Safety assessment of consumption of glabrous canary seed (Phalaris canariensis L.) in rats.

Canary seed is a nutrient-rich cereal grain; however, it has not been used in human food in part due to concerns regarding safety of consumption. Glabrous or hairless canary seed has potential human food use as trichomes are absent. The objective of the oral feeding studies reported here was to assess the safety of yellow and brown glabrous canary seed cultivars as human cereal foods. The first study was a 90-day rat oral toxicity study, which compared the effects of diets containing 50% of either brown dehulled glabrous, brown hulled glabrous, or brown hulled pubescent (hairy) hulled canary seed to a diet containing 50% wheat. No significant adverse effects were observed. In a 28-day and a 90-day study rats were fed yellow or brown glabrous canary seed groats in the AIN-76 diet at concentrations levels of 2.5%, 5% and 10%. The NOAELs in 90-day study were 5.15 g/kg/d and 5.23 g/kg/d for yellow and brown canary seed groats. Consumption of canary seed was associated with reduced incidence and severity of liver lipidosis as compared to controls. The combined results of these studies clearly demonstrate the safety of consumption of glabrous canary seed, and support its use as a human cereal grain.

Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies.

Aspartame is a methyl ester of a dipeptide used as a synthetic nonnutritive sweetener in over 90 countries worldwide in over 6000 products. The purpose of this investigation was to review the scientific literature on the absorption and metabolism, the current consumption levels worldwide, the toxicology, and recent epidemiological studies on aspartame. Current use levels of aspartame, even by high users in special subgroups, remains well below the U.S. Food and Drug Administration and European Food Safety Authority established acceptable daily intake levels of 50 and 40 mg/kg bw/day, respectively. Consumption of large doses of aspartame in a single bolus dose will have an effect on some biochemical parameters, including plasma amino acid levels and brain neurotransmitter levels. The rise in plasma levels of phenylalanine and aspartic acid following administration of aspartame at doses less than or equal to 50 mg/kg bw do not exceed those observed postprandially. Acute, subacute and chronic toxicity studies with aspartame, and its decomposition products, conducted in mice, rats, hamsters and dogs have consistently found no adverse effect of aspartame with doses up to at least 4000 mg/kg bw/day. Critical review of all carcinogenicity studies conducted on aspartame found no credible evidence that aspartame is carcinogenic. The data from the extensive investigations into the possibility of neurotoxic effects of aspartame, in general, do not support the hypothesis that aspartame in the human diet will affect nervous system function, learning or behavior. Epidemiological studies on aspartame include several case-control studies and one well-conducted prospective epidemiological study with a large cohort, in which the consumption of aspartame was measured. The studies provide no evidence to support an association between aspartame and cancer in any tissue. The weight of existing evidence is that aspartame is safe at current levels of consumption as a nonnutritive sweetener.

Oral developmental toxicity study of methylsulfonylmethane in rats.

Methylsulfonylmethane (MSM) is a metabolite of dimethyl sulfoxide, and occurs naturally at low levels in many foods. MSM has received wide attention as a dietary supplement to promote joint health. The objective of these studies was to determine the developmental toxicity potential of MSM when administered orally to pregnant rats during the period of major organogenesis and histogenesis. In a preliminary dose-finding study, distilled MSM microprill (i.e., microspherical pellets of MSM) was administered by oral gavage at dose levels of 0 (vehicle control), 50, 250, 500, and 1000 mg/kg/day to 8-9 sperm-positive female Sprague-Dawley rats/group/day on gestation days 6-20. No evidence of maternal or fetal toxicity was observed. For the definitive developmental study, four groups of 24-25 timed-bred primiparous female rats were administered 0, 50, 500, or 1000 mg MSM/kg/day via gavage on gestation days 6-20. Maternal feed consumption, body weight, body weight gain, uterus weight and corrected body weight/body weight gain were unaffected by treatment. No evidence of maternal toxicity, and no significant differences in litter viability, litter size, or litter body weight were detected. Fetal evaluations failed to show any biologically significant increase in the incidence of anomalies in the MSM treated groups, and no malformations were seen in any of the fetuses. No evidence of fetal mortality, alterations to growth, or structural alterations were observed in the fetuses of dams administered 50-1000 mg/kg/day. Therefore, under the conditions of this study, the no-observed-adverse-effect level (NOAEL) for maternal and developmental toxicity was 1000 mg/kg/day.

Enhanced estrogenic responses and sensitivity to azoxymethane following dietary soy isoflavone supplementation in older female rats.

Soy isoflavones are popular supplements among middle-aged and older women based on their potential protection against cancer and their use as alternative hormone replacement therapy. The purpose of this study was to investigate the effects of dietary soy isoflavones on early stage colon cancer in various ages of female rats. Young (1month), mature (11month) and old (22month) female Fisher 344 rats were fed either the control diet or a diet containing 0.4% soy isoflavone isolate for 1week, injected once with 20mg/kg azoxymethane (AOM) and maintained on the diets for another 15weeks. The concentration of isoflavones in the diet was 2g/kgdiet, composed of 1.2g/kg genistin, 0.7g/kg daidzin and 0.1g/kg other isoflavones including glycitin, acetylgenistin, acetyldaidzin, genistein, daidzein, and glycitein. There was no difference over all ages in the development of preneoplastic colonic aberrant crypt foci between rats fed the soy compared to the control diet, indicating that the soy diet did not provide protection against early stage colonic carcinogenesis. On the contrary, several adverse effects of soy supplementation in female AOM-treated rats were observed. Soy-supplemented rats had greater weight loss and a slower recovery of body weight following the AOM injection compared to rats fed the control diet and these changes increased with age. Five of the 21 rats fed the soy supplement died before the end of the experiment while all animals on the control diet survived to term. The density of normal crypts lining the colonic mucosa was reduced in rats fed the soy compared to control diet, indicating gastrointestinal damage. Uterine weights, serum estradiol and serum isoflavone levels were increased in mature and old female rats fed the soy-supplemented diets compared to age-matched controls, suggesting an increasing estrogenic response with age to isoflavone supplementation. These adverse effects of soy isoflavones in aged female animals need further examination because women, and particularly older women, are the prime target population for consumption of soy supplements.

Calmodulin-binding protein detection using a non-radiolabeled calmodulin fusion protein.

Calmodulin-binding proteins are involved in numerous cellular signaling pathways. The biotinylated-calmodulin overlay is a nonradioactive method widely used to detect calmodulin-binding proteins in tissue and cell samples. This method has several limitations; therefore, we developed a nonradioactive calmodulin-binding protein detection overlay using an S-tag-labeled calmodulin fusion protein. An expression system was used to generate a calmodulin fusion protein with an S-tag label, a 15 amino acid sequence that binds to a 105 amino acid S-protein. The S-protein is conjugated to horseradish peroxidase for final detection with a chemiluminescent substrate. The S-tag calmodulin was compared to purified calmodulin and biotinylated calmodulin in a calmodulin-dependent phosphodiesterase assay. The results of the calmodulin-dependent phosphodiesterase assay indicate that S-tag calmodulin induces higher phosphodiesterase activity than biotinylated calmodulin and lower activity than purified calmodulin. A comparison of the biotinylated and S-tag calmodulin overlay assays indicate that S-tag calmodulin is more sensitive than biotinylated calmodulin in the detection of calcineurin, a known calmodulin-binding protein. The overlay assay results also indicate that the S-tag calmodulin and biotinylated calmodulin detect similar calmodulin-binding proteins in colon epithelial cells. In conclusion, the S-tag calmodulin overlay assay is a consistent, sensitive, and rapid nonradioactive method to detect calmodulin-binding proteins.

Effects of indole-3-carbinol on immune responses, aberrant crypt foci, and colonic crypt cell proliferation in rats.

Male Sprague-Dawley rats were treated orally with indole-3-carbinol (13C) for 7 wk at levels of 150, 100, and 50 mg/kg body weight. The rats were injected with 10 mg/kg body weight of the colon carcinogen, azoxymethane (AOM) on d 2 and 9 of 13C treatment. At termination of the study, all rats were assessed for immune function (humoral immunity, specific cell-mediated immunity, and nonspecific cell-mediated immunity). Colonic tissue was collected and examined for the presence of aberrant crypt foci (ACF) and proliferation of crypt cells. Antibody responses to antigen challenge were significantly suppressed in the animals exposed to the high dose of 13C. Delayed-type hypersensitivity responses, natural killer cell activity, the number and multiplicity of ACF, and cell proliferation parameters were not significantly different from those of the controls. Therefore, there was no clear protective or enhancing effect of 13C on ACF numbers or colonic cell proliferation indices. There was no strong correlation between changes in immune responses and the preneoplastic biomarkers of colon cancer.

Increased susceptibility of adult rats to azoxymethane-induced aberrant crypt foci.

The purpose of this study was to compare azoxymethane-induced aberrant crypt foci development in the colons of young and adult rats. Young (4 weeks of age) and adult (50 weeks of age) Sprague-Dawley rats were treated with two weekly injections of azoxymethane or saline. Rats were killed either 6 or 14 weeks following the first injection, and the number, size and location of aberrant crypt foci were determined. At both the 6- and 14-week time points, the number of aberrant crypt foci in older rats was significantly greater than in young rats (P<0.01). A higher percentage of aberrant crypt foci were found in the region from the mid-colon to the cecum in older rats as compared to young rats. Colonic cell proliferation was evaluated using bromodeoxyuridine immunohistochemistry. Colonic cell proliferation indices in the rectal, mid-colon and cecal regions of young and older rats were similar in young compared to adult rats. Ten large ACF from each group were screened for mutations in the beta-catenin gene (Ctnnb1) by PCR single strand conformation polymorphism. No mutations were detected. These results demonstrate that older female rats are more susceptible to the induction of aberrant crypt foci by azoxymethane than young female rats. Differences in colonic cell proliferation or beta-catenin mutations in these two age groups do not appear to be responsible for differences in aberrant crypt foci development.

Ruminant gastrointestinal cell proliferation and clearance of Escherichia coli O157:H7.

Human infections with Escherichia coli O157:H7 cause hemorrhagic colitis that can progress to a life-threatening sequelae. The most common mode of disease transmission is ingestion of contaminated bovine food products, and it is well established that E. coli O157:H7 is a transient member of the bovine microbiota. However, the conditions that induce acquisition and subsequent clearance of this bacterium from the ruminant gastrointestinal tract (GIT) are not understood. Evidence that the rates of epithelial cell proliferation in the lower GIT of cattle are associated with the duration animals remained E. coli O157:H7 culture positive is presented. Cattle with slower rates of intestinal cell proliferation in the cecum and the distal colon were culture positive significantly longer than cohort cattle with faster cell proliferation rates. Cell death rates (apoptotic indices) between the short- and long-term culture-positive animals were not different. Typical grain-based finishing diets and forage-based growing diets did not effect GIT cell proliferation or the duration animals remained E. coli O157:H7 culture positive. To identify a dietary intervention that would effect GIT cell proliferation, we used sheep as a model ruminant. A fasting-refeeding regime that increased the rate of GIT cell proliferation was developed. The fasting-refeeding protocol was used in cattle to test the hypothesis that feeding interventions that increase the rate of GIT cell proliferation induce the clearance of E. coli O157:H7 from the bovine GIT.

Determining the geographic origin of potatoes with trace metal analysis using statistical and neural network classifiers.

The objective of this research was to develop a method to confirm the geographical authenticity of Idaho-labeled potatoes as Idaho-grown potatoes. Elemental analysis (K, Mg, Ca, Sr, Ba, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, S, Cd, Pb, and P) of potato samples was performed using ICPAES. Six hundred eight potato samples were collected from known geographic growing sites in the U.S. and Canada. An exhaustive computational evaluation of the 608 x 18 data sets was carried out using statistical (PCA, CDA, discriminant function analysis, and k-nearest neighbors) and neural network techniques. The neural network classification of the samples into two geographic regions (defined as Idaho and non-Idaho) using a bagging technique had the highest percentage of correct classifications, with a nearly 100% degree of accuracy. We report the development of a method combining elemental analysis and neural network classification that may be widely applied to the determination of the geographical origin of unprocessed, fresh commodities.

Dietary quercetin, immune functions and colonic carcinogenesis in rats.

Rats fed 100 mg/kg quercetin (QUE) daily for 7 weeks had significantly enhanced natural killer cell activity compared to their vehicle (VEH)-fed control. In contrast, rats fed 100 mg/kg QUE and treated with the colon carcinogen, azoxymethane had significantly reduced natural killer cell activity compared to their VEH-fed azoxymethane-treated control. There was no significant difference in natural killer cell activity between the two control groups. Antibody production and delayed-type hypersensitivity were not altered by QUE feeding in any treatment group. In vitro exposure of splenic natural killer cells to 1mM QUE significantly decreased natural killer cell cytotoxicity. Lower QUE concentrations produced a non-significant reduction in natural killer cell activity that was restored to control values at 1 x 10(-13)M QUE. The distribution, multiplicity and total number of colonic preneoplastic lesions, aberrant crypt foci, was not significantly different in the QUE-fed azoxymethane-treated rats when compared to azoxymethane-treated vehicle-fed rats at the conclusion of 7 week feeding period. We found no correlation between immune function and development of preneoplastic colon lesions in this study.

Effect of dietary chlorogenic acid on multiple immune functions and formation of aberrant crypt foci in rats.

Adult male Sprague-Dawley rats were fed 70 mg/kg body weight chlorogenic acid (CHA) for 7 wk. One CHA-fed group was also given 2 injections of the colon carcinogen azoxymethane (AZO) on d 2 and 9 of CHA treatment. Three major types of immune responses were assessed: antibody production, specific cell-mediated immunity, and nonspecific cell-mediated immunity. The formation of AZO-induced aberrant crypt foci (ACF) in the colon were observed, as was colonic cell proliferation. There were no significant effects of CHA treatment on any of the immune parameters examined or on formation of preneoplastic lesions or cell proliferation in the colon. The overall nonsignificant trends in immune function, colon cell proliferation, and ACF development were, however, more consistent with immunosuppression and enhanced preneoplasia.

Distribution of myristoyl-CoA:protein N-myristoyl transferase activity in rabbit intestine.

Myristoyl-CoA:protein N-myristoyl transferase (NMT) attaches the fatty acid, myristate, to the amino-terminal glycine residue of various proteins involved in cellular regulation and/or signal transduction. We report differences in the activity and properties of NMT in New Zealand rabbit small intestine, ascending colon and descending colon. The mucosa of the small intestine, ascending colon and descending colon was assayed for NMT activity using peptides of known myristoylated proteins (pp60src and catalytic subunit of cAMP dependent protein kinase). Total NMT activity per gram tissue was 5-fold higher in the small intestine and 1.5-fold higher in the ascending colon than in the descending colon. Smooth muscle from the colon also contained low levels of NMT activity. NMT activity was 2- to 3-fold higher in the particulate fraction than in the cytosolic fraction of the mucosa in the descending colon. The apparent molecular mass of NMT in the intestine mucosa was 78 kDa.

Increased N-myristoyltransferase activity observed in rat and human colonic tumors.

BACKGROUND: Colorectal cancer is one of the leading causes of cancer death in North America. Since treatment of colonic cancer remains difficult because of the lack of effective chemotherapeutic agents, it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs and inhibit the development or progression of this disease. Modification of proteins by myristoylation has been recognized as important in the function of various viral, oncogenic, and signal-transduction proteins and thus has been proposed as a target for chemotherapeutic drug design. However, the activity of the enzyme that catalyzes this modification, N-myristoyltransferase, has not been investigated in cancer relative to normal tissue. PURPOSE: The purpose of this study was twofold: 1) to investigate the activity of N-myristoyltransferase in azoxymethane-induced rat colonic cancer tissue compared with normal and normal-appearing rat colonic tissue and 2) to determine if similar differences would be observed in a small sample of human colonic tumors. METHODS: N-Myristoyltransferase activity was determined in 45 colonic tissue specimens from Sprague-Dawley rats--10 given injections of the colon carcinogen, azoxymethane, and three untreated. Tissue specimens included 35 colonic tumors of varying pathologic stages, seven specimens of normal-appearing adjacent mucosa, and three specimens of normal colonic mucosa. Colectomy specimens from five patients were assayed for N-myristoyltransferase activity. Subcellular distribution of N-myristoyltransferase activity was determined. Synthetic peptides of known myristoylated proteins--pp60src and cyclic adenosine monophosphate-dependent protein kinase--were used in kinetic analyses of N-myristoyltransferase in colonic cancer and normal-appearing colonic tissue. All P values are two-tailed. RESULTS: N-Myristoyltransferase activity was increased in rat colonic tumors compared with normal-appearing adjacent mucosa and normal mucosa (P = .0002). Elevation of N-myristoyltransferase activity was present in all tumors, including colonic polyps. Increased N-myristoyltransferase activity was also observed in human colonic tumors and was predominantly cytosolic. N-Myristoyltransferase of colonic cancer tissues had a similar Michaelis constant but an approximate twofold higher maximum velocity for both the pp60src- and cyclic adenosine monophosphate-dependent protein kinase-derived peptides compared with N-myristoyltransferase of normal-appearing tissue. CONCLUSIONS: This study demonstrates for the first time that N-myristoyltransferase activity is higher in colonic epithelial neoplasms than in normal-appearing colonic tissue and that an increase in N-myristoyltransferase activity appears at an early stage in colonic carcinogenesis.

Mammalian myristoyl CoA: protein N-myristoyltransferase.

Myristoyl CoA:Protein N-myristoyltransferase (NMT) is the enzyme which catalyses the covalent transfer of myristate from myristoyl CoA to the amino-terminal glycine residue of protein substrates. Although NMT is ubiquitous in eukaryotic cells, the enzyme levels and cellular distribution vary among tissues. In this article, we describe the properties of mammalian NMT(s) with reference to subcellular distribution, molecular weights, substrate specificity and the possible involvement of NMT in pathological processes. The cytosolic fraction of bovine brain contains majority of NMT activity. In contrast, rabbit colon and rat liver NMT activity was predominantly particulate. Regional differences in NMT activity have been observed in both rabbit intestine and bovine brain. Results from our laboratory along with the existing knowledge, provide evidence for the existence of tissue specific isozymes of NMT.

Resistance of aberrant crypt foci to apoptosis induced by azoxymethane in rats chronically fed cholic acid.

We have previously shown that chronic feeding of cholic acid to carcinogen treated rats reduces the number of putative preneoplastic lesions of colonic cancer, aberrant crypt foci (ACF), but enhances the growth of remaining ACF and the incidence of colonic tumors. The following study was conducted to further explore the effects of cholic acid on ACF growth by determining if ACF in cholic acid-fed animals display resistance to apoptotic cell death. ACF were induced in male Sprague-Dawley rats with two injections of azoxymethane (20 mg/kg body wt). Rats were divided into two groups and fed either the control AIN-76 diet or the AIN-76 diet containing 0.2% cholic acid. After 18 weeks, colonic apoptotic cell death was induced with an acute low dose of azoxymethane (10 mg/kg body wt). The number of cells, apoptotic bodies and bromodeoxyuridine (BUdR)-labeled cells were determined in colonic crypts comprising ACF and surrounding normal crypts in rats from each diet group. The number of apoptotic bodies per 100 cells was lower in ACF crypts than in normal-appearing crypts (P = 0.0034). Both normal and ACF crypts from rats fed the cholic acid diet had fewer apoptotic bodies per 100 cells than crypts from rats fed the control diet (P = 0.0102). These data suggest that ACF harbor resistance to induction of apoptosis. Chronic feeding of a diet containing 0.2% cholic acid results in the development of increased resistance to apoptosis. The lower rate of cell death in ACF may contribute to the enhanced growth of ACF and higher tumor incidence previously observed in cholic acid-fed animals.

Ability of aberrant crypt foci characteristics to predict colonic tumor incidence in rats fed cholic acid.

Aberrant crypt foci (ACF) are putative preneoplastic lesions of colon cancer which are being utilized currently as a biological end point to evaluate the induction and modulation of colon carcinogenesis. In several previous short-term studies, the unexpected reduction of ACF by the reported colonic tumor promoter cholic acid (CHA) emphasized the need for a systematic evaluation of the growth of ACF in response to a tumor promoter. The present study was conducted to determine if any characteristic(s) of ACF at various early stages of carcinogenesis would predict resulting tumor incidence in rats fed CHA. Male Sprague-Dawley rats received two injections of azoxymethane (20 mg/kg) and were fed either the AIN-76 diet or AIN-76 plus 0.2% CHA. The number, crypt multiplicity (number of crypts/focus), and size (area) of ACF were measured after 2, 8, 14, and 18 weeks in 5 rats/group. The number of ACF was lower (P < 0.033) in animals fed CHA at all time points. Average crypt multiplicity of ACF was greater (P = 0.045) from CHA-fed animals after 8 weeks compared to animals fed the AIN-76 diet. The average size of ACF was smaller in CHA-fed animals after 2 weeks and then tended to be larger than the sizes of the ACF from animals fed the AIN-76 diet. All remaining animals were killed after 18 weeks. Tumor incidence was higher (P < 0.001) in the CHA-fed group (63.2%) compared to the control diet group (29.4%). CHA-fed rats also had a higher number of tumors/tumor-bearing rat compared to control diet rats (1.96 versus 1.13). The main finding of this study is that the number of ACF at early time points did not predict tumor incidence. Crypt multiplicity was a consistent predictor of tumor outcome and should be measured in future studies using ACF as a biological end point. The CHA diet appears to provide a unique tumor-modulating environment that selectively enhances the growth of a smaller number of ACF leading to an increased number of tumors compared to a control diet. The mechanism(s) by which CHA mediates this effect warrants further investigation.

Reduction of aberrant crypt foci induced in rat colon with azoxymethane or methylnitrosourea by feeding cholic acid.

Recent studies in our laboratory have demonstrated that feeding cholic acid (CHA) to rats treated with a single dose of azoxymethane (AOM) reduces the growth of putative preneoplastic lesions, aberrant crypt foci (ACF), in a dose-dependent manner. This finding was unexpected since CHA has been reported to promote colon cancer in rats receiving multiple treatments of the colon carcinogen, methylnitrosourea (MNU). The main objective of the present investigation was to evaluate the effect of the type of carcinogen and treatment protocol on the induction and growth of ACF in conjunction with CHA treatment. Male Sprague-Dawley rats received 0, 1 or 2 treatments with AOM or MNU and were fed either the AIN-76A or AIN-76A plus 0.2% CHA diet for 4 weeks. The total number and average size of ACF were significantly reduced in CHA-fed animals regardless of the type or number of treatments of carcinogen. The greatest reduction of ACF due to CHA-feeding was seen in the distal colon. The average crypt multiplicity (number of crypts in each ACF) was not altered by diet or carcinogen treatment. Colonic cell proliferation (crypt height and number of mitotic figures) was significantly increased in CHA-fed animals compared to control diet animals. Therefore, feeding CHA for 4 weeks reduced the number and size of ACF in rats induced by 1 or 2 injections of AOM or MNU, despite stimulation of colonic cell proliferation. These findings suggest further investigation is needed to understand the mechanism of promotion by cholic acid and the value of number and growth characteristics of ACF as a biological endpoint in the pathogenesis of colon cancer.

Empowering nurses for politically astute change in the workplace.

While studies of the shortage of nurses have documented the need for nurses to play a greater role in decision-making processes in their workplaces, it cannot be assumed that nurses have the confidence or skills for making changes in the workplace in politically astute ways that will be effective. This article describes a continuing education program that was designed to prepare nurses to realize their potential power and to develop skills for effectively bringing about changes in their workplaces. Based on a feminist model of empowerment, the program content and methods reflected three dimensions of empowerment: consciousness-raising, building self-esteem, and skill development. Both short- and long-term evaluations (immediate and at 7 months) demonstrated that education can be a vehicle for empowering nurses to effectively bring about changes in their workplaces. The program was sponsored by the Manitoba Nurses Union, The University of Manitoba Continuing Education Division, and The University of Manitoba School of Nursing.

Effects of various high-fat diets on myocardial contractility and morphology in rats.

The effects of various high-fat diets (20% w/w) containing commercially available fats and oils (butter, corn oil, corn oil margarine, canola oil, canola oil margarine, soybean oil, soybean oil margarine, sunflower oil, sunflower oil margarine) on myocardial contractility and morphology and on plasma lipids were investigated in male Sprague-Dawley rats fed the diets for 16 weeks. Diets containing corn oil caused significantly (P less than or equal to .05) higher plasma total cholesterol levels than diets containing butter. Significant differences were also determined in lipoprotein levels. Plasma triglyceride levels were significantly (P less than or equal to .05) higher with butter than with sunflower oil or sunflower margarine. No significant differences among the groups occurred in blood pressure, heart rate, or myocardial contractility. Histological evaluation revealed that animals fed canola oil had the highest incidence and severity of myocarditis and fibrosis and that the degree of cardiac lipidosis was not correlated to the erucic-acid content of the diet. Myocardial damage was significantly (P less than or equal to .05) negatively correlated with stearic and palmitic acids and positively correlated with oleic acid. The results indicate that diets low in saturated fats may have adverse long-term effects on the heart.

Cardiovascular effects of mycotoxin T-2 after topical application in rats.

Evidence has been mounting that trichothecenes cause cardiac lesions and cardiovascular effects in general. T-2 toxin, dissolved in dimethyl sulfoxide, was applied in doses of 0, 1.0, 2.0 mg/kg to the skin of Sprague-Dawley rats. Twenty-four hours later, the cardiac function of the animals was assessed, followed by killing and histological examination. It was found that the arterial blood pressure values were lower in the 2.0 mg/kg group, the peak intraventricular pressure was lower in both the 1.0 and 2.0 mg/kg groups, and the resting systolic and diastolic blood pressure values of the 2.0 mg/kg group were lower than the 0 and 1.0 mg/kg groups. The 1.0 and 2.0 mg/kg groups had significantly lower epinephrine-stimulated intraventricular pressure values, indicating reduced contractility. Extended Q-T intervals in electrocardiograms of the 1.0 and 2.0 mg/kg groups suggested also impaired contractility. The histological examination gave equivocal results. It is concluded that topical applications of small doses of T-2 toxin have a noticeable negative effect on cardiovascular function.