Variables Influencing the Effect of a Meal on Brain Tryptophan

Previous work from our laboratory points to plasma free tryptophan being a useful predictor of brain tryptophan concentration in many circumstances. Other work, in particular various studies on the acute effects of food intake, has emphasized the roles of plasma total tryptophan and of plasma large neutral amino acids that compete with tryptophan for transport to the brain. We have now studied associations between the above variables under different dietary conditions. Rats were allowed to feed for restricted periods during a 12-h light-12-h dark cycle. In the first study, rats were given access to a carbohydrate diet for 2 h midway through the light cycle and following an 18-h fast. The resultant rise of brain tryptophan was explicable largely by the associated fall in large neutral amino acids. In a second study, rats were adapted to a regimen whereby they were allowed access to the standard laboratory diet for 4 h during the dark cycle for 3 weeks. A postprandial decrease in brain tryptophan was associated with a fall in free tryptophan and of its ratio to competing amino acids. The brain change could be attributed neither to changes in plasma total tryptophan (which increased) nor to changes of its ratio to the competers (which remained unchanged). Results as a whole are thus consistent with changes of plasma free tryptophan and large neutral amino acid concentrations affecting brain tryptophan concentration under different dietary circumstances. It is suggested that these influences serve to maintain brain tryptophan when dietary supplies are defective.     

Colonization factors of diarrheagenicE. coli and their intestinal receptors

WhileEscherichia coli is common as a commensal organism in the distal ileum and colon, the presence of colonization factors (CF) on pathogenic strains ofE. coli facilitates attachment of the organism to intestinal receptor molecules in a species- and tissue-specific fashion. After the initial adherence, colonization occurs, and the involvement of additional virulence determinants leads to illness. EnterotoxigenicE. coli (ETEC) is the most extensively studied of the five categories ofE. coli that cause diarrheal disease, and has the greatest impact on health worldwide. ETEC can be isolated from domestic animals and humans. The biochemistry, genetics, epidemiology, antigenic characteristics, and cell and receptor binding properties of ETEC have been extensively described. Another major category, enteropathogenicE. coli (EPEC), has virulence mechanisms, primarily effacement and cytoskeletal rearrangement of intestinal brush borders, that are distinct from ETEC. An EPEC CF receptor has been purified and characterized as a sialidated transmembrane glycoprotein complex directly attached to actin, thereby associating CF-binding with host-cell response. Three, additional categories ofE. coli diarrheal disease, their colonization factors and their host cell receptors are discussed. It appears that biofilms exist in the intestine in a manner similar to oral bacterial biofilms, and thatE. coli is part of these biofilms as both commensals and pathogens.Abbreviations CF colonization factor - CFA Colonization Factor Antigen - CS coli-surface-associated antigen - EAggEC enteroaggregativeE. coli - ECDD E. coli diarrheal disease - EHEC enterohemorrhagicE. coli - EIEC enteroinvasiveE. coli - EPEC enteropathogenicE. coli - ETEC enterotoxigenicE. coli - Gal galactose - GalNAc N-acetyl galactosamine - LT heat-labile toxin - NeuAc N-acetyl neuraminic acid - PCF Putative colonization factor - RBC red blood cells - SLT Shiga-like toxin - ST heat-stable toxin     

Osteoarthritis of weight bearing joints of lower limbs in former élite male athletes.

OBJECTIVE--To compare the cumulative 21 year incidence of admission to hospital for osteoarthritis of the hip, knee, and ankle in former élite athletes and control subjects. DESIGN--National population based study. SETTING--Finland. SUBJECTS--2049 male athletes who had represented Finland in international events during 1920-65 and 1403 controls who had been classified healthy at the age of 20. MAIN OUTCOME MEASURES--Hospital admissions for osteoarthritis of the hip, knee, and ankle joints identified from the national hospital discharge registry between 1970 and 1990. RESULTS--Athletes doing endurance sports, mixed sports, and power sports all had higher incidences of admission to hospital for osteoarthritis than controls. Age adjusted odds ratios compared with controls were 1.73 (95% confidence interval 0.99 to 3.01, P = 0.063) in endurance, 1.90 (1.24 to 2.92, P = 0.003) in mixed sports athletes, and 2.17 (1.41 to 3.32, P = 0.0003) in power sports athletes. The mean age at first admission to hospital was higher in endurance athletes (70.6) than in other groups (58.2 in mixed sports, 61.9 in power sports, and 61.2 in controls). Among the 2046 respondents to a questionnaire in 1985, the odds ratios for admission to hospital were similar in all three groups after adjusting for age, occupation, and body mass index at 20 (2.37, 2.42, 2.68). CONCLUSIONS--Athletes from all types of competitive sports are at slightly increased risk of requiring hospital care because of osteoarthritis of the hip, knee, or ankle. Mixed sports and power sports lead to increased admissions for premature osteoarthritis, but in endurance athletes the admissions are at an older age.     

Terminal deoxynucleotidyl transferase in AKR leukemic cells and lack of relation of enzyme activity to cell cycle phase.

Cholate and taurocholate uptakes were studied in presence of albumin using isolated rat hepatocytes. Albumin decreased nonspecific binding of both bile acids and inhibited cholate uptake noncompetitively and taurocholate uptake competitively. Although different bile acids except dehydrocholate inhibited both cholate and taurocholate uptake, their relative inhibitory potency was not the same for both bile acids. Uptake of both bile acids was characterized by a saturable as well as an unsaturable process both in presence and in absence of albumin. The results suggest that both bile acids may be transported by more than one carrier and taurocholate is transported more efficiently than cholate by hepatocytes.     

Electron-nuclear double resonance in melanins.

Electron-nuclear double resonance (ENDOR) signals from matrix protons interacting with the stable free radicals of "A"- and "B"-type melanins have been observed as a function of pH. In all samples the single line is similar in width and unusually narrow. The ENDOR reduction varies by more than a factor of 10, indicating a large sensitivity of relaxation properties of melanin to sample type. Signals were observed over a wide range of experimental conditions with good signal-to-noise ratio, establishing feasibility for further more detailed ENDOR studies. Incubation in D2O resulted in little change, indicating that the free radical is well buried or protected. No resolved hyperfine structure was seen, consistent with the generally accepted view that melanin is a heterogeneous polymer.     

Determination of acid α-naphthyl acetate esterase enzyme activity in peripheral blood leukocytes of gazelles (Gazella subgutturosa)

We examined gazelle peripheral blood leucocytes using the α-Naphthyl acetate esterase (ANAE) staining technique (pH 5.8). Our purpose was to determine the percentage of ANAE positive lymphocytes. The proportion of ANAE positive T-lymphocytes was 72%. T-lymphocytes showed an ANAE positive reaction, but eosinophilic granulocytes and monocytes also showed a positive reaction. By contrast, no reaction was detected in B-lymphocytes, neutrophil granulocytes or platelets. The reaction observed in T-lymphocytes was a red-brown coloration, usually 1–2 granules, but enough granules to fill the cytoplasm were detected rarely. As a result of ANAE enzyme staining, we concluded that the staining technique can be used as a cytochemical marker for gazelle T-lymphocytes.     

Different types of contractions in rat colon and their modulation by oxidative stress

The aim of this study was to investigate the modulation of in vitro rat colonic circular muscle contractions by dextran sodium sulfate (DSS)-induced inflammation and in spontaneous inflammation in HLA-B27 rats. We also examined the potential role of hydrogen peroxide (H(2)O(2)) in modulating excitation-contraction coupling. The muscle strips from the middle colon generated spontaneous phasic contractions and giant contractions (GCs), the proximal colon strips generated primarily phasic contractions, and the distal colon strips were mostly quiescent. The spontaneous phasic contractions and GCs were not affected by inflammation, but the response to ACh was suppressed in DSS-treated rats and in HLA-B27 rats. H(2)O(2) production was increased in the muscularis of the inflamed colon. Incubation of colonic muscle strips with H(2)O(2) suppressed the spontaneous phasic contractions and concentration and time dependently reduced the response to ACh; in the middle colon, it also increased the frequency of GCs. We conclude that H(2)O(2) mimics the suppression of the contractile response to ACh in inflammation. H(2)O(2) also selectively suppresses phasic contractions and increases the frequency of GCs, as found previously in inflamed dog and human colons.     

Structural differences in unbleached and mildly-bleached synthetic tyrosine-derived melanins identified by scanning probe microscopies

Using scanning tunneling microscopy (STM), we have imaged two types of mildly-bleached, synthetic tyrosine-derived melanins for comparison with the unbleached melanin from which they were prepared. These mildly-bleached melanins were generated by mild oxidation of the unbleached melanin, using either basic hydrogen peroxide or air/light. The unbleached melanin, and two mildly-bleached melanins, were independently deposited from very dilute tetrahydrofuran (THF) solutions onto highly oriented pyrolytic graphite (HOPG) substrate for STM imaging. Lateral dimensions (23 A, average of two directions) of structures from each of the three samples showed no differences. However, structures from both mildly-bleached melanins showed similar dramatic decreases (from approximately 15 A to approximately 5 A) in their STM-measured apparent heights, compared with structures from the unbleached melanin sample. These STM observations are compatible with structural models for unbleached and mildly-bleached melanins, incorporating a three-dimensional structure for unbleached melanin composed of multi-layered, pi-pi-stacked, carboxylic and amino variants of polyaromatic polymeric sheets. The STM-observed decrease in apparent heights after mild oxidation, which we associate with a change in stack height, has been confirmed by experiments using tapping mode atomic force microscopy (TM-AFM) for the unbleached and mildly-hydrogen-peroXide-bleached melanins (from approximately 14 A to approximately 6 A). In these TM-AFM experiments, the melanins were deposited directly onto magnesium cation-treated glass substrates in contact with methanolic solutions of each of the melanins. We interpret our mild-bleaching results as an oxidative conversion of the multi-layered, stacked sheets of mainly carboxylic and amino variants of polyquinhydrone-like moieties, to largely de-stacked, mildly-bleached melanin sheets. These oxidized and, hence, electron-deficient sheets should not readily form multi-layered, pi-pi interacting stacks, but instead appear to be either single-layer polyquinone sheets or, at most, double-layer polyquinhydrone sheets. The effects of such de-stacking on in vivo melanin photoprotection, and structural similarities between melanin derived from natural sources and the synthetic melanin samples used in this work are discussed.