scholarly journals Reduced nontarget embolization and increased targeted delivery with a reflux-control microcatheter in a swine model

Author(s):  
Silvia Rizzitelli ◽  
Nir Holtzman ◽  
Geert Maleux ◽  
Thierry De Baere ◽  
Fei Sun ◽  
...  
Author(s):  
Salvatore R. Aiello ◽  
Jenna B. Mendelson ◽  
Alvin Baetiong ◽  
Jeejabai Radhakrishnan ◽  
Raúl J. Gazmuri

Background We previously reported that resuscitation delivering electrical shocks guided by real‐time ventricular fibrillation amplitude spectral area (AMSA) enabled return of spontaneous circulation (ROSC) with fewer shocks, resulting in less myocardial dysfunction. We now hypothesized that AMSA could also guide delivery of epinephrine, expecting further outcome improvement consequent to less electrical and adrenergic burdens. Methods and Results A swine model of ventricular fibrillation was used to compare after 10 minutes of untreated ventricular fibrillation a guidelines‐driven (n=8) resuscitation protocol, delivering shocks every 2 minutes and epinephrine every 4 minutes, with an AMSA‐driven shocks (n=8) protocol, delivering epinephrine every 4 minutes, and with an AMSA‐driven shocks and epinephrine (ADSE; n=8) protocol. For guidelines‐driven, AMSA‐driven shocks, and ADSE protocols, the time to ROSC (mean±SD) was 569±164, 410±111, and 400±80 seconds ( P =0.045); the number of shocks (mean±SD) was 5±2, 3±1, and 3±2 ( P =0.024) with ADSE fewer than guidelines‐driven ( P =0.03); and the doses of epinephrine (median [interquartile range]) were 2.0 (1.3–3.0), 1.0 (1.0–2.8), and 1.0 (0.3–3.0) ( P =0.419). The ROSC rate was similar, yet survival after ROSC favored AMSA‐driven protocols (guidelines‐driven, 3/6; AMSA‐driven shocks, 6/6; and ADSE, 7/7; P =0.019 by log‐rank test). Left ventricular function and survival after ROSC correlated inversely with electrical burden (ie, cumulative unsuccessful shocks, J/kg; P =0.020 and P =0.046) and adrenergic burden (ie, total epinephrine doses, mg/kg; P =0.042 and P =0.002). Conclusions Despite similar ROSC rates achieved with all 3 protocols, AMSA‐driven shocks and ADSE resulted in less postresuscitation myocardial dysfunction and better survival, attributed to attaining ROSC with less electrical and adrenergic myocardial burdens.


2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide


2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>


2018 ◽  
Author(s):  
James Leighton ◽  
Linda M. Suen ◽  
Makeda A. Tekle-Smith ◽  
Kevin S. Williamson ◽  
Joshua R. Infantine ◽  
...  

With an average GI50 value against the NCI panel of 60 human cancer cell lines of 0.12 nM, spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. It is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive, however, and its development requires more efficient and step-economical synthetic access. Using novel and uniquely enabling direct complex fragment coupling alkallyl- and crotylsilylation reactions, we have developed a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is equipotent with the natural product, and have used that synthesis to establish that the C(15) acetate may be replaced with a linker functional group-bearing ester with only minimal reductions in potency.<br><div><br></div>


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