Distribution of Four Parasitic Helminth Species in One Pen-Free, Egg-Laying Housing Facility, and the Corresponding Efficacy of Nutraceutical and Pharmaceutical Administrations.

In the spring of 2019, adult (75 wk old) brown laying hens from a commercial, pen-free, egg-laying facility (11,000 birds per house) located in northwest Arkansas were obtained for the purposes of sourcing robust and evenly dispersed cestode infections for anticipated anthelmintic evaluations. To that end, four birds from each of six discrete sites (northwest, northcentral, northeast, southwest, southcentral, and southeast) in one production barn were obtained on two occasions, 8 days apart, and necropsied for helminth counts. A definite, repeated, location-to-location variation in infection incidence and magnitude was seen for each of the two cestode parasite species present and for one of the two nematode parasite species present. Burdens of Ascaridia galli were generally similar regardless of bird location, with site-specific mean totals per bird over both sampling days between 31 and 80. For the remaining helminths, infections were greatest for birds from the southern half of the building as opposed to the northern and from the western end of the barn as opposed to the central or eastern portions. Location-specific mean worm burdens over both sample dates ranged from 340 to 1133 (Heterakis gallinarum), 14 to 277 (Raillietina cesticillus), and 1 to 35 (Choanotaenia infundibulum). The greatest individual bird infections were 299 (A. galli), 3575 (H. gallinarum), 1015 (R. cesticillus), and 102 (C. infundibulum). The above counts are for all developmental stages combined (A. galli and H. gallinarum) and for scolexes only (R. cesticillus and C. infundibulum), as determined via standard collection and quantification procedures using both intestinal contents and overnight soaks. Immediately before the mapping study outlined above, birds were obtained from the east end of the source barn and used for the nematocidal evaluation of fenbendazole in the water (5 mg/kg body weight [BW] for 1 day), levamisole in the water (8 mg/kg BW for each of 2 days), herbal mixture in the feed (1 gm/4.5 kg BW each day for 5 days), diatomaceous earth (2% of total feed for 10 days), and a nutraceutical mixture feed supplement (2% of feed for 7 days). Based on arithmetic means for adult forms, control trial efficacies for A. galli and H. gallinarum were 0% and 12% for the nutraceutical feed additive, 0% and 22% for the diatomaceous earth feed additive, 0% and 26% for dietary herbals, 87% and 63% for levamisole, and 82% and 84% for fenbendazole, respectively. Only adult burdens of A. galli and H. gallinarum for fenbendazole- and levamisole-treated birds were significantly different from control bird levels (P ≤ 0.05).

What does the general public in the UK know about the risk to a developing foetus if exposed to alcohol in pregnancy? Findings from a UK mixed methodology study.

INTRODUCTION: Foetal alcohol spectrum disorders (FASD) are a set of preventable conditions where the foetus is exposed to alcohol in utero and as a result suffers adverse consequences. To develop a public health strategy related to FASD, it is important to first establish what is known by the public about this condition. This study aimed to assess the current level of knowledge about FASD in the UK general population. METHODS: A mixed methodology study was conducted using a 17-item questionnaire and focus group sessions. Four focus groups were held with an average of 10 people in each group. Semi-structured questions and thematic analysis of interviews alongside quantitative analysis of the questionnaire data was completed. The research was approved by an National Health service (NHS) research ethical committee. RESULTS: A total of 674 people responded to the questionnaire and a majority (86.7%) had heard about FASD, with most receiving their information from the media (26.2%) or from their work (27.7%). Four broad themes emerged. Overall these were: a general lack of knowledge about the subject; information about the subject needed to be personally relevant; there was a need for further education; and there was a lack of clarity in the current guidance on alcohol use in pregnancy. DISCUSSION AND CONCLUSIONS: Currently there appears to be a superficial level of knowledge about FASD in the UK general public. More detailed work in subgroups, such as young women, to identify their specific needs may be necessary before targeted public health and educational interventions can be developed to meet the needs of the general public.

Control trial and fecal egg count reduction test determinations of nematocidal efficacies of moxidectin and generic ivermectin in recently weaned, naturally infected calves.

An anthelmintic efficacy study was performed with young, naturally infected beef-type calves obtained at local farms. Presumably, the study calves had been recently weaned and had not been treated with a parasiticide prior to study acquisition. After blocking the 24 study calves in accordance with calculated Cooperia spp EPG counts, the calves were randomly allocated within each block to one of four treatment groups, resulting in 6 animals per treatment group (untreated controls, topical ivermectin at the rate of 500 mcg/kg BW [Noromectin Pour-On(®) Norbrook], topical moxidectin at the rate of 500 mcg/kg BW [Cydectin Pour-On(®) Boehringer Ingelheim Vetmedica (BIVM)] and injectable moxidectin at the rate of 200 mcg/kg BW [Cydectin(®) BIVM]. After treatment, the animals were penned by treatment group until necropsy. Fecal, strongyle egg count reduction percentages at 2 days post-treatment were 13, 52, 81 and 93 for control, topical ivermectin, topical moxidectin and injectable moxidectin treatment groups, respectively. In the same order as above, egg count reduction percentages at necropsy (15-18 days post-treatment) were -14, 91, 94 and 97. Based on geometric means for worm burdens quantified at necropsy, anthelmintic efficacies ranged from 96 to 100% for adult Oesophagostomum radiatum, Ostertagia ostertagi, Haemonchus placei and Trichostrongylus axei. Against adult Nematodirus helvetianus, percent efficacies based on geometric means were 56.7, 98.3 and 82.2 for topical ivermectin, topical moxidectin and injectable moxidectin, respectively; an observation that is guarded, as only 5 control animals were infected with adult N. helvetianus. Respective anthelmintic efficacies (%'s) against adult Cooperia oncophora and C. punctata were 93.0 and 73.4 (topical ivermectin), 99.3 and 99.9 (topical moxidectin) and 46.1 and 93.6 (injectable moxidectin). Judging from these data, it appears that treatment of calves soon after weaning with topical moxidectin is effective (>90% efficacy) for all common nematodes in cattle, but injectable moxidectin and topical ivermectin have limited effectiveness against Cooperia spp. With Cooperia spp and H. placei infections, the fecal egg count reduction test and the control trial determinations of anthelmintic effectiveness were in disagreement regarding injectable moxidectin and topical ivermectin.

Another look at LREC annual reports.

Almost the only readily available sources of information about the activities of UK research ethics committees are the annual reports that they have been required since 1991 to publish. This paper reports on a further study of those reports by the Bulletin.

Varying physiological response to arm-crank exercise in specific spinal injuries.

The purpose of this arm-crank ergometry (ACE) study was to provide a greater understanding of the influence to which specific cervical and thoracic spinal cord injuries contribute to reduction in optimal cardio-respiratory and metabolic function. Twenty five male volunteers aged 20 to 47 years participated. Twenty disabled wheelchair-confined spinal cord injured (SCI) subjects were equally divided into four 'site-specific' groups based on the lesion being within either high- or low- cervical or thoracic anatomical regions. Five physically non-disabled controls (As) were included. Measured variables tended to decrease progressively from As to high-level quadriplegics. Analysis revealed a high variance in maximum cardio-respiratory performance levels between groups (P < 0.001). These findings confirm that limitation to upper body physical capabilities in the SCI during high-intensity ACE is dependent on specific lesion site. Considerable variability in performance levels were measured in those suffering lesions within closely approximating anatomical regions. Results also suggest a greater importance in the location of cervical rather than thoracic injuries in contributing towards higher relative losses in maximal cardio-respiratory and metabolic potential. Alterations in body composition and varying severity of muscle paralysis likely also play a contributing role in reducing optimal metabolic function in SCI individuals. The importance for stringent classification techniques of spinal cord lesion site in predicting upper body physical exercise potential in the SCI has therefore been highlighted in this study.

Ethics committees in Italy--a time for change?

The Comitato Nazionale per la Bioetica (CNB) in Italy has recently produced an unprecedented discussion document on the state of ethics committees in Italy, with an invitation to interested parties to comment on proposed changes to their fundamental structure. After this consultation, and taking note of relevant official publications and the most recent national and international literature on the subject, the CNB proposes to produce a final, definitive document that will consider options for the future development of such committees.

Cannabinoid agonists and antagonists discriminated by receptor binding in rat cerebellum.

1. The effect of allosteric regulators on the binding affinity of a number of cannabinoid receptor ligands of varying efficacy in the rat cerebellum was investigated. 2. Radioligand ([3H]-SR141716A) competition curves were constructed in the presence or absence of sodium ions, magnesium ions and guanine nucleotides. 3. It was found that the presence of these allosteric regulators did not affect the affinity of the two antagonists used but did cause a significant decrease in the affinity of full and partial agonists. 4. This reduction in affinity ranged from a 3.67 fold rightward shift of the displacement curve of a mixed agonist/antagonist (3-(6-cyano-2-hexynyl)-delta-8-tetrahydrocannabinol-O-823) to a 38 fold rightward shift for 3-(1, 1-dimethyl-6-dimethylcarboxamide)-delta-8-tetrahydrocannabinol (O-1125), a full agonist. 5. In summary, the results of this study suggest a simple method for the inference of functional data using the classical radioligand binding assay.

Evaluation of the cannabinoid CB2 receptor-selective antagonist, SR144528: further evidence for cannabinoid CB2 receptor absence in the rat central nervous system.

The aim of this study was to characterize the activity of the cannabinoid CB2 receptor selective antagonist, N-[(1S)-endo-1,3,3-trimethyl bicyclo[2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le-3-carboxamide] (SR144528) in a number of biochemical assays and to look for evidence of cannabinoid CB2 receptors in the rat central nervous system. SR144528 displaced [3H]CP 55,940 ((-)-3-[2-hydroxyl-4-(1,1-dimethylheptyl)-phenyl]-4-[3-hydroxyprop yl]cyclohexan-1-ol) from binding sites in CB2- and CB1-transfected cells (Ki = 0.67+/-0.30 and 33.0+/-5.09 nM) and from rat cerebellum and whole brain membrane homogenates (Ki = 54.7+/-9.70 and 54.8+/-7.86 nM). In the GTPgammaS binding assay, SR144528 antagonized a number of cannabinoid receptor agonists (K(B) values ranging from 26.3 to 76.6 nM) in rat cerebellar membranes and in rat whole brain membranes (K(B) = 50.8 nM). SR144528 also antagonized CP 55,940-stimulated GTPgammaS binding in a CB2-expressing cell line (K(B) = 6.34 nM). In Xenopus oocytes co-expressing the CB1 receptor and G-protein coupled inwardly rectifying K+ channels (GIRK 1/4), SR144528 antagonized WIN 55212-2((R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl)methyl]pyrolo [1,2,3-de]-1,4-benzoxazin-6-yl](1-naphthalenyl)methanone) -stimulated K+ currents (K(B) = 558 nM). In summary, this report characterizes the cannabinoid CB2 receptor-selective cannabinoid antagonist, SR144528, and additionally suggests an absence of cannabinoid CB2 receptors in the rat central nervous system, an observation confirmed by Northern blot.

An investigation into the structural determinants of cannabinoid receptor ligand efficacy.

1. A number of side-chain analogues of delta8-THC were tested in GTPgammaS binding assay in rat cerebellar membranes. O-1125, a saturated side-chain compound stimulated GTPgammaS binding with an Emax of 165.0%, and an EC50 of 17.4 nM. 2. O-1236, O-1237 and O-1238, three-enyl derivatives containing a cis carbon-carbon double bond in the side-chain, stimulated GTPgammaS binding, acting as partial agonists with Emax values ranging from 51.3-87.5% and EC50 values between 4.4 and 29.7 nM. 3. The stimulatory effects of O-1125, O-1236, O-1237 and O-1238 on GTPgammaS binding were antagonized by the CB1 receptor antagonist SR 141716A. The K(B) values obtained ranged from 0.11-0.21 mM, suggesting an action at CB1 receptors. 4. Five-ynyl derivatives (O-584, O-806, O-823, O-1176 and O-1184), each containing a carbon-carbon triple bond in the side-chain, did not stimulate GTPgammaS binding and were tested as potential cannabinoid receptor antagonists. 5. Each -ynyl compound antagonized the stimulatory effects of four cannabinoid receptor agonists on GTPgammaS binding. The K(B) values obtained, all found to be in the nanomolar range, did not differ between agonists or from cerebellar binding affinity. 6. In conclusion, alterations of the side-chain of the classical cannabinoid structure may exert a large influence on affinity and efficacy at the CB1 receptor. 7. Furthermore, this study confirms the ability of the GTPgammaS binding assay to assess discrete differences in ligand efficacies which potentially may not be observed using alternative functional assays, thus providing a unique tool for the assessment of the molecular mechanisms underlying ligand efficacies.

Lactational passage of fusaric acid from the feed of nursing dams to the neonate rat and effects on pineal neurochemistry in the F1 and F2 generations at weaning.

Fusaric acid is produced by several species of Fusarium and is found in corn, corn-based foods and feeds, wheat, barley, and other cereal grains. Given parenterally to rats, the mycotoxin affects neurochemical parameters in the pineal gland associated with growth and maturation. Since little information exists concerning the dietary effects of fusaric acid, the mycotoxin was mixed with feed at 10, 75, and 200 ppm and fed ad libitum to pregnant rats (F0 dams) from d 11-12 of gestation, through parturition and weaning (F1 generation). On d 4 postpartum, F1 pups were culled to 9-10 pups/litter; the stomach colostrum was collected from the culls and analyzed for fusaric acid. The mycotoxin in the colostrum (ng fusaric acid/100 mg colostrum) was directly related to the amount consumed by the nursing dams (i.e., 200 ppm pups, 3547 ng; 75 ppm pups, 1449 ng; 10 ppm pups, 80 ng; controls pups, 18 ng). All other animals survived, and appeared normal, healthy, and in good pelage. F0 dam feed consumption and dam and pup weights were not statistically different, but there was an inverse relation between pup average weight gain and amount of fusaric acid in the diets (i.e., weight gains: control pup > 10 ppm pup > 75 ppm pups > 200 ppm pups). At weaning, the F1 pups were randomly assigned to two groups per treatment: one group (F1A) for reproduction and fusaric acid effects on the F2 generation, and another group (F1B) for neurochemical comparisons. The F1A rats were maintained on their respective diets to age 13-14 wk; animals were bred (i.e., control males x control females, 10 ppm x 10 ppm, etc.) and the F1A dams and F2 pups were monitored as already described. Weight gains and fusaric acid in stomach colostrum from the F2-culls were analogous to the F1 generation. On d 5-6 and 7-8 postpartum, using litter weight gains as an indication of milk production in the F1A dams (controls vs. 200 ppm), the controls gained 32.5% (p < .01) and 13.3% (p < .02), respectively, more than 200 ppm F2 pups. At weaning, no differences were observed in neurochemicals in the pineal gland for the F1 generation. However, in the F2 200 ppm male and female weanlings, fusaric acid decreased pineal serotonin (males, p < or = .001; females, p < or = .15) and tyrosine (males, p < or = .04; females, p < or = .07). The results indicate fusaric acid in diets at < or = 0.3 ppm (i.e., background control diet) lactationally passes from nursing dams to the neonate; in weanlings, at 200 ppm, fusaric acid decreases pineal serotonin and tyrosine. The data also suggest limited neonate weight gains may be related to either decreased milk production in dams or mycotoxin effects on the neonate. This is the first report of fusaric acid's lactational passage from the feed of nursing dams to neonates and the oral suppression of pineal serotonin and tyrosine in offspring.

Fusaric acid in Fusarium moniliforme cultures, corn, and feeds toxic to livestock and the neurochemical effects in the brain and pineal gland of rats.

Fusaric acid is produced by several species of Fusarium, which commonly infect corn and other agricultural commodities. Since this mycotoxin may augment the effects of other Fusarium toxins, a gas chromatography/mass spectrometry method of analysis in feeds was developed. Fusaric acid was analyzed as the trimethylsilyl-ester from F. moniliforme-cultures, -contaminated corn screenings, and feeds toxic to livestock. The mycotoxin was found in all samples and ranged from 0.43 to 12.39 micrograms/g sample. Also, fusaric acid was tested for its neurochemical effects in the brain and pineal gland of rats. Animals were dosed intraperitoneally (100 mg/kg body weight) 30 min prior to the onset of the dark phase (lights out) and the effects were studied at 1.5, 3.5, and 5.5 h after treatment. Brain serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), tyrosine (TYRO), and dopamine (DA) were increased (P < 0.05) by fusaric acid, and norepinephrine (NEpi) was decreased (P < 0.05). Analogously, DA in the pineal gland increased and NEpi decreased (P < 0.05). Pineal N-acetylserotonin (NAc5HT) was increased (P < 0.05), whereas pineal 5HT and its two major metabolites 5HIAA and 5-hydroxytryptophol (5HTOL) decreased (P < 0.05). Elevated brain TYRO and brain and pineal DA, with decreased NEpi, may be consistent with fusaric acid's partial inhibitory effect on tyrosine-hydroxylase and its inhibitory effect on dopamine-beta-hydroxylase, respectively. Elevated pineal Nac5HT is consistent with decreased pineal 5HT and the increased pineal DA, and support the dopaminergic stimulatory activity of the enzyme responsible for the conversion of 5HT to NAc5HT. This is the first report of fusaric acid's in vivo effect on pineal DA, NEpi, 5HT, and NAc5HT in rats, and a relation for the effects on TYRO, 5HT, and 5HIAA in brain tissue. The results indicate fusaric acid alters brain and pineal neurotransmitters and may contribute to the toxic effects of Fusarium-contaminated feeds.

Fumonisin- and AAL-Toxin-Induced Disruption of Sphingolipid Metabolism with Accumulation of Free Sphingoid Bases.

Fumonisins (FB) and AAL-toxin are sphingoid-like compounds produced by several species of fungi associated with plant diseases. In animal cells, both fumonisins produced by Fusarium moniliforme and AAL-toxin produced by Alternaria alternata f. sp. lycopersici inhibit ceramide synthesis, an early biochemical event in the animal diseases associated with consumption of F. moniliforme-contaminated corn. In duckweed (Lemna pausicostata Heglem. 6746), tomato plants (Lycopersicon esculentum Mill), and tobacco callus (Nicotiana tabacum cv Wisconsin), pure FB1 or AAL-toxin caused a marked elevation of phytosphingosine and sphinganine, sphingoid bases normally present in low concentrations. The relative increases were quite different in the three plant systems. Nonetheless, disruption of sphingolipid metabolism was clearly a common feature in plants exposed to FB1 or AAL-toxin. Resistant varieties of tomato (Asc/Asc) were much less sensitive to toxin-induced increases in free sphinganine. Because free sphingoid bases are precursors to plant "ceramides," their accumulation suggests that the primary biochemical lesion is inhibition of de novo ceramide synthesis and reacylation of free sphingoid bases. Thus, in plants the disease symptoms associated with A. alternata and F. moniliforme infection may be due to disruption of sphingolipid metabolism.

Neuromuscular responses of elderly women to tasks of increasing complexity imposed during walking.

The purpose of this electromyographic study was to examine the effects of age on lower limb muscle response characteristics during reaction tasks of varying complexity when standing and walking. Ten young (mean age 22 years) and ten elderly (mean age 68 years) women participated in the investigation. No differences between groups were recorded in muscle activation times (MAT) in response to a visual light directional stimulus (LDS) during all standing reaction tasks. All the women required a longer period of time to respond to LDS when walking than standing. Completion of complex walking reaction tasks produced significantly longer (P < 0.001) MAT in all subjects than the more simple walking reaction tasks. Delays in neuromuscular response were significantly greater (P < 0.05) in the older women as the complexity of the walking reaction task increased. Movement behaviour of subjects during the walking reaction trials suggested that relatively greater demands were placed on the neuromuscular systems of the elderly during those tasks of greatest complexity. It was postulated that these movements were directed more at compensating for a reduced neuromuscular ability to control efficiently balance homeostasis. The results of this study provide further support for the hypothesis that delays in the central processing of information during reaction tasks may occur with ageing.

Twenty years of oral contraception.

PIP: This is a survey article on the development of OCs (oral contraceptives). It traces OC development and research through the original combined synthetic estrogen-synthetic progestagen, the sequential regime, the progestagen-only preparation, and injectable hormonal agents, Clinical studies performed with different preparations of OC are cited. Adverse effects which have been shown to be associated with OC usage are mentioned. Acceptability of OCs, despite adverse publicity, has grown. It is predicted that the popularity of OCs will rise once again, particularly after publication of the results of certain studies which show that the cardiovascular hazards associated with OCs are not confirmed. Removal of OCs from restricted medical distribution will also tend to increase their popularity.^ieng

[Clinical studies on Ovostat--a combined oral contraceptive with a low dose of lynestrenol]. / Klinische Untersuchung mit Ovostat--einem kombinierten oralen Kontrazeptivum mit einer niedrigen Dosis Lynestrenol

PIP: Experience with the oral contraceptive Ovostat (.1 mg mestranol and 1 mg lynestrenol) in 324 women (5714 cycles) is reported. Only 1 pregnancy was observed, in a patient who had forgotten several pills. Side effects included headache (11 patients), nervousness (5 patients), amenorrhea (4 patients), and chloasma (3 patients). Breakthrough bleeding and spotting were rare. Cervical mucus (samples on Days 9-11 and 13-15 in 50 women) was uniformly inhospitable to sperm: low viscosity, negative Farn test, constant pH. Endometrial biopsy showed tissue typical of "suppressed" endometrium.^ieng