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Biomedical subjects

L A Schroeder

Publications and source records attributed to L A Schroeder.

At least 19 recordsLinked to original sources

Serum visceral protein levels reflect protein-calorie repletion in neonates recovering from major surgery.

Protein catabolism resulting from acute metabolic stress causes significant postoperative decreases in visceral proteins, including albumin (Alb) and prealbumin (PA). Although clinical trials have suggested an advantage of PA over Alb in monitoring the visceral protein response to nutritional supplementation following surgery, the capability of the neonate to generate such a response has yet to be evaluated. Therefore, this study was undertaken to determine if PA is superior to Alb in assessing postoperative repletion of the visceral protein pool in neonates. Serum Alb and PA levels were measured and energy balance (EB) and protein intake (PI) were recorded in 10 neonates less than 48 hours after major surgery and again following 4 consecutive days of positive EB. Resting energy expenditure (REE) was measured using indirect calorimetric methodology. Mean PI (g/kg/d) was lower (0.78 +/- 0.78) and mean EB (kcal/kg/d) was negative (-2.92 +/- 10.05) less than 48 hours postoperatively compared with mean PI (2.52 +/- 0.57; P = .0006) after 4 consecutive days of positive EB (34.84 +/- 16.5; P = .0004). Mean percent change (mean% delta) from negative EB to positive EB was significantly greater for PA (100%; P = .0002) as compared with Alb (18.5%). These data appear to support the conclusion that serial serum PA levels are superior to Alb to monitor the visceral protein response to nutritional supplementation in neonates following surgery.

Energy Intake↗

Thiamin and vitamin B6 intakes and erythrocyte transketolase and aminotransferase activities in morbidly obese females before and after gastroplasty.

To assess the need for postoperative vitamin supplements, intakes and nutritional status of thiamin (B1) and vitamin B6 were studied in 18 female gastroplasty patients who received a placebo or different levels of supplemental vitamins. Postoperative erythrocyte transketolase basal (BA) and thiamin pyrophosphate-stimulated (SA) activities and activity coefficients (AC) correlated significantly with B1 intake. Despite a decrease in apotransketolase, low thiamin intakes were associated with increased AC values during the first 3 months. With return to low B1 intakes following repletion during month 4, the AC values remained normal with low total activities. Both alanine (EALT) and aspartate (EAST) aminotransferase apoenzyme levels declined and AC values increased significantly during the first 3 months. Although the EALT-indices were more sensitive to changes in B6 intake than the EAST-indices, the EASTBA and SA correlated most consistently with the intake. Postoperative dietary intakes of both vitamins were inadequate for maintenance of normal activities of these erythrocyte enzymes. Although B1 intake of greater than or equal to 1.0 mg/day was adequate for maintenance of normal thiamin status in most subjects of this study, supplementation with greater than or equal to 1.5 mg/day is prudent even though it may not prevent the early postoperative loss of apotransketolase. Vitamin B6 intake at the current recommended dietary allowance (1.6 mg) was not adequate to maintain coenzyme saturation of the erythrocyte aminotransferases. Marginal intake of other nutrients may have affected the utilization of both thiamin and vitamin B6.

Adult↗

Amino acid analysis by high-performance liquid chromatography with methanesulfonic acid hydrolysis and 9-fluorenylmethylchloroformate derivatization.

Experiments were undertaken to verify a method for complete amino acid analysis of plant and animal tissues and waste products from a single hydrolysis and high-performance liquid chromatographic run. Using methanesulfonic acid, hydrolysis of cytochrome c at 115 degrees C for 22 h yielded recoveries equal to or higher than hydrolysis at 115 degrees C for 70 h or at 150 degrees C for 22 h. Triple evacuation of the hydrolysis tube alternated with nitrogen flush gave recovery improvements over single evacuation. Refrigerated storage of samples under vacuum for up to 4 days between hydrolysis and further analysis was not different from immediate analysis. However, recoveries of several amino acids were reduced by refrigerated storage in air. Recoveries of individual amino acids were determined by hydrolysis of biological samples with and without added cytochrome c. Although recoveries from biological samples were lower for several amino acids, precision was sufficient to allow quantitation after correction for incomplete recoveries. Derivatization with 9-fluorenylmethylchloroformate (FMOC) was chosen because derivatives are formed with both primary and secondary amino acids, derivatives are quite stable, and detection may be either UV absorbance or fluorescence. Derivative yield is sensitive to the pH of the reaction mixture. A pH of 8.0 gave reproducible derivative yield for all physiological amino acids. Solvent extraction of excess FMOC, when compared to addition of amantadine to react with excess FMOC, gave both higher recoveries and greater precision. Following derivatization, samples could be kept at 4 degrees C for at least 24 h before high-performance liquid chromatographic analysis without loss of response. Derivative yield and detector response were constant across a wide range of molar ratio of FMOC to total amino acids. Gradient elution was required to separate FMOC derivatives on a reversed-phase column. The capability of the pumping system to produce exponential gradients permitted rapid and easy fine-tuning of the gradient.

Amino Acids↗

Riboflavin intakes and status of morbidly obese females during the first postoperative year following gastroplasty.

Eighteen women participated in a prospective study to assess the need for supplemental riboflavin after gastroplasty. Three groups of five patients received either a placebo or 0.6 or 1.2 mg riboflavin daily for up to 12 months, except during months 4 and 7 when all participants were given a "one-a-day" supplement containing 1.7 mg riboflavin. Dietary intakes of riboflavin decreased from 1.43 +/- 0.17 mg before the operation to 0.70 +/- 0.07 mg at 3 months, and then increased to 1.02 +/- 0.17 mg by 6 months. Even at 12 months, only 33% of the subjects had dietary intakes greater than or equal to 1.2 mg. All those with total intakes less than or equal to 1.7 mg at 3 months had impaired riboflavin status, as indicated by an erythrocyte gluthatione reductase activity coefficient greater than 1.40 and an erythrocyte riboflavin concentration less than 372 nmol/L. In contrast, 62% of the same subjects had urinary riboflavin excretion in the acceptable range. Supplemental intake of 1.7 mg riboflavin appeared to prevent tissue depletion in all subjects.

Adult↗

Stereospecificity of SP1 and SP2 substance P receptors.

Previous studies with N-terminal fragments of substance P (SP) have suggested the existence of two separate SP receptor populations. SP1 receptors are found in guinea pig ilea and rat colons. SP2 receptors are found in mouse spinal cords and rat salivary glands. We have now found that substitution of Gly9 in substance P's C-terminal hexapeptide leads to an analog (L-Pro9 SP6-11) which selectively and potently stimulates SP2 receptors. In contrast, substitution of the same residue with D-Proline results in a potent and selective agonist for SP1 receptors. The data dramatically confirm the distinction between SP1 and SP2 receptors and demonstrate that the two receptors have distinct stereochemical architectures.

Animals↗

Use of substance P fragments to differentiate substance P receptors of different tissues.

The C- and N-terminal fragments of substance P were compared to the parent molecule with respect to their ability to: (a) contract the isolated guinea pig ileum, (b) induce salivation in the rat, (c) excite single cat dorsal horn neurones, and (d) induce scratching by intracranial injections in mice. C-terminal fragments as small as the heptapeptide were potent SP agonists on all assay systems. C-terminal fragments containing five amino acids or less were, at most, only weakly active. The C-terminal hexapeptide was a potent SP receptor stimulant on the isolated guinea pig ileum and, when directly applied by microiontophoresis, on cat dorsal horn neurons. However, the same compound was only 2-5% as potent as substance P in eliciting salivation and scratching in vivo, an indication that this fragment may be especially labile to enzymatic degradation. N-terminal fragments were totally inactive on the isolated guinea pig ileum. On the rat salivation and central nervous system assays, however, N-terminal fragments were capable of weak SP-like activity. It is concluded that SP receptors exist in multiple forms which we have labelled SP1 and SP2 receptors for those insensitive or sensitive to N-terminal fragments, respectively.

Animals↗

Sensory and motor functions of spinal cord substance P.

Low doses of D-Pro2-D-Phe7-D-Trp9-substance P, as specific substance P antagonist, depressed the scratching and biting behaviors elicited by intrathecal injections of substance P, and cutaneous application of algesic substances. Higher antagonist doses caused hindlimb paralysis. This suggests that substance P is a neurotransmitter for primary nociceptor afferents and may also have an important function in motor control.

Animals↗

Spinal and Supraspinal sites for morphine and nefopam analgesia in the mouse.

Using the tail-flick and hot-plate assays, morphine and nefopam were tested for analgesic activity following intraperitoneal (i.p.), intracranial (i.c.) and intraspinal (i.s.) injection in mice. By the i.p. route, morphine was equipotent on both analgesic tests. Nefopam was one-third as potent as morphine on the hot-plate test, but did not affect the tail-flick. Intracranial morphine was more effective on the hot-plate than on the tail-flick, but i.s. morphine was most potent on the tail-flick. Naloxone, 0.5 mg/kg i.p., totally reversed morphine's effects on the tail-flick, but only partially reversed these actions on the hot-plate, suggesting the possibility that morphine's effects on the mouse hot-plate test may be mediated via multiple receptor types. Nefopam was more potent by the i.c. route than by the i.p. route, but its was inactive spinally. Nefopam analgesia was unaffected by naloxone treatment. It is concluded that nefopam is a novel, centrally acting, non-narcotic analgesic.

Analgesia↗

Morphine does not antagonize the substance P mediated excitation of dorsal horn neurons.

Multibarrelled microelectrodes were used to test the effects of iontophoretically released substance P (SP), morphine, glutamate, and naloxone on spinal cord dorsal horn neurons. Cells excited by SP were also excited by noxious stimuli, a finding consistent with the hypothesis that SP is the neurotransmitter released by primary nociceptor afferents to excite dorsal horn neurons. Iontophoretic morphine failed to depress the SP-induced discharges. Indeed, iontophoretic morphine frequently potentiated the SP responses. In addition to potentiating SP-induced discharges, iontophoretic morphine frequently increased both the spontaneous activity of dorsal horn neurons and the activity evoked in these cells by noxious cutaneous heat and iontophoretic glutamate. Naloxone did not antagonize these excitatory effects. Intravenous morphine only depressed spontaneous discharges. Nevertheless, iontophoretic morphine still produced excitatory effects in spinal animals pretreated with analgesic doses of intravenous morphine. It is concluded that such excitatory effects are toxic actions indicative of supratherapeutic morphine concentrations in the vicinity of the neuron being studied. Intravenously administered morphine depressed the spontaneous activity of dorsal horn neurons of spinal cats, but failed to depress their responses to SP. Morphine also failed to antagonize SP's biological effects in peripheral systems (contraction of isolated guinea pig ileum, rabbit hypotensive effect, rat sialogogic response). It is concluded that morphine is not a substance P receptor antagonist. The results are discussed with respect to the hypotheses that (1) the spinal analgesic effects of systemically administered morphine occur on presynaptic terminals of sensory neurons, and (2) an SP antagonist might be a unique analgesic agent.

Animals↗

Cadmium and nickel influence on blood pressure, plasma renin, and tissue mineral concentrations.

Weanling rats were fed a casein-based diet containing either 150 ppm cadmium, 500 ppm nickel, or the combination of these metals for 16 wk. Blood pressure of rats fed the diet with cadmium decreased after 8 wk, but this effect was counteracted by dietary nickel. Cadmium caused a depletion of iron and resulted in an accumulation of zinc in liver and kidney of rats. Nickel partially counteracted the iron loss due to cadmium. In a second experiment, the inclusion of 10 or 20 ppm cadmium in drinking water for 24 mo did not result in elevated blood pressure in normal or genetically hypertensive rats. Cadmium had no effect on the plasma renin levels in either experiment. Low intake of cadmium (10 or 20 ppm) in drinking water resulted in elevated cadmium content in hair. Thus, our data do not indicate that high levels of cadmium contribute to hypertension.

Animals↗

A quantitative analgesic assay in the rabbit based on the response to tooth pulp stimulation.

A DC ramp voltage was used to stimulate rabbit tooth pulps. Thresholds to elicit chewing movements were extremely stable in the absence of drug treatment. Using cumulative dosing of analgesic drugs, potency and efficacy measurements could be readily obtained. Narcotic analgesics were the most effective analgesics on this test, followed by two centrally acting non-narcotics (nefopam and baclofen). Antipyretic/anti-inflammatory analgesics and centrally acting non-analgesic drugs elevated thresholds by lesser amounts or were inactive. It is concluded that the rabbit tooth pulp assay is suitable for the qualitative and quantitative determination of analgesic activity.

Analgesics↗