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Biomedical subjects

R G Rees

Publications and source records attributed to R G Rees.

7 recordsLinked to original sources

Glycine nitrogen in total parenteral nutrition: two prospective clinical trials comparing the efficacy of high and low glycine containing amino acid solutions.

Glycine has been regarded as a poor source of nitrogen for total parenteral nutrition. Two prospective randomised cross over controlled clinical trials were undertaken to compare the efficacy of high and low glycine containing amino acid solutions in parenterally fed malnourished hypoalbuminaemic patients with gastrointestinal disease. In the first study (n = 9), amino acid solutions in which glycine accounted for 23% and 4% of total nitrogen were compared. No statistically significant difference was found in urea nitrogen/total urinary nitrogen excretion (mean (SEM) 83.4 (1.4) v 81.6 (1.7)%, p = 0.31), nitrogen balance (-1.9 (2.4) v -0.6 (2.0) g/day, p = 0.31) or plasma protein concentrations and blood urea nitrogen. In the second extended study (n = 5), there was no significant difference in net whole body protein synthesis (+1.3 (4.7) v-0.2 (3.7) mg/kg/hour, p = 0.69) or fractional (0.403 (0.070) v 0.480 (0.41)%/hour, p = 0.68) and absolute albumin synthesis rates (6.0 (0.9) v 7.2 (0.06) mg/kg/hour, p = 0.22), on comparing solutions of 25% and 8% glycine nitrogen. In addition, a significantly higher proportion of total urinary nitrogen comprised urea when patients received the low glycine containing amino acid source (81.4 (2.5) v 83.8 (3.2)%, p = 0.04). It is concluded that there are no apparent short term nutritional or metabolic disadvantages to using amino acid solutions that contain up to 25% of nitrogen as glycine in total parenteral nutrition.

Adult

Do patients with moderately impaired gastrointestinal function requiring enteral nutrition need a predigested nitrogen source? A prospective crossover controlled clinical trial.

This prospective double blind randomised seven day crossover controlled clinical trial was carried out to determine whether enterally fed patients with moderately impaired gastrointestinal function require a predigested nitrogen (N) source compared with whole protein. Twelve malnourished patients with varying gastrointestinal abnormalities, who required enteral feeding, received 2.25 l of one of two isocaloric isonitrogenous enteral diets (1 kcal/ml, 4.8 g nitrogen/l) containing either predominantly medium chain peptides (tetra or higher peptides) or whole protein as the nitrogen source. Nitrogen absorption and balance were calculated from dietary intake and analysis of 24 hour total urinary and faecal nitrogen for the last five days of each study period. There was no significant difference in either stool weight (110 (SEM) (49) v 111 (32) g/d), nitrogen absorption (91 (2) v 89 (2)%) or nitrogen balance (+1.0 (1.3) v +0.6 (1.4) g nitrogen/d) between the peptide and whole protein nitrogen sources when all patients are considered. There was, however, evidence to suggest a nutritional advantage from administering an enteral diet whose nitrogen source comprises oligopeptides, rather than whole protein, to a subgroup of patients with small bowel disease.

Dietary Proteins

Paradoxical responses of hypothalamic corticotropin-releasing factor (CRF) messenger ribonucleic acid (mRNA) and CRF-41 peptide and adenohypophysial proopiomelanocortin mRNA during chronic inflammatory stress.

We have determined the time course of the neuroendocrine response of Piebald-Viral-Glaxo (PVG) rats during the development of mycobacterially induced adjuvant arthritis. Anterior pituitary POMC mRNA increased at the time of onset of mycobacterially induced arthritis, but, paradoxically, coincident with the first signs of arthritis there was a consistent fall in CRF mRNA in the hypothalamic paraventricular nucleus. Coincident with this fall in CRF message, there was a corresponding decrease in CRF-41 peptide release into the hypophysial portal blood (HPB). In contrast, however, vasopressin release into the HPB was increased. There was an increase in adrenal weight associated with the development of arthritis, reflecting chronic activation of the HPA axis, which was reflected by increased circulating corticosterone concentrations. The synthetic adjuvant CP20961, which has different antigenic determinants, also caused an increase in POMC mRNA in the anterior pituitary, a decrease in CRF mRNA in the hypothalamic paraventricular nucleus, and a decrease in CRF-41 peptide release into the HPB in PVG rats 28 days after the induction of the arthritis. The arginine vasopressin level was not significantly different from the control value. In Sprague-Dawley rats, mycobacterial adjuvant resulted in a similar increase in POMC mRNA in the anterior pituitary 28 days after injection of the adjuvant. In this strain of rat there was no corresponding change in CRF mRNA. While there are some strain differences in the degree of change in CRF mRNA, both strains showed a common paradox of a marked increase in adenohypophyseal POMC mRNA not associated with increased CRF mRNA or peptide release. In the PVG strain of rat, CRF actually appears to be inhibited. The mechanisms involved in this disparity are unclear.

Adrenal Cortex Hormones

Distribution of nerve endings and sensory neuropeptides in rat synovium, meniscus and bone.

The nervous system collects information from the outer world by specific senses and from the interior milieu by somatic senses. This information is processed and stored in memory and affects various bodily functions through the efferent arm of the nervous system. The efferent chemical neuropeptide message is transported intra-axonally to the site of action, which imparts site-specificity to the peripheral, paracrine neuropeptide effects. In the present study, immunohistochemistry using the immunoperoxidase method with nickel amplification was applied to visualize the topographical distribution of articular nerve fibres and nerve endings using the markers PGP 9.5 and synaptophysin, respectively. Furthermore, to get a comprehensive idea of the sensory innervation of the articular and para-articular tissue, antisera to calcitonin gene-related peptide (CGRP) and substance P were employed. Samples were collected after fixation by perfusion followed by immersion in fixative and decalcification by a special method, which also allows studies of the bone innervation. PGP 9.5- and synaptophysin-immunoreactive type IVa and IVb nerve fibres and endings were found in the synovial lining and sublining tissue and in the vascularized peripheral parts of the menisci. Furthermore, periosteum, bone marrow and the epiphyseal growth plates were also innervated, whereas innervation of the diaphyseal and metaphyseal bone was more sparse. PGP 9.5- and synaptophysin-immunoreactive nerves were also characterized by their CRGP, and to some extent, substance P content. Because of their distribution, the peripheral peptide-containing type IVa and IVb nerve fibres and nerve endings are in a position to participate in the pathogenesis of arthritis, including aspects of nociception, tissue remodelling and neurogenic inflammation.

Animals

Innervation of bone from healthy and arthritic rats by substance P and calcitonin gene related peptide containing sensory fibers.

Mechanical stress causes remodelling of bone, a transformation of bone structure by physical forces through an unknown mechanism. Inflammation also affects bone structure, through altered use and the production of various inflammatory mediators. The peripheral nervous system may play both a sensory and an efferent role in the mechanical and inflammatory influences on bone structure. We studied the occurrence of substance P and calcitonin gene related peptide (CGRP) containing nerves in periosteal tissue, bone marrow, diaphysis and epiphysis of the ankle and knee joints of healthy and adjuvant arthritic rats. In arthritic animals, only ankle joints were affected by the inflammation. The periosteum was richly innervated both in healthy and arthritic animals. In arthritic rats few nerve fibers penetrated the woven, callous bone underlying the periosteum. Also bone marrow contained substance P and CGRP immunoreactive nerves in normal bone, whereas the hypercellular bone marrow of arthritic rats showed a decrease in the density of substance P and CGRP containing fibers. Epiphysis had a dense innervation compared to diaphysis. In contrast to large erosions, small peripheral erosions contained some CGRP immunoreactive fibers, perhaps as a sign of attempts of reactive repair. Our results suggest a local delivery system of potent peptide regulatory factors in bone, a system also affected by the pathophysiology of arthritis.

Animals

Increased calcitonin gene-related peptide (CGRP), substance P, and enkephalin immunoreactivities in dorsal spinal cord and loss of CGRP-immunoreactive motoneurons in arthritic rats depend on intact peripheral nerve supply.

The distribution of peptides thought to be involved in pain modulation--substance P, calcitonin gene-related peptide (CGRP), and enkephalin--were studied in the spinal cord and dorsal root ganglia of polyarthritic rats and in rats with one sciatic nerve sectioned prior to induction of arthritis. In arthritic rats there was a bilateral increase of CGRP- and substance P-immunoreactive fibers and appearance of enkephalin-immunoreactive cell bodies in the dorsal horn of the lumbar (L4) spinal cord when compared to controls. In the corresponding dorsal root ganglia there were significant increases of CGRP- (P less than 0.02) and substance P- (P less than 0.001) immunoreactive cell bodies compared to controls. In the ventral horn of the control rats CGRP-immunoreactive motoneurons were abundant but were significantly (P less than 0.001) reduced in the arthritic spinal cord. Less pronounced changes were seen in the contralateral L4 spinal cord of arthritic rats with unilateral sciatic nerve section. In the ipsilateral dorsal horn, however, CGRP- and substance P-immunoreactive fibers were markedly depleted, and no enkephalin cell bodies were present. Furthermore, a number of CGRP-immunoreactive motoneurons were observed. In the ipsilateral L4 ganglia CGRP- (P less than 0.02) and substance P- (P less than 0.02) immunoreactive cells were significantly decreased compared to the contralateral side. The data suggest that pain perception is linked to complex interactions between CGRP, substance P, and enkephalin in sensory pathways and an intact peripheral input. The loss of CGRP-immunoreactive motoneurons may reflect muscular dysfunction associated with the arthritic condition.

Animals