Clinical Potential of an Enzyme-Based Novel Therapy for Cocaine Overdose

It is a grand challenge to develop a truly effective medication for treatment of cocaine overdose. The current available, practical emergence treatment for cocaine overdose includes administration of a benzodiazepine anticonvulsant agent (e.g. diazepam) and/or physical cooling with an aim to relieve the symptoms. The inherent difficulties of antagonizing physiological effects of drugs in the central nervous system have led to exploring protein-based pharmacokinetic approaches using biologics like vaccines, monoclonal antibodies, and enzymes. However, none of the pharmacokinetic agents has demonstrated convincing preclinical evidence of clinical potential for drug overdose treatment without a question mark on the timing used in the animal models. Here we report the use of animal models, including locomotor activity, protection, and rescue experiments in rats, of drug toxicity treatment with clinically relevant timing for the first time. It has been demonstrated that an efficient cocaine-metabolizing enzyme developed in our previous studies can rapidly reverse the cocaine toxicity whenever the enzyme is given to a living rat, demonstrating promising clinical potential of an enzyme-based novel therapy for cocaine overdose as a successful example in comparison with the commonly used diazepam

H2O2-Responsive Vesicles Integrated with Transcutaneous Patches for Glucose-Mediated Insulin Delivery

A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia

Mixed-crystal infrared studies of chain folding in polyethylene single crystals: Effect of crystallization temperature

Mixed crystals of polyethylene (PEH) and various-molecular-weight perdeuterated polyethylenes (PEDs) have been prepared at 80°C and their infrared spectra compared with those of samples grown at 55°C. Concentrations of 80 PEH/1 PED were required in the former case to eliminate segregation effects whereas 40 PEH/1 PED sufficed in the latter. Resolution of the observed CD 2 bend contour was most reasonably achieved with a crystalline singlet and two crystalline doublets, in addition to a contribution (ca. 15%) from the noncrystalline component. The singlet, comprising about 20% of the crystalline area, contains contributions from both isolated stems and (200) adjacent reentry folding. Random reentry folding is therefore not a predominant mode of chain organization in polyethylene single crystals. The inner of the two doublets arises from adjacent reentry folding along single (110) planes, and is present for all PED molecular weights. For low-molecular-weight fractions this splitting is consistent with the number of stems of one PED molecule allowed in the crystal. The outer doublet arises from multiple (110) plane adjacency, and is present for intermediate and high molecular weights. An analysis of both doublets suggests that at high molecular weights a single molecule can crystallize with noncontiguous regions of adjacent stem domains.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38669/1/180200705_ftp.pd

Vibrational analysis of 2,3-dichlorobutanes

Using intensity changes from liquid to solid for meso- and racemic-2,3-dichlorobutanes, and preliminary normal mode calculations based on a force field for secondary chlorides, we have been able to identify the bands associated with the trans and gauche conformers of these molecules and thereby to refine a force field for secondary Cl atoms on vicinal C atoms. This has permitted assignment of the SHCl, as well as SHH and SHH', C---Cl stretch modes in such molecules.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25391/1/0000840.pd

Mixed-crystal infrared studies of chain folding in melt-crystallized polyethylene

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38732/1/130210209_ftp.pd