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Acute and subacute toxicity of tyramine, spermidine, spermine, putrescine and cadaverine in rats.

The acute and subacute toxicity of five biogenic amines-tyramine, spermidine, spermine, putrescine and cadaverine-were examined in Wistar rats. Tyramine and cadaverine had a low acute oral toxicity of more than 2000 mg/kg body weight. Putrescine had an acute oral toxicity of 2000 mg/kg body weight and spermidine and spermine each of 600 mg/kg body weight. All amines investigated caused a dose-related decrease in blood pressure after intravenous administration, except for tyramine, where an increase was found. In 6-wk studies the biogenic amines were administered in the diet to groups of 10 male and 10 female rats. Tyramine and cadaverine were given at levels of 0, 200, 2000 or 10,000 ppm, spermine and putrescine at levels of 0, 200, 2000 or 5000 ppm and spermidine at levels of 0, 20, 200 or 500/1000 ppm in the first study and at levels of 0 or 10,000 ppm in a second study. Spermine was the most toxic. The high dose level showed a great number of changes, such as emaciation, aggressiveness, convulsions and paralysis of the hind legs. Growth, food intake and water intake were considerably decreased. Slight anaemia (males) and changes in plasma clinical chemistry occurred. The relative weights of the thyroid, adrenals, spleen and heart were increased and that of the liver decreased. Impaired kidney function, together with renal histopathological changes and changes in plasma electrolytes and urea, occurred with spermine. Histopathological examinations also revealed decreased glycogen content in the liver, reduction of spermatogenesis, severe depletion of splenic white pulp, acute involution of the thymus and moderate myocardial degeneration in the heart. Myocardial degeneration was also seen in one mid-dose male. Adverse effects were also observed in the top dose groups of all other amines. Decreased body weights associated with diminished food intake were generally seen. Slight increases in packed cell volume, haemoglobin concentration and thrombocytes occurred with cadaverine. With spermidine, decreased plasma creatinine, calcium and inorganic phosphate were observed and decreased potassium levels with cadaverine. The no-observed-adverse-effect level was 2000 ppm (180 mg/kg body weight/day) for tyramine, cadaverine and putrescine, 1000 ppm (83 mg/kg body weight/day) for spermidine and 200 ppm (19 mg/kg body weight/day) for spermine.

Administration, Oral↗

Effects of fumonisin B1 in pregnant rats. Part 2.

The developmental toxicity of purified fumonisin B1 (FB1), a mycotoxin from the common corn fungus Fusarium moniliforme, was examined in Charles River rats. Pregnant rats were dosed orally on gestation days 3-16 at 0, 6.25, 12.5, 25 or 50 mg FB1/kg body weight/day. FB1 was not teratogenic at the doses tested. At 50 mg/kg, maternal toxicity (inappetence, emaciation, lethargy, death, resorption of entire litters) and foetal toxicity (increased number of late deaths, decreased foetal body weight, decreased crown rump length, increased incidence of hydrocephalus, increased incidence of skeletal anomalies) were seen. The foetal toxicity observed at 50 mg/kg may be related to maternal toxicity. Histopathological evaluation of tissues from dams of control and all treated groups revealed dose-related toxic changes in kidney and liver tissues. Acute toxic tubular nephrosis was seen in kidneys from all treated groups. Hepatocellular cytoplasmic alteration and individual cellular necrosis of the liver was seen in the two high-dose groups. Sphinganine (Sa) and sphingosine (So) were measured in day-17 adult and foetal tissues. Dose related increases in Sa/So ratios were seen in maternal liver, kidney, serum and brain, but there was no effect on foetal liver, kidney and brain. These data suggest that FB1 does not cross the placenta and further suggest that the observed foetal toxicity is a secondary response to maternal toxicity.

Animals↗

Isolation of Neospora caninum from the brain of a naturally infected adult dairy cow.

Neospora caninum was isolated from the brain of a 2-year-old dairy cow that had aborted confirmed N. caninum-infected fetuses on two occasions. The cow had an indirect fluorescent antibody titer of 1:1600 to N. caninum. The cow was killed 24 days after its second abortion and the brain was bioassayed for N. caninum in nude mice. Multifocal areas of perivascular cuffing and glial nodules were observed in the cerebrum and mesencephalon of the cow, but N. caninum was not identified in histological sections of the brain. All three nude mice inoculated with brain homogenate of the cow, developed emaciation and paralysis. Microscopical examination of the nude mice revealed systemic N. caninum infection with demonstrable tachyzoites in various organs. The parasites isolated from fresh mouse brain were transferred successfully into Vero cell cultures. PCR procedure on the purified tachyzoites obtained from the Vero cell cultures amplified the specific DNA sequence for N. caninum.

Animals↗

A field study to estimate the prevalence of Trypanosoma equiperdum in Mongolian horses.

From May to July 2000, a cross-sectional study was conducted to estimate the prevalence of Trypanosoma equiperdum in the horse population of the central province (Tuv aimag) of Mongolia. On average, four herds were selected from each of the 29 aimag subdivisions (119 herds). From each herd, 10 horses were sampled in proportion to sex and age categories in the respective herds (1190 horses). Sera from 1122 horses were analysed for T. equiperdum antibodies using two serological assays, the complement fixation test (CFT) and the enzyme-linked immunosorbent assay (ELISA). The crude estimate of the CFT and the ELISA seroprevalence was 7.6 and 6.7%, respectively. Concordance between the CFT and ELISA results was high (96%). The highest number of CFT positive animals was detected in one herd in Möngönmorit (6/10), followed by herds in Bayandelger (5/10) and in Bayantsagaan (5/10). Poor body condition was significantly correlated with positive serological status in both CFT and ELISA. A history of abortion appeared to be a risk factor for both CFT and ELISA seropositivity. Blood samples of all horses belonging to herds with at least three (3/10) seropositive animals (CFT and/or ELISA) were analysed by light microscopy and by PCR using a Trypanosoma (Trypanozoon) brucei specific primer pair. No trypanosomes or any other haemoparasites could be detected in Giemsa stained thin blood smears. Eight out of the 130 samples (6.2%) analysed by PCR gave positive signals. Seven out of the eight PCR positive horses were also serologically positive. One PCR (and ELISA) positive stallion from Möngönmorit showed emaciation, scrotal and preputial oedema and an oedematous skin plaque. From the serological and DNA-based results it is concluded, that trypanosome infections occur in horses in the Tuv aimag of Mongolia. Since at present neither serological nor DNA-based tests allow a subspecies specific identification within the subgenus Trypanozoon, no definitive diagnosis can be given for T. equiperdum. Whether the examined herds are infected with T. equiperdum or with T. evansi, the causative agent of surra, remains an open question. However, based on the clinical findings, the negative parasitological results and the concentration of conspicuous seroprevalences in single herds, circumstantial evidence supports the existence of infections with the causative agent of dourine.

Animals↗

Outbreaks of trypanosomosis due to Trypanosoma vivax in cattle in Bolivia.

This paper reports the first occurrence of bovine trypanosomosis due to Trypanosoma vivax in Bolivia. T. vivax was identified in thin blood smears of 159 cattle from the Provinces of Velaco (57), Nuflo de Chavez (20), Guayaros (30) and Chiquitos (52), and in 86.20% of 29 cattle from Laguna Concepción examined by microhematocrit test. The clinical signs observed were fever, anemia, abortion, progressive weakness, loss of appetite, lethargy, substantial weight loss in a relatively short time, and progressive emaciation.

Abortion, Veterinary↗

Studies of infectivity and pathogenicity of an isolate of Trypanosoma evansi in Yankasa sheep.

The course of experimental infection and pathogenicity of an isolate of Trypanosoma evansi were investigated using eight infected and six uninfected control Yankasa sheep. The sheep were each infected intravenously via the jugular vein with approximately 2.0 x 10(6) T. evansi parasites. The effects of the parasite on body temperature, packed cell volume (PCV), haemoglobin, erythrocytes, total protein, were monitored three times a week for approximately 9 weeks. Body weights were determined once every week for the duration of the experiment. The results showed that all the infected sheep were positive for the parasite. The prepatent period varied between 3 and 6 days. T. evansi produced parasitaemic waves at an average of 8.3 days interval. Two distinct forms of the disease were produced namely, acute (4-14 days postinfection), and chronic (43-59 days postinfection). Anaemia was a distinct feature of the disease. While the mean rectal temperatures were significantly elevated (P < 0.05), the mean values of the haematological parameters of the infected sheep dropped significantly (P < 0.05) compared to the preinfection levels. Observed clinical signs included pale mucous membrane, epiphora, loss of appetite, emaciation, dullness and rough hair coat together with fluctuating pyrexia which in most cases coincided with rise in parasitaemia. It is suggested that the isolate of T. evansi is pathogenic for Yankasa sheep.

Animals↗

A lectin from an edible mushroom Pleurotus ostreatus as a food intake-suppressing substance.

In an experiment in which rats were allowed free access to food and water, the rats did not eat the diet containing a mushroom Pleurotus ostreatus even if they were emaciated. A P. ostreatus lectin (POL) was isolated from the mushroom as the food intake-suppression principle. In hemagglutination inhibition assays, Me-alphaGalNAc was the most potent inhibitor among the monosaccharides tested. Among all the sugars tested, 2'-fucosyllactose (Fucalpha1-->2Galbeta1-->4Glc) was the strongest inhibitor and its inhibitory potency was five times greater than that of Me-alphaGalNAc. POL exhibited a binding ability to bovine submaxillary mucin (BSM) and asialo-BSM and the other glycoproteins were inert to the binding. The food intake-suppressing activity of POL was dependent on the dose. The diet containing 0.1% POL caused a 50% decrease in the food intake of rats against the control.

Amino Acids↗

Altered energy metabolism in anorexia nervosa.

Optimal nutritional rehabilitation of anorexia nervosa requires more information concerning actual energy and substrate requirements. To this end, indirect calorimetry was performed in female patients (n=34, age 20.9+/-1.2 yr, body mass index [BMI] 15.6+/-0.2 kg/m(2); mean+/-SEM) soon after commencement of refeeding and at the time of discharge from hospital (n=18, BMI 19.0+/-0.3 kg/m(2)). Healthy female controls (n=18, age 24.6+/-1.3 yr, BMI 21.6+/-0.6 kg/m(2)) were also tested. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured in the fasting state, followed by diet-induced thermogenesis (DIT) and RQ over a 4 h period following a 100 g oral glucose load. Compared with post-refeeding patients and controls, pre-refeeding patients had a high basal RQ and a low REE, with a paradoxically higher DIT (13.2+/-0.9% of REE vs. 8.3+/-1.2% and 8.6+/-0.9% in post-refeeding patients and controls, respectively). RQ values in pre-refeeding patients exceeded unity following the glucose load, probably reflecting net lipogenesis, whereas in the post-refeeding patients, post-glucose RQ was similar to that of controls, suggesting premature curtailment of lipogenesis. These data demonstrate energy wasting in emaciated patients with anorexia nervosa. Biological repair processes could account for disproportionate energy loss early in refeeding and there may be some later impediment to full restoration of fat stores.

Adolescent↗

Epidemiology of paratuberculosis in wild ruminants studied by restriction fragment length polymorphism in the Czech Republic during the period 1995-1998.

In two studies carried out during the period 1995-1998, paratuberculosis was diagnosed in domestic and wild ruminants in the Czech Republic. The isolated Mycobacterium avium subspecies paratuberculosis strains were analysed by standardised restriction fragment length polymorphism (RFLP) [Pavlik, I., Horvathova, A., Dvorska, L., Bartl, J., Svastova, P., du Maine, R., Rychlik, I., 1999. J. Microbiol. Methods 38, 155-167]. In December 1992, 19 late pregnant Charolais heifers were imported to the Czech Republic from Hungary (original import from France to Hungary). One 11-month-old heifer roamed in the wild in a range of approximately 15-20km for 7 months from November 1993 to May 1994. Upon capture, the animal showed clinical signs of paratuberculosis (emaciation and diarrhoea). Seven other animals from the same herd were infected with the identical RFLP type B-C1 of M. paratuberculosis. During the period 1995-1996, samples were taken and examined from the small intestine and corresponding lymph nodes of 84 wild ruminants: 19 red deers (Cervus elaphus) and 65 roe-deers (Capreolus capreolus). These wild ruminants originated from 44 different locations within the same district from as the infected escaped heifer. Five M. paratuberculosis strains were isolated: one strain of RFLP type B-C1 from a stag and three strains of RFLP type B-C1 and one strain of RFLP type B-C9 from roe-deer. The three wild ruminants (one stag and two roe-deer) infected with the same RFLP type B-C1 were detected in the same area as the heifer, suggesting that this was the likely infection source. However, the infection source of the roe-deer infected with strain of RFLP type B-C9 was obviously different, and the stags that escaped from the farm were purchased from an area infected with this RFLP type. In the second study carried out during 1997-1998 in the whole Czech Republic (divided into 76 districts), 718 wild ruminants were examined from 90% of the districts. M. paratuberculosis was isolated from 25 (3.5%) animals from the wild, from farms and from game parks: 7.1% of 132 red deers, 1.5% of 336 roe-deers, 3.9% of 178 fallow deers (Dama dama), and 4.2% of 48 moufflons (Ovis musimon). This study discovered three RFLP types (B-C1, D-C12 and M-C16). A surprising finding was that of M. paratuberculosis (RFLP type B-C1) infection in roe-deer and a fallow deer in their natural habitat. The infection source was determined to have originated from two imported Holstein and Limousine cattle herds infected with the same strain. In the case of a mother and daughter roe-deer infected with RFLP type M-C16 and a fallow deer infected with RFLP type D-C12, all roaming in their natural habitat, the infection source was not discovered. The highest incidence of clinically ill wild ruminants was found in farmed red deer, and no relationship was found between the RFLP type or ruminant species and clinical status of animal.

Animals↗

Contact rates between wild and domestic canids: no evidence of parvovirus or canine distemper virus in crab-eating foxes.

Evaluating the risk of disease spill-over from domestic dogs to wildlife depends on knowledge of inter-specific contact rates and/or exposure to aetiological agents in dog environments. Here, contact rates of crab-eating foxes (Cerdocyon thous) with sympatric domestic dog populations were measured over 25months in Amazon Brazil. Foxes and dogs were serologically and clinically monitored for exposure to canine parvovirus (CPV-2) and canine distemper virus (CDV), pathogens known to have caused wildlife population declines elsewhere. Twenty-two of 24 (92%) tagged foxes visited one or more houses in a median 2 (range 1-3) villages per night where dog densities ranged from 7.2 to 15.4 per km(2) (mean 9.5 per km(2)). Foxes spent an average 6.4% (0-40.3%) of their 10h nocturnal activity period in villages, the equivalent of 38m (range 0-242) per night. The rate of potential exposure to disease agents was thus high, though varied by 3 orders of magnitude for individual foxes. Overall, 46% of the fox population was responsible for 80% of all contacts. None of the 37 monitored foxes however showed serological or clinical evidence of infection with CPV-2 or CDV. Seroprevalences for CPV-2 and CDV antibodies in the local domestic dog population were 13% (3/23) and 9% (2/23), respectively, and 89% of 97 monitored pups born during the study presented clinical signs consistent with active CPV-2 infection (haemorrhagic diarrhoea, vomiting, rapid morbidity and emaciation). Although there was no evidence for infection with either virus in foxes, the high level of contact of foxes with peridomestic habitats suggests that the probability of potential spill-over infections from dogs to foxes is high.

Age Factors↗

Forced oral opening for cadavers with rigor mortis: two approaches for the myotomy on the temporal muscles.

Forensic dentistry plays an essential role in personal identification procedures. An adequate interincisal space of cadavers with rigor mortis is required to obtain detailed dental findings. We have developed intraoral and two directional approaches, for myotomy of the temporal muscles. The intraoral approach, in which the temporalis was dissected with scissors inserted via an intraoral incision, was adopted for elderly cadavers, females and emaciated or exhausted bodies, and had a merit of no incision on the face. The two directional approach, in which myotomy was performed with thread-wire saw from behind and with scissors via the intraoral incision, was designed for male muscular youths. Both approaches were effective to obtain a desired degree of an interincisal opening without facial damage.

Adult↗

Mortality and clinical features in cases of death among epileptic children.

At a follow-up study of 385 patients with epilepsy beginning under age 15, 22 (5.7%) had died during the first 10 years after the onset of epilepsy and another 11 (2.9%) between 11 and 24 years. Mortality was significantly high in cases with the following clinical features: (1) epilepsy with onset before the first birthday (mortality being 25.5%), (2) symptomatic epilepsy in etiology (17.2%), (3) infantile spasms (40.7%), tonic epilepsy (33.3%) or myoclonic epilepsy (33.3%) as compared with grand mal (5.9%) in seizure type and (4) developmental retardation at the first visit (25.5%). Seizures were not controlled in 31 out of 33 patients at the time of death. The causes of death were status epilepticus or convulsion in 10, pneumonia in 5, severe emaciation in 3, "cerebral palsy" in 5, and drowning, suffocation, traffic accidents or acute lymphocytic leukemia, in one each, and unknown in 6. Most of the patients died at home.

Adolescent↗

Golgi study on the homozygote (Ml/Ml) of macular mutant mouse.

The macular mutant mouse shows X-linked recessive inheritance and its hemizygote (Ml/y) is considered to be an appropriate model of Menkes kinky hair disease (MKHD). In this study the homozygote (Ml/Ml) was bred by coupling CuCl2-treated Ml/y with Ml/+ and was clinically and neuropathologically examined. The Ml/Ml had white fur color and curly whiskers from day 3, showed ataxia and tonic seizure on day 8 and gradually lost weight after day 10. It died with severe emaciation around day 15. These clinical features were improved by CuCl2 injection. Quantitative analysis showed that the dendritic arborization of the pyramidal cell in the treated Ml/Ml was delayed on days 14, 20, 30, 45 and 90 in comparison with that of the age-matched +/y. In the cerebellum of the Ml/Ml on day 14, some of the Purkinje cells showed abnormal changes such as somal sprouts, spine-like structures on the surface of the soma and stem dendrites, thick stem dendrites, multiple focal swellings of the stem and distal dendrites, reduction in the size of dendritic trees and axonal focal swellings. These changes were gradually improved in the Ml/Ml with CuCl2 treatment after day 20, with the exception of the multiple focal swellings of the stem and distal dendrites. The dendritic focal swelling gradually decreased after day 45. These clinical and neuropathological features of the Ml/Ml are almost same as those of the Ml/y. In our mutant mouse, when the treated Ml/Ml is coupled with the treated Ml/y all offspring from the Ml/Ml are genetically Ml/y or Ml/Ml. Our study indicates that these fetal mice may be useful for studying the pathological and biochemical condition of prenatal MKHD.

Animals↗

Neurological manifestations of knockout mice with beta-galactosidase deficiency.

We succeeded in producing the beta-galactosidase-deficient knockout mouse by gene targeting in embryonic stem cells. The mutant mice developed progressive spastic diplegia within a few months after birth, and died of emaciation at 7-10 months of age. This is an authentic murine model of human GMI-gangliosidosis, and is useful for studies of its pathogenesis and treatment.

Animals↗

Preclinical and clinical manifestations of paratuberculosis (including pathology).

The term Johne's disease immediately brings to mind an image of an emaciated, debilitated ruminant with bottlejaw and fluid, pipestream diarrhea. However, the clinical case is merely the tip of the iceberg in terms of the total number of infected animals on the farm. If the clinically affected animal was born on the farm, a minimum of 25 other animals are probably infected and less than 30% of those will be detectable by currently available tests. Infected animals in the early stages of the disease progress slowly over a period of months or several years to stages that may be detected by antigen detection tests and antibody-based diagnostic tests. The duration of each stage of infection depends on age at the time of exposure and the dose of organisms ingested. The lack of tests sensitive enough to detect infected animals in the earliest stages of disease is a serious obstacle to eradication of Johne's disease. The animals with overt infection may be culled from the herd immediately on detection. However, the animals that are shedding organisms below the threshold of detectability and have not mounted an immune response remain behind to contaminate the environment and infect herdmates.

Animals↗

Relationship between nutrition and reproduction in beef cattle.

The primary nutrient consideration for optimum reproductive performance in beef cattle is energy. Low energy intake delays the onset of puberty in heifers and bulls. Heifers should reach approximately 66 per cent of mature body weight by 14 to 15 months of age and be bred 30 days prior to breeding the main cow herd. Body conditioning scores (BCS) (1 = emaciated, 9 = obese) should be used to evaluate pregnant cows entering their third trimester. Cows should calve with body conditioning score 5 to 7. Forage quality and environmental factors influence maximum dry matter intake and nutrient requirements and must be considered in the clinical setting. Crude protein dietary content should be 11 to 12 per cent for lactating beef cattle. Mineral (calcium, phosphorus, magnesium, potassium, sulfur, sodium, chloride) nutrition is not a major cause of decreased reproductive performance in beef cattle. Trace mineral deficiencies (particularly selenium, copper, and zinc) can cause decreased reproductive performance. Diagnosis of these trace mineral deficiencies can be confirmed by elemental analysis of blood or tissues.

Animal Nutritional Physiological Phenomena↗

[Severe hypophosphoremia in a patient on parenteral nutrition with phosphorus enrichment].

A twenty-four year old patient showed severe hypophosphataemia after emergency surgery for colectasia. A critical study of the case isolated the factors which had favoured the development of this metabolic complication. The necessity for great care in the nutrition of emaciated patients as well as that of a phosphorus supply adapted to the metabolic status of the patient were emphasized. Frequent measurement of serum phosphate was recommended for patients undergoing intravenous hyperalimentation.

Adult↗

[Postoperative hypophosphoremia in digestive surgery. Influence of the parenteral diet].

Twenty-seven non emaciated patients undergoing major visceral surgery were randomly divided into two different groups according to the postoperative parenteral diet (100% glucose versus 50% fat 50% glucose). All patients received the same anaesthetic protocol and, peroperatively, none received any glucose. In the postoperative phase, parenteral feeding was started on the day of operation (18.5-21.8 kcal X kg-1) and was continued for a minimum of four days (37-44 kcal X kg-1 X 24 h-1). All patients received intravenous insulin and phosphorus (0.15 mmol X kg-1 X 24 h-1). During five days, daily measurements of serum phosphate and glucose levels were made and nitrogen balance was studied. For all these parameters, there was no evidence of any significant difference between the two groups. A significant fall in plasma phosphate occurred in each group on the first postoperative day, was maximum on the second and lasted until the fourth. This fall was not influenced by parenteral diet. No patients in this study developed symptoms of phosphate depletion. The glucose levels increased significantly and the nitrogen sparing effect was similar in both groups. The mechanism of hypophosphataemia seemed to be an intracellular transfer under the influence of hyperglycaemia and high plasma insulin levels rather than an increase in urinary phosphate excretion. The advantage of using lipid solutions did not appear under the dietary conditions studied. Indeed a glucose supply greater than or equal to 3 mg X kg-1 X min-1 seemed to induce a maximum intracellular transfer of phosphorus. Because of this, phosphate supplementation and frequent measurement of serum phosphate are recommended for patients undergoing major visceral surgery and postoperative intravenous feeding.

Blood Glucose↗