ABSTRACT
Familial hypercholesterolemia (FH) is a common but underdiagnosed genetic disorder affecting cholesterol metabolism, leading to atherosclerotic disease. The relationship between retinal microvascular changes and the presence of atheroma in patients with FH (FH group), and in comparison to volunteers without FH (CT group), needs further investigation. This cross-sectional study was conducted in a university hospital between October 1, 2020 and May 31, 2021. Cardiovascular data, including the Coronary Artery Calcium (CAC) score, were recorded for FH patients. Macula angiograms were acquired using swept-source optical coherence tomography angiography (SS OCT-A) to analyze both the superficial capillary plexus (SCP) and deep capillary plexus (DCP). A total of 162 eyes of 83 patients were enrolled in the FH group and 121 eyes of 78 volunteers in the CT group. A statistically significant association was found between the CAC score and both vessel density (ß = -0.002 [95% CI, -0.004; -0.0005], p = 0.010) and vessel length (ß = -0.00005 [95% CI, -0.00008; -0.00001], p = 0.010) in the DCP. The FH group had a significantly lower foveal avascular zone circularity index than the CT group in multivariate analysis (0.67 ± 0.16 in the FH group vs. 0.72 ± 0.10 in the CT group, ß = 0.04 [95% CI, 0.002; 0.07], p = 0.037). Retinal microvascularization is altered in FH and retinal vascular densities are modified according to the CAC score.
ABSTRACT
Scabies is a major and potentially growing public health problem worldwide with an unmet need for acaricidal agents with greater efficacy and improved pharmacological properties for its treatment. The objective of the present study was to assess the efficacy and describe the pharmacokinetics profile of a novel acaricide, afoxolaner (AFX), in a relevant experimental porcine model. Twelve pigs were experimentally infested and either treated with 2.5 mg/kg single dose oral AFX (n = 4) or 0.2 mg/kg, two doses 8 days apart, oral ivermectin ([IVM] n = 4) or not treated for scabies (n = 4). The response to treatment was assessed by the reduction of mite counts in skin scrapings as well as clinical and pruritus scores over time. Plasma and skin pharmacokinetics profiles for both AFX and IVM were evaluated. AFX efficacy was 100% at days 8 and 14 posttreatment and remained unchanged until the study end (day 45). IVM efficacy was 86% and 97% on days 8 and 14, respectively, with a few mites recovered at the study end. Clinical and pruritus scores decreased in both treated groups and remained constant in the control group. Plasma mean residence times (MRT) were 7.1 ± 2.4 and 1.1 ± 0.2 days for AFX and IVM, respectively. Skin MRT values were 16.2 ± 16.9 and 2.7 ± 0.5 days for AFX and IVM, respectively. Overall, a single oral dose of AFX was efficacious for the treatment of scabies in experimentally infested pigs and showed remarkably long MRTs in plasma and, notably, in the skin.
Subject(s)
Antiparasitic Agents/pharmacology , Antiparasitic Agents/pharmacokinetics , Isoxazoles/pharmacology , Isoxazoles/pharmacokinetics , Naphthalenes/pharmacology , Naphthalenes/pharmacokinetics , Sarcoptes scabiei/drug effects , Scabies/drug therapy , Acaricides/pharmacokinetics , Acaricides/pharmacology , Animals , Disease Models, Animal , Female , Humans , Ivermectin/pharmacokinetics , Ivermectin/pharmacology , Scabies/metabolism , Scabies/parasitology , Skin/metabolism , Skin/parasitology , Swine , Swine Diseases/drug therapy , Swine Diseases/metabolism , Swine Diseases/parasitologyABSTRACT
The ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the method is high (about 20-30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays [VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu)] with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the "gold standard" VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.
