Relative exposure to psychiatric conditions and medications in pharmacy education.

INTRODUCTION: Common psychiatric conditions occur at rates similar to chronic medical conditions. This study aimed to evaluate the exposure to psychiatric disease states as comorbidities in relation to other common chronic conditions within the curriculum at one college of pharmacy. METHODS: Researchers reviewed course activities for instances of specific conditions as comorbidities. The comorbidities evaluated fell into two categories: psychiatric and non-psychiatric. The primary outcome was the frequency each comorbidity appeared within course content. Secondary outcomes included characterization of instances of comorbidities, including the semester, course topic, and corresponding step of the Pharmacists' Patient Care Process. Prevalence data were analyzed for the health system where students conducted experiential learning. RESULTS: Overall, hypertension, diabetes, and hyperlipidemia appeared as comorbidities more frequently in the curriculum than depression and anxiety, despite similar prevalence patterns between these conditions. Students received the most exposure to these conditions as comorbidities during team-based learning case activities in therapeutics courses taught during the second professional year. CONCLUSIONS: This study found that psychiatric conditions were represented as comorbidities less frequently in the curriculum, despite similar prevalence patterns with other common comorbid disease states. With this knowledge, educators may identify potential opportunities for enhancing the curriculum around psychiatric illnesses.

Systematic evaluation of the effect of different apolipoprotein A-I mimetic peptides on the performance of synthetic high-density lipoproteins in vitro and in vivo.

Synthetic high-density lipoproteins nanomedicine (sHDL) composed of apolipoprotein A-I (ApoA-I) mimetic peptides and lipids have shown very promising results for the treatment of various cardiovascular diseases. Numerous efforts have also been made to design different ApoA-I mimetic peptides to improve the potency of sHDL, especially the efficiency of reverse cholesterol transport. However, the way in which ApoA-I mimetic peptides affect the properties of sHDL, including stability, cholesterol efflux, cholesterol esterification, elimination in vivo, and the relationship of these properties, is still poorly understood. Revealing the effect of these factors on the potency of sHDL is important for the design of better ApoA-I mimetic peptides. In this study, three widely used ApoA-I mimetic peptides with different sequences, lengths, LCAT activation and lipid binding affinities were used for the preparation of sHDL and were evaluated in terms of physical/chemical properties, cholesterol efflux, cholesterol esterification, remodeling, and pharmacokinetics/pharmacodynamics. Our results showed that ApoA-I mimetic peptides with the highest cholesterol efflux and cholesterol esterification in vitro did not exhibit the highest cholesterol mobilization in vivo. Further analysis indicated that other factors, such as pharmacokinetics and remodeling of sHDL, need to be considered in order to predict the efficiency of cholesterol mobilization in vivo. Thus, our study highlights the importance of using the overall performance, rather than in vitro results alone, as the blueprint for the design and optimization of ApoA-I mimetic peptides.

Stability of Ketoprofen Methylester in Plasma of Different Species.

BACKGROUND: Pharmacokinetic and pharmacodynamic assessment of ester-containing drugs can be impacted by hydrolysis of the drugs in plasma samples post blood collection. The impact is different in the plasma of different species. OBJECTIVE: This study evaluated the stability of a prodrug, ketoprofen methylester (KME), in commercially purchased and freshly collected plasma of mouse, rat, dog, cat, pig, sheep, cattle and horse. METHODS: KME hydrolysis was determined following its incubation in commercially purchased and freshly collected plasma of those species. Different esterase inhibitors were evaluated for prevention of the hydrolysis in rat, dog and pig plasma. RESULTS: KME was rapidly hydrolyzed in both commercially purchased and freshly collected plasma of mouse, rat, and horse. The hydrolysis was initially quick and then limited in cat plasma. KME hydrolysis was minimum in commercially purchased plasma of dog, pig, sheep and cattle but substantial in freshly collected plasma of those species. Different esterase inhibitors showed different effects on the stability of KME in rat, dog and pig plasma. CONCLUSION: These results indicate that plasma of different species has different hydrolytic activities to estercontaining drugs. The activities in commercially purchased and freshly collected plasma may be different and species-dependent. Esterase inhibitors have different effects on preventing hydrolysis of the ester-containing drugs in the plasma of different species.

Characterization of apolipoprotein A-I peptide phospholipid interaction and its effect on HDL nanodisc assembly.

Background: Synthetic HDLs (sHDLs), small nanodiscs of apolipoprotein mimetic peptides surrounding lipid bilayers, were developed clinically for atheroma regression in cardiovascular patients. Formation of HDL involves interaction of apolipoprotein A-I (ApoA-I) with phospholipid bilayers and assembly into lipid-protein nanodiscs. Purpose: The objective of this study is to improve understanding of physico-chemical aspects of HDL biogenesis such as the thermodynamics of ApoA-I-peptide membrane insertion, lipid binding, and HDL self-assembly to improve our ability to form homogeneous sHDL nanodiscs that are suitable for clinical administration. Methods: The ApoA-I-mimetic peptide, 22A, was combined with either egg sphingomyelin (eSM) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) phospholipid vesicles to form sHDL. The sHDL assembly process was investigated through lipid vehicle solubilization assays and characterization of purity, size, and morphology of resulting nanoparticles via gel permeation chromatography (GPC), dynamic light scattering (DLS), and transmission electron microscopy (TEM). Peptide-lipid interactions involved were further probed by sum frequency generation (SFG) vibrational spectroscopy and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR). The pharmacokinetics of eSM-sHDL and POPC-sHDL nanodiscs were investigated in Sprague Dawley rats. Results: sHDL formation was temperature-dependent, with spontaneous formation of sHDL nanoparticles occurring only at temperatures exceeding lipid transition temperatures as evidenced by DLS, GPC, and TEM characterization. SFG and ATR-FTIR spectroscopy findings support a change in peptide-lipid bilayer interactions at temperatures above the lipid transition temperature. Lipid-22A interactions were stronger with eSM than with POPC, which resulted in the formation of more homogeneous sHDL nanoparticles with longer in vivo circulation time as evidenced the PK study. Conclusion: Physico-chemical characteristics of sHDL are in part determined by phospholipid composition. Optimization of phospholipid composition may be utilized to improve the stability and homogeneity of sHDL.