Self-organization of two-dimensional incompressible viscous flow in a friction-free box.
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Journal Article↗
Biomedical subjects
Y Kondoh
Publications and source records attributed to Y Kondoh.
Sustained high levels of circulatory interleukin-8 are associated with a poor outcome in patients with adult respiratory distress syndrome.
Neutrophils are reported to be a major factor in the pathogenesis of the adult respiratory distress syndrome (ARDS). We measured serial levels of circulatory interleukin (IL)-8 and neutrophil elastase in 16 patients with ARDS at the onset, on day 3 and on day 7 and studied the relationship of these levels to the clinical course. Circulatory IL-8 levels of all the patients at the onset were significantly elevated compared with controls, mean +/- SE, 30.0 +/- 6.7 pg/ml and 3.3 +/- 0.3 pg/ ml, respectively. There was a significant correlation between IL-8 and neutrophil elastase levels at the onset (r = 0.65, p < 0.01). In nonsurvivors circulatory IL-8 levels were significantly higher than those of survivors throughout the study. There were significant differences in oxygenation, as reflected by PaO2/FIO2 ratios, between survivors and nonsurvivors at day 7, mean +/- SE, 208.5 +/- 21.9 and 113.5 +/- 9.6, respectively. In conclusion, we have shown that the level of circulatory IL-8 is elevated in patients with ARDS, and sustained high levels of circulatory IL-8 might be correlated with a poor outcome.
Adult↗
[Optimum dose study of cefozopran in the pediatric field].
Cefozopran (SCE-2787, CZOP) was administered to patients with pediatric infections three to four times daily by intravenous injection or 30-minute intravenous drip infusion, and investigations were made in individual cases, on relationships among doses, pharmacokinetics, effects on pathogenic bacteria and MIC against them, and clinical effects. The following results on optimal doses of CZOP were obtained. 1. Clinical cases in which CZOP was administered at a dose of 10 mg (potency)/kg The subjects were 7 patients including 4 patients with pneumonia. Severities of the diseases were severe in one of the patients with pneumonia, and moderate in the other patients. The MIC against pathogenic bacteria (4 strains) isolated from these cases ranged from 0.2 to 1.56 micrograms/ml. The serum concentrations were in a range between 1.4 and 7.6 micrograms/ml at 4 hours after administration. In some cases, the serum concentrations were lower than the MICs, though slightly. In the clinical evaluation, CZOP was excellent in 3 cases, good in 2 cases and fair in 1 case. The evaluation was impossible in 1 case. The efficacy rate was 83.3% (5/6). In bacteriological evaluation, 3 out of the 4 strains disappeared. Adverse reactions and abnormal laboratory test values were not observed. 2. Cases in which CZOP was administered at a dose of 20 mg (potency)/kg The subjects were 5 patients including 2 with pneumonia, and severities were severe in one of the patients with pneumonia, and moderate in the other patients. The MICs against the pathogenic bacteria (3 strains) isolated from these cases ranged from 0.1 to 1.56 micrograms/ml. While, serum concentrations at 4 hours after administration were in a range between 3.0 and 7.7 micrograms/ml sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 1 case and good in four cases, with an efficacy rate of 100% (5/5). In the bacteriological evaluation, all the 3 strains disappeared. No adverse reactions were observed, but an abnormal laboratory test value showing eosinophilia was noted in one case. 3. Cases in which CZOP was administered at a dose of 40 mg (potency)/kg The subjects were 5 patients including 3 with pneumonia. The severity was moderate in 2 of the pneumonia patients, and severe in the other three cases. The MICs against the pathogenic bacteria (4 strains) isolated from these cases were in a range between 0.1 and 0.78 micrograms/ml. The serum concentrations at 4 hours after administration ranged from 6.5 to 21.9 micrograms/ml, sufficiently exceeding the MICs. In the clinical evaluation, CZOP was excellent in 4 cases and good in 1 case, with an efficacy rate of 100% (5/5). The efficacy rate in the bacteriological evaluation was also 100%. As adverse reaction, red urine was observed in one case. Eosinophlia was noted in one case in the laboratory tests. When CZOP was administered to patients with pediatric infections at a dose of 10 mg (potency)/kg, the clinical effect of the drug was insufficient in a case in which serum concentration of CZOP at 4 hours after administration was lower than the MICs against the pathogenic bacteria. When CZOP was administered at a dose of 20 mg (potency)/kg, sufficient concentrations were obtained, and the drug efficacies were found to be excellent or good in all cases. Therefore, the effective dose normally used is considered to be 20 mg (potency)/kg. When CZOP was administered at a dose of 40 mg (potency)/kg, the drug was found to be excellent or good in all of the cases although the severities were high in more than half of the cases tested. In addition, the rate of excellent efficacies was 80% (4/5). Furthermore, no severe adverse reactions were observed. It was, therefore, confirmed that CZOP should be administered at a dose of 40 mg (potency)/kg in severe or intractable cases.
Bacterial Infections↗
[Pharmacokinetic, bacteriological and clinical studies on cefozopran in neonates and premature infants. A study of cefozopran in the perinatal co-research group].
The following results were obtained in pharmacokinetic, bacteriological and clinical investigations of a cephem antibiotic for injection, cefozopran (SCE-2787, CZOP), administered to neonates and premature infants. 1. Pharmacokinetics (1) Half-lives (T 1/2's) of CZOP in 0-day-old (less than 24 hours after birth) neonates and premature infants were longer than those in 1-day-old or older infants. When half-lives were compared between 0-day-old neonates and 0-day-old premature infants, longer half-lives were observed in premature infants. (2) When CZOP was intravenously administered to 1-day-old or older neonates and premature infants at a dose of 20 mg/kg, no differences were noted in blood concentrations between neonates and premature infants from 30 minutes to 6 hours after administration as well as T 1/2's. (3) Blood concentration of CZOP administered at doses of 10, 20 and 40 mg/kg were dose-dependent. (4) Urine excretion rates of CZOP administered to 1-day-old or older neonates and premature infants were approximately 30 to 60% in the first 6 hours after administration. Urine excretion rates in 0-day-old neonates and premature infants were low. 2. Clinical results (1) Of a total of 136 cases to which CZOP was administered, clinical efficacy evaluation was possible in 96 cases, and safety evaluation in 132 cases. (2) The clinical efficacy rates were 78.6% (22/28) in 28 cases in which causative organisms were detected (Group A), and 97.1% (66/68) in 68 cases in which no such organisms were detected (Group B), with the total efficacy rate (Groups A and B) of as high as 91.7% (88/96). (3) Bacteriological evaluations were made with 33 strains isolated from the 28 cases of Group A. Elimination rates for Gram-positive and Gram-negative bacteria were 88.2% (15/17) and 92.3% (12/13), respectively, with the total elimination rate of 90.0% (27/30). No microbial substitution was noted. (4) As an adverse reaction, diarrhea was noted in one case (0.8%). Abnormal laboratory test values were noted in 15 cases (12.3%) including eosinophilia, elevated GPT, and elevated gamma-GTP. All of these abnormalities were transitory, and none of them critical. As a result of above pharmacokinetic and clinical investigations, CZOP is considered to be highly useful in the treatment of indicated infections in neonates and premature infants. It appears that 20 mg/kg of CZOP can be administered by intravenous injection or intravenous drip infusion to neonates and premature infants aged 0-day (less than 24 hours after birth) once or twice daily, to those aged 1 (24 or more hours after birth) to 7 days twice or three times daily, and to those aged 8 or more days three to four times daily, and that the dose can be increased up to 40 mg/kg in cases of critical or intractable infections.
Bacterial Infections↗
[Rapidly progressing BOOP in a patient with positive anti-Jo-1 antibody: response to corticosteroid pulse and immunosuppressant therapy].
A 61-year-old woman was admitted to our hospital with a two week history of knee-joint pain, dry coughing and dyspnea on exertion. A chest roentgenogram revealed bilateral patchy and infiltrative shadows. Laboratory examination revealed high CK and aldolase levels. Although myositic symptoms were absent, the respiratory symptoms rapidly worsened and respiratory failure developed. An open-lung biopsy and a muscle biopsy were done. The open-lung biopsy specimen showed bronchiolitis obliterans organizing pneumonia (BOOP), but the muscle biopsy specimen revealed non-specific findings. After 4 weeks of intravenous intermittent high-dose corticosteroid therapy, 50mg of cyclophosphamide was given daily, along with 20mg of prednisolone on alternate days. There were marked clinical, physiological and roentgenographic improvements. A test for anti-Jo-1 antibody was positive, which suggested that this patients had pulmonary manifestations of polymyositis/dermatomyositis. Although BOOP can have an indolent course and a good prognosis, it may rapidly worsen and respiratory failure may develop, in which case it should be treated aggressively with a combination of intravenous high-dose corticosteroids and immunosuppressants.
Antibodies, Antinuclear↗
[Effect of long-term treatment with an inhaled corticosteroid on bronchial hyper-responsiveness and clinical asthma in asthmatic subjects].
We studied retrospectively the effect of long-term treatment with an inhaled corticosteroid on bronchial hyperresponsiveness (BHR) and clinical asthma in moderate-severe asthmatic subjects. Fifty-eight patients who had used beclomethasone dipropionate (BDP) over one year, were enrolled in this study. BHR was measured before and after treatment with BDP by the methods recommended by Japanese Society of Allergology. Moreover we examined the clinical factors and the frequency of acute exacerbations. The results as follows: 1) The mean age was 48.8 years and the mean asthma history was 9.2 years. The mean dose and mean time of BDP administration was 801 micrograms/day and 28.1 months, respectively. 2) Patients during BDP treatment over one year showed about 6-fold mean improvements in BHR, but there were many patients who showed no improvements in BHR. 3) We retrospectively divided all the patients into two groups. Namely, the improved group (n = 25) showed more than 4 fold improvement in BHR and unchanged group (n = 33), less than 4-fold. But there were no significant differences in clinical characteristics and %FEV1 during treatment with BDP. 4) The unchanged group had more near fatal episodes in the past than the improved group. 5) There was significant decrease in acute exacerbation during treatment with BDP, but the unchanged group had more acute exacerbations than the improved group during treatment with BDP. These results indicates that there are many patients who had no improvement on BHR with long term BDP treatment and they have more acute exacerbations due to various stimuli. In conclusion, asthma is recognized chronic inflammatory disease and inhaled corticosteroid therapy has been recommended as the first line therapy. We must further study the clinical problems and underlying mechanisms concerning about treatment with an inhaled corticosteroid.
Anti-Asthmatic Agents↗
Regional myocardial function curve of the ventricle.
To understand the pathophysiology of diseased hearts, we devised a new regional myocardial function curve and investigated its properties. Regional work per unit volume of the myocardium (RWM) was calculated by integrating mean wall stress (sigma) with respect to the natural logarithm of the reciprocal of wall thickness [ln(1/H)] over a cardiac cycle. Regarding the end-diastolic ln(1/H) as the preload for the region of concern on the assumption that the myocardium is incompressible, we defined the relation between RWM and end-diastolic ln(1/H) as the regional myocardial function curve. In ten mongrel dogs, we measured left ventricular pressure, left ventricular internal diameter, and wall thickness with a catheter-tip micromanometer and ultrasonic dimension gauges during volume loading to obtain the regional myocardial function curve. We examined the sensitivity of the regional myocardial function curve to changes in contractile state (isoproterenol, propranolol) and changes in afterload (pressure loading by a balloon-occlusion catheter). The linear fit to the data points of the regional myocardial function curve under each condition always achieved a very good correlation coefficient (greater than 0.62). Isoproterenol increased the slope of the regional myocardial function curve from 9.7 +/- 0.9 (SEM) mJ/cm3 to 14.4 +/- 1.0 mJ/cm3 (P < 0.01), with no significant changes in the x-intercept, while propranolol decreased it to 5.6 +/- 1.2 mJ/cm3 (P < 0.01) with no significant changes in the x-intercept.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Self-organization of solitons for the dissipative Korteweg-de Vries equation.
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Journal Article↗
Dynamics of neurons controlling movements of a locust hind leg: Wiener kernel analysis of the responses of proprioceptive afferents.
1. The response properties of proprioceptive sensory neurons providing input to the local circuits controlling leg movements of the locust have been analysed by the Wiener kernel method. The proprioceptor, the femoral chordotonal organ, encodes the position and movements of the tibia about the femorotibial joint. 2. Intracellular recordings were made from sensory neurons while the apodeme of the organ was moved with a band-limited Gaussian white noise signal with a cutoff frequency of 27, 58, or 117 Hz. To define the input-output characteristics of the neurons, the first- and second-order Wiener kernels were computed by a cross-correlation between the spike response of the afferents and the white noise stimulus. 3. White noise stimulation elicited sustained spiking in 50 out of 54 afferents throughout the 20 s periods of stimulation and recording. The first-order kernels, the linear response properties, of these afferents were of six basic types that were dependent on the cutoff frequency of the white noise stimulus. These included 1) flexion-sensitive afferents that were primarily position sensitive irrespective of stimulus frequency, 2) flexion-sensitive afferents that were position sensitive at low frequencies but also coded velocity at higher frequencies, 3) flexion-sensitive afferents that coded velocity at all stimulus frequencies, 4) flexion-sensitive afferents that coded velocity at low stimulus frequencies but also acceleration at high frequencies, 5) extension-sensitive afferents that coded velocity at all stimulus frequencies, and 6) extension-sensitive afferents that coded velocity at low stimulus frequencies and acceleration at high frequencies. A seventh type contained the four remaining afferents that adapted rapidly to the stimulus within 3-5 s. These were all extension-acceleration sensitive irrespective of stimulus frequency. 4. The gain curves (produced by Fourier transform of the 1st-order kernels) and the power spectra of the linear models (produced by convolving the 1st-order kernels with the white noise) demonstrated that responses in the position-sensitive afferents are representative of a constant gain low-pass filter with a cutoff frequency of approximately 80 Hz, whereas those in the velocity- and acceleration-sensitive afferents are band passed, having peaks at 80 Hz. 5. The main nonlinearity was a signal compression in which the diagonal peak(s) of the second-order nonlinear kernels offset one or more peaks of the first-order kernels and represents a rectification or directional sensitivity of the afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
Afferent Pathways↗
Neural computation of motion in the fly visual system: quadratic nonlinearity of responses induced by picrotoxin in the HS and CH cells.
1. A computational model accounting for motion detection in the fly was examined by comparing responses in motion-sensitive horizontal system (HS) and centrifugal horizontal (CH) cells in the fly's lobula plate with a computer simulation implemented on a motion detector of the correlation type, the Reichardt detector. First-order (linear) and second-order (quadratic nonlinear) Wiener kernels from intracellularly recorded responses to moving patterns were computed by cross correlating with the time-dependent position of the stimulus, and were used to characterize response to motion in those cells. 2. When the fly was stimulated with moving vertical stripes with a spatial wavelength of 5-40 degrees, the HS and CH cells showed basically a biphasic first-order kernel, having an initial depolarization that was followed by hyperpolarization. The linear model matched well with the actual response, with a mean square error of 27% at best, indicating that the linear component comprises a major part of responses in these cells. The second-order nonlinearity was insignificant. When stimulated at a spatial wavelength of 2.5 degrees, the first-order kernel showed a significant decrease in amplitude, and was initially hyperpolarized; the second-order kernel was, on the other hand, well defined, having two hyperpolarizing valleys on the diagonal with two off-diagonal peaks. 3. The blockage of inhibitory interactions in the visual system by application of 10-4 M picrotoxin, however, evoked a nonlinear response that could be decomposed into the sum of the first-order (linear) and second-order (quadratic nonlinear) terms with a mean square error of 30-50%. The first-order term, comprising 10-20% of the picrotoxin-evoked response, is characterized by a differentiating first-order kernel. It thus codes the velocity of motion. The second-order term, comprising 30-40% of the response, is defined by a second-order kernel with two depolarizing peaks on the diagonal and two off-diagonal hyperpolarizing valleys, suggesting that the nonlinear component represents the power of motion. 4. Responses in the Reichardt detector, consisting of two mirror-image subunits with spatiotemporal low-pass filters followed by a multiplication stage, were computer simulated and then analyzed by the Wiener kernel method. The simulated responses were linearly related to the pattern velocity (with a mean square error of 13% for the linear model) and matched well with the observed responses in the HS and CH cells. After the multiplication stage, the linear component comprised 15-25% and the quadratic nonlinear component comprised 60-70% of the simulated response, which was similar to the picrotoxin-induced response in the HS cells. The quadratic nonlinear components were balanced between the right and left sides, and could be eliminated completely by their contralateral counterpart via a subtraction process. On the other hand, the linear component on one side was the mirror image of that on the other side, as expected from the kernel configurations. 5. These results suggest that responses to motion in the HS and CH cells depend on the multiplication process in which both the velocity and power components of motion are computed, and that a putative subtraction process selectively eliminates the nonlinear components but amplifies the linear component. The nonlinear component is directionally insensitive because of its quadratic non-linearity. Therefore the subtraction process allows the subsequent cells integrating motion (such as the HS cells) to tune the direction of motion more sharply.
Animals↗
Simultaneous visualization of Q-bands and FISH signals using a novel fluorochrome.
We developed a new HNPP-azo dye method for detection of fluorescence in situ hybridization (FISH) signals on Q-banded chromosomes by use of a newly synthesized fluorochrome, HNPP (3-hydroxy-N-2'-biphenyl-2-naphthalenecarboxamide phosphate ester), which reacts enzymatically with alkaline phosphatase and azo dye. The FISH staining method permits simultaneous detection of orange HNPP signals on chromosomal sites labeled by Q-banding, allowing the assignment of small (440-1,200 bp) probes.
Animals↗
New 1,4-benzodiazepin-2-one derivatives as gastrin/cholecystokinin-B antagonists.
A novel series of 1-aroylmethyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one derivatives was prepared and evaluated for activity as gastrin/cholecystokinin (CCK)-B receptor antagonists. In vitro binding studies showed that some derivatives exhibited potent affinity for gastrin CCK-B receptor and high selectivity over peripheral CCK(CCK-A) receptor. Furthermore these compounds potently inhibited pentagastrin-induced gastric acid secretion upon intravenous administration in an in vivo model in rats. Structure-activity relationship studies of this series suggested that 1-[(R)-2,3-dihydro-1-(2,3-dihydro-1-(2-methylphenacyl)-2-oxo-5-phe nyl-1H-1,4-benzodiazepin-3-yl]-3-(3-methylphenyl)urea (35b, YM022) was the optimal compound with IC50 values of 0.17, 0.11 and 150 nM for gastrin, CCK-B and CCK-A receptors, respectively, and an ED50 value of 9.5 nmol/kg (i.v.) in rats. The absolute configuration of the precursor of YM022, an (R)-3-amino-1,3-dihydro-2H-1,4-benzodiazepin-2-one derivative ((R)-25), was determined by X-ray crystallographic analysis of its (S) mandelate. It would be expected that YM022, a potent and selective gastrin CCK-B receptor antagonist, inhibits gastric acid secretion without inducing gastrin-mediated side effects such as hypergastrinemia and hyperplasia of oxyntic mucosa.
Anesthetics↗
Deletion of the Wilson's disease gene in hereditary hepatitis LEC rats.
LEC rats develop disorder of cooper metabolism and hepatitis similar to those of human Wilson's disease. We recently demonstrated that the gene responsible for hepatitis (hts) of LEC rats is homologous to Wilson's disease gene (WD). The present study showed a deletion of at least 90 base pair of WD cDNA in LEC rats, which corresponds to nucleotides 3981 to 4071 in human WD cDNA sequence. This deletion was linked with hepatic copper accumulation and hepatitis, and considered to be a primary mutation for hepatic disorder in the LEC rat. The WD gene was assigned to rat chromosome 16 at band q12.2-q12.4 by fluorescence in situ hybridization (FISH).
Animals↗
[Effect of dosing schedule on efficacy of corticosteroid inhalation in chronic asthma].
A randomized study was conducted for 4 weeks to evaluate the effect of twice daily inhalation of beclomethasone dipropionate (BDP) inhalation (group A) as compared to four times a day inhalation (group B) in chronic asthma. Patients were randomly allocated to receive BDP at a dosage of eight puffs twice daily (800 micrograms/day, group A) or four puffs four times daily (800 micrograms/day, group B). Forty four patients entered the study but eleven were excluded because of their insufficient records or unfitness to eligibility criteria. There was no significant difference in patients' characteristics such as types, and severity of diseases between the two groups. Daily keeping of symptom scores, twice daily measurement of morning and night peak expiratory flow (PEF) and checking of the drug consumption were performed throughout the study. There was no significant difference in the mean %PEF either at 2 and 4 weeks at the study between the two groups. Symptom scores, asthmatic scores, bronchial hyperresponsiveness, pulmonary function tests (FVC, FEV1, FEV1%) and serum cortisol levels also showed no significant difference between the two groups. These results indicate that twice daily inhalation of BDP (800 micrograms/day) for four weeks caused the same effects on the patients with chronic bronchial asthma as 4 times daily inhalation did. Therefore, twice daily inhalation therapy with BDP is recommended for chronic bronchial asthma patients.
Administration, Inhalation↗
[Diagnosis of acute respiratory distress syndrome: analysis of bronchoalveolar lavage fluid].
To better understand the pathogenesis of acute respiratory distress syndrome (ARDS), we analyzed bronchoalveolar lavage fluid (BALF) from patients with ARDS (n = 89, survival rate = 56.2%), who were admitted to our intensive care units over the past 7 years. ARDS was diagnosed when the lung injury score proposed by Murray et al was greater than 2.5. The BALF had very high centrations of albumin, a marker of permeability edema, along with remarkably high neutrophil counts, percent neutrophils, neutrophil-elastase, and interleukin-8, markers of neutrophil-related lung injury. In addition, the level of IL-8 in BALF was higher in non-survivors than in survivors. Levels of thrombin-antithrombin complex fibrin degenerative product and soluble thrombomodulin (recently recognized as a natural anticoagulant combined with vascular endothelial cells) were very high in BALF from patients with ARDS. Moreover, the level of soluble thrombomodulin in BALF was higher in non-survivors than in survivors. There were significant relationships between these neutrophil-related markers and markers of abnormal coagulation. The results of the BALF analysis suggest that accumulation and activation of neutrophils can affect thrombomodulin on vascular endothelial cells, which can activate thrombin and cause the coagulopathy seen in ARDS.
Adult↗
Quantitative distribution of rat brain monoamine oxidase A by [14C]clorgyline autoradiography.
The distribution of functionally active monoamine oxidase type A (MAO-A) was investigated by in vivo quantitative autoradiography using [14C]clorgyline in normal, conscious rat brain. [14C]clorgyline was synthesized by the methylation reaction of N-desmethylclorgyline using [14C]methyliodide. Sixty minutes after [14C]clorgyline administration (1.58 MBq/animal i.v.), the brains were removed and prepared for autoradiography by washing the brain sections with 5% trichloroacetic acid solution to remove the nonbinding free tracer. The amount of MAO-A was calculated from the regional acid-insoluble tissue radioactivity and the specific activity of the tracer. The highest amount of MAO-A (5.84 nmol/g tissue) was found in the locus coeruleus. The interpeduncular nucleus, habenular nucleus, fasciculus retroflexus, and solitary tract nucleus possessed over 1.6 nmol/g tissue of MAO-A. Among 23 regions of interest, the lowest amount of MAO-A (0.37 nmol/g tissue) was found in the globus pallidus. The findings of this study suggest that the pattern of MAO-A parallels both in neuroanatomical distribution and in density that of norepinephrine and serotonin innervation. The MAO-A concentration was, however, relatively low in the dopamine-related areas. This corresponded to the previous results obtained by histochemical analysis. In addition, among the white matter structures, a high amount of MAO-A was found specifically in the fasciculus retroflexus.
Animals↗
Does the anabolic metabolism of L-[2-18F]fluorophenylalanine and L-[2,6-3H]phenylalanine differ in the cerebrum and the cerebellum?
The anabolism of isotopically labeled amino acids was compared between the cerebrum and the cerebellum in conscious rat at three feeding conditions. After L-[2-18F]fluorophenylalanine and L-[2,6-3H]phenylalanine injections, the incorporation rate of both radioactivity into protein fraction showed no difference between the cerebrum and the cerebellum at normal condition, but the lipid fraction in the cerebellum was higher than that in the cerebrum in any conditions. These results show the usefulness of L-[2-18F]fluorophenylalanine as a positron emission tomography tracer and different anabolic rate of the amino acids to lipid between the cerebrum and cerebellum.
Animals↗
Carbon sources for D-lactate formation in rat liver.
Carbon sources for D-lactate formation were investigated in vitro using 6,000 x g supernatant of rat liver homogenate and by rat liver perfusion in situ. As carbon sources, L-threonine, glucose, glycerol, acetone, and acetoacetate were tested. Glycerol was the best substrate for D-lactate formation via methylglyoxal in rat liver. Glucose was the second most preferred substrate, while L-threonine, acetone, and acetoacetate were poor substrates for D-lactate formation. Glycerol was several times more effective than normal as a substrate of D-lactate in the supernatants of liver homogenates of diabetic and starved rats, while it was less effective as a substrate of L-lactate. The glycerol kinase [EC 2.7.1.30] activities in livers increased in the diabetic and starved states. These and other results can explain why the plasma concentration of D-lactate increases several-fold after running and why the D-lactate contents in plasma, liver, and skeletal muscle are markedly increases in diabetic and starved rats.
Acetoacetates↗