Neurotoxic potential of gadodiamide after injection into the lateral cerebral ventricle of rats

PURPOSE: Results of a previous report showed that, if administered by intraventricular injection to access tissue normally protected by the blood-brain barrier, gadopentetate dimeglumine produced acute excitation, persistent ataxia, and widespread brain lesions in rats at 5-micromol/g brain but not at 3.8-micromol/g brain. The present study using gadodiamide was undertaken to see whether the effects were agent-specific. METHODS: Rats, surgically prepared with a lateral ventricular cannula, were administered a slow injection at 2 microL/min of gadodiamide into the lateral ventricle, and behavioral and neuropathologic changes were noted. RESULTS: Both gadodiamide and gadopentetate dimeglumine produced focal and generalized myoclonus over several hours. Gadodiamide did not produce the medium-term tremor or persistent ataxia seen after treatment with gadopentetate dimeglumine. Neuropathologic changes developed over 1 to 3 days and took three distinct forms: vacuolated thalamic lesions closely resembling those produced by gadopentetate dimeglumine; small but similar vacuolated symmetrical caudate lesions not produced by gadopentetate dimeglumine; and severe swelling and astrocytic hypertrophy and hyperplasia in the cerebellar vermis, again not produced by gadopentetate dimeglumine. Unlike gadopentetate dimeglumine, gadodiamide produced no spinal cord lesions. The cerebellar changes were seen at 1.25-micromol/g brain and above, behavioral changes at 2.5-micromol/g brain and above, and thalamic and caudate lesions at 10-micromol/g brain, the maximal dose used. Markedly reducing the rate of injecting the same volume over 28 hours prevented the acute excitation but did not reduce the severity of the morphologic effects. CONCLUSION: The acute excitatory effects of high intraventricular doses of gadopentetate dimeglumine and gadodiamide are similar and appear to be attributable to local action at the infusion site, but differences exist between the two agents in the character and topography of the distant morphologic changes. The cerebellum was the brain area most sensitive to gadodiamide in this experimental model. It is unlikely that gadodiamide would gain access to the brain at these tissue doses when used intravenously for conventional clinical imaging, but our experimental model suggested that it had some unexpectedly specific neuropathologic potential.     

Occupational exposure to HIV: experience at a tertiary care center

We examined our hospital-based occupational health clinic's experience with combination antiretroviral therapy for postexposure prophylaxis for human immunodeficiency virus (HIV). Over a 12-month period, 68 workers started postexposure prophylaxis: 23 with zidovudine and lamivudine and 45 with zidovudine, lamivudine, and indinavir. Fifty-one (75%) of the 68 workers starting postexposure prophylaxis reported one or more side effects. Side effects were more common among those taking three drugs. Many workers failed to complete the recommended 28-day regimen because of the side effects of the various treatments. The estimated mean cost for evaluations, prophylaxis, and monitoring of exposed workers was $669 per reported exposure. In our experience, major challenges in carrying out the current HIV postexposure prophylaxis guidelines include expeditious source testing, improved staff education and prevention measures, and scrupulous monitoring of workers taking combination antiretroviral drugs for postexposure prophylaxis, with consideration of alternate regimens for intolerant workers.     

Some Functional and Utilization Characteristics of Sesame Flour and Proteins

Sesame defatted flour was prepared from dehulled seeds and the proteins extracted by isoelectric precipitation from an alkaline suspension of the flour. Temperature and pH effects on viscosity of a protein dispersion were measured using a Brookfield viscometer. Emulsifying capacity and emulsion stability were measured in mayonnaise and meat-type emulsions, respectively. Sesame flour was texturized by a simple method to produce a ground meat-like product with a hydration capacity of 380–440%. Sensory evaluation of meat loaves with 0–40% meat replaced by hydrated textured defatted sesame flour indicated no significant difference between samples. Viscosity of sesame protein dispersions at 90°C increased with increasing pH. The proteins did not form a self-supporting gel. Their emulsifying capacity proved to be relatively high when compared with traditional proteins.     

Milk production and plasma gossypol of cows fed cottonseed and oilseed meals with or without rumen-undegradable protein

Twenty-four multiparous Holstein cows were randomly assigned at calving to treatment diets using a modified split-plot design to determine the effects of protein source on milk production and composition. The treatment diets consisted of an 80:20 combination of corn and alfalfa silages and whole cottonseed at 12% of the dietary dry matter (DM). The treatment diets were formulated to contain 17% crude protein (CP) and 20% acid detergent fiber on a DM basis. One of the following sources of supplemental CP was included in each treatment diet: 1) cottonseed meal, 2) cottonseed meal plus a rumen-undegradable protein (RUP) supplement, 3) soybean meal, and 4) soybean meal plus an RUP supplement. Cows were fed the initial treatment diet for 6 wk and then were switched to the other oilseed meal source but continued to receive the same amount of RUP during the second period of the study. Milk production and composition were not affected by treatment diet. Cows fed treatment diets without RUP supplementation consumed more DM and thus more CP. Supplementation with RUP resulted in greater milk production efficiency per unit of DM consumed. Cows fed treatment diets containing cottonseed meal had higher plasma gossypol concentrations than did cows fed treatment diets containing soybean meal. Plasma gossypol concentrations for all cows in each group were below the recommended upper limit that is considered to be safe. Data suggest that cottonseed meal in the diet can be substituted for soybean meal, resulting in similar milk production and composition.     

Mathematical Models for Nonsymmetric Freezing of Beef

A microscopic balance with simultaneous change of phase together with equations for predicting the thermal properties as a function of the ice content and a cryoscopic descent model are used to simulate the nonsymmetric freezing of a beef slab. The equations are solved numerically to obtain temperature profiles as well as freezing times. Comparison with experimental results shows good agreement. A variation of the thermal center position throughout the freezing process is detected and assumptions to predict its position in the different periods of freezing are supplied. On the basis of these assumptions a simplified model for calculating processing times in plate freezers is proposed, showing good agreement with experimental freezing times and with predictions obtained from the numerical model.     

FOOD TEXTURE MEASUREMENTS IN CANADA

A survey of the food industry, government agencies and educational institutions dealing with foods has been conducted to establish the nature and extent to which instrumental texture measurements are employed in Canada. Two hundred and fifteen questionnaires were sent out and 123 (57%) returned. Of those replying, 52% were using texture evaluation instruments. Within the food industry the use of texture measuring instruments was as follows: meat 36%; fish 20%; canner/freezer 79%; dairy 42%; confectionery 73%; baking 50%; fats and oils 78%; multi product 77%; beverage 0%. Most widely used instruments in the quality control area were rotational viscometers and penetrometers. The more complex instruments, such as the Universal Testing Machine and the Shear Press, were used to a larger extent in the research area. The use of some instruments appeared to be restricted to particular commodity groups. The questionnaire dealt among other things with the use of taste panels, statistical evaluation of results, and the need for expanded use of instruments. There was general agreement that more standardization of methods is desirable.     

The role for NES1 serine protease as a novel tumor suppressor

Previously (Liu et al, Cancer Res., 56: 3371-3379, 1996), we isolated a novel serine protease-like gene--Normal Epithelial Cell Specific-1 (NES1)--that is expressed in normal mammary epithelial cells but is down-regulated in most breast cancer cell lines. Here, we demonstrate that stable expression of NES1 in the NES1-negative MDA-MB-231 breast cancer cell line suppressed the oncogenicity as revealed by inhibition of the anchorage-independent growth and tumor formation in nude mice. Fluorescence in situ hybridization localized the NES1 gene to chromosome 19q13.3, a region that contains genes for related proteases (including the prostate-specific antigen) and is rearranged in human cancers. Similar to breast cancer cell lines, prostate cancer cell lines also lacked NES1 mRNA and protein expression. Together, these results strongly suggest a tumor-suppressor role for NES1 in breast and prostate cancer.