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Biomedical subjects

George Francis

Publications and source records attributed to George Francis.

5 recordsLinked to original sources

Diabetes, leukoencephalopathy and rage.

Longstanding diabetes mellitus damages kidney, retina, peripheral nerve and blood vessels, but brain is not usually considered a primary target. We describe direct involvement of the brain, particularly white matter, in long-term (9 months) experimental diabetes of mice, not previously modeled, correlating magnetic resonance (MR) imaging with quantitative histological assessment. Leukoencephalopathy and cerebral atrophy, resembling that encountered in diabetic humans, developed in diabetic mice and was accompanied by time-related development of cognitive changes in behavioural testing. Increased RAGE (receptor for advanced glycation end products) expression, a mediator of widespread diabetic complications, increased dramatically at sites of white matter damage in regions of myelination. RAGE expression was also elevated within neurons, astrocytes and microglia in grey matter and within oligodendrocytes in white matter. RAGE null diabetic mice had significantly less neurodegenerative changes when compared to wild-type diabetic mice. Our findings identify a robust and novel model of cerebral, particularly white matter, involvement with diabetes associated with abnormal RAGE signaling.

Animals↗

Exposure of tilapia pituitary cells to saponins: insight into their mechanism of action.

Cell permeation and durable effects of triterpenoidal saponin preparations from soybean (SbS), Quillaja saponaria Molina (QsS) and Gypsophila paniculata (GypS), were studied. A concentration-dependent change in hemolysis rates was observed when cells were incubated with QsS or GypS, but not with SbS. Dose dependence was also observed for the leakage of lactate dehydrogenase (LDH; MW 142,000) and of Luteinizing Hormone (LH; MW 35,000) from tilapia pituitary dispersed cells. Exposure of pituitary fragments to a combination of GnRH and GypS or QsS, resulted in a significantly high release of LH. GypS were shown to be more potent in inducing hemolysis of human RBC's and LH release from tilapia pituitary fragments. Interestingly, tilapia pituitary fragments treated with QsS were able to secrete LH in a characteristic manner, in response to a second Gonadotropin Releasing Hormone (GnRH) pulse, while fragments exposed to GypS did not respond to the second hormone pulse. The rapid recovery of pituitary fragments after the removal of QsS, may suggest a rearrangement of membranes rather than pore formation as the mechanism of action of QsS. Understanding the structural features underlying the reversible rearrangement of membranes and the lack of hemolysing activity by specific saponins may lead to the development of novel bioactive drugs.

Animals↗

Effects of long term feeding of Quillaja saponins on sex ratio, muscle and serum cholesterol and LH levels in Nile tilapia (Oreochromis niloticus (L)).

Seventeen-day-old Nile tilapia fry were fed a standard diet (C) or diets containing 50-700 mg kg(-1) Quillaja saponin (QS) extract (groups S50, S150, S300, S500 and S700). After the first 8 weeks, 30 randomly selected tilapia from each of the treatments were placed in separate aquaria and fed the standard diet without saponins from then on (these were designated S50/C, S150/C, S300/C, S500/C and S700/C). The fish grew from an initial average weight of approximately 30 mg to a final average weight of 79 g during the 6-month feeding period. The difference between the average weight of C-fed tilapia and the treatment with the highest average weight after 6 months was 53.5%. The sex ratio of tilapia in the saponin-fed groups deviated from the normal 50:50 male:female ratio, with the S700 group showing a significantly higher number of males. Quillaja saponin stimulated LH release from dispersed tilapia pituitary cells in vitro. This effect was abolished in the presence of dilute calf serum. Serum LH values did not show any diet-dependent trend in either male or female tilapia in vivo. In both continuously saponin-fed and only-initially saponin-fed groups, the average serum (but not muscle) cholesterol levels in males showed an increasing trend (R(2) values of 0.62 and 0.69) with increasing dietary saponin level. It was concluded that dietary QS has the potential to change the sex-ratio in favour of males. More investigations are required to determine the mechanism of action and the optimum dietary level of QS for maximum effects.

Animals↗

The biological action of saponins in animal systems: a review.

Saponins are steroid or triterpenoid glycosides, common in a large number of plants and plant products that are important in human and animal nutrition. Several biological effects have been ascribed to saponins. Extensive research has been carried out into the membrane-permeabilising, immunostimulant, hypocholesterolaemic and anticarcinogenic properties of saponins and they have also been found to significantly affect growth, feed intake and reproduction in animals. These structurally diverse compounds have also been observed to kill protozoans and molluscs, to be antioxidants, to impair the digestion of protein and the uptake of vitamins and minerals in the gut, to cause hypoglycaemia, and to act as antifungal and antiviral agents. These compounds can thus affect animals in a host of different ways both positive and negative.

Animals↗

Visualizing a sphere eversion.

The mathematical process of everting a sphere (turning it inside-out allowing self-intersections) is a grand challenge for visualization because of the complicated, ever-changing internal structure. We have computed an optimal minimax eversion, requiring the least bending energy. Here, we discuss techniques we used to help visualize this eversion for visitors to virtual environments and viewers of our video The Optiverse.

Algorithms↗