Lythrum hyssopifolia (lesser loosestrife) poisoning of sheep in Victoria.

OBJECTIVE: To document an ovine disease attributed to the consumption of Lythrum hyssopifolia (lesser loosestrife). PROCEDURES: Historical and histological review of field and experimental cases. RESULTS: 1-20% mortality occurred in sheep flocks grazing paddocks where L. hyssopifolia was the predominant green vegetation. Well-documented disease outbreaks occurred in summer on nine farms across Victoria between 1974 and 2002. Liver damage occurred in all nine outbreaks, with kidney damage in at least eight. Hepatocyte necrosis was usually zonal to midzonal (zone 2) in the liver samples from four farms and periacinar (zone 3) in those from three farms, but some livers showed only single-cell necrosis. Multinucleate hepatocytes near necrotic areas were a feature in six cases. Proximal tubular epithelium appeared to be the primary renal target and brown granules were often present in renal tubules. Biochemical and histological evidence of liver and kidney damage was obtained from two sheep experimentally pen-fed harvested L. hyssopifolia. CONCLUSION: Chemicals in L. hyssopifolia are toxic to ovine hepatocytes and renal tubular epithelial cells.

The case for iron repletion as a promoter in testicular cancer.

The incidence of testicular cancer has increased considerably in this century. Current hypotheses (most specifically, those concerning environmental estrogens) show inconsistencies with this increase, either in terms of time course or individual exposure to proposed promoters. This new hypothesis, which attributes the increased incidence in testicular cancer to our current more iron-replete dietary status, is devoid of these inconsistencies. Evidence to support this hypothesis includes the following: (a) the iron-related mechanism of drugs used in the treatment of testicular cancer, (b) dietary associations with disease frequency, (c) the similarity of time course between historic increases in testicular cancer incidence and dietary iron availability, and (d) potential genetic associations with hemochromatosis. The link between incidence of the cancer and cyptorchidism is also addressed. The article concludes with potential experimental approaches to test the hypothesis.

Aerobic bacterial flora of addled raptor eggs in Saskatchewan.

In south-central Saskatchewan, Canada, in 1986, 1987 and 1989, the aerobic bacterial flora was evaluated from 75 unhatched raptor eggs of three species: 42 of the Swainson's hawk (Buteo Swainsoni), 21 of the ferruginous hawk (Buteo regalis), and 12 of the great horned owl (Bubo virginianus). In addled Swainson's hawk eggs, the most common bacterial genera were Enterobacter (18 eggs), Escherichia (12), and Streptococcus (10). Seven great horned owl eggs and six ferruginous hawk eggs also contained Escherichia coli. Salmonella spp. were not isolated. These bacteria were interpreted as secondary contaminants and not the primary cause of reproductive failure.

Proposed role for a combination of citric acid and ascorbic acid in the production of dietary iron overload: a fundamental cause of disease.

This paper presents a review of the significant body of literature liking dietary iron overload, not only to heart disease, but also to cancer, diabetes, osteoporosis, arthritis, and possibly other disorders. Following an analysis of our understanding of the mechanistic role iron plays in oxidative damage, an interpretation of the fact that plasma concentrations of several antioxidants are decreased in the presence of disease is offered. Evaluation of (1) age-related dietary trends over time and (2) factors involved in iron absorption leads to the hypothesis that the combination of citric acid and ascorbic acid (a synergistic pair of strong enhancers) is instrumental in causing a deleterious increase in iron load in aging populations. Iron overload may be the most important common etiologic factor in the development of the diseases mentioned; therefore, the synergistic combination of citric and ascorbic acids may play a major role in our worsening disease statistics. Evidence to support this hypothesis and possible experiments to test it are included. This combination needs further study, particularly because the iron overload produced may be correctable.

Efficient storage, computation, and exposure of computer-generated holograms by electron-beam lithography.

An efficient storage format was developed for computer-generated holograms for use in electron-beam lithography. This method employs run-length encoding and Lempel-Ziv-Welch compression and succeeds in exposing holograms that were previously infeasible owing to the hologram's tremendous pattern-data file size. These holograms also require significant computation; thus the algorithm was implemented on a parallel computer, which improved performance by 2 orders of magnitude. The decompression algorithm was integrated into the Cambridge electron-beam machine's front-end processor.Although this provides much-needed ability, some hardware enhancements will be required in the future to overcome inadequacies in the current front-end processor that result in a lengthy exposure time.

Phenotypic, embryonic, and neonatal effects of a gene for sex-linked imperfect albinism (Sal-s) in chickens.

Gross phenotypic observations, histology, and tissue culture showed that the gene for sex-linked imperfect albinism that occurred at the University of Saskatchewan (Sal-s), allows a small amount of melanin pigment to be deposited in eyes and feathers. Melanin pigment accumulates in retinal pigment epithelial and cultured neural crest cells, but neural crest cells pigmenting the feathers transfer their pigment as it is produced, and this is seen as a constant amount of color in successive generations of feathers. Despite differences from early reports, it would appear that the phenotype produced by Sal-s is essentially the same as that produced by other Sal mutations. Albinos have a high incidence of lesions in the regions of the navel, the hocks, and the nares, similar to those associated with other hypomelanic mutations in the chicken. Yolk contents appear to be used more slowly by albinos late in incubation. The increased size of the yolk sacs probably contributes directly to producing the navel lesions and indirectly to variation in hatch weight. Albinos have small bursae of Fabricius, reduced hatchability, and early growth.

Effects of imperfect albinism (sal-s) on egg production in two lines of chickens.

Two trials were conducted with two different lines of chickens to determine whether a gene for sex-linked imperfect albinism (sal-s) affected various egg production traits. In a line with relatively good egg production, sexual maturity was delayed for albino compared with nonalbino hens, but overall egg production by albinos was higher. The increased production resulted in eggs with reduced yolk and shell weights. Albumen weights were not affected, and because the eggs from albinos were smaller, Haugh unit scores were higher. In another trial, sexual maturity of hens of a heavy line was not affected by the genotype, but these hens did not receive controlled lighting during the growing period. Egg production curves of these hens were very similar to those seen in the first trial. The laying house mortality rates were not affected by the sal-s gene, despite several periods of high environmental temperature. These trials suggest that sal-s could be used in a sex-linked cross of commercial layers or broiler breeders.

Effects of imperfect albinism (sal-s) on growth in a heavy line of chickens.

Four trials compared growth, feed efficiency, and mortality of albino (sal-s) and nonalbino chickens under conditions approximating those used commercially for broilers. Early body weight reductions of albino chicks were substantial, but by a normal market age for broilers in North America, albinos weighed only 3 to 5% less than nonalbinos. The early mortality rate of albinos was elevated. Overall feed efficiency was not affected by the sal-s gene. An increased incidence of lesions of the navel, hocks, and nares was observed, but regression analyses showed them to be relatively unimportant in the determination of body weights. Heritability estimates showed that the lesions would be very difficult to eliminate through selective breeding. It is proposed that the gene could be used to sex either commercial broilers or their dams.

Quisqualate receptors in epileptic fowl: the absence of coupling between quisqualate and N-methyl-D-aspartate receptors.

The ability of excitatory amino acid receptor agonists, AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) and quisqualate to produce seizures was determined in 1-2 day old epileptic and non-epileptic (carrier) chicks. Both compounds produced prolonged clonic seizures in epileptic chicks at doses which were not convulsant in carrier chicks. Seizures produced in epileptics by AMPA were suppressed by the quisqualate antagonist CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), but were not prevented by pretreatment with competitive (2-amino-7-phosphonoheptanoic acid, APH) or non-competitive (MK-801) NMDA (N-methyl-D-aspartate) receptor antagonists. These data do not support the hypothesis that NMDA receptors work in concert with quisqualate receptors. Binding sites for [3H]AMPA were characterized in cerebral hemispheres of both epileptic and carrier chicks. Analysis of the data revealed no significant alterations in the binding affinity (KD) or the number of binding sites (Bmax) of AMPA to tissue preparations from epileptic chickens when compared to carriers. The latter data does not explain the increased susceptibility of epileptic fowl to the convulsant effects of quisqualate and AMPA.

Attenuation of febrile seizures in epileptic chicks by N-methyl-D-aspartate receptor antagonists.

Experimental febrile seizures can be evoked in epileptic chicks by elevation of their body temperature. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists [(3-(+/- )2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), DL-2-amino-7-phosphosphonoheptanoic acid (APH), DL-2-amino-5-phosphonovaleric acid (APV), D-alpha-aminoadipic acid (AAA), and DL-alpha, epsilon-diaminopimelic acid (DAP)] and the noncompetitive NMDA antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5, 10-imine maleate (MK-801) produced dose-dependent increases in latency to the onset of seizures. Of the drugs tested, MK-801 had the highest potency followed in order by CPP = APH greater than APV much greater than AAA greater than DAP. There was a high correlation (r = 0.995) between the dose capable of doubling seizure latency and the affinity of the competitive NMDA antagonists for the NMDA receptor as determined by in vitro binding assays. These data suggest that NMDA receptor mediated mechanisms may be involved in the production of seizures in response to hyperthermia.

Megalencephaly in the epileptic chicken: a morphometric study of the adult brain.

The epileptic chicken is a genetic model of generalized epilepsy in which epilepsy is combined with megalencephaly. We have performed a morphometric study of the brains of adult epileptic hens, using heterozygous carrier hens as controls. There is no obvious disorder of cell form or of architectural arrangement in the megalencephalic brains. We have found that the enlargement of the epileptic brain is not uniform: it is most marked in the telencephalon, and is present to a lesser degree in the cerebellum, but neither the optic tectum nor the diencephalic nucleus rotundus shows a significant increase in size. The enlarged regions are characterized by a decrease in the packing density of neurons. There is an increase in the total neuron population in some of the enlarged areas (archistriatum), despite the lower density per unit volume, but in other enlarged areas (hippocampus) there is no difference in total neuron numbers. The glial cells, by contrast, show no significant alteration in packing density. These findings suggest that the megalencephaly of the epileptic chicken is due to an increase in neuron size, with a contribution from increased numbers of neurons and glial cells. The epileptic chicken may provide a valuable model for further dynamic studies of aberrant neuronal development, and of structural-functional relationships in epilepsy.

The relationship between anticonvulsant activity and receptor affinity of N-methyl-D-aspartate antagonists in epileptic fowl.

The N-methyl-D-aspartate (NMDA) receptor antagonists [(3-(+/-)2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), +/- 2-amino-7-phosphonoheptanoic acid (2AP7), +/- 2-amino-5-phosphonovaleric acid (2AP5), D-alpha-aminoadipic acid (alpha AA), and +/- alpha, epsilon-diaminopimelic acid (DAP)] were tested for anticonvulsant activity in epileptic chickens. There was a high correlation between anticonvulsant potencies (ED50) and the affinity for the NMDA receptor measured by displacement of L-[3H]glutamate from synaptosomal membranes. The high seizure susceptibility is not due to abnormalities in the NMDA receptor as comparison of KD, Bmax and Ki values in synaptosomal preparations from epileptic and non-epileptic chickens indicated no differences in NMDA receptor binding receptor characteristics.

Use of interferometry in preschool children.

Any procedure that can help to predict the outcome of treatment for a vision disorder is a desired clinical goal. Interferometry has shown such an ability for predicting the post-treatment visual acuities in amblyopia and other vision disorders. In this study, we investigated the effectiveness of using interferometry with preschool children, aged 3-5 years. We determined that they can be reliably tested in 5-10 minutes using a non-verbal, forced choice technique. Due to developmental differences, the 3-year-olds needed slightly more time to test and were more variable in their responses than the 4-years-olds. Overall, the prognostic value of interferometer visual acuity measures should be considered for use in preschool children with visual acuity disorders, e.g., amblyopia.

Protection by GABA agonists, gamma-hydroxybutyric acid, and valproic acid against seizures evoked in epileptic chicks by hyperthermia.

With microwave diathermy, febrile seizures were produced in epileptic chicks aged 2-5 days. Drugs that enhance GABAergic activity (i.e., GABA, muscimol, and progabide), as well as valproic acid and gamma-hydroxybutyric acid, produced dose-dependent increases in latency to onset of seizures.

The cytogenetics of domestic geese.

Hybrids were produced between an African male and several Pilgrim female domestic geese. Partial karyotypes revealed a difference in the fourth largest pair of autosomal chromosomes. This chromosome pair was metacentric in the African, submetacentric in the Pilgrim, and heteromorphic in the hybrids. A similar difference between the putative wild ancestors of the African and Pilgrim breeds has been reported by others. These findings provide cytological evidence to support the traditional opinion that the African breed was derived from the Asiatic swan goose (Anser cygnoides) and the Pilgrim breed was derived from the European greylag goose (Anser anser).

Benzodiazepine antagonist Ro 15-1788 (flumazepil) attenuates the anticonvulsant activity of diazepam in epileptic fowl.

The ability of the imidazobenzodiazepine Ro 15-1788 to displace diazepam from brain membranes in vitro and to antagonize the anticonvulsant activity of diazepam in vivo was determined in epileptic fowl. At doses of 1.0 mg/kg and higher, Ro 15-1788 significantly attenuated the anticonvulsant action of diazepam (1.0 mg/kg) in epileptic chickens. Ro 15-1788 alone exerted no anticonvulsant activity even in doses as high as 10 mg/kg. Specific binding of 10 nM [3H]diazepam to whole homogenate fractions prepared from cerebral hemispheres of epileptic fowl was inhibited by Ro 15-1788 with an IC50 of 8.5 nM and the Ki was determined to be 4.25 nM. These results suggest that Ro 15-1788 competes directly with diazepam for a binding site involved in producing anticonvulsant activity.

Anatomical defects associated with a feathering mutant (Ottawa naked) in domestic fowl.

An autosomal recessive mutation (Ottawa naked, nk) that causes abnormal feathering, fusion of the third and fourth toes, and low viability has been reported previously in the chicken. In the present study mutant individuals were examined from three different stocks: the original one in which the mutant was found and two outbred F2 stocks. Defects of the tail region were observed in all mutants from the original stock (20/20) and in 64% (16/25) of the mutants produced from the outcrossed stocks. The severity of the defects ranged from mild distortion and scoliosis of the coccygeal vertebrae to absence of all vertebrae from the lumbosacral level caudad. Forty percent (16/40) of the mutants from the original stock lacked caudal portions of the kidneys to varying degrees. Edematous areas were observed in 22% (15/67) of the embryos examined at 14 days of incubation. Other defects observed in the mutant embryos but not studied in detail are abnormal patterning or absence of scales, absence of the caudal spinal cord in embryos with severe rumplessness, and failure of the three metatarsal bones to fuse into a single element. Since all structures affected in the mutants differentiate primarily from or may be dependent upon the mesoderm, it is suggested that the site of gene action lies within this germ layer. A decrease was observed in both incidence and severity of the various defects following outcrossing, which suggests the presence of modifiers that influence the expression of the trait.

Integrated electromyographic measurement of abdominal motor blockade during bupivacaine epidural anesthesia for lower abdominal and pelvic surgery.

The onset and regression of abdominal motor blockade was monitored with integrated electromyography in eighteen patients undergoing pelvic or lower abdominal surgery during lumbar epidural anesthesia using 0.75% bupivacaine with 1:200,000 epinephrine. The integrated electromyograph (EMG) was measured at the T-6, T-8, T-10 and T-12 dermatomes during a standardized head-raising test before anesthesia and at fixed time intervals thereafter for a minimum of four hours. Simultaneous measurements were made of abdominal sensory block (analgesia to Allis forceps pinch expressed in dermatomes) and lower limb motor blockade (Bromage scale). Motor block at a given dermatome level was defined as reduction of the integrated EMG amplitude to less than 20% of control. Mean maximum level of sensory block was T-4.2 +/- 0.6 (SEM) mean maximum level of motor block was T-8.8 +/- 0.5. The mean motor sensory differential varied between 4.5 +/- 0.6 and 5.3 +/- 0.9 segments over the 4-hr study period. Mean time to maximum abdominal sensory block was 28 +/- 3 min, and maximum abdominal motor block was 29 +/- 6 min. Mean time to two-segment regression of abdominal motor block was 94 +/- 18 min and to two-segment regression of abdominal sensory block, was 150 +/- 18 min.

Anticonvulsant effects of ivermectin in genetically-epileptic chickens.

In genetically-photosensitive epileptic chickens, the anti-parasitic agent ivermectin, at 1.0 and 5.0 mg/kg, decreased or prevented seizures induced by intermittent photic stimulation without any side-effects on the central nervous system. The latency and duration of this anti-convulsant effect was dose-dependent. When combined with diazepam, ivermectin prolonged the anti-convulsant action of diazepam.

Evidence for the pharmacological relevance of benzodiazepine receptors to anticonvulsant activity.

Each of a series of benzodiazepines was found to be effective in preventing convulsions evoked by intermittent photic stimulation of epileptic chickens. There was a high correlation between the anticonvulsant potencies (mean effective dosages) and the affinity of the agents for the putative benzodiazepine receptor as measured by displacement of [3H]diazepam from binding sites on chicken synaptosomal membranes. This correlation in a genetic model of epilepsy provides further evidence that benzodiazepines exert their anticonvulsant effects by interacting with the benzodiazepine receptor.