design-use-low-cost-automated-morbidostat-for-adaptive-evolution

Design and Use of a Low Cost, Automated Morbidostat for Adaptive Evolution of Bacteria Under Antibiotic Drug Selection

We describe a low cost, configurable morbidostat for characterizing the evolutionary pathway of antibiotic resistance. The morbidostat is a bacterial ...

National Tsing Hua University

Trimethylated chitosan (TMC) surface-modified poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (TMC/PLGA-NP) were synthesized as a drug carrier for brain delivery. TMC was covalently coupled to the surface of PLGA nanoparticles (PLGA-NP) via a carbodiimide-mediated link. The zeta potential of TMC/PLGA-NP was about 20mV with a mean diameter around 150nm. 6-coumarin loaded PLGA-NP and TMC/PLGA-NP were injected into the caudal vein of mice, and fluorescent microscopy of brain sections showed a higher accumulation of TMC/PLGA-NP in the cortex, paracoele, the third ventricle and choroid plexus epithelium, while no brain uptake of PLGA-NP was observed. There was no pronounced difference in cell viability between TMC/PLGA-NP and PLGA-NP as shown by MTT assay. Behavioral testing showed that the injection of coenzyme Q(10) loaded TMC/PLGA-NP greatly improved memory impairment, restoring it to a normal level, but the efficacy was slight for loaded PLGA-NP, without TMC conjugation. The senile plaque and biochemical parameter tests confirmed the brain-targeted effects of TMC/PLGA-NP. These experiments show that TMC surface-modified nanoparticles are able to cross the blood-brain barrier and appear to be a promising brain drug delivery carrier with low toxicity.

Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain.

The central nervous system is known to play important roles in the regulation of renal sodium excretion. The present study was designed to reveal the interrelationship between cholinergic pathway in the magnocellular paraventricular nucleus (PVN) and the natriuresis induced by brain cholinergic stimuli. The results indicated that urinary sodium excretion was significantly increased at 40 min after intracerebroventricular (ICV) injection of carbachol (CBC). Immunohistochemical studies showed that CBC increased choline acetyltransferase-immunoreactivity (ChAT-IR) in the magnocellular PVN and renal proximal convoluted tubule (PCT), respectively. After pretreatment with atropine, urinary sodium excretion was significantly reduced, and carbachol-increased ChAT-IR in the magnocellular PVN and PCT was also significantly decreased. These results suggested that brain cholinergic stimuli induced the natriuresis and increased the activity of cholinergic neurons in the magnocellular PVN and cholinergic system in the PCT. The blockade of muscarinic receptor completely abolished the natriuresis and partially inhibited carbachol-exerted stimulatory effects in the magnocellular PVN and PCT. To summarize, brain cholinergic pathway and peripheral cholinergic system in kidney were found to contribute to the natriuresis following brain cholinergic stimulation. Our findings revealed novel evidence that PVN was involved in the natriuresis via humoral mechanisms.

Article	Year
Trimethylated chitosan-conjugated PLGA nanoparticles for the delivery of drugs to the brain. Biomaterials\| PubMed ID: 19853292	2010
The interrelationship between cholinergic pathway in the magnocellular paraventricular nucleus and natriuresis. General physiology and biophysics\| PubMed ID: 25926548	2015

Chun Y. Wang

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