Effects of stress on amino acids and related compounds in various tissues of fasted rats

The purpose of this study was to examine the effect of stress on the free amino acid pattern of plasma and various organs. Two groups of rats were deprived of food, for 24 hrs. One group was sacrificed after this time (fasting control representing mostly free endogenous amino acids) and the second group was first restrained in wire cages for 120 min before being sacrificed (fasting stress representing mostly the effects of stress on endogenous free amino acids). A third group had free access to food and was sacrificed at the same time (fed control representing mostly free amino acids absorbed from the gut and endogenous free amino acid metabolism). Fasting (as compared to fed controls) reduced alanine and arginine but increased ethanolamine, glutamic acid and glutamine in the plasma; increased ethanolamine, phosphoethanolamine and glutamic acid in the liver; increased carnosine, glutamic acid, phosphoethanolamine and glutamine in the ventricle; increased oxidized glutathione in the aorta; decreased alanine, aspartic acid, glutamic acid, leucine and methionine and increased glutamine in the pancreas; and decreased arginine in skeletal muscle. Fasting plus stress (as compared to fasting controls) reduced alanine and glutamine in the plasma; increased methionine in the liver; increased ethanolamine, GABA, and glutamic acid in the aorta; reduced arginine, glutamic acid, glutamine, leucine and methionine but increased ethanolamine in the ventricle; reduced ammonia and ethanolamine but increased histidine, isoleucine, leucine, lysine, phenylalanine, tyrosine and valine in the pancreas; and reduced ammonia in skeletal muscle. Fasting plus stress affects the amino acid composition of plasma and various of tissues but effects seen were individually different and strongly substance and tissue specific. Plasma changes did not coincide with tissue changes. Changes in the endogenous pattern of amino acids and related compounds in response to stress could be first indications of stress induced organ pathology.     

Recurrent liver failure with severe rhabdomyolysis after liver transplantation for carbon tetrachloride intoxication

Acute liver failure due to intoxication is a rare indication for liver transplantation which a usually has a good prognosis. We herein report the case of a young male, who underwent orthotopic liver transplantation for acute liver failure due to carbon tetrachloride intoxication. Apart from hepatic and renal failure, the patient also developed severe rhabdomyolysis, which has not thus far been described as a toxic effect of this chemical agent. Despite forced hyperventilation, which is known to be the most effective means of eliminating the specifically lipophylic agent, as well as excessive plasma exchange following intravenous administration of fat emulsions, liver failure recurred when blood carbon tetrachloride concentrations were already at non-toxic levels. Retransplantation of the liver together with a kidney was only temporarily successful, since the patient died due to aspergillus sepsis. Based on this experience, we would recommend that whenever possible in patients with carbon tetrachloride intoxication, liver transplant should be delayed until most of the toxic agent has been eliminated in order to prevent fatal graft damage.     

Pancreatic cancer: treatment with neutron irradiation alone and with chemotherapy

PURPOSE: To evaluate neutron irradiation alone and with chemotherapy to treat inoperable pancreatic cancer. MATERIALS AND METHODS: Between 1977 and 1994, 173 patients (60 men, 113 women, aged 43-77 years [mean, 59 years]) with unresectable adenocarcinoma of the exocrine pancreas were treated, 106 with neutron irradiation alone and 67 with concomitant chemotherapy (fluorouracil [5-FU]). At follow-up, which was performed at 2-month intervals until death (range, 4-64 months), clinical status was recorded, noting the presence of overt metastasis and the onset of any major complications. Actuarial (Kaplan-Meier) survival tables were computed for both groups. RESULTS: For neutron irradiation alone and neutron irradiation plus chemotherapy, median survival times were 6 months and 9 months, respectively; actuarial survival rates at 3 years were 0 and 7%, respectively; major reactions (grade 3 or higher [scale of the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer]) occurred in 19 (18%) and 17 (25%) patients, respectively; and severe complications (grade 4) occurred in five (5%) and four (6%) patients, respectively. Most deaths were due to metastatic disease rather than to failure of local control. CONCLUSIONS: Neutron irradiation obliterated pancreatic adenocarcinoma at the primary site but has no effect on long-term survival. With more effective concomitant chemotherapy to prevent metastasis, local control of pancreatic cancer with neutron irradiation could lead to increased long-term survival.     

Using GPS to measure ground complex permittivity

In personal satellite communications, ground specular reflection may be received along with the direct signal. To characterise this effect at L-band, fade measurements were taken over grass and asphalt surfaces using a GPS receiver. By matching experimental results to a simulation, ground electrical characteristics were derived, showing a novel method for their measurement     

Low- and high-density lipoproteins as mitogenic factors for vascular smooth muscle cells: individual, additive and synergistic effects

The mitogenic activities of low (LDL)- and high (HDL)-density lipoproteins have been examined in cultures of human vascular smooth muscle cells (VSMC). LDL and HDL3 dose-dependently (EC50 values approximately 50 micrograms/ml) stimulated DNA and protein synthesis ([3H]-thymidine and [3H]-leucine incorporation, respectively) in the absence of exogenously added mitogens. The synthetic responses of VSMC to combinations of LDL and HDL3 were additive, indicating that each lipoprotein mediates discrete effects. LDL or HDL3 promoted VSMC proliferation under strict mitogen-free conditions, but this growth response was not sustained. VSMC exposed to combinations of lipoproteins (either LDL or HDL3) and growth factors (either PDGF-BB, EGF, bFGF or IGF) exhibited synergistic DNA synthesis responses. In the combined presence of PDGF-BB and either LDL or HDL3, VSMC proliferation was sustained. Anionized lipoprotein preparations (oxidized, acetylated, carbamylated or malonimylated) also stimulated DNA and protein synthesis. Since the antioxidant beta-hydroxylated toluene did not block the effect of native LDL on DNA synthesis, and fucoidin, a specific competitor for the 'scavenger' receptor, did not inhibit oxidized LDL-induced DNA synthesis, activation of mitogenic signals by lipoproteins does not depend on lipid peroxidation. Rather, the apparent intrinsic mitogenic potential of lipoproteins may depend upon their direct activation of replication-coupled signal transduction systems.     

Toxicology of chemical mixtures: challenges for today and the future

A major challenge for the toxicologist involved in safety evaluation of chemical mixtures is to test the hypothesis that as a rule exposure to mixtures of chemicals at (low) non-toxic doses of the individual chemicals is of no health concern. A series of repeated dose studies in rats with defined mixtures of chemicals with the same or different target organs revealed that exposure to a combination of chemicals compared with exposure to the individual compounds did not constitute an evidently increased hazard, provided each chemical was administered at a level similar to, or slightly lower than, its own 'No-Observed-Adverse-Effect-Level'. The results of subacute oral toxicity studies in rats with defined mixtures of nephrotoxicants with similar mode of action underlined the applicability of the additivity assumption for a mixture of chemicals with simple similar action. Safety evaluation of complex chemical mixtures is a challenge that can be tackled as follows: first, identify the (e.g. ten) most risky chemicals in the mixture, and, second, assess the hazard and the potential health risk of the mixture of the most risky chemicals, using procedures developed for defined mixtures. To identify interactions between individual compounds, a most promising testing strategy appeared to be a statistical approach using a fractional two-level factorial design. A challenge for today and the future is to gradually substitute mixture-oriented (real life-oriented) standard setting for (unrealistic) single chemical-oriented standard setting.     

Murine epidermal lipoxygenase (Aloxe) encodes a 12-lipoxygenase isoform

Using a combination of conventional screening procedures and polymerase chain reaction cloning, we have isolated a cDNA encoding an epidermis-type 12-lipoxygenase (e12-lipoxygenase) from mouse epidermis. The open reading frame corresponds to a protein of 662 amino acids and was found to be 99.8% identical to the ORF of an epidermal lipoxygenase gene Aloxe, described recently [Van Dijk et al. (1995) Biochim. Biophys. Acta 1259, 4-8]. When expressed in human embryonic kidney cells the recombinant protein could be shown to synthesize 12(S)-HETE from arachidonic acid. By fluorescence in situ hybridization the e12-lipoxygenase gene was localized to chromosome band 11 B1-B3.