In the present study, poly(l-lactic acid) (PLLA) and poly(lactide-co-glycolide) (PLGA) hybrid nanoparticles were developed for intranasal delivery of galantamine, a drug used in severe to moderate cases of Alzheimer’s disease. Galantamine (GAL) was adsorbed first in hierarchical porous carbon (HPC). Formulations were characterized by FT-IR, which showed hydrogen bond formation between GAL and HPC. Furthermore, GAL became amorphous after adsorption, as confirmed by XRD and differential scanning calorimetry (DSC) studies. GAL was quantified to be 21.5% w/w by TGA study. Adsorbed GAL was nanoencapsulated in PLLA and PLGA, and prepared nanoparticles were characterized by several techniques. Their sizes varied between 182 and 394 nm, with an exception that was observed in nanoparticles that were prepared by PLLA and adsorbed GAL that was found to be 1302 nm in size. DSC thermographs showed that GAL was present in its crystalline state in nanoparticles before its adsorption to HPC, while it remained in its amorphous phase after its adsorption in the prepared nanoparticles. It was found that the polymers controlled the release of GAL both when it was encapsulated alone and when it was adsorbed on HPC. Lastly, PLGA hybrid nanoparticles were intranasally-administered in healthy, adult, male Wistar rats. Administration led to successful delivery to the hippocampus, the brain area that is primarily and severely harmed in Alzheimer’s disease, just a few hours after a single dose.
Previous studies have shown that cortical interneurons, presumably GABAergic, are among the targets of the noradrenaline (NA)-containing cortical afferents and that NA interacts with neuropeptides at various cellular levels. The present study attempts to characterize further the cortical targets of the NA afferents by examining, at the light and the electron microscopic level, the anatomical relationships of the NA fibers with three subpopulations of cortical interneurons, those containing somatostatin (SRIF), neuropeptide Y (NPY) or vasoactive intestinal polypeptide (VIP). For this purpose, a double preembedding immunoprocedure with antibodies against NA and SRIF, NPY or VIP was combined with the gold-substituted silver peroxidase method. Light microscopic examination showed that NA fibers contact perikarya and proximal dendrites of the SRIF, NPY and VIP neurons. However, NA fibers, while found to form pericellular arrays around NPY neurons and, to a lesser extent, around SRIF neurons, were seen to target VIP cortical cells with single terminal varicosities. Electron microscopy revealed that all peptidergic populations examined represent synaptic targets for the NA fibers. The NAergic synapses, localized onto the cell body and proximal dendrites of the peptidergic neurons, were always of the symmetrical variety. Results of the present study provide the morphological basis for the explanation of the functional interaction between the NA cortical afferent system and the intrinsic cortical elements.
African swine fever (ASF) poses a major threat to swine health and welfare worldwide. After several European countries have reported cases of ASF, Greece confirmed officially the first positive case on 5 February 2020. The owner of a backyard farm in Nikoklia, a village in Serres regional unit, Central Macedonia, reported a loss of appetite, weakness, dyspnea, and the sudden death of 6 domestic pigs. Necropsy was performed in one gilt and findings were compatible with acute to subacute septicemic disease. Predominantly, hyperemic enlargement of spleen and lymph node enlargement and/or hemorrhage were observed. Description of vague clinical signs by the farmer suggested a limited resemblance to ASF-acute infection. However, the disease could not be ruled out once septicemic condition including splenomegaly, was diagnosed macroscopically at necropsy. In addition, considering the farm’s location near to ASF protection zones, a further diagnostic investigation followed. Confirmation of the disease was obtained using a series of diagnostic tests on several tissue samples. Further clinical, molecular, and epidemiologic evaluation of the farm was performed. According to the contingency plan, authorities euthanized all 31 pigs on the farm, whilst blood testing revealed ASF virus infection. Further emergency measures were implemented to contain the spread of the disease.