Losses caused by gastrointestinal nematode infections in Dorper lambs under two nutritional status / Prejuízos causados pelas infecções por nematoides gastrintestinais em cordeiros Dorper submetidos a dois manejos nutricionais

Abstract The aim of this study was to evaluate the effect of two nutritional statuses on the productive performance of Dorper lambs naturally infected with gastrointestinal nematodes. Thirty-two lambs, grazing together on the same pasture, were allocated into four experimental groups: (G1) infected-supplemented diet, (G2) control-supplemented diet, (G3) infected-basal diet, and (G4) control-basal diet. Control animals received suppressive treatment with monepantel every two weeks, while precautionary anthelmintic treatments were given to all lambs of the infected groups with packed cell volume (PCV) <23%. There was reduction in the PCV means of all groups, which was more pronounced in the infected lambs that also presented reduction in total plasma protein values in comparison with the controls. Weight gain was affected by diet and infection status (P < 0.05). Daily body weight gain was 0.170 kg in the G1, 0.205 kg in the G2, 0.085 kg in the G3, and 0.116 kg in the G4. The cold carcass weight was 4.1% and 13.7% higher in controls in comparison with infected lambs, respectively, in the supplemented and basal diets. The infected groups, despite receiving precautionary anthelmintic treatments to prevent deaths due to haemonchosis, presented reduction in the production parameters in comparison with the controls.

Resumo O experimento teve por objetivo determinar o efeito de dois níveis de nutrição no desempenho produtivo de cordeiros Dorper naturalmente infectados por nematoides gastrintestinais. Trinta e dois cordeiros, mantidos juntos na mesma pastagem, foram alocados em quatro grupos experimentais: (G1) infectado-suplementado, (G2) controle-suplementado, (G3) infectado-dieta basal e (G4) controle-dieta basal. Os cordeiros suplementados receberam diariamente concentrado em quantidade equivalente a 2% do peso corporal (PC), enquanto na dieta basal receberam apenas uma pequena quantidade de concentrado (0,35% do PC). Os animais controles receberam tratamento supressivo com anti-helmíntico a cada duas semanas e os infectados foram tratados individualmente quando apresentaram volume globular (VG) <23%. Houve redução nas médias de VG em todos os grupos, as quais foram mais pronunciadas nos animais dos grupos infectados, que também apresentaram redução nos valores de proteína plasmática total em comparação com os controles. Houve efeito significativo da dieta e da infecção no ganho de peso (P <0,05). O ganho em peso diário foi de 0,170 kg no G1, 0,205 kg no G2, 0,085 kg no G3 e 0,116 kg no G4. Os grupos infectados, apesar de receberem tratamentos anti-helmínticos preventivos que evitaram mortes por haemonchose, apresentaram redução nos parâmetros produtivos em comparação com os controles.

Losses caused by gastrointestinal nematode infections in Dorper lambs under two nutritional status.

The aim of this study was to evaluate the effect of two nutritional statuses on the productive performance of Dorper lambs naturally infected with gastrointestinal nematodes. Thirty-two lambs, grazing together on the same pasture, were allocated into four experimental groups: (G1) infected-supplemented diet, (G2) control-supplemented diet, (G3) infected-basal diet, and (G4) control-basal diet. Control animals received suppressive treatment with monepantel every two weeks, while precautionary anthelmintic treatments were given to all lambs of the infected groups with packed cell volume (PCV) <23%. There was reduction in the PCV means of all groups, which was more pronounced in the infected lambs that also presented reduction in total plasma protein values in comparison with the controls. Weight gain was affected by diet and infection status (P < 0.05). Daily body weight gain was 0.170 kg in the G1, 0.205 kg in the G2, 0.085 kg in the G3, and 0.116 kg in the G4. The cold carcass weight was 4.1% and 13.7% higher in controls in comparison with infected lambs, respectively, in the supplemented and basal diets. The infected groups, despite receiving precautionary anthelmintic treatments to prevent deaths due to haemonchosis, presented reduction in the production parameters in comparison with the controls.

Current anthelmintic treatment is not always effective at controlling strongylid infections in German alpaca herds.

BACKGROUND: Endoparasites are considered a major health problem of South American camelids as shown in a recent survey among German and Austrian camelid owners. Although prophylactic and therapeutic measures such as application of anthelmintics are commonly used, treatment efficacy is usually not assessed. Owners have expressed significant concerns regarding the effect of antiparasitic therapy, so this study aimed to evaluate the outcome of anthelmintic treatment in German alpaca herds with different drugs. RESULTS: Overall, 617 samples from 538 clinically healthy alpacas > 1 year-old from 27 farms (n = 11-157 animals/herd) were examined. The most common parasites detected by flotation were Eimeria spp. (75.1%) followed by strongylids (55.0%), Nematodirus spp. (19.3%), cestodes (3.1%) and Trichuris (2.7%). After initial coproscopical examination by flotation and strongylid egg quantification by the McMaster technique, positive animals excreting at least 150 eggs per gram of faeces were included in a faecal egg count reduction test (FECRT) using fenbendazole (n = 71 samples), moxidectin (n = 71) or monepantel (n = 66). Pre-treatment larval cultures (n = 23 positive pooled farm samples) revealed Haemonchus (87% of the farms), Cooperia (43.5%), Trichostrongylus (21.7%), Ostertagia (13.0%), Nematodirus and Oesophagostomum (4.3% each). Fenbendazole treatment reduced egg excretion by 45%, moxidectin by 91% and monepantel by 96%. On the farm level, 13/18 farms that used fenbendazole, 6/6 farms that used moxidectin and 2/5 farms that used monepantel had individual FECR values < 90% (fenbendazole) or < 95% (moxidectin, monepantel). Haemonchus and Cooperia were overrepresented on the farms with reduced treatment efficacy. CONCLUSIONS: Gastrointestinal strongylids are common in German alpacas and fenbendazole in particular was not sufficiently effective to reduce strongylid egg excretion. Although the FECRT could not unambiguously determine anthelmintic resistance in the present study, the finding that small ruminant strongylids, especially Haemonchus, are common in alpacas indicates that determination of effective anthelmintic doses, monitoring of efficacy and adapted (selective) treatment regimens must be implemented as part of sustainable deworming practices in this species in accordance with recommendations for ruminants.

The intake of dry cashew apple fiber reduced fecal egg counts in Haemonchus contortus-infected sheep.

Helminthiasis is a common disease in which parasite resistance is frequently caused by inadequate administration of anthelmintics in small ruminant production. Since phytotherapy may be an adjuvant for parasite control, we assessed whether the ingestion of cashew apple fiber (Anacardium occidentale) would reduce Haemonchus contortus infection in Santa Inês sheep. Twenty-one male sheep with mean age of 240 ±â€¯9.7 days were dewormed, infected with 4000 L3 of H. contortus Embrapa2010 (day 0 - D0) and on D28 were divided into three equally sized experimental groups: 1) control (no treatment), 2) treated with anthelmintic (monepantel, 2.5 mg/kg PV) and 3) cashew apple fiber (0.3% BW) for 7 days of adaptation plus 28 days (D63). The animals were weighed weekly for diet adjustment and individual EPGs were performed twice a week. Corn silage was given ad libitum after each animal had eaten all the cashew apple fiber, which always occurred due to its palatable flavor. The silage, cashew apple fiber and leftovers were weighed daily and the samples were analyzed for dry matter. In cashew apple fiber, the total polyphenol contents were determined spectrophotometrically and the phenol compounds were identified by LC-MS. Cashew apple fiber contained 93.6% DM, 13.0% CP, 68.7% NDF, 47.6% FDA, 1.3% MM, 1.9% EE and 22.3% LIG. Twenty phenolic compounds were detected, among them phenolic acids and flavonoids, including glycosylated ones. The general EPG averages were statistically different among control, anthelmintic and cashew groups (3449, 14 and 2070, respectively), while the mean total weight gain did not differ (3.21, 3.20 and 1.94 kg, respectively) (p < 0.05). In relation to the control group, the anthelmintic showed efficacy of 99.6% and the cashew apple fiber 40.8%. Phenolic compounds appear to play an important role in the anthelmintic activity of cashew apple fiber. Thus, its use as an adjuvant in the control of H. contortus can be encouraged in regions where it is available at low cost, mitigating the use of veterinary drugs, reducing environmental contamination by agroindustrial residues and promoting the more sustainable production of small ruminants.

Supplementation with dry Mimosa caesalpiniifolia leaves can reduce the Haemonchus contortus worm burden of goats.

Gastrointestinal nematodes (GINs) cause considerable economic losses in grazing goat herds. At present, GIN control cannot rely on conventional anthelmintic (AH) drugs because parasites have developed resistance against such drugs. Thus, alternative control methods are being sought to reduce the dependence on AH. Many tannin-rich plants exhibit AH activity and may be used as alternatives for GIN control. Mimosa caesalpiniifolia is a tannin-rich shrub consumed by small ruminants in Brazil. This study evaluated the in vivo AH effect of M. caesalpiniifolia leaf powder supplementation on GIN egg fecal excretion and worm burden in goats. Plant leaves were harvested, dried and ground to obtain a powder. Twenty-four castrated male goats, aged six to eight months, with a mean body weight of 15.0 ±â€¯2.5 kg were used in the experiment. Animals were infected orally with 16,000 larvae comprising 50% Haemonchus spp., 41% Trichostrongylus spp. and 9% Oesophagostomum spp. Once the infection was patent, the goats were distributed into four groups of six animals. The control group received concentrate without condensed tannins (CTs) and did not receive any drench against GINs. The monepantel group received concentrate without CTs and were drenched once with monepantel. The other two groups received the M. caesalpiniifolia leaf powder in two periods of seven consecutive days (days 1-7 and 14-21), with one of the groups also receiving 10 g of polyethyleneglycol (PEG)/day. The animals were weighed weekly, and individual fecal eggs counts (FECs) were performed daily. After 28 days, the animals were humanly slaughtered, and the worm burden was estimated. Although live weight gain and FECs did not differ among the groups (P > 0.05), post-mortem worm counts showed a reduction in Haemonchus contortus adult worm burden (57.7%) in goats of the CT group compared to control goats (P < 0.05). The addition of PEG did not diminish AH activity in the CT + PEG group (66.9% reduction compared to the control). No AH effect against other GIN species was found. The result for the addition of PEG suggested that the observed AH activity was associated with plant secondary compounds, as opposed to CTs. As expected, no AH effect against Oesophagostomum columbianum was found for the monepantel group showed. Thus, feeding dry leaves of M. caesalpiniifolia represent a promising alternative for the control of GIN infections in goats.

Effects of ERK1/2 kinases inactivation on the nigrostriatal system of Krushinsky-Molodkina rats genetically prone to audiogenic seizures.

Recently, we demonstrated that inhibition of ERK1/2 activity by SL-327 treatment blocks seizure behavior in Krushinsky-Molodkina (KM) rats, which was mediated by altering of GABA and glutamate release mechanism in the hippocampus. Basal ganglia representing various subcortical cell groups play a significant role in the regulation of motor activity, including epileptiform seizures. OBJECTIVES:  To verify if nigrostriatal system could be also affected by SL-327 treatment we analyzed the expression of tyrosine hydroxylase, D1 and D2 dopamine receptors, NR2B subunit of NMDA receptor as well as vesicular glutamate transporter VGLUT2 and glutamic acid decarboxylases GAD65/67 in the striatum and substantia nigra of KM rats. METHODS: Animals were injected i.p. with SL-327 (50 mg/kg) 60 min before audio stimulation. After audiogenic stimulation the brains of control and SL 327 treated rats were removed for further immunohistochemical and biochemical analysis. RESULTS:  Obtained results demonstrated a decrease activity in synapsin I, and accumulation of VGLUT2 in the striatum after blockade of audiogenic seizure (AGS) by SL 327 that could lead to inhibition of glutamate release. While in the striatum GAD65/67 level was diminished, in the substantia nigra GAD65/67 was increased showing enhanced inhibitory output to the compact part of the substantia nigra. Analysis of dopaminergic system showed a significant reduction of tyrosine hydroxylase activity and expression in the substantia nigra, and decreased D1 and D2 receptor expression in the striatum. In summary, we propose that changes in the nigrostriatal system could be mediated by inhibitory effect of SL 327 on AGS expression.

[ANTHELMINTIC SUBSTANCES: MAIN CLASSES, PROBLEMS, TRENDS IN DEVELOPMENT AND PROSPECTS].

The review chronologically considers the main classes of the currently available anthelminthic substances: early anthelmintic compounds, benzimidazoles, imidazolthiazoles, tetrahydropyrimidines, avermectins and milbemycins, and salicylanilides. Great attention is paid to novel substances (emodepside, monepantel, derquantel, tribendimidine) and promising developments. Some aspects of the molecular mechanisms of action of anthelmintics, their resistance, and alternative dehelmintization methods are discussed.

Inhibition of ERK1/2 signaling prevents epileptiform behavior in rats prone to audiogenic seizures.

It has recently been proposed that extracellular signal-regulated kinases 1 and 2 (ERK1/2) are one of the factors mediating seizure development. We hypothesized that inhibition of ERK1/2 activity could prevent audiogenic seizures by altering GABA and glutamate release mechanisms. Krushinsky-Molodkina rats, genetically prone to audiogenic seizure, were recruited in the experiments. Animals were i.p. injected with an inhibitor of ERK1/2 SL 327 at different doses 60 min before audio stimulation. We demonstrated for the first time that inhibition of ERK1/2 activity by SL 327 injections prevented seizure behavior and this effect was dose-dependent and correlated with ERK1/2 activity. The obtained data also demonstrated unchanged levels of GABA production, and an increase in the level of vesicular glutamate transporter 2. The study of exocytosis protein expression showed that SL 327 treatment leads to downregulation of vesicle-associated membrane protein 2 and synapsin I, and accumulation of synaptosomal-associated protein 25 (SNAP-25). The obtained data indicate that the inhibition of ERK1/2 blocks seizure behavior presumably by altering the exocytosis machinery, and identifies ERK1/2 as a potential target for the development of new strategies for seizure treatment. Extracellular signal-regulated kinases 1 and 2 (ERK1/2) are one of the factors mediating seizure development. Here we report that inhibition of ERK1/2 by SL 327 prevented seizure behavior and this effect was dose-dependent and correlated with ERK1/2 activity. Accumulation of VGLUT2 was associated with differential changing of synaptic proteins VAMP2, SNAP-25 and synapsin I. The obtained data indicate that the inhibition of ERK1/2 alters neurotransmitter release by changing the exocytosis machinery, thus preventing seizures.

Potential drug development candidates for human soil-transmitted helminthiases.

BACKGROUND: Few drugs are available for soil-transmitted helminthiasis (STH); the benzimidazoles albendazole and mebendazole are the only drugs being used for preventive chemotherapy as they can be given in one single dose with no weight adjustment. While generally safe and effective in reducing intensity of infection, they are contra-indicated in first-trimester pregnancy and have suboptimal efficacy against Trichuris trichiura. In addition, drug resistance is a threat. It is therefore important to find alternatives. METHODOLOGY: We searched the literature and the animal health marketed products and pipeline for potential drug development candidates. Recently registered veterinary products offer advantages in that they have undergone extensive and rigorous animal testing, thus reducing the risk, cost and time to approval for human trials. For selected compounds, we retrieved and summarised publicly available information (through US Freedom of Information (FoI) statements, European Public Assessment Reports (EPAR) and published literature). Concomitantly, we developed a target product profile (TPP) against which the products were compared. PRINCIPAL FINDINGS: The paper summarizes the general findings including various classes of compounds, and more specific information on two veterinary anthelmintics (monepantel, emodepside) and nitazoxanide, an antiprotozoal drug, compiled from the EMA EPAR and FDA registration files. CONCLUSIONS/SIGNIFICANCE: Few of the compounds already approved for use in human or animal medicine qualify for development track decision. Fast-tracking to approval for human studies may be possible for veterinary compounds like emodepside and monepantel, but additional information remains to be acquired before an informed decision can be made.

The striatal-enriched protein tyrosine phosphatase gates long-term potentiation and fear memory in the lateral amygdala.

BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders.

The role of the extracellular signal-regulated kinase signaling pathway in mood modulation.

The neurobiological underpinnings of mood modulation, molecular pathophysiology of manic-depressive illness, and therapeutic mechanism of mood stabilizers are largely unknown. The extracellular signal-regulated kinase (ERK) pathway is activated by neurotrophins and other neuroactive chemicals to produce their effects on neuronal differentiation, survival, regeneration, and structural and functional plasticity. We found that lithium and valproate, commonly used mood stabilizers for the treatment of manic-depressive illness, stimulated the ERK pathway in the rat hippocampus and frontal cortex. Both drugs increased the levels of activated phospho-ERK44/42, activated phospho-ribosomal protein S6 kinase-1 (RSK1) (a substrate of ERK), phospho-CREB (cAMP response element-binding protein) and phospho-B cell lymphoma protein-2 antagonist of cell death (substrates of RSK), and BDNF. Inhibiting the ERK pathway with the blood-brain barrier-penetrating mitogen-activated protein kinase (MAP kinase)/ERK kinase (MEK) kinase inhibitor SL327, but not with the nonblood-brain barrier-penetrating MEK inhibitor U0126, decreased immobility time and increased swimming time of rats in the forced-swim test. SL327, but not U0126, also increased locomotion time and distance traveled in a large open field. The behavioral changes in the open field were prevented with chronic lithium pretreatment. SL327-induced behavioral changes are qualitatively similar to the changes induced by amphetamine, a compound that induces relapse in remitted manic patients and mood elevation in normal subjects. These data suggest that the ERK pathway may mediate the antimanic effects of mood stabilizers.