Resonant Doppler effect in systems with variable delay.

We demonstrate that a time-varying delay in nonlinear systems leads to a rich variety of dynamical behaviour, which cannot be observed in systems with constant delay. We show that the effect of the delay variation is similar to the Doppler effect with self-feedback. We distinguish between the non-resonant and the resonant Doppler effect corresponding to the dichotomy between conservative delays and dissipative delays. The non-resonant Doppler effect leads to a quasi-periodic frequency modulation of the signal, but the qualitative properties of the solution are the same as for constant delays. By contrast, the resonant Doppler effect leads to fundamentally different solutions characterized by low- and high-frequency phases with a clear separation between them. This is equivalent to time-multiplexed dynamics and can be used to design systems with well-defined multistable solutions or temporal switching between different chaotic and periodic dynamics. We systematically study chaotic dynamics in systems with large dissipative delay, which we call generalized laminar chaos. We derive a criterion for the occurrence of different orders of generalized laminar chaos, where the order is related to the dimension of the chaotic attractor. The recently found laminar chaos with constant plateaus in the low-frequency phases is the zeroth-order case with a very low dimension compared to the known high dimension of turbulent chaos in systems with conservative delay. This article is part of the theme issue 'Nonlinear dynamics of delay systems'.

Faculty professional development in emergent pedagogies for instructional innovation in dental education.

Innovative pedagogies have significantly impacted health professions' education, dental education included. In this context, faculty, defined in this study as instructor in higher education, has been increasingly required to hone their instructional skills. The purpose of this exploratory study was to share the design, implementation and preliminary outcomes of two programmes to enhance dental faculty's instructional skills, the Teaching and Learning Seminar Series and the Course Director Orientation. Data sources included faculty and student surveys developed and administered by the researchers; data extracted from the learning management system; reports from the learning analytics tool; and classroom observations. Participants' satisfaction, self-reported learning, instructional behavioural change, and impact on student learning behaviours and institutional practice were assessed borrowing from Kirkpatrick's 4-level model of evaluation of professional development effectiveness. Initial findings showed that faculty in both programmes reported positive learning experiences. Participants reported that the programmes motivated them to improve instructional practice and improved their knowledge of instructional innovation. Some faculty reported implementation of new instructional strategies and tools, which helped create an active and interactive learning environment that was welcomed by their students. The study contributes to literature and best practice in health sciences faculty development in pedagogy and may guide other dental schools in designing professional development programmes.

Discovery of τ Neutrino Appearance in the CNGS Neutrino Beam with the OPERA Experiment.

The OPERA experiment was designed to search for ν_{µ}→ν_{τ} oscillations in appearance mode, i.e., by detecting the τ leptons produced in charged current ν_{τ} interactions. The experiment took data from 2008 to 2012 in the CERN Neutrinos to Gran Sasso beam. The observation of the ν_{µ}→ν_{τ} appearance, achieved with four candidate events in a subsample of the data, was previously reported. In this Letter, a fifth ν_{τ} candidate event, found in an enlarged data sample, is described. Together with a further reduction of the expected background, the candidate events detected so far allow us to assess the discovery of ν_{µ}→ν_{τ} oscillations in appearance mode with a significance larger than 5σ.

Molecular characterization of cat factor XII gene and identification of a mutation causing factor XII deficiency in a domestic shorthair cat colony.

Coagulation factor XII (FXII) may be important in cardiovascular and inflammatory diseases. We have identified and characterized a naturally occurring mutation in the feline FXII gene that results in a mutant protein and enzymatic loss of activity. Feline intron/exon gene structure and sequence were acquired by comparing DNA sequences obtained from a fragmented Felis catus genomic sequence and the National Center for Biotechnology Information's Cross Species Megablast of multiple species' FXII gene sequences. Fourteen exons ranging in size from 57 to 222 base pairs were confirmed spanning 8 Kb on chromosome A1. The 1828-base pair feline FXII messenger RNA (mRNA) sequence contains an open reading frame that encodes a protein of 609 amino acids with high homology to human FXII protein. Total RNA and mRNA purified from liver tissue of 4 wild-type/normal and 8 FXII-deficient cats confirmed the predicted mRNA sequence and identified one important single-nucleotide polymorphism (SNP). A single base deletion in exon 11 of the FXII coding gene in our colony of cats results in deficient FXII activity. Translation of the mRNA transcript shows a frame shift at L441 (C441fsX119) resulting in a nonsense mutation and a premature stop codon with a predicted 560-amino acid protein. The mutant FXII protein is truncated in the 3' proteolytic light chain region of the C-terminus, explaining its loss of enzymatic activity. This study is the first molecular characterization of the feline FXII gene and the first identification of an FXII mutation in the domestic cat, providing insights into the origin and nature of feline FXII deficiency.

Pedi-R-MAPP: The development of a nutritional awareness tool for use in remote paediatric consultations using a modified Delphi consensus.

BACKGROUND & AIMS: The Remote Malnutrition Application (R-MAPP) was developed during the COVID-19 pandemic to provide support for health care professionals (HCPs) working in the community to complete remote nutritional assessments, and provide practical guidance for nutritional care. The aim of this study was to modify the R-MAPP into a version suitable for children, Pediatric Remote Malnutrition Application (Pedi-R-MAPP), and provide a structured approach to completing a nutrition focused assessment as part of a technology enabled care service (TECS) consultation. METHODS: A ten-step process was completed: 1) permission to modify adult R-MAPP, 2) literature search to inform the Pedi-R-MAPP content, 3) Pedi-R-MAPP draft, 4) international survey of HCP practice using TECS, 5) nutrition experts invited to participate in a modified Delphi process, 6) first stakeholder meeting to agree purpose/draft of the tool, 7) round-one online survey, 8) statements with consensus removed from survey, 9) round-two online survey for statements with no consensus and 10) second stakeholder meeting with finalisation of the Pedi-R-MAPP nutrition awareness tool. RESULTS: The international survey completed by 463 HCPs, 55% paediatricians, 38% dietitians, 7% nurses/others. When HCPs were asked to look back over the last 12 months, dietitians (n = 110) reported that 5.7 ± 10.6 out of every 10 appointments were completed in person; compared to paediatricians (n = 182) who reported 7.5 ± 7.0 out of every 10 appointments to be in person (p < 0.0001), with the remainder completed as TECS consultations. Overall, 74 articles were identified and used to develop the Pedi-R-MAPP which included colour-coded advice using a traffic light system; green, amber, red and purple. Eighteen participants agreed to participate in the Delphi consensus and completed both rounds of the modified Delphi survey. Agreement was reached at the first meeting on the purpose and draft sections of the proposed tool. In round-one of the online survey, 86% (n = 89/104) of statements reached consensus, whereas in round-two 12.5% (n = 13/104) of statements reached no consensus. At the second expert meeting, contested statements were discussed until agreement was reached and the Pedi-R-MAPP could be finalised. CONCLUSION: The Pedi-R-MAPP nutrition awareness tool was developed using a modified Delphi consensus. This tool aims to support the technological transformation fast-tracked by the COVID-19 pandemic by providing a structured approach to completing a remote nutrition focused assessment, as well as identifying the frequency of follow up along with those children who may require in-person assessment.

Pharmaceutical principles of acid inhibitors: unmet needs.

Despite the well-established benefits of currently approved delayed-release proton pump inhibitors (PPIs) in the treatment of acid-related diseases, the unmet needs are still present and although often frustrating, they challenge clinicians. The unmet needs relate to the lack of complete control of acid secretion with oral PPI administration in the management of patients with gastroesophageal symptoms. These substantial groups of patients, who do not respond completely to standard doses of PPIs, are nonresponders, and their lack of response should be considered as PPI failure. Several mechanisms could explain PPI failure: differences in pharmacokinetics, PPI formulation, dosing time and diet, noncompliance, transient lower esophageal sphincter relaxations, esophageal hypersensitivity, and nocturnal acid breakthrough. To increase the quality of life of these patients and avoid multiple medical consultations and unnecessary investigations, we have to go one step forward and use combined therapy or look towards new treatments beyond acid suppression.

Visual receptive fields of neurons in inferotemporal cortex of the monkey.

Neurons in inferotemporal cortex (area TE) of the monkey had visual receptive fields which were very large (greater than 10 by 10 degrees) and almost always included the fovea. Some extended well into both halves of the visual field, while others were confined to the ipsilateral or contralateral side. These neurons were differentially sensitive to several of the following dimensions of the stimulus: size and shape, color, orientation, and direction of movement.

Neuromodulation in a minipig MPTP model of Parkinson disease.

Large animal neuroscience enables the use of conventional clinical brain imagers and the direct use and testing of surgical procedures and equipment from the human clinic. The greater complexity of the large animal brain additionally enables a more direct translation to human brain function in health and disease. Economical, ethical, scientific and practical issues may on the other hand hamper large animal neuroscience. Large animal neuroscience should therefore either be performed in order to examine large animal species dependent problems or to complement promising small animal basic studies by constituting an intermediate research system, bridging small animal CNS research to the human CNS. We have, accordingly, during the last ten years used the Gottingen minipig to examine neuromodulatory treatment modalities such as stem cell transplantation and deep brain stimulation directed towards Parkinson disease. This has been accomplished by the development of a MPTP-based large animal model of Parkinson disease in the Gottingen minipig and the development of stereotaxic and surgical approaches needed to manipulate the Gottingen minipig CNS. The instituted changes in the CNS can be evaluated in the live animal by brain imaging (PET and MR), cystometry, gait analysis, neurological evaluation and by post mortem examination based on histology and stereological analysis.

Delayed and fractional use of enzymatic debridement with nexobrid for extensive burn injury: a case report.

Selective enzymatic debridement is increasingly being used in cases of burn wounds. However, until now the use of Nexobrid has been limited to 15% of total body surface area (TBSA) and immediate use on admission day. A 61-year-old Caucasian male suffered a severe burn injury that affected 95% TBSA. After surgical escharotomy and tracheotomy on admission day, we successfully performed a fractional enzymatic debridement of 54% of the TBSA in three different sessions within four days. This case report reveals that a delayed and fractional application of Nexobrid to more than 15% TBSA is possible.

Le débridement enzymatique sélectif des brûlures est de plus en plus utilisé. Cependant, cette technique était jusqu'ici limitée à 15% de la surface corporelle totale (SCT). Nous rapportons le cas d'un homme de 61 ans brûlé sur 95% SCT. Après une trachéotomie et des incisions de décharge le jour de son entrée, nous avons réalisé un débridement enzymatique sur 54% SCT sur 4 j en 3 séances. Cette observation montre que l'utilisation séquentielle de Nexobrid® permet de traiter plus de 15% SCT.

The role of catabolism in controlling tissue concentrations of nicotinamide nucleotide coenzymes.

A previous report from this laboratory (Bender, D.A., Magboul, B.I. and Wynick, D. (1982) Brit. J. Nutr. 48, 119-127) suggested that the hydrolysis of the nicotinamide nucleotides NAD and NADP may be an important factor in controlling the tissue content of these coenzymes. Further studies presented here support this suggestion. Both nuclear poly(ADPribose) synthetase and microsomal NAD glycohydrolase showed activity towards both NAD+ and NADP+, and the two nucleotides were mutually competitive. The reduced nucleotides, NADH and NADPH, were not substrates for either enzyme. In rats that were maintained for 24 h under conditions of hypoxia (O2/N2, 1:9) there was an increase in the proportion of nicotinamide nucleotides present in the liver in the reduced form, and an increase in the total concentration of nucleotides in the liver. In rats that were maintained for 24 h under conditions of hyperoxia (O2/N2, 7:3) there was no change in either the proportion of nicotinamide nucleotides in the liver present in the reduced form or in the total tissue control of the nucleotides. There was an increase in the urinary excretion of kynurenine suggesting an increase in the oxidative metabolism of tryptophan.

The preferred route of kynurenine metabolism in the rat.

It has been suggested (Ueda, T., Otsuka, H. and Goda, K. (1978) J. Biochem. 84, 687-696) that direct cleavage of kynurenine, catalysed by kynureninase, followed by microsomal hydroxylation of the resultant anthranilic acid, may provide an alternative to the established pathway of kynurenine metabolism that involves direct hydroxylation followed by cleavage to 3-hydroxyanthranilic acid. To test this suggestion, anthranilic acid was administered to rats; there was no increase in either the concentration of nicotinamide nucleotides in the liver or the urinary excretion of N1-methyl nicotinamide. However, injection of either kynurenine or 3-hydroxyanthranilic acid did increase the concentration of nicotinamide nucleotides in the liver. The kinetics of kynurenine hydroxylase (Km = 1.8 +/- 0.6.10(-5) mol/l) and kynureninase (Km = 2.5 +/- 0.8.10(-4) mol/l, liver steady-state kynurenine = 4.9 +/- 0.9 mumol/kg) are such that the preferred route of kynurenine metabolism is probably by way of hydroxylation rather than cleavage.

Treatment utilization by patients with personality disorders.

OBJECTIVE: Utilization of mental health treatment was compared in patients with personality disorders and patients with major depressive disorder without personality disorder. METHOD: Semistructured interviews were used to assess diagnosis and treatment history of 664 patients in four representative personality disorder groups-schizotypal, borderline, avoidant, and obsessive-compulsive-and in a comparison group of patients with major depressive disorder. RESULTS: Patients with personality disorders had more extensive histories of psychiatric outpatient, inpatient, and psychopharmacologic treatment than patients with major depressive disorder. Compared to the depression group, patients with borderline personality disorder were significantly more likely to have received every type of psychosocial treatment except self-help groups, and patients with obsessive-compulsive personality disorder reported greater utilization of individual psychotherapy. Patients with borderline personality disorder were also more likely to have used antianxiety, antidepressant, and mood stabilizer medications, and those with borderline or schizotypal personality disorder had a greater likelihood of having received antipsychotic medications. Patients with borderline personality disorder had received greater amounts of treatment, except for family/couples therapy and self-help, than the depressed patients and patients with other personality disorders. CONCLUSIONS: These results underscore the importance of considering personality disorders in diagnosis and treatment of psychiatric patients. Borderline and schizotypal personality disorder are associated with extensive use of mental health resources, and other, less severe personality disorders may not be addressed sufficiently in treatment planning. More work is needed to determine whether patients with personality disorders are receiving adequate and appropriate mental health treatments.

Anterograde degeneration in the superior colliculus following kainic acid and radiofrequency lesions of the macaque pulvinar.

Several studies have reported behavioral deficits following thermocoagulation of the primate pulvinar. However, these deficits may have resulted from damage to corticotectal fibers as they pass through the pulvinar. To evaluate this possibility and to determine whether kainic acid can be used to destroy pulvinar cells without damaging corticotectal fibers, we compared anterograde degeneration in the superior colliculus following kainic acid and radiofrequency lesions of the pulvinar. Kainic acid injections into the pulvinar produced total loss of neuronal perikarya within the inferior and lateral pulvinar. Four to 7 days following the kainic acid lesions, terminal and fiber degeneration within the superior colliculus was no greater than that produced by control injections of saline. By contrast, thermocoagulation lesions of the inferior and lateral pulvinar produced dense fiber and terminal degeneration throughout the superficial and intermediate layers of the superior colliculus. We conclude that whereas thermocoagulation of the pulvinar severely damages the corticotectal tract, kainic acid lesions spare these fibers of passage. Thus kainic acid lesions should provide an effective tool for studying the functional significance of the pulvinar.

Synthesis of aziridinylallylaminophosphine oxides and sulfides as potential adjuvant cancer chemotherapeutic agents.

Bis (1-aziridinyl)(hexahydro-1H-azepin-1-yl)phosphine sulfide, an active anticancer agent with low hematopoietic toxicity in animals and man, was recommended several years ago for breast cancer adjuvant chemotherapy as an alternate drug to thiotepa. This hope had led to the syntheses of aziridinylallylaminophosphine oxides or sulfides (compounds I-XVII) in our laboratories. The resurgent interest in this area of cancer chemotherapy encouraged us to report our synthetic work as well as their evaluation as both anticancer agents and insect chemosterilants. Based on observed antitumor activity in animals, low chemosterilant activity in female species (insects and rats), and histochemical observation of tissue toxicity in rat testes but not in ovaries, these new agents are of potential interest to the breast cancer adjuvant chemotherapy program.

Lethal familial pellagra-like skin lesion associated with neurologic and developmental impairment and the development of cataracts.

A new hereditary defect of tryptophan metabolism is described in a Sudanese family with a high degree of consanguinity. It has an autosomal recessive pattern of inheritance. The condition manifests as a pellagra-like skin rash within 8 weeks after birth, with signs of cerebellar ataxia and developmental retardation. Cataracts develop early, and to date none of the ten affected children has survived beyond 2 years of age. Biochemically, the condition is characterized by an apparent impairment of the ability to synthesize quinolinic acid and nicotinamide nucleotides from tryptophan, which might be due to abnormally high activity of the enzyme picolinate carboxylase.

Day care center attendance and diarrheal morbidity in Colombia.

This study was designed to determine whether day care center attendance was associated with increased risk of diarrheal disease among poor children in an urban, developing country setting. From July 17 to December 18, 1988, mothers of 493 Colombian children less than 5 years old (241 attendees and 252 nonattendees) were interviewed weekly about diarrheal events during the previous week. The incidence of diarrhea was greater for day care center attendees than for nonattendees (3.2 vs 2.0 episodes per child-year, P < .0005). For children less than 2 years of age, attendees experienced 7.2 episodes/child-year vs 3.5 episodes per child-year for nonattendees (P < .0005). Analyses controlling for water source and availability, excreta disposal, socioeconomic status, and duration of follow-up showed that the increased diarrheal risk was limited to children younger than 3 years of age spending more than 30 hours per week in the centers. In addition, although the risk among attendees of suffering diarrheal episodes of longer duration was fairly constant across levels of socioeconomic status, this risk was inversely proportional to socioeconomic status for nonattendees. In summary, the increase in risk of diarrhea among young, full-time day care attendees was modest, yet important, because diarrhea continues to be a major cause of morbidity and mortality in Colombian children.

Metabolites of (18)F-FDG and 3-O-(11)C-methylglucose in pig liver.

UNLABELLED: PET uses (18)F-FDG widely to estimate glucose metabolism in vivo. Dynamic PET data are evaluated by kinetic models of the metabolic pathways. Knowledge of the metabolites of FDG is of critical importance for the interpretation of kinetic PET studies. The purpose of this study was to determine the metabolic pathways of FDG and 3-O-(11)C-methylglucose (MG) in liver tissue in vivo. It is usually assumed that MG is not metabolized and FDG is converted to (18)F-FDG-6-phosphate (FDG-6-P). METHODS: The study was performed on 6 anesthetized 40-kg pigs that were given the 2 tracers intravenously. The content of metabolites was determined in successive liver tissue biopsies. Freeze-clamped liver tissue samples were subjected to extraction by acetonitrile at -5 degrees C to -10 degrees C, and extracts were analyzed by radio-high-performance liquid chromatography (radio-HPLC). The findings were identified by means of radio-HLPC measurements of the products of in vitro enzymatic reactions. RESULTS: The applied extraction technique provided almost quantitative recovery of the radioactivity from tissue. After MG injection, only MG was detectable in the liver tissue; no labeled metabolites were found. After FDG injection, 2 metabolites were identified, FDG-6-P and 2-(18)F-fluoro-2-deoxy-6-phosphogluconate (FD-6-PG1). The tissue content of FDG increased rapidly, and, after 5 min, only FDG was identified; hereafter, the fraction of FDG decreased to approximately 40% of the tissue radioactivity after 180 min. After 20 min, FDG-6-P was found in each of the pigs and it increased throughout the measurement period of 180 min, with a somewhat slower rise at late time points. FD-6-PG1 began to appear in the liver tissue after 45 min and increased throughout the 180-min experiment, with the increase somewhat slower than that of FDG-6-P. After 180 min, approximately 40% of the metabolites was attributed to FD-6-PG1. The content of other metabolites was <2%, even after 180 min. CONCLUSION: After the FDG injection, not only FDG-6-P but also FD-6-PG1 were formed in the liver. Any possible incorporation of FDG into glycogen was of minor importance.

Liver kinetics of glucose analogs measured in pigs by PET: importance of dual-input blood sampling.

UNLABELLED: Metabolic processes studied by PET are quantified traditionally using compartmental models, which relate the time course of the tracer concentration in tissue to that in arterial blood. For liver studies, the use of arterial input may, however, cause systematic errors to the estimated kinetic parameters, because of ignorance of the dual blood supply from the hepatic artery and the portal vein to the liver. METHODS: Six pigs underwent PET after [15O]carbon monoxide inhalation, 3-O-[11C]methylglucose (MG) injection, and [18F]FDG injection. For the glucose scans, PET data were acquired for 90 min. Hepatic arterial and portal venous blood samples and flows were measured during the scan. The dual-input function was calculated as the flow-weighted input. RESULTS: For both MG and FDG, the compartmental analysis using arterial input led to systematic underestimation of the rate constants for rapid blood-tissue exchange. Furthermore, the arterial input led to absurdly low estimates for the extracellular volume compared with the independently measured hepatic blood volume of 0.25 +/- 0.01 mL/mL (milliliter blood per milliliter liver tissue). In contrast, the use of a dual-input function provided parameter estimates that were in agreement with liver physiology. Using the dual-input function, the clearances into the liver cells (K1 = 1.11 +/- 0.11 mL/min/mL for MG; K1 = 1.07 +/- 0.19 mL/min/mL for FDG) were comparable with the liver blood flow (F = 1.02 +/- 0.05 mL/min/mL). As required physiologically, the extracellular volumes estimated using the dual-input function were larger than the hepatic blood volume. The linear Gjedde-Patlak analysis produced parameter estimates that were unaffected by the choice of input function, because this analysis was confined to time scales for which the arterial-input and dual-input functions were very similar. CONCLUSION: Compartmental analysis of MG and FDG kinetics using dynamic PET data requires measurements of dual-input activity concentrations. Using the dual-input function, physiologically reasonable parameter estimates of K1, k2, and Vp were obtained, whereas the use of conventional arterial sampling underestimated these parameters compared with independent measurements of hepatic flow and hepatic blood volume. In contrast, the linear Gjedde-Patlak analysis, being less informative but more robust, gave similar parameter estimates (K, V) with both input functions.

Monoclonal antibodies against HIV type 1 integrase: clues to molecular structure.

Eleven murine hybridoma clones were selected for their ability to produce anti-HIV-1 integrase (IN) antibodies. Competition and epitope mapping studies allowed segregation of the monoclonal antibodies (MAbs) into four distinct classes. The five MAbs that comprise the first class showed high affinity for epitopes within an N-terminal domain of 58 amino acids that includes a conserved zinc finger motif. The second class, with two MAbs, showed high affinity for epitopes within 29 amino acids at the C terminus. Another two MAbs, which constitute the third class, displayed moderate affinities for epitopes that mapped to regions within the highly conserved catalytic core referred to as the D,D(35)E domain. One of these MAbs showed significant cross-reactivity with HIV-2 IN and weak, but detectable, cross-reactivity with RSV IN. The remaining two MAbs, which comprise the fourth class, exhibited fairly low binding affinities and appeared to recognize epitopes in the zinc finger motif domain as well as the C-terminal half of the IN protein. The MAbs can be used for immunoprecipitation and immunoblotting procedures as well as for purification of HIV-1 IN protein by affinity chromatography. We show that several can also be used to immunostain viral IN sequences in HIV-1-infected T cells, presumably as a component of Gag-Pol precursors. Finally, analysis of our mapping and competition data suggests a structure for mature IN in which the C terminus approaches the central core domain, and the N and C termini touch or are proximal to each other. These MAbs should prove useful for further analyses of the structure and function of IN both in vitro and in vivo.

The effects of oestrogen administration on tryptophan metabolism in rats and in menopausal women receiving hormone replacement therapy.

The effects of the administration of oestrogens on the activity of hepatic tryptophan oxygenase have been assessed both directly (by measurement of enzyme activity in vitro) and indirectly (by measurement of urinary excretion of tryptophan metabolites) in rats, and indirectly in menopausal women receiving hormone replacement therapy. Intraperitoneal administration of 500 micrograms of oestradiol or ethinyl oestradiol/kg body wt had no effect on the activity of tryptophan oxygenase in homogenates of liver from mature (13-week-old) female rats. Both adrenalectomy and ovariectomy led to a reduction in the activity of tryptophan oxygenase in homogenates of liver from mature rats; again there was no effect of giving 500 micrograms of oestradiol/kg body wt by intraperitoneal injection. Intraperitoneal administration of 210 micrograms of oestrone sulphate/kg body wt for 1 or 2 days before killing, or its incorporation in the diet for up to 8 weeks at an equivalent dose rate, had no effect on the activity of tryptophan oxygenase in homogenates of liver from ovariectomized 6-14-week-old female rats. Intraperitoneal administration of 500 micrograms oestradiol/kg body wt to intact mature female rats together with 500 mg tryptophan/kg body wt caused a reduction in the urinary excretion of xanthurenic and kynurenic acids, kynurenine and N1-methyl nicotinamide. When peri- and post-menopausal women were treated with ethinyl oestradiol (20 micrograms/day) or piperazine oestrone sulphate (3 mg/day) for 3 months, there was an increase in the concn of tryptophan in plasma, with no change in the urinary excretion of xanthurenic and kynurenic acids and kynurenine. This study provides no evidence for the induction of tryptophan oxygenase by oestrogens in rats or human beings.