last decade, measuring...

Plasminogen activator inhibitors

Chemicals/CAS: fibrin, 9001-31-4; plasminogen activator inhibitor, 105844-41-5; plasminogen activator, 9039-53-6; Carrier Proteins; Glycoproteins; Plasminogen Activators, EC 3.4.21.-; Plasminogen Inactivators; Protease Inhibitors; protease-nexin

Fibrinolysis and calcium [fibrinolyse und kalzium]

Chemicals/CAS: calcium chloride, 10043-52-4; calcium, 7440-70-2; citric acid, 126-44-3, 5949-29-1, 77-92-9, 8002-14-0; edetic acid, 150-43-6, 60-00-4