Ameliorating the in vivo antimalarial efficacy of artemether using nanostructured lipid carriers.

Cerebral malaria (CM) is a fatal neurological complication of Plasmodium falciparum infection that affects children (below five years old) in sub-Saharan Africa and adults in South-East Asia each year having the fatality rate of 10-25%. The survivors of CM also have high risk of long term neurological or cognitive deficits. The objective of the present investigation was to develop optimised nanostructured lipid carriers (NLCs) of artemether (ARM) for enhanced anti-malarial efficacy of ARM. NLCs of ARM were prepared by a combination of high speed homogenisation (HSH) and probe sonication techniques. Preliminary solubility studies for ARM showed highest solubility in trimyristin (solid lipid), capmul MCM NF (liquid lipid) and polysorbate 80 (surfactant). Trimyristin and capmul showed superior miscibility at a ratio of 70:30.The optimised NLC formulation has the particle size (PS) of: 48.59 ± 3.67 nm, zeta potential (ZP) of: -32 ± 1.63 mV and entrapment efficiency (EE) of: 91 ± 3.62%. In vitro cell line (human embryonic kidney fibroblast cell line (HEK 293 T)) cytotoxicity studies showed that prepared formulation was non-toxic. The results of in vivo studies in CM induced mice prevented the recrudescence of parasite after administration of NLCs of ARM. Additionally, NLCs of ARM showed better parasite clearance, higher survival (60%) in comparison to ARM solution (40%). Also it was observed that lesser entrapment of Evans blue stain (prepared in PBS as solution) in the NLCs of ARM treated brains of C57BL/6 mice than ARM solution treated mice. Hence NLCs of ARM may be a better alternative for improving therapeutic efficacy than ARM solution.

The Effect of Monopolar and Bipolar Electrocoagulation in Spinal Cord

The monopolar and bipolar coagulation lesions were generated in the spinal cord of rabbits. Microscopic study, and the distance from surface lesion center to its margin, the lesion depth, the extent of lesion in cross section, and the area of cross section through the lesion center of monopolar and bipolar electrocoagulation in generation of spinal cord lesion were studied by Evans blue and hematoxylin-eosin stain. The results were as follows : 1) Microscopically, the lesions were characterized by ground substance depigmentation, vacuolization and neuronal damage with pyknotic and angulated nuclei and loss of detail. In section stained with Evans blue, the lesion was demarcated with blue-green discoloration of the parenchyma and superficial necrosis was at coagulation sites. 2) The distance from surface lesion center to its margin was proportionally increased as the increase of magnitude of electric current for monopolar and bipolar coagulation, while the distance was independent of the mode coagulation and stain. 3) The depth of lesion was proportionally increased as the increase of magnitude of electric current for monopolar and bipolar coagulation, while the depth was also independent of the mode coagulation, but the depth of Evans blue stain was 2 times than H-E stain. 4) The extent of lesion in cross section was increased as the increase of magnitude of electric current for both coagulation modes, while the extent was independent of the mode of coagulation and stain, too. 5) The area of cross section through the lesion center was gradually increased as the increase of magnitude of electric current for both coagulation modes, while the area was independent of the mode of coagulation and stain.

The Effect of Monopolar and Bipolar Electrocoagulation in Brain

The monopolar and bipolar coagulation lesions were generated in the cerebral cortex of rabbits. Microscopic study, and the distance from cortical lesion center to its margin, the lesion depth, the extent of lesion in coronal section, and the area of coronal section at electrocoagulation in generation of brain lesion were studied by Evans blue and hematoxylin-eosin stain. The results were as follows : 1) Microscopically, the lesions were characterized by ground substance depigmentation, vacuolization and neuronal damage with pyknotic nuclei and loss of detail. In section stained with Evans blue, the lesion was demarcated with blue-green discoloration of the parenchyma and superfical cortical necrosis was coagulation sites. 2) The distance from cortical lesion center to its margin was proportionally increased as the increase of magnitude of electric current for monopolar and bipolar coagulation, while the distance was independent of the mode coagulation and stain. 3) The depth of lesion was proportionally increased as the increase of magnitude of electric current for monopolar and bipolar coagulation, while the distance was independent of the mode coagulation and stain. 4) The extent of lesion in coronal section was increased the increase of magnitude of electric current for both coagulation modes, while the extent was independent of the mode of coagulation and stain, too. 5) The area of coronal section at cortical lesion center was gradually increased as the increase of magnitude of electric current for both coagulation modes, while the area of Evans blue stain was 2 times as H-E stain in monopolar mode and the area of Evans blue stain was 1.3 times as H-E stain in bipolar mode.