Tanshinone IIA attenuates demyelination and promotes remyelination in A. cantonensis-infected BALB/c mice.

BACKGROUND: Angiostrongylus cantonensis infection can cause demyelination in the central nervous system, and there is no effective treatment. METHODS: We used dexamethasone, Tanshinone IIA (TSIIA) and Cryptotanshinone(Two traditional Chinese medicine monomers) in combination with albendazole (AB, a standard anti-helminthic compound) to observe their therapeutic effect on demyelination in A. cantonensis-infected mice. Luxol fast blue staining and electron microscope of myelin sheath, Oligodendrocyte (OL) number and myelin basic protein (MBP) expression in brain was detected in above groups. RESULTS: TSIIA+AB facilitated OL proliferation and significantly increased both myelin sheath thickness and the population of small-diameter axons. In addition, TSIIA treatment inhibited the expression of inflammation-related factors (interleukin [IL]-6, IL-1ß, tumor necrosis factor [TNF]-α, inducible nitric oxide synthase [iNOS]) rather than inhibiting eosinophil infiltration in brain. TSIIA also decreased microglial activation and shifted their phenotype from M1 to M2. CONCLUSIONS: Taken together, these results provide evidence that TSIIA combined with AB may be an effective treatment for demyelination caused by A. cantonensis infection and other demyelinating diseases.

Body Protein Reserves Sustain Maternal Performance in Early Lactation but Dietary Protein Is Necessary to Maintain Performance and Immune Responses to Nippostrongylus brasiliensis in Lactating Rats.

Background: It has been shown that dietary protein supplementation during lactation boosts immunity in Nippostrongylus brasiliensis-infected periparturient rats. It is not known whether body protein reserves accumulated during gestation have a similar effect during lactation. Objective: This study aimed to quantify the impact of body protein reserves and dietary protein supplementation on maternal performance and immune responses to N. brasiliensis during lactation. Methods: Multiparous female Sprague-Dawley rats were administered a primary infection of N. brasiliensis before mating and were restriction-fed either 60 g [low-protein diet gestation (Lge)] or 210 g [high-protein diet gestation (Hge)] crude protein (CP) per kilogram of dry matter (DM) until parturition. From parturition onward, dams were restriction-fed either 100 g [low-protein diet lactation (Lla)] or 300 g [high-protein diet lactation (Hla)] CP per kilogram of DM, generating 4 different dietary treatments. A subset of rats was sampled before parturition; postparturition, dams were secondarily infected with N. brasiliensis and samples were collected at days 5 and 11 postparturition. Results: Maternal performance until parturition, as measured by pup weight, was better in Hge rats than in Lge rats [Lge: 4.84 g; Hge: 6.15 g; standard error of the difference (SED): 0.19]. On day 11, pup weights of dams with reduced protein reserves fed protein during lactation (Lge-Hla; 20.28 g) were higher than their counterparts from Hge-Lla dams (17.88 g; SED: 0.92). Worm counts were significantly different between Lge-Lla-fed (253; 95% CI: 124, 382) and Hge-Hla-fed (87; 95% CI: 22, 104) dams on day 11 (P = 0.024). The expression of splenic interleukin 13 (Il13) and arachidonate 15-lipoxygenase (Alox15) was significantly higher (P < 0.05) in Hge-Hla dams compared with Lge-Lla dams on day 5. Conclusions: Although protein reserves were adequate to maintain maternal performance in the early stage of lactation in dams infected with N. brasiliensis, they were not adequate to maintain maternal performance and effective immune responses at later stages. Dietary protein supplementation was required to achieve this.

How does the suppression of energy supplementation affect herbage intake, performance and parasitism in lactating saddle mares?

Agroecology opens up new perspectives for the design of sustainable farming systems by using the stimulation of natural processes to reduce the inputs needed for production. In horse farming systems, the challenge is to maximize the proportion of forages in the diet, and to develop alternatives to synthetic chemical drugs for controlling gastrointestinal nematodes. Lactating saddle mares, with high nutritional requirements, are commonly supplemented with concentrates at pasture, although the influence of energy supplementation on voluntary intake, performance and immune response against parasites has not yet been quantified. In a 4-month study, 16 lactating mares experimentally infected with cyathostome larvae either received a daily supplement of barley (60% of energy requirements for lactation) or were non-supplemented. The mares were rotationally grazed on permanent pastures over three vegetation cycles. All the mares met their energy requirements and maintained their body condition score higher than 3. In both treatments, they produced foals with a satisfying growth rate (cycle 1: 1293 g/day; cycle 2: 1029 g/day; cycle 3: 559 g/day) and conformation (according to measurements of height at withers and cannon bone width at 11 months). Parasite egg excretion by mares increased in both groups during the grazing season (from 150 to 2011 epg), independently of whether they were supplemented or not. This suggests that energy supplementation did not improve mare ability to regulate parasite burden. Under unlimited herbage conditions, grass dry matter intake by supplemented mares remained stable around 22.6 g DM/kg LW per day (i.e. 13.5 kg DM/al per day), whereas non-supplemented mares increased voluntary intake from 22.6 to 28.0 g DM/kg LW per day (13.5 to 17.2 kg DM/al per day) between mid-June and the end of August. Hence total digestible dry matter intake and net energy intake did not significantly differ between supplemented and non-supplemented mares during the second and third cycles. In conclusion, supplementing lactating mares at pasture should not be systematic because their adaptive capacities enable to increase herbage intake and ensure foal growth. Further research is needed to determine the herbage allowance threshold below which supplementation is required.

The anthelmintic efficacy of papaya latex in a rodent-nematode model is not dependent on fasting before treatment.

In earlier studies of the anthelmintic activity of plant cysteine proteinases (CPs), a period of food deprivation was routinely employed before administration of CPs, but there has been no systematic evaluation as to whether this does actually benefit the anthelmintic efficacy. Therefore, we assessed the effect of fasting on the efficacy of CPs from papaya latex (PL) against Heligmosomoides bakeri in C3H mice. We used a refined, supernatant extract of papaya latex (PLS) with known active enzyme content. The animals were divided into three groups (fasted prior to treatment with PLS, not fasted but treated with PLS and fasted but given only water). The study demonstrated clearly that although food deprivation had been routinely employed in much of the earlier work on CPs in mice infected with nematodes, fasting has no beneficial effect on the efficacy of PLS against H. bakeri infections. Administration of CPs to fed animals will also reduce the stress associated with fasting.

Enteric infection acts as an adjuvant for the response to a model food antigen.

Oral administration of soluble protein Ags typically induces Ag-specific systemic nonresponsiveness. However, we have found that feeding a model food protein, OVA, to helminth-infected mice primes for a systemic OVA-specific Th2 response. In this report we show that, in addition to creating a Th2-priming cytokine environment, helminth infection up-regulates costimulatory molecule expression on mucosal, but not peripheral, APCs. To examine the consequences of mucosal infection for the T cell response to orally administered Ag, we adoptively transferred transgenic, OVA-specific, T cells into normal mice. We found that helminth infection enhances the expansion and survival of transgenic T cells induced by Ag feeding. Transfer of 5,6-carboxyfluorescein diacetate succinimidyl ester-labeled donor cells showed that T cell proliferation in response to Ag feeding takes place primarily in the mesenteric lymph nodes. Upon subsequent peripheral exposure to Ag in adjuvant, the proliferative capacity of the transferred transgenic T cells was reduced in noninfected mice that had been fed OVA. Helminth infection abrogated this reduction in proliferative capacity. Our data suggests that enteric infection can act as an adjuvant for the response to dietary Ags and has implications for allergic responses to food and the efficacy of oral vaccination.