Inhibition of indoleamine 2,3-dioxygenase 1/2 prevented cognitive impairment and energetic metabolism changes in the hippocampus of adult rats subjected to polymicrobial sepsis.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection that may affect the brain. We investigated the role of indoleamine 2,3-dioxygenase (IDO-1/2) inhibition on long-term memory and energetic metabolism after experimental sepsis by caecal ligation and perforation (CLP). Experimental sepsis increased the activity of complexes I, II-III and IV at 24h after CLP, and IDO-1/2 inhibition normalized the activity of these complexes in the hippocampus. Wistar rats presented impairment of habituation and aversive memories 10days after CLP. Adjuvant treatment with the IDO inhibitor prevented long-term cognitive impairment triggered by sepsis.

The clinical efficacy of paremyd with and without dapiprazole in subjects with light and dark brown irides.

BACKGROUND: Paremyd, a mydriatic formulation of 0.25% tropicamide and 1.0% hydroxyamphetamine hydrobromide provides adequate dilation for binocular indirect ophthalmoscopy in young Caucasians. We studied the clinical effectiveness of Paremyd in dilating heavily pigmented eyes by comparing its mydriatic efficacy in Blacks, Asians and Caucasians with light and dark brown irides. We also evaluated the efficacy of one drop of dapiprazole (Rev-Eyes) in reversing Paremyd-induced mydriasis in our subject sample. METHODS: In a masked, randomized, controlled experimental design, several visual functions which included pupillary dilation, near visual acuity, amplitude of accommodation, ocular hyperemia, and discomfort glare were measured at 30-min intervals, for a total of 300 min, in subjects dilated with a single drop of Paremyd in each eye. Ease of binocular indirect ophthalmoscopy was also assessed. A 3-way analysis of variance was used to assess changes in these measures as function of irides color/pigmentation (designated as light or dark brown iris color), presence or absence of dapiprazole, and test time interval. RESULTS: We found that subjects in our light brown irides group (mainly Caucasians) dilated faster than subjects in our dark brown irides group (mainly Blacks). Dapiprazole increased the speed of recovery from pupillary dilation for all subjects, but more so for those with light rather than dark brown irides. Similarly, subjects with light rather than dark brown irides recovered accommodative function more quickly. Although neither the use of dapiprazole nor the degree of iris color/pigmentation was significantly related to visual acuity or glare discomfort, there was a clear trend that these visual measures were affected to a greater degree in subjects with dark brown (primarily Blacks) rather than light brown irides. Overall, Paremyd provided adequate dilation for binocular indirect ophthalmoscopy in all subjects irrespective of iris color/pigmentation. CONCLUSIONS: Our data indicate that a single drop of Paremyd provides adequate mydriasis, without significant side effects, for routine fundus examination of all subjects, independent of iris color/pigmentation. Furthermore, a single drop of dapiprazole was effective in speeding the return of pupillary dilation in most subjects, but had no significant effect on accommodation, near visual acuity or glare discomfort. Side effects such as stinging upon instillation, conjunctival hyperemia, and a few instances of ptosis, with possible additional cost to patients, appear to lessen its overall clinical benefit.

The "harlequin" sign and congenital Horner's syndrome.

When trying to establish the likely anatomical site (preganglionic or postganglionic) of a lesion causing congenital Horner's syndrome, the distribution of facial flushing (the "harlequin" sign), may be seen. In babies and young children, facial flushing is a relatively simple clinical sign to demonstrate, compared with facial sweating. In unilateral facial flushing the areas that do not flush are almost always identical to the anhidrotic areas. However, neither facial flushing nor testing the pupil reactions with pholedrine or hydroxyamphetamine can be relied on to predict the probable site of any lesion causing congenital Horner's syndrome. Two patients with congenital Horner's syndrome are presented which demonstrated the "harlequin" sign and in whom clinical examination and pharmacological testing gave conflicting evidence for localisation of the site of the causative lesion. The presentation of congenital Horner's syndrome should be investigated and include MRI or CT to exclude a serious underlying cause.