Biochemical effects of two promoters of hepatocarcinogenesis in rats

The effects of two promoters of hepatocarcinogenesis--phenobarbital and butylated hydroxytoluene (BHT)--on five hepatic biochemical parameters were examined in adult female rats. Phenobarbital given orally in two doses each of 110 mg/kg 21 and 4 hr before the rats were killed caused large increases in hepatic ornithine decarboxylase (ODC) activity and cytochrome P-450 content. Extending the number of phenobarbital treatments to five increased the hepatic enzyme induction and also caused a minor decrease in hepatic glutathione and a small increase in serum alanine aminotransferase activity. Two oral doses of 700 mg BHT/kg (20% of the LD50) caused hepatic DNA damage and induction of both ODC activity and cytochrome P-450 content. When the dose of BHT was reduced from 700 to 140 mg/kg no significant effects on the biochemical parameters were found. Both promoters of hepatocarcinogenesis were identified by their induction of ODC, a marker for promotional potential, but only BHT showed a potential for carcinogenic initiation. The biochemical parameters examined, particularly the alkaline elution technique for DNA damage, ornithine decarboxylase activity and serum alanine aminotransferase, may constitute a useful assay system for examining a compound's potential for carcinogenic initiation, carcinogenic promotion and cellular toxicity.     

Naloxone-reversible analgesia as a result of stimulation of the habenula in the rat

Electrical stimulation of rat habenular complex induces analgesia, evaluated by the tail-flick test, dependent on intensity of stimulation with a long post-effect, that is reversible by naloxone and without behavior effects at less that 400 mA. Bilateral destruction of habenula fails to provoke hyperesthesia but causes more marked long-term tolerance effects than in controls. Anatomy suggests that the habenula activates an inhibitory descending system in the spinal cord with a probable relay in the dorsal raphe and involving an endogenous opioid-dependent stage.     

Response of rats to diets of equal chemical score: effect of lysine or threonine as the limiting amino acid and of an amino acid excess

The effect of lysine or threonine deficiency with or without excesses of all other amino acids was evaluated in a 21-d feeding study with male rats. Four amino acid mixtures were designed to be first limiting for the rat in lysine or threonine and contained either 0 or 50% excess of nonlimiting amino acids. These mixtures were incorporated into purified diets to provide seven levels [20-140% of the National Research Council (NRC) requirement] of the limiting amino acid. Food intake, body weight gain and carcass composition were measured for each rat to determine the effects of the identity of the limiting amino acid and of amino acid excess on the response to dietary chemical score. Significant effects and/or interactions of the identity of the limiting amino acid (i.e., Lys or Thr) and the presence of excess amino acids were seen for each of the measured responses. At equivalent dietary percentages of the NRC requirement, threonine deficiency supported greater body weight gain than did lysine deficiency. At equivalent deficiencies (Lys vs. Thr) threonine-deficient rats were more susceptible to adverse effects of excess amino acids. When the limiting amino acids were incorporated into the diet through incremental addition of the deficient amino acid mixture, rats responded to levels of lysine or threonine in excess of the NRC requirement. These results suggest that the current NRC requirements for these amino acids are too low and that aspects of the dietary amino acid composition other than the percentage deficit of the limiting amino acid can be important determinants of animal response.     

Identification of single dissimilar odors is achieved by humans with a single sniff

The duration that a single odor needs to be sniffed for identification was determined for 18 humans. A hot wire anemometer and an oscilloscope were used to monitor the duration, volume and inhalation rate of sniffs. In Experiment 1 subjects used 1, 3 or 5 natural sniffs, or an unlimited number of natural sniffs to sample seven dissimilar single odors of moderate perceived intensity, and demonstrated that each odor could be identified with a single sniff. In Experiment 2 subjects demonstrated that each of the odors could be identified with the shortest sniff (0.42 sec) they could physically achieve. In Experiment 3 tests with two of the odorants at several concentrations showed that sniff duration influences identification over a narrow range of concentrations that is just above the recognition threshold. These results together with earlier data that described the optimum conditions for the detection of an odor and the perception of odor intensity, provide information that is necessary for the development of a standard olfactometer and standard methods for human olfactory measurements.     

Giant axonal neuropathy: central abnormalities demonstrated by evoked potentials

Previous studies of giant axonal neuropathy have reported clinical and pathological findings that indicate involvement of the central nervous system. We studied 3 boys with giant axonal neuropathy, who were 14 to 16 years of age, using auditory, visual, and somatosensory evoked potentials. Absence of waveforms and prolongation of peak and interwave latencies were found. Abnormalities were noted in all modalities. The auditory brainstem evoked response in particular indicated a significant increase in brainstem conduction time. These studies add clinical neurophysiological confirmation of the central nervous system involvement in this disorder and may also provide a means of quantitative evaluation of its progression.     

Effect of immunoglobulin depositions of glomerular sialic acids in patients with IgA nephropathy

A study of double immunofluorescence-staining of immunoglobulins and sialic acids in the glomeruli from patients with IgA nephropathy is described. Renal biopsy specimens from patients with IgA nephropathy were stained with rhodamine-labeled antihuman IgA, IgG or IgM antisera and then stained with FITC-labeled Limulus polyphemus (LPA), Tricum vulgaris (WGA) or antihuman C3 antisera. Marked positive stainings of IgA and C3 and positive binding of LPA or WGA were observed in the glomerular mesangial areas from patients with IgA nephropathy. LPA or WGA were not bound with glomerular capillary walls from patients with moderate and advanced stages of IgA nephropathy, although depositions of IgA and C3 were markedly observed in such walls. There was a significant inverse correlation between the deposition of IgA and the binding of LPA or WGA in glomerular capillary walls obtained from these patients with IgA nephropathy. The levels of proteinuria from patients with moderate and advanced stages of IgA nephropathy were significantly higher than those with minimal and slight stages of such disease. It is suggested that the decrease of sialic acids in glomerular capillary walls might be due to a deposition of IgA in some patients with IgA nephropathy. It is concluded that high levels of proteinuria might be due to the decrease of sialic acids in glomerular capillary walls from patients with moderate and advanced stages of IgA nephropathy.