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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 163 records · Page 9Linked to original sources
PubMed1998

Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome.

The hypothesis that psychosis arises as a part of the genetic diversity associated with the evolution of language generates the prediction that illness will be linked to a gene determining cerebral asymmetry, which, from the evidence of sex chromosome aneuploidies, is present in homologous form on the X and Y chromosomes. We investigated evidence of linkage to markers on the X chromosome in 1) 178 families multiply affected with schizophrenia or schizoaffective disorder with a series of 16 markers spanning the centromere (study 1), and 2) 180 pairs of left-handed brothers with 14 markers spanning the whole chromosome (study 2). In study 1, excess allele-sharing was observed in brother-brother pairs (but not brother-sister or a small sample of sister-sister pairs) over a region of approximately 20 cM, with a maximum LOD score of 1.5 at DXS991. In study 2, an association between allele-sharing and degree of left-handedness was observed extending over approximately 60 cM, with a maximum lod score of 2.8 at DXS990 (approximately 20 cM from DXS991). Within the overlap of allele-sharing is located a block in Xq21 that transposed to the Y chromosome in recent hominid evolution and is now represented as two segments on Yp. In one of two XX males with psychosis we found that the breakpoint on the Y is located within the distal region of homology to the block in Xq21. These findings are consistent with the hypothesis that an X-Y homologous determinant of cerebral asymmetry carries the variation that contributes to the predisposition to psychotic illness.

Female↗
PubMed1998

The role of corticotropin-releasing factor and corticosterone in stress- and cocaine-induced relapse to cocaine seeking in rats.

We have shown previously that footshock stress and priming injections of cocaine reinstate cocaine seeking in rats after prolonged drug-free periods (Erb et al., 1996). Here we examined the role of brain corticotropin-releasing factor (CRF) and the adrenal hormone corticosterone in stress- and cocaine-induced reinstatement of cocaine seeking in rats. The ability of footshock stress and priming injections of cocaine to induce relapse to cocaine seeking was studied after intracerebroventricular infusions of the CRF receptor antagonist D-Phe CRF12-41, after adrenalectomy, and after adrenalectomy with corticosterone replacement. Rats were allowed to self-administer cocaine (1.0 mg/kg/infusion, i.v) for 3 hr daily for 10-14 d and were then placed on an extinction schedule during which saline was substituted for cocaine. Tests for reinstatement were given after intermittent footshock (10 min; 0.5 mA) and after priming injections of saline and cocaine (20 mg/kg, i.p.). Footshock reinstated cocaine seeking in both intact animals and animals with corticosterone replacement but not in adrenalectomized animals. The CRF receptor antagonist D-Phe CRF12-41 blocked footshock-induced reinstatement at all doses tested in both intact animals and animals with corticosterone replacement. Reinstatement by priming injections of cocaine was only minimally attenuated by adrenalectomy and by pretreatment with D-Phe CRF12-41. These data suggest that brain CRF plays a critical role in stress-induced, but only a modulatory role in cocaine-induced, reinstatement of cocaine seeking. Furthermore, the data show that although reinstatement of cocaine seeking by footshock stress requires minimal, basal, levels of corticosterone, stress-induced increases in corticosterone do not play a role in this effect.

Adrenal Glands↗
PubMed1998

Method of purification affects some interfacial properties of pulmonary surfactant proteins B and C and their mixtures with dipalmitoylphosphatidylcholine.

Two methods were employed for preparation of lipid extracts from porcine lung surfactant. Pulmonary surfactant proteins SP-B and SP-C were isolated from the extracts using gel-exclusion chromatography on LH-60 with chloroform:methanol acidified with hydrochloric acid. Monolayers of pure SP-B or SP-C isolated from butanol lipid extracts spread at the air-water interface showed larger molecular areas than those determined in films of SP-B or SP-C isolated from chloroform surfactant extracts. Aqueous dispersions of dipalmitoylphosphatidylcholine (DPPC) supplemented with 2.5 and 5.0 wt% of SP-B or SP-C obtained from butanol extracts adsorbed faster to the air-water interface than their counterparts reconstituted with proteins isolated from chloroform extracts. Surface pressure-area characteristics of spread monolayers of DPPC plus SP-B or SP-C did not depend on the method of isolation of the proteins. The diagrams of the mean molecular areas vs. composition for the monolayers of DPPC plus SP-B or SP-C showed positive deviations from the additivity rule, independently of the procedure used for preparation of lipid extract surfactant. Matrix-assisted laser desorption/ionization spectrometry of the proteins isolated from different extraction solvents was consistent with some differences in the chemical compositions of SP-Bs. Butylation of SP-B during extraction of surfactant pellet with butanol may account for the differences observed in the molecular masses of SP-Bs isolated by the two different extraction protocols. The study suggests that the method of purification of SP-B and SP-C may modify their ability to enhance the adsorption rates of DPPC/protein mixtures, and this may be relevant to the formulation of protein-supplemented lipids for exogenous treatment of pulmonary surfactant insufficiency.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

A quantitative assay for assessing allelic proportions by iterative gap ligation.

A variety of techniques are currently available for detecting point mutations in DNA. These techniques are frequently not sensitive enough to be applied as quantitative assays in evaluation of relative occurrence of alleles in cases of polymorphism or when variations in allelic gene expression are being evaluated at the level of RNA. We report here the establishment of an iterative gap ligation (IGL) assay that is both quantitative and sensitive. The design of the assay is such that ligation of an upstream to a downstream primer across a single nucleotide gap will only occur if the gap is filled with a deoxynucleotide complementary to the wild-type or mutant sequence. Under conditions in which excess upstream primer saturates the template concurrently with limiting amounts of downstream primer quantitative ligation is absolutely dependent on provision of the appropriate gap filling nucleotide. When gap ligation occurs in a single incubation, or cycle, the amount of ligated product is a linear function of the relative amount of mutant sequence, with a sensitivity and detection limit of approximately 3% over a range of relative concentrations of 0-100%. When the reaction occurs over multiple cycles, or iterations, gap ligation becomes a non-linear function such that small changes in the relative proportions of alleles produce a disproportionately large amount of ligation. As a consequence, the sensitivity and limits of detection of the assay improve to 0.2% after only 8 cycles. The development of this assay provides a unique means of quantifying allelic polymorphisms in both DNA and RNA (after initial amplification by PCR or RT-PCR) and should be applicable to any experimental settings in which nucleic acids from tissues or mixed populations of cells are being evaluated.

Alleles↗
PubMed1998

Mutations of the p53 gene in canine lymphoma and evidence for germ line p53 mutations in the dog.

Mutations of the p53 gene are associated with a number of non-lymphoid cancers of the dog. The present study investigates the p53 gene status within canine patients treated for primary and secondary lymphoma. Three out of eight patients exhibited p53 gene mutations. These included one patient with a germ line mutation and two patients with de novo p53 mutations associated with the secondary lymphoma. Allelic loss of the p53 gene was also observed within primary and secondary tumours of the three canine patients. The results indicate that germ line p53 mutations exist in dogs and may be involved in the known predisposition of some breeds to cancer. The presence of therapy-related p53 point mutations was found to be associated with chemoresistant secondary lymphomas. A causative role for DNA-damaging chemotherapy in de novo mutation of the p53 gene is discussed. Characterization of p53 inactivation in canine tumorigenesis may provide a valuable clinical model for assessing the efficacy and optimal therapeutic regimens of anti-cancer agents.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Introduction of the Multilink stent into routine angioplasty practice: early angiographic and clinical outcome.

To assess the early outcome of implantation of the Multilink stent in everyday angioplasty practice, we prospectively collected procedural and 1-mo follow-up data on the first 126 patients (93 male, mean age 61+/-9 yr) in 3 centers. One hundred and seventy-four stents were implanted for 134 lesions: left anterior descending artery in 46%, circumflex in 20%, right coronary artery in 31%, and protected left main in 3%. The indication was elective in 56%, a suboptimal result in 43%, and bailout in 1%. Stents were deployed at 10.8+/-1.9 atmospheres and postdilated to 15.7+/-2.4 atmospheres. There were 115 patients who received ticlopidine and aspirin, 10 received aspirin alone, and 1 received warfarin and aspirin following the procedure. The reference diameter increased from 3.02+/-0.44 mm pre- to 3.13+/-0.43 mm postprocedure, with the minimal luminal diameter increasing from 0.82+/-0.47 to 2.86+/-0.45 mm (diameter stenosis 73% pre- and 9% postprocedure). The procedural success rate was 93.7%. There were no deaths, 1 (0.8%) Q- and 5 (4.0%) non-Q-wave myocardial infarctions, 3 (2.4%) emergency bypass operations, and 1 (0.8%) repeat angioplasty during the hospital admission (median stay, 1 day). There were 2 (1.6%) cases of subacute stent thrombosis. At 1-mo follow-up there were no additional events, with 88% of patients remaining free of angina. Implantation of the Multilink stent is safe and effective in everyday angioplasty practice, with a complication rate comparable to those of published trials of carefully selected patients.

Adult↗
PubMed1998

Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome.

Recent investigations suggest a role for neurally mediated hypotension (NMH) in the symptomatology of chronic fatigue syndrome (CFS) in adults. Our previous observations in children with NMH and syncope (S) unrelated to CFS indicate that the modulation of sympathetic and parasympathetic tone measured by indices of heart rate variability (HRV) is abnormal in children who faint during head-up tilt (HUT). In order to determine the effects of autonomic tone on HUT in children with CFS we performed measurements of HRV during HUT in 16 patients aged 11-19 with CFS. Data were compared to 26 patients evaluated for syncope and with 13 normal control subjects. After 30 minutes supine, patients were tilted to 80 degrees for 40 minutes or until syncope occurred. Time domain indices included RR interval, SDNN, RMSSD, and pNN50. An autoregressive model was used to calculate power spectra. LFP (.04-.15 Hz), HFP (.15-.40Hz), and TP (.01-.40Hz). Data were obtained supine (baseline) and after HUT. Thirteen CFS patients fainted (CFS+, 5/13 pure vasodepressor syncope) and three patients did not (CFS-). Sixteen syncope patients fainted (S+, all mixed vasodepressor-cardioinhibitory) and 10 did not (S-). Four control patients fainted (Control+, all mixed vasodepressor-cardioinhibitory) and nine did not (Control-). Baseline indices of HRV were not different between Control+ and S+, and between Control- and S-, but were depressed in S+ compared to S-. HRV indices were strikingly decreased in CFS patients compared to all other groups. With tilt, SDNN, RMSSD, and pNN50 and spectral indices decreased in all groups, remaining much depressed in CFS compared to S or control subjects. With HUT, sympathovagal indices (LFP/HFP, nLFP, and nHFP) were relatively unchanged in CFS, which contrasts with the increase in nLFP with HUT in all other groups. With syncope RMSSD, SDNN, LFP, TP, and HFP increased in S+ (and Control+), suggesting enhanced vagal heart rate regulation. These increases were not observed in CFS+ patients. CFS is associated with NMH during HUT in children. All indices of HRV are markedly depressed in CFS patients, even when compared with already low HRV in S+ or Control+ patients. Sympathovagal balance does not shift toward enhanced sympathetic modulation of heart rate with HUT and there is blunting in the overall HRV response with syncope during HUT. Taken together these data may indicate autonomic impairment in patients with CFS.

Adolescent↗
PubMed1998

CP-154,526, a selective, non-peptide antagonist of the corticotropin-releasing factor1 receptor attenuates stress-induced relapse to drug seeking in cocaine- and heroin-trained rats.

We have found that peptide antagonists of corticotropin-releasing factor (CRF) receptors attenuate reinstatement of heroin and cocaine seeking induced by footshock. Here we examined the effect of a nonpeptide, selective CRF1 receptor antagonist, CP-154,526, on reinstatement of heroin and cocaine seeking induced by footshock. Rats were trained to self-administer heroin or cocaine (0.1 and 1.0 mg/kg per infusion, i.v., respectively) for 9-12 days. Extinction sessions were given for up to 14 days, during which saline was substituted for the drugs. Tests for reinstatement were then conducted after exposure to intermittent footshock (10 or 15 min, 0.5 mA). The footshock stressor reliably reinstated extinguished cocaine- and heroin-taking behavior. Pretreatment with CP-154,526 (15 and 30 mg/kg, s.c.) significantly attenuated the reinstatement effect of the stressor in both heroin- and cocaine-trained rats. CP-154,526, administered in the absence of the footshock stressor, did not affect extinguished drug seeking. In addition, in a separate experiment, CP-154,526 was shown not to alter high rates of lever pressing for a 10% sucrose solution, suggesting that the suppression of lever pressing in stress-induced reinstatement is not caused by a performance deficit. These results extend previous reports on the role of CRF in reinstatement of drug seeking induced by stressors. The present data also suggest that, to the extent that exposure to environmental stressors provoke relapse to drug use in humans, systemically effective CRF receptor antagonists may be of use in the treatment of relapse to drug use.

Animals↗
PubMed1998

Acamprosate suppresses the expression of morphine-induced sensitization in rats but does not affect heroin self-administration or relapse induced by heroin or stress.

Acamprosate (calcium-acetyl homotaurinate) is a new compound used in the treatment of alcohol abuse. Because of the putative link between alcoholism and the endogenous opioid systems in both humans and laboratory animals, we tested in rats the effects of acamprosate on behavioral and neurochemical effects of opioid drugs related to their abuse potential. These included sensitization to the behavioral effects of morphine, morphine-induced dopamine (DA) release in the nucleus accumbens (NAS), intravenous (i.v.) heroin self-administration and relapse to heroin seeking in drug-free rats. In experiment 1, rats were injected daily with either morphine (10 mg/kg, s.c.) or saline for 14 days. Three days later in a test for the expression of sensitization, an injection of morphine (10 mg/kg) resulted in increased locomotor activity and enhanced DA release in the NAS in rats previously exposed to morphine. Acamprosate (two injections of 200 mg/kg, 12 h apart; i.p.) suppressed the expression of the sensitized responses, but did not alter the effects of morphine in drug-naive control rats. In experiment 2, it was found that acamprosate (two injections of 50-200 mg/ kg; i.p.) had no consistent effects on i.v. heroin self-administration (50 100 microg/kg per infusion) and, in experiment 3, that acamprosate (100-200 mg/ kg, i.p.) did not alter reinstatement of drug seeking induced by priming injections of heroin (0.25 mg/kg, s.c.) or a footshock stressor (15 min; 0.5 mA) after a 5- to 8-day period of extinction. Thus, although acamprosate attenuated the expression of sensitized locomotor activity and DA release in the NAS, it did not have any consistent effect on either the intake of heroin during the maintenance phase or the relapse to heroin seeking in a drug-free state. Thus, to the extent that the self-administration and the reinstatement procedures provide valid preclinical models for drug use and relapse in humans, our data suggest that acamprosate may not be effective in altering drug-taking behavior in heroin users.

Acamprosate↗
PubMed1998

Phase transitions in films of lung surfactant at the air-water interface.

Pulmonary surfactant maintains a putative surface-active film at the air-alveolar fluid interface and prevents lung collapse at low volumes. Porcine lung surfactant extracts (LSE) were studied in spread and adsorbed films at 23 +/- 1 degrees C using epifluorescence microscopy combined with surface balance techniques. By incorporating small amounts of fluorescent probe 1-palmitoyl-2-nitrobenzoxadiazole dodecanoyl phosphatidylcholine (NBD-PC) in LSE films the expanded (fluid) to condensed (gel-like) phase transition was studied under different compression rates and ionic conditions. Films spread from solvent and adsorbed from vesicles both showed condensed (probe-excluding) domains dispersed in a background of expanded (probe-including) phase, and the appearance of the films was similar at similar surface pressure. In quasistatically compressed LSE films the appearance of condensed domains occurred at a surface pressure (pi) of 13 mN/m. Such domains increased in size and amounts as pi was increased to 35 mN/m, and their amounts appeared to decrease to 4% upon further compression to 45 mN/m. Above pi of 45 mN/m the LSE films had the appearance of filamentous materials of finely divided dark and light regions, and such features persisted up to a pi near 68 mN/m. Some of the condensed domains had typical kidney bean shapes, and their distribution was similar to those seen previously in films of dipalmitoylphosphatidylcholine (DPPC), the major component of surfactant. Rapid cyclic compression and expansion of LSE films resulted in features that indicated a possible small (5%) loss of fluid components from such films or an increase in condensation efficiency over 10 cycles. Calcium (5 mM) in the subphase of LSE films altered the domain distribution, decreasing the size and increasing the number and total amount of condensed phase domains. Calcium also caused an increase in the value of pi at which the maximum amount of independent condensed phase domains were observed to 45 mN/m. It also induced formation of large amounts of novel, nearly circular domains containing probe above pi of 50 mN/m, these domains being different in appearance than any seen at lower pressures with calcium or higher pressures in the absence of calcium. Surfactant protein-A (SP-A) adsorbed from the subphase onto solvent-spread LSE films, and aggregated condensed domains in presence of calcium. This study indicates that spread or adsorbed lung surfactant films can undergo expanded to condensed, and possibly other, phase transitions at the air-water interface as lateral packing density increases. These phase transitions are affected by divalent cations and SP-A in the subphase, and possibly by loss of material from the surface upon cyclic compression and expansion.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1998

Induction of Fos expression in the circadian system by unsignaled light is attenuated as a result of previous experience with signaled light: a role for Pavlovian conditioning.

A circadian clock responsive to light is located in the hypothalamic suprachiasmatic nucleus. In rodents, light induces the expression of the transcription factor Fos in cells of the suprachiasmatic nucleus and this effect is associated with light-induced resetting of the circadian clock. Until recently, it was thought that the induction of Fos in the suprachiasmatic nucleus was mediated by a mechanism uniquely sensitive to photic cues. We have shown, however, using Pavlovian conditioning procedures, that a nonphotic stimulus that has been repeatedly paired with light can, in the absence of light, induce Fos expression in the suprachiasmatic nucleus. In the present study we asked whether, as a result of conditioning, the ability of light alone to induce Fos expression in the suprachiasmatic nucleus might be altered. We suspected that once the mechanism mediating Fos expression in the suprachiasmatic nucleus had become tuned to receiving light signaled by a conditioned stimulus, the response to presentation of light alone would be diminished. To study this possibility we investigated whether induction of Fos expression in the suprachiasmatic nucleus by unsignaled light would be altered as a result of previous experience with signaled light. Consistent with our hypothesis, we found that a series of conditioning trials not only confers upon a nonphotic stimulus the ability to activate the mechanism mediating Fos expression in the suprachiasmatic nucleus, but also reduces the efficacy of light itself to activate this mechanism.

Circadian Rhythm↗
PubMed1998

A role for serotonin in the circadian system revealed by the distribution of serotonin transporter and light-induced Fos immunoreactivity in the suprachiasmatic nucleus and intergeniculate leaflet.

Components of the circadian system, the suprachiasmatic nucleus and the intergeniculate leaflet receive serotonin input from the raphe nuclei. Manipulations of serotonin neurotransmission disrupt cellular, electrophysiological, and behavioural responses of the circadian system to light, suggesting that serotonin plays a modulatory role in photic regulation of circadian rhythms. To study the relation between serotonin afferents and light-activated cells in the suprachiasmatic nucleus and intergeniculate leaflet, we used immunostaining for the serotonin transporter and for the transcription factor, Fos. Serotonin transporter, a plasma membrane protein located on serotonin neurons, regulates the amount of serotonin available for neurotransmission by re-accumulating released serotonin into presynaptic neurons; expression of Fos in the suprachiasmatic nucleus identifies light-activated cells involved in photic resetting of circadian clock phase. In the suprachiasmatic nucleus, immunostaining for serotonin transporter revealed a dense plexus of fibres concentrated primarily in the ventrolateral region. In the intergeniculate leaflet, serotonin transporter immunostaining identified vertically-oriented columns of fibres. Serotonin transporter immunostaining was abolished by pretreatment with the serotonin neurotoxin, 5,7-dihydroxytryptamine. Exposure to light for 30 min during the dark phase of the light cycle induced Fos expression in the ventrolateral suprachiasmatic nucleus and intergeniculate leaflet regions. In both structures the Fos-expressing cells were encircled by serotonin transporter-immunoreactive fibres often in close apposition to these cells. These results support the idea that serotonin activity plays a modulatory role in processing of photic information within the circadian system.

Animals↗
PubMed1998

Conditioned fear suppresses light-induced resetting of the circadian clock.

The possibility that circadian rhythms can be modulated by emotional state is suggested by clinical evidence of altered physiological and endocrine rhythms in primary depression and related affective disorders and is supported by experiments in humans and laboratory animals showing that stress disrupts circadian rhythmicity. How emotional state might modulate circadian rhythms is not known. Here we report that induction of the emotional state of fear disrupts a process essential for stable entrainment of circadian rhythms, the resetting of the circadian clock by environmental light. A cellular correlate of light-induced clock resetting, expression of the transcription factor Fos in the suprachiasmatic nucleus of the hypothalamus (the circadian clock), and a behavioral measure of clock resetting, phase shifts in free-running activity rhythms, were found to be suppressed in rats exposed to light in a context made to induce fear by previous pairings with intermittent footshock. These findings show that fear disrupts a physiological process mediating light-induced clock resetting and suggest a mechanism through which emotional state could modulate circadian rhythms.

Animals↗
PubMed1998

Antimicrobial properties of plant essential oils and essences against five important food-borne pathogens.

The antimicrobial properties of 21 plant essential oils and two essences were investigated against five important food-borne pathogens, Campylobacter jejuni, Salmonella enteritidis, Escherichia coli, Staphylococcus aureus and Listeria monocytogenes. The oils of bay, cinnamon, clove and thyme were the most inhibitory, each having a bacteriostatic concentration of 0.075% or less against all five pathogens. In general, Gram-positive bacteria were more sensitive to inhibition by plant essential oils than the Gram-negative bacteria. Campylobacter jejuni was the most resistant of the bacteria investigated to plant essential oils, with only the oils of bay and thyme having a bacteriocidal concentration of less than 1%. At 35 degrees C, L. monocytogenes was extremely sensitive to the oil of nutmeg. A concentration of less than 0.01% was bacteriostatic and 0.05% was bacteriocidal, but when the temperature was reduced to 4 degrees, the bacteriostatic concentration was increased to 0.5% and the bacteriocidal concentration to greater than 1%.

Bacteria↗
PubMed1998

Comparison of the merits of measuring equine chorionic gonadotrophin (eCG) and blood and faecal concentrations of oestrone sulphate for determining the pregnancy status of miniature horses.

The relative merits of measuring blood concentrations of equine chorionic gonadotrophin (eCG, previously known as pregnant mare serum gonadotrophin (PMSG)), or oestrone sulphate (OS), or faecal OS concentrations for determining pregnancy status in miniature horses were investigated. Pregnant mares between 40 and 140 days after mating had serum eCG concentrations > 1 I.U. mL-1, with the highest concentrations occurring between days 50 and 120. However, eCG measurements were susceptible to returning a 'false positive' diagnosis of pregnancy. Plasma OS concentrations ranged from 0.1 to 3.6 ng mL-1 in non-pregnant mares, whereas pregnant mares beyond 100 days post-mating all had plasma OS concentrations > 30 ng mL-1. Faecal OS concentrations ranged from 4 to 89 ng g-1 in non-pregnant mares. For faecal samples collected from pregnant mares 150 days or more after mating, 97% of samples had OS concentrations > 85 ng g-1, the value 3 standard deviations above the mean non-pregnant value. None had values below 67 ng g-1, the value 2 standard deviations above the mean non-pregnant value. These results show that measurement of eCG is suitable for determining pregnancy status in miniature mares between 40 and 100 days post-mating. However, mares returning a 'pregnant' diagnosis should undergo a blood OS test 100 or more days after mating to eliminate the possibility of a 'false positive' diagnosis. Measuring blood OS is recommended as the method of choice for determining pregnancy status in miniature mares 100 or more days after mating. Faecal OS measurements provide a non-invasive alternative to blood OS testing from 150 days post-mating. However, the discrimination between 'pregnant' and 'non-pregnant' levels of OS is not as great in faeces as it is in blood.

Animals↗
PubMed1998

Effect of diet on the urinary excretion of hippuric acid and other dietary-derived aromatics in rat. A complex interaction between diet, gut microflora and substrate specificity.

1. A combined in vivo and in vitro study has been devised to investigate an observation, obtained by 1H NMR of urine, that Alp:AprSD (Wistar derived) rats kept under standard husbandry conditions did not excrete urinary hippuric acid (HA). meta-(hydroxyphenyl)-propionic acid ¿m-HPPA¿ was identified as the major aromatic component in urine samples lacking HA. 2. Examination of urine from Alp:APrSD and Zücker (obese negative) rats fed various diets showed that the lack of HA/presence of m-HPPA was due to diet and not to the strain of animal. This observation was reinforced by the demonstration that the administration of benzoic acid (BA) to rats not previously excreting urinary HA resulted in the return of this component to the urinary excretion profile. Thus rats receiving the standard diet were still capable of glycine conjugation. 3. Changing the diet of rats excreting m-HPPA led to the cessation of m-HPPA excretion and the return of HA urine excretion. Interestingly, switching back to the original diet did not cause the loss of HA and the re-emergence of m-HPPA. 4. In vitro studies on the two enzyme systems responsible for glycine conjugation (benzoyl CoA:synthetase and benzoyl CoA:glycine N-acyltransferase) in isolated liver mitochondria showed that m-HPPA did not inhibit either enzyme. However, m-HPPA was not found to be a substrate for the first reaction step explaining why it was found in the urine as the free acid and not as a glycine conjugate. 5. The absence and presence of m-HPPA and hippuric acid is suggested to be due to a combination of differences in dietary precursors of substrates for glycine conjugation and a dietary dependent redistribution of the intestinal microflora responsible for breakdown of plant phenolics and aromatic amino acids. Taken collectively this study emphasises how a simple diet change can cause a profound change in metabolism.

Acyltransferases↗
PubMed1998

An algorithm to optimize perioperative blood management in surgery.

Innovation in surgical blood management has been fueled by patients' perceptions of the risks associated with allogeneic blood transfusions and by surgeons' attitudes toward the use of allogeneic blood. The challenge is to determine the best blood management strategy to implement in the individual patient, particularly in patients with anemia who are at high risk of allogeneic blood transfusion. An algorithm to estimate safe blood loss based on individual patient parameters has been developed. The algorithm uses patient weight, gender, and preoperative hematocrit level to derive the volume of blood loss that can be tolerated while maintaining a target postoperative hematocrit level. Because the margin of safe blood loss can be anticipated, the most appropriate blood conservation option(s) can be implemented and perioperative blood management can be optimized.

Algorithms↗