Verapamil-induced "primary" polydipsia

An 11-month-old male infant with recurrent supraventricular tachycardia (SVT) was treated with oral verapamil. Shortly thereafter he developed marked changes in behavior including lethargy, intensely increased thirst and urination, and irritability when denied fluids. "Primary" polydipsia was diagnosed following an evaluation which showed no evidence of adrenal insufficiency, diabetes insipidus, diabetes mellitus, hypercalcemia, hyperosmolality, or renal disease. The symptoms resolved 1 week after verapamil was discontinued.     

Genetic effects of 1,3-butadiene and associated risk for heritable damage

A summary of the results of the studies conducted in the EU Project "Multi-endpoint analysis of genetic damage induced by 1,3-butadiene and its major metabolites in somatic and germ cells of mice, rats and man" is presented. Results of the project are summarized on the detection of DNA and hemoglobin adducts, on the cytotoxic and clastogenic effects in somatic and germinal cells of mice and rats, on the induction of somatic mutations at the hprt locus of experimental rodents and occupationally exposed workers, on the induction of dominant lethal mutations in mice and rats, and on heritable translocations induced in mice, after exposure to butadiene (BD) or its major metabolites, butadiene monoepoxide (BMO), diepoxybutane (DEB) and butadiene diolepoxide (BDE). The primary goal of this project was to collect experimental data on the genetic effects of BD in order to estimate the germ cell genetic risk to humans of exposure to BD. To achieve this, the butadiene exposure are based on data for heritable translocations and bone marrow micronuclei induced in mice and chromosome aberrations observed in lymphocytes of exposed workers. A doubling dose for heritable translocations in human germ cells of 4900 ppm/h is estimated, which, assuming cumulative BD exposure over the sensitive period of spermatogenesis, corresponds to 5-6 weeks of continuous exposure at the workplace to 20-25 ppm. Alternatively, the rate of heritable translocation induction per ppm/h of BD exposure is estimated to be approximately 0.8 per million live born, compared to a spontaneous incidence of balanced translocations in humans of approximately 800 per million live born. These estimates have large confidence intervals and are only intended to indicate orders of magnitude of human genetic risk. These risk estimates are based on data from germ cells of BD-exposed male mice. The demonstration that clastogenic damage was induced by DEB in preovulatory oocytes at doses which were not ovotoxic implies that additional studies on the response of mammalian female germ cells to BD and its metabolites are needed. The basic assumption of the above genetic risk estimates is that experimental mouse data obtained after BD exposure can be extrapolated to humans. Several points exist in the present report and in the literature which contradict this assumption: (1) the level of BMO-hemoglobin adducts was significantly elevated in BD-exposed workers; however, it was considerably lower than would have been predicted from comparable rat and mouse exposures; (2) the concentrations of the metabolites DEB and BMO were significantly higher in mouse than in rat blood after BD exposure. Thus, while metabolism of BD is qualitatively similar in the two species, it is quantitatively different; (3) no increase of HPRT mutations was shown in 19 workers exposed on average to 1.8 ppm of BD, while in a different population of workers from a US plant exposed on average to 3.5 ppm of BD, a significant increase of HPRT variants was detected; and (4) data from cancer bioassays and cancer epidemiology suggest that rat is a more appropriate model than mouse for human cancer risk from BD exposure. However, the dominant lethal study in rats gave a negative result. At present, we do not know which BD metabolite(s) may be responsible for the genetic effects even though the bifunctional alkylating agent DEB is the most likely candidate for the induction of clastogenic events. Unfortunately, methods to measure DEB adducts in hemoglobin or DNA are only presently being developed. Despite these several uncertainties the use of the mouse genetic data is regarded as a justifiable and conservative approach to human genetic risk estimation given the considerable heterogeneity observed in the biotransformation of BD in humans.     

Extrusion studies of mixtures containing certain meat offals: Part 1-Objective properties

A study was made of thermoplastically extruded products prepared from soy grits incorporating varying percentages of offal. Beyond 35% incorporation no satisfactory extrudate could be prepared. A comparison was therefore made of the expansion ratio, density and hydratability of extrudates prepared from mixes containing 20% and 35% of bovine or porcine offal with those containing soy grit alone. The offal sources consisted of untreated or alkali-extracted bovine and porcine lung and bovine tripe (rumen and reticulum) and bovine tripe extracted by sodium dodecyl sulphate (SDS). Under the determined optimum operating conditions, extrudates from all offal/soy mixtures had lower expansion ratios and rehydratability than those from soy grits alone. Nevertheless, mixtures containing 20% or 35% alkali-extracted offal protein expanded more (greatest expansion at 170°C), had lower density and greater hydratability than those containing these proportions of untreated offal or SDS-extracted offal protein. (The latter expanded most between 175-180°C.) Whereas the incorporation of SDS-extracted bovine or porcine lung protein failed to yield textured extrudates, the incorporation of SDS-extracted bovine tripe protein at the 20% level did so. Effects due to source were otherwise small.     

The nutritive value of protein isolates and fibres from meat industry by-products

Protein isolates extracted from rumen, lung and plasma by alkaline solubilisation were spun into protein fibres and were evaluated for protein quality by rat feeding trials and by amino acid analyses. The net protein utilisation (NPU) of the fibres ranged from 53·0 to 76·9 for plasma and rumen fibres respectively, methionine plus cystine and valine being limiting amino acids. Lysine was not found to be a limiting amino acid in any sample and lysine availability was high in isolates and fell only slightly on spinning. There was a marked discrepancy between chemical score and NPU for rumen isolate and it is postulated that an anti-nutritional factor, possibly a trypsin inhibitor, normally present in bovine organs, could be active in the isolate by lowering methionine availability to the animal and decreasing NPU. Spinning the proteins, however, either destroys the inhibitor or decreases its concentration since NPU and chemical score become equal.     

Effect of oxygen and storage temperature on intermediate moisture meat products

During storage of glycerol desorbed intermediate moisture meats at 38°C it was found that, for both protein crosslinking and loss of haemoprotein character to occur, oxygen must be present. However, collagen degradation, as monitored by the formation of water-soluble hydroxyproline containing fragments, still occurred in the absence of oxygen although the rate of degradation was slower than that observed in aerobically stored samples. The rates of the various deteriorative reactions also varied with storage temperature, there being the expected decrease in rate with temperature for both the crosslinking and haemoprotein breakdown reactions. However, the temperature dependence of the collagen breakdown reaction was apparently more complex as there was no measurable breakdown, even during several months of storage, at temperatures of 17°C and below.     

Differential diagnosis of pulmonary circular focusses by means of analytic-synthetical picture evaluation (author''s transl)]

Hyperamylasemia was noted in 17 (19%) of a group of 91 hospitalized heroin addicts. Thirteen of the 17 were in acute respiratory distress (12 with so-called "heroin lung" syndrome and one with status asthmaticus). Isoamylase analysis in the hyperamylasemic patients demonstrated S-type isoamylase dominance in 15, P-type isoamylase dominance in one and essentially equivalent P- and S-type isoamylase elevations in one. It would appear from these data that the hyperamylasemia after heroin in most persons addicted to the use of this drug arises from the sources other than the pancreas. Changes in the lungs occurring in association with heroin addiction seem to have an important role among the possible contributory factors.     

Microbiological quality of sausages containing chickpea flour (Cicer arietinum)

English-type fresh skinless pork sausages in which 30% of the protein was replaced by unheated chickpea flour or by chickpea flour heated at 80°C for 1 h were evaluated microbiologically. During storage at 0°C, but not 22°C, incorporation of unheated chickpea flour lowered the microbiological quality of the sausages, but incorporation of chickpea flour previously heated at 80°C for 1 h led to no less of microbiological quality.     

Adjuvant therapy for osteosarcoma in dogs: results of randomized clinical trials using combined liposome-encapsulated muramyl tripeptide and cisplatin

Two randomized, double-blind clinical trials in dogs with spontaneous appendicular osteosarcoma treated with combination chemoimmunotherapy are reported. In both trials, dogs without overt metastasis underwent complete amputation of the affected limb. In trial 1, 40 dogs were treated with cisplatin chemotherapy [(CDDP), 70 mg/m2 i.v. every 28 days x 4]. Following CDDP, dogs without evidence of overt metastasis (n = 25) were randomized to receive liposome-encapsulated muramyl tripeptide phosphatidylethanolamine ](L-MTP-PE), 2 mg/m2 i.v.) or placebo liposomes (lipid equivalent) twice weekly for 8 weeks. Of 14 dogs in the placebo group, 13 (93%) died of metastasis; the median survival time was 9.8 months. Of 11 dogs in the L-MTP-PE group, 8 (73%) developed metastasis; the median survival time was 14.4 months, which was significantly longer than that of the placebo group (P < 0.01). In trial 2, 64 dogs received CDDP (70 mg/m2 i.v. every 21 days x 4) and were randomized to concurrently receive L-MTP-PE (2 mg/m2 i.v.) twice or once weekly, or placebo liposomes once weekly for 8 weeks. Median survival times were 10.3, 10.5, and 7.6 months, respectively. There were no significant differences among the three treatment groups in trial 2. Survival times for dogs receiving L-MTP-PE in trial 1 were significantly longer than those for dogs in trial 2 that received four doses of CDDP concurrently with twice weekly L-MTP-PE (P < 0. 04). The results of the first trial confirm our previous observation that L-MTP-PE has antimetastatic activity in dogs with osteosarcoma when given following amputation. The results of the second trial demonstrate that there is no survival advantage of administering L-MTP-PE concurrently with CDDP.     

Gelatinase A (MMP-2) and cysteine proteinases are essential for the degradation of collagen in soft connective tissue

Epidermal growth factor (EGF) is a potent mitogen for normal mouse mammary epithelial cells grown in primary culture. EGF activation of the EGF-receptor (EGF-R) induces intrinsic tyrosine kinase activity which results in EGF-R autophosphorylation and tyrosine phosphorylation of other intracellular substrates involved in EGF-R signal transduction. Genistein and erbstatin are anticancer agents which have been shown to be potent tyrosine kinase inhibitors. However, the effects of these compounds in modulating EGF-dependent normal mammary epithelial cell proliferation is presently unknown. Therefore, studies were conducted to determine the effects of genistein and erbstatin on EGF-dependent proliferation, and EGF-R levels and autophosphorylation in normal mouse mammary epithelial cells grown in primary culture and maintained in serum-free media. Chronic treatment with 6.25-100 microM genistein or 1-16 microM erbstatin significantly decreased EGF-dependent mammary epithelial cell proliferation in a dose-responsive manner. However, the highest doses of genistein (100 microM) and erbstatin (16 microM) were found to be cytotoxic. Additional studies showed that acute treatment with 6.25-400 microM genistein did not affect EGF-R levels or EGF-induced EGF-R autophosphorylation, while acute treatment with 1-64 microM erbstatin caused a slight reduction in EGF-R levels, but had no effect on EGF-dependent EGF-R autophosphorylation in these cells. In contrast, chronic treatment with similar doses of genistein or erbstatin resulted in a large dose-responsive decrease in EGF-R levels, and a corresponding decrease in total cellular EGF-R autophosphorylation intensity. These results demonstrate that the inhibitory effects of chronic genistein and erbstatin treatment on EGF-dependent mammary epithelial cell proliferation is not due to a direct inhibition of EGF-R tyrosine kinase activity, but results primarily from a down-regulation in EGF-R levels and subsequent decrease in mammary epithelial cell mitogenic-responsiveness to EGF stimulation.