Topical ivermectin improves allergic skin inflammation.

BACKGROUND: Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. METHODS: Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. RESULTS: Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. CONCLUSION: Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases.

Dehydroepiandrosterone and neurotrophins favor axonal growth in a sensory neuron-keratinocyte coculture model.

We have previously shown that axonal growth from a subset of sensory neurons was promoted by keratinocytes when the two cell types were co-cultured in a low calcium medium. This phenomenon involves the production of one or several diffusible factors. Here we show that the neuritogenic effect of keratinocytes was significantly reduced in the case of rat primary sensory dorsal root ganglion (DRG) neurons, or completely suppressed in the case of the sensory neuron cell line ND7-23, when the activity of neurotrophin receptors (Trk receptors) was blocked with K252a. This trophic effect apparently involved the activation of tyrosine kinase receptors A and B (TrkA and TrkB) expressed by subpopulations of small- to medium-sized DRG neurons, or only of TrkA receptors in the case of ND7-23 neurons. A residual neurite growth promoting effect of keratinocytes persisted in a fraction of DRG neurons after Trk receptor blockade. This effect was mimicked by the steroid dehydroepiandrosterone (DHEA) but not by other steroids such as pregnenolone, progesterone or 17beta-estradiol. The use of pharmacological agents which inhibit different steps of steroidogenesis indicated that DHEA was probably synthesized from cholesterol in keratinocytes. Our results strongly suggest that DHEA might act as a neurotrophic signal derived from keratinocytes to promote axonal outgrowth from a subpopulation of sensory neurons.

[Exploration of traumatic brain-injury attention difficulty by event-related potentials]. / Exploration des troubles attentionnels des traumatisés crâniens avec les potentiels évoqués cognitifs.

OBJECTIVE: To specify, in cognitive processing leading to an action, the localization of difficulties in attention following severe, traumatic brain injury. METHOD: Stimulus-locked and response-locked event-related potentials were recorded during a Stroop task in 25 patients with traumatic brain injury and 25 control subjects approximately 4 months after the accident. The latency and amplitude of the waves were compared between the two groups and correlated with clinical data. RESULTS: The reaction times of brain-injured patients were significantly longer than those of the control group, but neither the number of errors nor the interference differed between the groups. Electrophysiological recordings showed early abnormalities between 100 and 200 ms after stimulus onset. The key area could be the medial occipitotemporal side connected with frontal regions. Recordings also showed disruptions in motor program monitoring, which implied frontomedial areas. CONCLUSION: This protocol allows for precisely dating cognitive abnormalities. Future studies should relate cognitive with neuropsychological abnormalities and examine the possibilities of later regression.

Brain and hippocampus fatty acid composition in phospholipid classes of aged-relative cognitive deficit rats.

The aim of this work was to study the composition of long chain fatty acids and the n-6 and n-3 fatty acid ratios in aged and young Wistar rats in brain and hippocampus, related to relative cognitive deficits. The aged animals showed cognitive deficits during acquisition of a memory task (delayed alternation). In brain, results showed a decrease in palmitoleic and palmitic acid percentages in all the studied phospholipid classes and in the phosphatidylserine and phosphatidylcholine classes, respectively, in old rats, compared to the young ones. There was also an increase in oleic and stearic acid amounts in the sphingomyelin, phosphatidylserine and phosphatidylinositol classes and in the phosphatidylserine and phosphatidylcholine classes, respectively. Arachidonic acid amount was decreased in old rats, compared to the young ones, in the phosphatidylserine and phosphatidylinositol classes. Total n-6 and n-3 fatty acid amounts were both decreased in all phospholipid classes, with a stable n-6/n-3 ratio. Our results confirm that arachidonic acid concentration is decreased in aged rats and that this reduction, more significant in phosphatidylserine and phosphatidylinositol classes, should be related to the fact that low concentrations of arachidonic acid are observed during activation of glutamate receptor.

Incorporation of delta 6- and delta 5-desaturation fatty acids in liver microsomal lipid classes of obese Zucker rats fed n - 6 or n - 3 fatty acids.

The aim of this work was to study the effect of dietary n - 6 (as borage oil) and of n - 3 (as fish oil) fatty acids on the incorporation--in liver microsomal lipid classes--of fatty acids involved in delta 6- and delta 5-desaturations in obese Zucker rats compared with their lean littermates and with Wistar control rats. We observed that body and liver weights were decreased when obese Zucker rats were fed the fish oil diet. The major part of the radioactivity was recovered, in the obese Zucker rats, into the neutral lipids and especially into the triacylglycerols, while it was recovered into the phospholipid classes, especially into phosphatidylcholine, in the two other strains. Results show, in all phenotypes, an increased alpha-linolenic acid delta 6-desaturation in PL classes when the rats were fed the fish oil diet. However, a decreased linoleic acid delta 6- and delta 5-desaturation was observed in obese Zucker rats fed the fish oil diet. The fish oil diet favours the n - 3 fatty acid biosynthesis and incorporation into liver microsomal lipid classes to the prejudice of the n - 6 fatty acid series. The fatty acid incorporation is simultaneously regulated by the genetical phenotype and dietary fatty acids.

Age-related changes in antioxidant defence mechanisms and peroxidation in isolated hepatocytes from spontaneously hypertensive and normotensive rats.

The effects of age and hypertension on the antioxidant defence systems and the lipid peroxidation in rat isolated hepatocytes were studied. Four different age groups (1, 3, 6 and 12 months) were considered in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Age-associated changes were observed on vitamin E status, glutathione (GSH) level, MDA formation and glutathione peroxidase (GSH-Px) activity in both strains. Maximal levels or activities of these parameters were found at 3 and 6 months, except for MDA which was low at 3 months. Then, a fall was observed at 12-month-old compared to 6-month values. In addition, GSH-Px activity was significantly lower in SHR than in WKY rats, except at the age of one month. The decrease of this enzyme activity could induce an increased cellular generation of radical species and lipid peroxidation, which might be link to hypertension.

Age-related changes in delta 6 and delta 5 desaturase activities in rat liver microsomes.

Age-related changes in delta 6 desaturation of [1-14C]alpha-linolenic acid and [1-14C]linoleic acid and in delta 5 desaturation of [2-14C]dihomo-gamma-linolenic acid were studied in liver microsomes from Wistar male rats at various ages ranging from 1.5 to 24 mon. Desaturase activities were expressed both as specific activity of liver microsomes and as the capacity of whole liver to desaturate by taking into account the total amount of liver microsomal protein. delta 6 Desaturation of alpha-linolenic acid increased from 1.5 to 3 mon and then decreased linearly up to 24 mon to reach the same desaturation capacity of liver measured at 1.5 mon. The capacity of liver to desaturate linoleic acid increased up to 6 mon and then remained constant, whereas microsomal specific activity was equal at 1.5 and 24 mon of age. The capacity of liver to convert dihomo-gamma-linolenic acid to arachidonic acid by delta 5 desaturation decreased markedly from 1.5 to 3 mon. It then increased to reach, at 24 mon, the same level as that observed at 1.5 mon. Age-related changes in the fatty acid composition of liver microsomal phospholipids at the seven time points studied and of erythrocyte lipids at 1.5 and 24 mon were consistent with the variations in desaturation capacity of liver. In particular, arachidonic acid content in old rats was slightly higher than in young rats whereas contents in linoleic and docosahexaenoic acids varied little throughout the life span.(ABSTRACT TRUNCATED AT 250 WORDS)

Incorporation into liver microsomal lipids of linoleic and stearic acids and of their respective products of delta 6 and delta 9 desaturation, gamma-linolenic and oleic acids: effect of age and of blackcurrant seed oil.

The incorporation of [1-14C]linoleic and [1-14C]stearic acid and of their delta 6 and delta 9 desaturation products (gamma-linolenic and oleic acids, respectively) into different classes of lipids was studied in liver microsomes of rats in function of the diet (blackcurrant seed oil diet, containing gamma-linolenic acid, versus control diet) and in function of age (3, 6 and 9 months). After delta 6 desaturation, total radioactivity was distributed between phospholipids, especially phosphatidylcholine, and neutral lipids. The desaturation product, gamma-linolenic acid, was totally recovered in the phospholipid fraction. Blackcurrant seed oil, which decreased the rate of delta 6 desaturation in 6- and 9-month-old rats, also decreased the incorporation of radioactivity in total phospholipids, especially in phosphatidylcholine. At 6 months of age, after delta 9 desaturation, the majority of radioactivity was recovered in neutral lipids principally as oleic acid, the desaturation product. The precursor, stearic acid, was highly incorporated into phospholipids, especially in rats on a diet of blackcurrant seed oil.

Elongation and desaturation of arachidonic and eicosapentaenoic acids in rat liver. Effect of clofibrate feeding.

The fatty acid elongation-desaturation ability of 5,8,11,14-eicosatetraenoic (20:4(n-6)) and 5,8,11,14,17-eicosapentaenoic (20:5(n-3)) acids was determined in both liver microsomal and light mitochondrial (rich in peroxisomes) fractions of untreated and clofibrate treated rats. The elongation and the subsequent desaturation steps were performed in the corresponding favorable media. 20:5(n-3) elongation was about 2-times more extensive than that of 20:4(n-6). Clofibrate feeding for 10 days resulted in a marked decrease in the elongation rate with the two substrates, while the delta 4 desaturation rate was increased. There were small differences in the elongation rate between the microsomal and light mitochondrial fractions, however, the relative delta 4 desaturation rate was higher in the light mitochondrial fraction than microsomes.

Effects of age and dietary essential fatty acids on desaturase activities and on fatty acid composition of liver microsomal phospholipids of adult rats.

The combined effects of age and dietary n-6 and n-3 fatty acids were studied in 3-, 6- and 9-month-old rats. At each age, two groups were fed diets containing 5% (w/w) of vegetable oils rich in either 18:3n-6 (borage group) or 18:3n-6 plus 18:4n-3 (black currant group), for a period increasing with age. A control group was fed the essential fatty acids 18:2n-6 and 18:3n-3 only. For each group, delta 6, delta 5 and delta 9 desaturase activities were measured in liver microsomes, and fatty acid composition was determined in microsomal phospholipids. Desaturase activity varied as a function of age and dietary lipids. delta 6 Desaturation of 18:3n-3 was more sensitive to these factors while delta 6 desaturation of 18:2n-6 and delta 9 desaturation were more dependent on season than the other two. Desaturase activity was influenced more by the black currant than by the borage diet, especially at 6 and 9 months of age. A large proportion of arachidonic acid was maintained in the microsomes independent of the diet. Changes in the fatty acid composition did not strictly reflect the differences in desaturase activities. The effects of the two factors (age and diet) on the activities of the desaturases are complex, suggesting that the enzymes are susceptible to other factors as well.

[Nonspecific immunostimulating activity of Bordetella bronchiseptica bacterin in tests on mice and calves]. / Nespecifická imunostimulacní aktivita bakterinu Bordetella bronchiseptica v testech na mysích a telatech.

Three experimental models were used to verify the effectiveness of immunostimulant preparations of microbial origin. Of the four microbial species, used in the tests with the stimulation of mice against subsequent infection with the virulent strain of Pasteurella multocida, the highest resistance-increasing power was recorded in Bordetella bronchiseptica. There were large differences in stimulation activity between its strains, ranging from those with a low activity up to strain 6229, which increased the LD50 of the infected mice to a level 72 times as high as in the control. The differences in the survival of the mice also varied within the range between immunostimulation and infection, the best effect being obtained when the mice were stimulated 48 h before the infection. No significant difference was recorded between the use of the bacterin of B. bronchiseptica alone or B. bronchiseptica bacterine with oil adjuvant. The immunostimulant activity of B. bronchiseptica was also demonstrated in the model of sublethally irradiated mice in which the preventive administration 24 h before irradiation led to earlier and faster regeneration of the lymphoid tissue: this led to a higher weight of the spleen, to an increase in the number of peripheral leucocytes, and increased activity of chemiluminiscence six days after irradiation. The bacterine of B. bronchiseptica was also used at different concentrations and in combinations with other substances to stimulate two-month-old clinically healthy calves. The most pronounced effect was obtained after the administration of B. bronciseptica bacterine with oil adjuvant and after administration of the same substances together with vitamin A: twenty-four hours after these treatments there was an increased number of peripheral leucocytes and after 2-4 days an increased activity was observed in the MSHP particle phagocytosis test and in the chemiluminiscence test. The activity of lymphocytes in the blastic transformation test was insignificantly increased seven days after stimulation.

The effect of dietary alpha-bromopalmitate on blood lipids in the rat.

When alpha-bromopalmitate was fed to rats for 9-30 days, the level of serum triacylglycerol increased up to 2-fold over the concentration of controls. alpha-Bromopalmitate treatment had no effect on concentration of complex lipids in liver, while the triacylglycerol level in heart was significantly enhanced. From metabolic studies using isolated hepatocytes and liver microsomes, it is suggested that the increased serum triacylglycerol level after alpha-bromopalmitate feeding is mainly due to reduced fatty acid oxidation in both liver and peripheral tissues, and to a lesser extent, to inhibited fatty acid uptake and esterification.

Use of polyvalent cow colostrum in the prevention of enteric infections in calves and piglets.

Colostrum of cows immunized with a polyvalent vaccine against enteropathogenic strains of Escherichia coli gave good protection to piglets and calves against enteric coli infections. Bovine immunoglobulin (IgG1) and its precipitable fragments persisted in the small intestine of piglets for 6 hours after oral administration. The proteolytic breakdown of porcine colostral IgG2, which occurs predominantly in the small intestine proceeded at a higher rate than that of heterologous bovine colostral IgG1. Colostrum of cows immunized with transmissible gastroenteritis (TGE) virus by intramammary administration protected newborn piglets from virulent TGE virus on oral administration. The prevention of enteric coli infections in suckling piglets and calves in Czechoslovakia is based on vaccination of pregnant cows and sows and on additional passive protection of weanlings by oral administration of dried or liquid immune colostrum or serum of cows vaccinated with polyvalent vaccines prepared from enteropathogenic strains of E. Coli.