Focal interstitial CC chemokine receptor 7 (CCR7) expression in idiopathic interstitial pneumonia.

BACKGROUND/AIMS: Idiopathic interstitial pneumonias (IIPs) are a diverse grouping of chronic pulmonary diseases characterised by varying degrees of pulmonary fibrosis. The triggers of the fibroproliferative process in IIP remain enigmatic but recent attention has been directed towards chemokine involvement in this process. METHODS: The expression of two chemokine receptors, CCR7 and CXCR4, and their respective ligands, CCL19, CCL21, and CXCL12, were examined in surgical lung biopsies (SLBs) from patients with IIP. Transcript and protein expression of these receptors and their ligands was compared with that detected in histologically normal margin SLBs. RESULTS: CCR7 and CXCR4 were detected by gene array and real time polymerase chain reaction analysis and CCR7, but not CXCR4, expression was significantly raised in usual interstitial pneumonia (UIP) relative to biopsies from patients diagnosed with non-specific interstitial pneumonia (NSIP) or respiratory bronchiolitis/interstitial lung disease (RBILD). CCR7 protein was expressed in interstitial areas of all upper and lower lobe UIP SLBs analysed. CCR7 expression was present in 50% of NSIP SLBs, and CCR7 was restricted to blood vessels and mononuclear cells in 75% of RBILD SLBs. Immune cell specific CXCR4 expression was seen in IIP and normal margin biopsies. CCR7 positive areas in UIP biopsies were concomitantly positive for CD45 (the leucocyte common antigen) but CCR7 positive areas in all IIP SLBs lacked the haemopoietic stem cell antigen CD34, collagen 1, and alpha smooth muscle actin. CONCLUSION: This molecular and immunohistochemical analysis showed that IIPs are associated with abnormal CCR7 transcript and protein expression.

Amino acids are still as exciting as ever.

Glutamate is probably the most important excitatory transmitter in the vertebrate central nervous system. Its multiple functional roles in the brain and spinal cord make therapeutic manipulation of these systems fraught with difficulties. There has, however, been recent progress in pharmacological manipulations of NMDA receptor subtypes and non-NMDA receptors, and understanding of the roles of NAAG, that promise rapid advances in pain control.

Protein requirements of adults from an evolutionary perspective.

It is argued that the observed minimum needs for protein and individual amino acids by adult humans and animals may merely reflect the diet that their predecessors consumed in the course of their evolution. The ability to adapt to diets with a lower proportion of protein than was ever encountered in practice would have given no competitive advantage. This can explain the limited ability to reduce rates of amino acid catabolism. The protein requirement of domestic cats, obligate carnivores, corresponds to approximately 20% of their energy requirement. Humans adapt to lower levels (approximately 6%). Some urge that higher protein intakes, resulting in higher rates of protein synthesis and turnover, are desirable and that, in general, the more prosperous and successful groups eat more protein. But cause and effect may be reversed. Are higher rates of turnover and catabolism necessarily beneficial? Objective data are still not available.

The bioavailability for humans of bound niacin from wheat bran.

Ethanolic wheat bran extracts were dialyzed and dried on starch. One portion [bound niacin (BN)] was cooked in steam; another [alkali-treated bound niacin (ABN)] was made alkaline with calcium oxide and then cooked. The niacin in BN was bound to large molecules (gel filtration); in ABN it was free. Three subjects each consumed a standard daily diet containing approximately 20 mg niacin equivalents. Urine was collected throughout. From day 14, each received three doses in random order at 8-day intervals. The doses, each spread over 2 days, were of BN and ABN, containing 35 mg niacin and 24 mg pure nicotinic acid. The above base-line response in urinary metabolites (N1-methylnicotinamide + N1-methyl-2-pyridone-5-carboxamide) over the 6 days from the beginning of each dose was equivalent to 24% of ingested niacin after BN, 62% after ABN and 89% after nicotinic acid. The niacin in BN appeared mostly unavailable.

Evidence that [Phe1 psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2, a peripheral ORL-1 receptor antagonist, acts as an agonist in the rat spinal cord.

[Phe1 psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2, a pseudopeptide analogue of nociceptin is an antagonist in peripheral assays. Here, using in vivo electrophysiological recordings of dorsal horn neurones, [Phe1 psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2 appears to have agonist activity after spinal administration. The noxious evoked activity of the neurones was inhibited by [Phe1 psi(CH2-NH)Gly2]nociceptin-(1-13)-NH2, which was as potent as nociceptin itself.

Solution crystallisation via a submerged liquid-liquid phase boundary: oiling out.

In many situations the process of crystallisation from solution is known to occur via metastable crystalline states (polymorphs or solvates). Here we present what we believe to be a novel example of small molecule crystallisation in which the initial separation of a solute rich liquid phase precedes the crystallisation event. We believe this occurs because a submerged liquid-liquid phase boundary is accessible within the metastable zone of the crystal nucleation process.

Neuronal inhibitory effects of methadone are predominantly opioid receptor mediated in the rat spinal cord in vivo.

This study aims to assess whether the antinociceptive actions of methadone are mediated solely through opioid mechanisms, or whether its reported affinity for NMDA receptors has physiological relevance in vivo. Methadone is a mu-opioid receptor agonist reported to relieve pain unresponsive to other opioids. It is a racemic mixture comprising d- and l-optical isomers; the d-isomer has a lower affinity for opioid receptors, and both also exhibit NMDA receptor binding, likely to indicate antagonist activity. d -Methadone is antinociceptive in behavioural studies via non-opioid mechanisms, which could include functional NMDA receptor-blocking activity. Here we investigate the ability of d - and dl -methadone to inhibit noxious and innocuous electrically-evoked responses of dorsal horn neurones in the anaesthetized rat. Racemic methadone (5, 25, 50, 250 microg) applied spinally, dose-relatedly inhibited the C-fibre evoked response, input and wind-up of the neurones, with a profile resembling that of morphine. d-Methadone (5, 25, 50, 250, 500 microg) was also inhibitory, although less potent by a factor of between 13 and 48 depending on the neuronal measure; its profile of inhibition resembled that of the racemic mixture rather than an NMDA receptor antagonist. Both compounds had minimal effects on Abeta-fibre-evoked activity. The inhibitory effects of both d - and dl -methadone on noxious-evoked activity were naloxone reversible. The naloxone reversibility of d -methadone inhibitions is best interpreted as indicative of a purely opioid mechanism of action. However, the ability of naloxone to reverse the effects of d -methadone may also reflect a degree of synergy between weak NMDA antagonist and opioid agonist activity.

Peripheral administration of low pH solutions causes activation and sensitisation of convergent dorsal horn neurones in the anaesthetised rat.

This is the first study to examine the effects of peripheral administration of acid on the activity of dorsal horn neurones in vivo. Extracellular recordings from convergent neurones revealed increases in neuronal activity evoked by administration of low pH solutions into the peripheral receptive field. Threshold for activity ranged from pH 5.85 to 2.5. The magnitude of responses increased with decreasing pH; maximum effects were achieved with pH 2.5 (648+/-181 action potentials/60 s, as compared to control-evoked activity of 86.3+/-29 action potentials/60 s). Activity lasted for up to 60 s, likely to represent the time for which the solutions were able to surmount the buffering capacity of the intact hindpaw. Significant sensitisation of the neurones to both innocuous (von Frey filament 9 g) and noxious (30 g) mechanical punctate stimuli was also observed.

Catastrophic phase inversion in region II of an ionomeric polymer-water system.

Previous work has identified distinct regions, on a phase inversion map, for dispersions of polyurethane ionomer (PUI) and water. In this study, events that occur, before, during, and after catastrophic phase inversion (provoked by adding water to polyurethane ionomer (PUI) in the RII regions of the phase inversion map) have been studied in order to characterise the inversion mechanism. Before phase inversion, initial water addition leads to the hydration of ionic groups and eventually water drops start to form in the hydrophobic portions of the polymer matrix. At the phase inversion point, the PUI-water interface restructures and the ionomer disintegrates into a dispersion of spherical particles enclosed by a continuous aqueous phase. It is suggested that pseudo-drop structures are formed simultaneously during the production of the small polymer-in-water drops. After phase inversion, water addition dilutes the emulsion and destroys the apparent ionic-centre-rich environment surrounding any isolated ionic groups on a particle surface. The larger water-in-polymer drops are likely to have participated in the phase inversion and the smaller water drops form the primary water drops in the multiple emulsions. The resultant emulsions are stable over a period of a few months but very few multiple drops remain after 1(1/4) years.

Different dispersion regions during the phase inversion of an ionomeric polymer-water system.

Catastrophic phase inversion is induced by changing the phase ratio in a liquid-liquid dispersion and is widely used during the dispersion stage in the production of aqueous polyurethane ionomer (PUI) colloids. In the work reported here, water was added to polyurethane ionomer prepolymer (PUIp) until the water became the continuous phase. Three different dispersion regions have been discovered by changing the ionic group content. Stable emulsions containing small polymer drops were produced in Region I. Stable coarse emulsions containing a mixture of drop structures were produced in Region II, but only temporary dispersions could be produced in Region III. Conductivity measurements could not always be used to detect the phase inversion points effectively because the PUIp was swollen by water. Therefore, torque change measurements have been used in conjunction with the conductivity measurements to detect the phase inversion points for all three dispersion regions. Scanning electron microscopy (SEM) and optical microscopy were used to obtain images of these dispersions in the different regions. A catastrophic phase inversion map is used to represent the changes that occur in the PUIp-W dispersions. This map is plotted using the ionic group content as the ordinate and water content (at the phase inversion points) as the abscissa.

Nutritional significance of cross-link formation during food processing.

When proteins are severely heated, in the presence or absence of sugars, the fall in nutritional value appears to be largely, although not completely, explained by reduced protein digestibility. All amino acids are considerably reduced in availability; which is in contrast to early Maillard damage which occurs under mild conditions of heating or storage in the presence of reducing sugars and affects mainly lysine. It seems that corss-linkages are formed in the severely heated protein or protein-sugar mixes and that these reduce the rate of protein digestion. When freeze-dried chicken muscle (15% H2O content) was severely heated its protein shown a great fall in digestibility but its value for supporting growth in the rat had fallen even more. Aspartyl-lysine and glutamyl-lysine cross-linkages, which had been formed during heating, appeared to be as digestible as the total N component and it seems that once they are released from the protein chain they can be absorbed and utilized.

The effects of alkali-cooking of corn and supplementation with amaranth seed on its deficiencies in lysine and tryptophan.

Corn, made into tortillas (flat cakes baked from lime-treated corn) is the staple food of Mexico. The amino acid deficiencies of tortillas (TT) and boiled corn (BC), and the supplementary value of amaranth seed (PA), another traditional Mexican food, roasted to the point of "popping", were studied. The feeding tests were 14-day PER trials using weanling rats; each diet contained 8.95% crude protein, all from corn, or with PA providing 3.6% protein and corn the remainder, with vitamin and mineral supplements. In addition each diet was supplemented with lysine (lys) so that tryptophan (trp) would be the first limiting amino acid or vice versa. In no comparison did TT give a significantly different value from BC. With trp limiting, the mean PER for the two corn preparations alone was 1.55, and with PA, 2.22. The amaranth had shown a high trp value (1.55 g/16g N). g N). With lys limiting, the mean PER for corn was 1.15; adding PA failed to improve this. Popping amaranth also reduced its reactive lysine value (by dye-binding) from 5.9 to 4.0 g/16g N. It appears that making tortillas has no adverse effect on protein value, but that 'popping' can reduce the value of amaranth seeds. The higher PER for corn with trp as the limiting amino acid (rather than lys) was due to lower ad libitum food intake with the same weight gain.