Teriflunomide, cognition and MRI: A longitudinal study.

BACKGROUND: As cognitive impairment in multiple sclerosis (MS) is a frequent and disabling symptom, it is particularly important to identify treatments that have proven efficacy in this aspect of the disease. Several disease-modifying therapies for MS have been evaluated and shown to have a potential effect on cognition and its neurobiological correlates, but to date there is very little data on Teriflunomide (TRF). The aim of this study is to explore the influence of TRF on comprehensive cognitive function and its MRI correlations (global and focal brain volume) in relapsing-remitting multiple sclerosis (RRMS) after two years of therapy. METHODS: Twenty-four patients with RRMS were evaluated at baseline and after two years of treatment with BCcogSEP, a French translation of the Brief Repeatable Battery (BRB-N) including 3 additional tests. We explored the performance evolution for each test and correlation with MRI data for all patients. We also differentiated MS patients with and without cognitive impairment. RESULTS: After two years of treatment, an improvement is observed at the Selective Reminding Test for mean number of words (p = 0.044), learning (p = 0.018), and delayed recall (p = 0.002) and at GoNoGo task (p = 0.022). At MRI, the corpus callosum volume variation correlates positively with SRT total recall test (p = 0,047). Intergoup analysis shows that the evolution of group performance differs only for the SRT total recall test. The comparison of patients with or without cognitive impairment showed a clear difference in white matter substance volume (p = 0,003) and in the Percentage Brain Volume Change (p = 0,016). CONCLUSION: Results suggest that TRF treatment in RRMS has a positive effect in cognitive function, and specifically on long term verbal memory and inhibition. Neuroimaging data suggest a link between cognition and global and focal white matter volume, particularly in the corpus callosum which is involved in anatomical disconnection syndrome and therefore brain plasticity capacities.

Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis.

Ovarian estrogen exerts both positive and negative feedback control over luteinizing hormone (LH) secretion during the ovulatory cycle. Estrogen receptor (ER) alpha but not ERbeta knockout mice lack estrogen feedback. Thus, estrogen feedback appears to be primarily mediated by ERalpha. However, it is now recognized that, in addition to binding to estrogen response elements (EREs) in DNA to alter target gene transcription, ERalpha signals through ERE-independent or nonclassical pathways, and the relative contributions of these pathways in conveying estrogen feedback remain unknown. Previously we created a knockin mouse model expressing a mutant form of ERalpha (AA) with ablated ERE-dependent but intact ERE-independent activity. Breeding this allele onto the ERalpha-null (-/-) background, we examine the ability of ERE-independent ERalpha signaling pathways to convey estrogen feedback regulation of the female hypothalamic-pituitary axis in vivo. ERalpha-/AA exhibited 69.9% lower serum LH levels compared with ERalpha-/- mice. Additionally, like wild type, ERalpha-/AA mice exhibited elevated LH after ovariectomy (OVX). Furthermore, the post-OVX rise in serum LH was significantly suppressed by estrogen treatment in OVX ERalpha-/AA mice. However, unlike wild type, both ERalpha-/AA and ERalpha-/- mice failed to exhibit estrous cyclicity, spontaneous ovulation, or an afternoon LH surge response to estrogen. These results indicate that ERE-independent ERalpha signaling is sufficient to convey a major portion of estrogen's negative feedback actions, whereas positive feedback and spontaneous ovulatory cyclicity require ERE-dependent ERalpha signaling.

Melittin synthesis in the venom system of the honey bee (Apis mellifera L.).

The amount of melittin (measured by a direct hemolytic assay) contained in the venom system of single honey bees (Apis mellifera), of known age, increases from the time of eclosion to an age of about 4 weeks when about 500 micrograms of melittin is present. In older bees (5-6 weeks) the melittin level falls to about 250 micrograms. Measurements of the incorporation of [3H]leucine (injected into the haemolymph) into melittin show that melittin synthesis is most active in bees aged between 1 and 2 weeks after eclosion. The melittin content of the venom system changes as the summer progresses. Melittin levels in a bee of any age greater than 1 week are lower in mid-August than in a bee of the same age in early June.

Use of ELISA for detection of immunoglobulins G and M that recognize Salmonella dublin lipopolysaccharide for prediction of carrier status in cattle.

Immunoglobulin reactions to Salmonella dublin in serum and milk from 4 groups of lactating cows were measured by an indirect ELISA. The groups consisted of (1) cows that were natural carriers of S dublin in the mammary gland, (2) experimentally infected cows that did not become carriers, (3) cows inoculated with a commercial S dublin bacterin, and (4) cows used as S dublin-negative controls. Milk and serum samples were obtained at monthly intervals. Models for predicting carrier status were developed by use of stepwise logistic regression. Independent variables consisted of serum and milk IgG and IgM titers to S dublin lipopolysaccharide and a ratio of IgG to IgM. The utility of a single sample vs multiple samples obtained at 1-month or 2-month intervals was tested by comparison of goodness-of-fit chi 2 P values for 8 models predicting carrier status. Immunoglobulin reactions specific to S dublin were a significant predictor of carrier status (P less than 0.001). Serum IgG titers specific for S dublin were the most important variable for predicting carrier status. Two serum IgG titers to S dublin obtained 2 months apart was a better predictor of carrier status than measurement of the IgG:IgM ratio from a single serum sample. Immunoglobulin recognizing S dublin epitopes also were detected in milk samples. In milk, performing 2 ELISA 60 days apart to determine IgG and IgM reactions to S dublin appeared to be useful for the prediction of carrier status, but was not as accurate as models for serum immunoglobulin reactions.

Phospholipase A2 in venom extracts from honey bees (Apis mellifera L.) of different ages.

We measured phospholipase A2 activity in the venom of worker honey bees (Apis mellifera L.) of known ages using chemical (titrimetric) and radioallergosorbent methods. The two techniques give similar results. Low levels of phospholipase A2 are present in the venom system at the time of eclosion. Phospholipase A2 activity in the venom increases steadily through the 10 days after eclosion. Maximal phospholipase A2 levels (about 40 micrograms phospholipase A2/venom sac) are maintained through the rest of the life of a worker bee in summer.

[A new concept in surgical treatment of anal incontinence]. / Ein neues Konzept in der chirurgischen Behandlung der analen Inkontinenz.

A new treatment of anal incontinence has been presented. This method combines the postanal repair of Parks with a sphincteroplasty by autologous large saphenous vein. The vein has no trophic requirements and has a high containing economy. Manometrically, a highly active high pressure zone has been proven. Histologic examinations have shown flubless healing in the intestinal wall of the free vein transplant when prestretched accordingly.

Quantitative autoradiographic study of labeled RNA in rabbit optic nerve after intraocular injection of (3H)uridine.

The distribution of labeled RNA in the optic nerve of the rabbit was studied by quantitative ultrastructural autoradiography after the intraocular injection of [(3)H]uridine. The highest density of silver grains related to [(3)H]RNA (27-40 grains/100 microm(2)) was found in glial cell perikarya; a slightly lower density was present in the glial nuclei (19-20 grains/100 microm(2)). Axons (4-5 grains/100 microm(2)) and myelin (2-3 grains/100 microm(2)) had the lowest grain densities. 74-83% of all counted grains were located outside the axons. By comparing the grain density distribution over the axon with that expected in the case of an exclusive labeling of the surrounding myelin and glial cell processes, it was concluded that the axons contained a number of grains representing [(3)H]RNA significantly higher than that expected to scatter from myelin and glial processes. Most of these grains were concentrated at the periphery of the axon and were not related to axonal mitochondria.