Progesterone release from a silicone intravaginal ring in pigtailed macaques

Background: Heterosexual HIV transmission continues to spread worldwide. Intravaginal rings (IVRs) formulated with antiretroviral drugs hold great promise for HIV prevention in women. IVRs provide the benefit of being coitally-independent and coitally-covert for an extended period. As a proof-of-concept, we tested the in vivo release of progesterone from a silicone elastomer vaginal ring device. Methods: Six female pig-tailed macaques were treated with a GnRH agonist (Lupron) prior to ring placement. Four macaques received a progesterone-loaded silicone ring, and two macaques received a blank silicone ring. Blood, vaginal swabs, CVL, and/or biopsies were collected during ring placement, and after ring removal. Results: The median plasma progesterone levels for macaques with a progesterone IVR were 13,973 pg/ml (day 3), 12,342 pg/ml (day 7), 10,112 pg/ml (day 14), 8445 pg/ml (day 21) and 8061 pg/ml (day 28), with a significant decrease from day 14 to day 21 (P = 0.0286). The median plasma progesterone levels for macaques with a blank IVR were 221±±± ±±88 pg/ml. Macaques with a progesterone IVR had CVL progesterone levels of 20,935 pg/ml (day 7), 6892 pg/ml (day 21) and 11,515 pg/ml (day 28). Macaques with a blank IVR had CVL progesterone levels of 29 �± 13 pg/ml. There were no disturbances to the normal vaginal microflora, and plasma and CVL cytokine analysis did not indicate a proinflammatory response due to ring placement. The vaginal biopsies did not display any pathology following ring removal. Overall, the IVRs were well tolerated without any indication of inflammation or significant changes in the vaginal compartment.

The relationship between CA/C ratio and individual differences in dynamic accommodative responses while viewing stereoscopic images

The oculomotor synergy as expressed by the CA/C and AC/A ratios was investigated to examine its influence on our previous observation that whereas convergence responses to stereoscopic images are generally stable, some individuals exhibit significant accommodative overshoot. Using a modified video refraction unit while viewing a stereoscopic LCD, accommodative and convergence responses to balanced and unbalanced vergence and focal stimuli (BVFS and UBVFS) were measured. Accommodative overshoot of at least 0.3 D was found in 3 out of 8 subjects for UBVFS. The accommodative response differential (RD) was taken to be the difference between the initial response and the subsequent mean static steady-state response. Without overshoot, RD was quantified by finding the initial response component. A mean RD of 0.11 +/- 0.27 D was found for the 1.0 D step UBVFS condition. The mean RD for the BVFS was 0.00 +/- 0.17 D. There was a significant positive correlation between CA/C ratio and RD (r = +0.75, n = 8, p <0.05) for only UBVFS. We propose that inter-subject variation in RD is influenced by the CA/C ratio as follows: an initial convergence response, induced by disparity of the image, generates convergence-driven accommodation commensurate with the CA/C ratio; the associated transient defocus subsequently decays to a balanced position between defocus-induced and convergence-induced accommodations.

The incidence of corpora amylacea (CA) in the optic nerve of patients with Alzheimer's disease

Corpora amylacea (CA) are spherical or ovoid bodies 50-50 microns in diameter. They have been described in normal elderly brain as well as in a number of neurodegenerative disorders. In this study, the incidence of CA in the optic nerves of Alzheimer's disease (AD) patients was compared with normal elderly controls. Samples of optic nerves (MRC Brain Bank, Institute of Psychiatry) were taken from 12 AD patients (age range 69-94 years) and 18 controls (43-82 years). Optic nerves were fixed in 2% buffered glutaraldehyde, post-fixed in osmium tetroxide, embedded in epoxy resin and then sectioned to a thickness of 2 microns. Sections were stained with toluidine blue. CA were present in all of the optic nerves examined. In addition, a number of similarly stained but more irregularly shaped bodies were present. Fewer CA were found in the optic nerves of AD patients compared with controls. By contrast, the number or irregularly shaped bodies was increased in AD. In AD, there may be a preferential decline in the large diameter fibres which may mediate the M-cell pathway. Hence, the decline in the incidence of CA in AD may be associated with a reduction in these fibres. It is also possible that the irregualrly shaped bodies are a degeneration product of the CA.