Determination of stability constants of the inclusion complexes of β-blockers in heptakis (2,3-dimethyl-6-sulfato)-β-cyclodextrin

The beta-blockers possess at least one chiral center and the S(-)-enantiomer shows higher affinity for binding to the beta-adrenergic receptors than antipode. The stability constants of acebutolol, celiprolol, propranolol and terbutaline in the inclusion complexes with single-isomer heptakis (2,3-dimethyl-6-sulfato)-beta-cyclodextrin (HDMS-beta-CD) were determined by capillary electrophoresis. The approximation and linear double reciprocal methods were adapted with comparable results. Among the beta-blockers studied, propranolol had the lowest stability constant but the highest enantioselectivity, indicating that the magnitudes of the stability constants carried little information about enantioseparation. The magnitudes of enantioselectivities between the enantiomer pair were in the order of propranolol > celiprolol > terbutaline > acebutolol.     

PET Radioligands for Imaging of Tau Pathology: Current Status

The incidence of Alzheimer’s disease (AD), a progressive neurodegenerative disorder, continues to soar with the rapid growth of the elderly population, thus creating an enormous social and economic burden. Although disease-modifying drugs to treat AD are not yet available, several candidate drugs are in clinical trials. Most of these drugs are expected to be effective at the early stages of the disease, and therefore the early and accurate diagnosis of AD will be a critical factor in efforts to improve the prognosis of patients with AD. This review focuses on lead radioligands developed to date and their preclinical data in order to facilitate the development of tau-specific positron emission tomography radioligands that are of great interest to the scientific community.     

Protocatechuic acid extends lifespan and increases stress resistance in Caenorhabditis elegans

Veronica peregrina has a wide range of types of constituents with various pharmacological properties. Here in this study, we isolated protocatechuic acid (PCA) from V. peregrina and examined PCAs effects on the lifespan and stress tolerance using Caenorhabditis elegans model system. We found that lifespan of wild-type worms was significantly lengthened in the presence of PCA in a dose dependent manner. PCA also elevated tolerance of worms against osmotic, heat shock, and oxidative stress. We also demonstrated antioxidant capacity of PCA by checking intracellular reactive oxygen species level and antioxidant enzyme activities such as catalase and superoxide dismutase. We further investigated several factors including pharyngeal pumping rate and progeny production that might influence prolonged lifespan and enhanced stress tolerance by PCA. Interestingly, both factors were significantly reduced after PCA exposure, indicating PCA exerts longevity activity by shifting food intake and reproduction at least in part. In addition, PCA-treated aged worms showed increased body movement compared to untreated controls suggesting PCA could enhance healthspan as well as lifespan.     

Total Talar Extrusion without Soft Tissue Attachments

Total talar extrusion without a soft tissue attachment is an extremely rare injury and is rarely reported. Appropriate treatment remains controversial. We describe the long-term outcomes of two patients who had complete talar extrusion without remaining soft tissue attachment treated with arthrodesis. Both of our patients had complications such as infection and progressive osteolysis. We suggest reimplantation of the extruded talus after thorough debridement as soon as possible as a reasonable option unless the talus is contaminated or missing, because an open wound may arise from inside to outside.