Comparative effects of dehydroepiandrosterone sulfate on ventricular diastolic function with young and aged female mice

The adrenal steroid hormone dehydroepiandrosterone (DHEA) and its sulfated derivative [DHEA(S)] have been extensively studied for their potential anti-aging effects. Associated with aging, DHEA levels decline in humans, whereas other adrenal hormones remain unchanged, suggesting that DHEA may be important in the aging process. However, the effect of DHEA(S) supplementation on cardiac function in the aged has not been investigated. Therefore, we administered to young and old female mice a 60-day treatment with exogenous DHEA(S) at a dose of 0.1 mg/ml in the drinking water and compared the effects on left ventricular diastolic function and the myocardial extracellular matrix composition. The left ventricular stiffness (beta) was 0.30 +/- 0.06 mmHg/mul in the older control mice compared with 0.17 +/- 0.02 mmHg/mul in young control mice. Treatment with DHEA(S) decreased left ventricular stiffness to 0.12 +/- 0.03 mmHg/mul in the older mice and increased left ventricular stiffness to 0.27 +/- 0.04 mmHg/mul in young mice. The mechanism for the DHEA(S)-induced changes in diastolic function appeared to be associated with altered matrix metalloproteinase activity and the percentage of collagen cross-linking. We conclude that exogenous DHEA(S) supplementation is capable of reversing the left ventricular stiffness and fibrosis that accompanies aging, with a paradoxical increased ventricular stiffness in young mice.     

Influence of dystocia on white blood cell and blood neutrophil counts in mares

A retrospective study was done on total white blood cell (WBC) and blood neutrophil counts of 41 mares referred to one of two veterinary hospitals for correction of dystocia. The mares were 2 to 19 years of age and included draft, light, and pony breeds. The WBC and neutrophil counts were performed at varying intervals from time of admission to 10 d after delivery of the feti. Retrospective analyses of WBC and neutrophil counts from 10 normal foaling mares from two Pennsylvania breeding farms (Thoroughbred and Trakehner) and from 14 normal foaling pony mares were done as controls. Mean WBC (10446 +/- 2296 cells/mul) and neutrophil (6850 +/- 2136 cells/mul) counts on the day of delivery in mares with normal parturition were slightly elevated over values reported as normal in the literature. The mean blood cell counts gradually declined to 6124 +/- 1255 WBC/mul and 3692 +/- 409 neutrophils/mul on Day 2 postpartum and returned to normal baseline values by Day 3 postpartum (8868 +/- 2693 WBC/mul, 4298 +/- 1966 neutrophils/mul). No toxic neutrophils were present in mares with normal delivery. Mean WBC (11346 +/- 3298 cells/mul) was elevated on the day of delivery in mares with dystocia as a result of neutrophilia with a left shift (9297 +/- 3298 neutrophils/mul). An apparently faster decline occurred in WBC and neutrophil counts of mares with dystocia than in mares with normal delivery, until a marked leukopenia (3905 +/- 1292 WBC/mul) and neutropenia (1570 +/- 1340 neutrophils/mul) occurred on Day 3 postpartum. The leukopenia and neutropenia persisted until Day 5 postpartum. Toxic neutrophils were present in several mares with dystocia.     

谷氨酸及NMDA受体拮抗剂MK-801对大鼠伏核痛兴奋神经元电活动的影响

本文研究了谷氨酸(glutamic acid,Glu)及其NMDA受体拮抗剂5-甲基二氢丙环庚烯亚胺马来酸(MK-801)对人鼠伏核(nucleus accumbens,NAc)痛兴奋神经元(pain-excitation neurons,PEN)痛诱发反应的影响。电刺激坐骨神经作为伤害性刺激,用玻璃微电极记录NAc的PEN放电,观察脑室内注射Glu和NAc内注射MK-801对大鼠NAc中PEN伤害性诱发活动的影响。结果显示,伤害性刺激可使NAc的PEN电活动增强;脑室内注射Glu(10nmol／10μl)可使NAc的PEN伤害性诱发放电频率增加;NAc内注射MK-801(1．0nmol／0．5μl)可阻断这种作用;MK-801本身也可部分抑制PEN伤害性诱发反应。上述结果表明,Glu对PEN伤害性反应的易化作用是通过NMDA受体介导的：Glu和NMDA受体参与NAc伤害性信息传递的调制。     

Micromethod of ultracentrifugation in cesium chloride]

The micromethod of ultracentrifugation in cesium chloride is described. Band destributions have been analysed by the direct scanning of microtubes with the differential doublewave micro-spectrophotometer at 260 nm. The 10(-8)-10(-9) g of DNA or ribosomes are enough for one analysis, tube volume is 2 mul. The method described permits the simultaneous centrifugation of several probe scores. The error of the beyoant density determination is 0.001 g/sm3 relatively internal standard. DNA's from 5 types of Acetabularia were analysed by the developed technique.     

Excitatory acidic amino acids and the cation content and sodium ion flux of isolated tissues from the brain

1. Sample from the neocortex and piriform cortex of guinea pigs and rats were incubated in inulin-containing glucose-saline. Their intracellular (non-inulin) space contained 19-27muequiv. of Na(+)/g. of original tissue. These values were stable between 30 and 100min. after incubation commenced, but addition of (22)NaCl to the neocortical samples showed them to be associated with a flux of 400muequiv. of Na(+)/g. of tissue/hr. 2. Addition of 0.5-10mm-l-glutamic acid or 0.1mm-N-methyl-dl-aspartic acid rapidly increased the tissue's Na(+) content; N-acetyl-dl-aspartic acid was without action. 3. During the first 1-1.5min. after the addition of l-glutamic acid to neocortical samples their Na(+) content increased at 600muequiv./g. of tissue/hr., and the rate of (22)Na(+) influx corresponded to 1230muequiv. of Na(+)/g./hr. These rates were calculated to be sufficiently rapid to account for loss of the tissue's normal membrane potential within 1-2sec. of the addition of the acid. 4. In addition, a rapid but more limited loss of K(+) took place after the addition of l-glutamic acid or the methylaspartic acid; on continued incubation tissue K(+) content increased, as also did the intracellular volume of the tissue, from its original 670mul./g. to 1100mul./g. 5. Interpretation of these and of associated changes is offered in terms that involve a cation pump and the permeability changes associated with the nerve impulse.     

Short-term regulation of multidrug resistance-associated protein 3 in rat and human hepatocytes

The short-term regulation of multidrug resistance-associated protein 3 (Mrp3/MRP3) by cAMP and PKC was investigated in sandwich-cultured rat and human hepatocytes and isolated perfused rat livers. The modulator glucagon (500 nM) and the phorbol ester PMA (0.1 muM) were utilized to increase intracellular cAMP and PKC levels, respectively. In glucagon-treated rat hepatocytes, efflux of the Mrp3 substrate 5-(6)-carboxy-2',7'-dichlorofluorescein (CDF) increased approximately 1.5-fold, even in hepatocytes treated with the organic anion transporter (Oatp) inhibitor sulfobromophthalein (BSP). Confocal microscopy revealed more concentrated Mrp3 fluorescence in the basolateral membrane (less diffuse staining pattern) with glucagon treatment. PMA had no effect on Mrp3 activity or localization in sandwich-cultured rat hepatocytes. Glucagon and PMA treatment in isolated perfused rat livers resulted in a threefold increase (14 +/- 4.6 mul.min(-1).g liver(-1)) and a fourfold decrease (1.3 +/- 0.3 mul.min(-1).g liver(-1)) in CDF basolateral clearance compared with control livers (4.7 +/- 2.3 mul.min(-1).g liver(-1)), whereas CDF biliary clearance was not statistically different. In sandwich-cultured human hepatocytes, glucagon treatment resulted in a 1.3-fold increase in CDF efflux and a concomitant increase in MRP3 fluorescence in the basolateral membrane. In summary, cAMP and PKC appear to be involved in the short-term regulation of Mrp3/MRP3, as demonstrated by alterations in activity and localization in rat and human hepatocytes.     

Tremor following intracerebral carbachol injection. 1.Carbachol sensitivity of various brain structures]

Tremor produced by intracerebral injection of carbachol. I. Susceptibility of different brain areas to carbachol Microinjections of carbachol into the lateral ventricle of rats caused tremor depending on dose. Intensity and duration of motor effects after injection of carbachol (30 mug/3 mul bilateral) into different brain areas were found to depend on localization: strongest tremor was elicited by injections into the nucleus caudatoputamen and cortex cerebri, moderate tremor by administration into the substantia nigra reticularis, globus pallidus and thalamic brain regions. Target areas of mean sensitivity were demonstrated in more rostral and caudal parts of the formatio reticularis. The injection of carbachol into the nucleus ruber, nucleus linearis and substantia nigra compacta brought about lowest tremor values. Ablation of the site of injection from the remaining brain abolished tremor induced by carbachol contrary to the tremor induced by oxotremorine.     

Dried Plasmodium falciparum-infected samples as positive controls for malaria rapid diagnostic tests

ABSTRACT: BACKGROUND: Rapid diagnostic tests (RDTs) are central to fulfilling the WHO's recommendation for parasitologic confirmation of all suspected cases of malaria. RDT performance may be compromised when exposed to the high temperature conditions typical of most malaria endemic regions. However, a systematic method to monitor RDT quality and performance in endemic countries is lacking at the present time. Current methods to monitor RDT performance in the field include comparing results from RDTs to diagnoses made by light microscopy and observing health workers perform tests. These methods are not substitutes for direct quality control. In this study, the suitability of dried Plasmodium falciparuminfected blood as quality control samples for malaria RDTs was evaluated. METHODS: Three cultured strains of P. falciparum at 200 and 2,000 parasites/mul were tested on 10 brands of RDT. After baseline testing to determine initial reactivity, aliquots of parasite-infected blood were air dried, stored at 35 degreesC, room temperature (~25 degreesC) or 4 degreesC for one, four and 12 weeks and were then tested on the 10 RDTs after rehydration. Extended stability testing of dried blood stored at 4 degreesC was done using P. falciparum strain 3D7 at 1,000 and 2,000 parasites/mul. RESULTS: All dried blood samples at 2,000 parasites/mul retained reactivity (100 % sensitivity) at all three temperatures and time points for all nine RDT brands that detect histidine-rich protein-2 (HRP2). The dried blood samples with 200 parasites/mul were detected by six of the nine HRP2-based RDTs at all storage temperatures and time points. The sensitivity for two of the three remaining HRP2-based RDTs was 100 % up to four weeks of storage at all temperatures but dropped to 87.5 % at week 12. Of the four RDTs that detect plasmodium lactate dehydrogenase (pLDH) in a pan-specific manner, alone or in combination with HRP2, the detection of pLDH in samples with 2,000 parasites/muL was 100 % for two RDTs and 80 % for the other two RDTs. The mean level for detection of pLDH at 200 parasites/mul was low (29 %), with a range of 0 % to100%, which was partly attributable to weak initial baseline reactivity. Reactivity of dried 3D7 at 1,000 and 2,000 parasites/mul stored at 4 degreesC was retained at 100 % for up to 52 weeks for both HRP2 and pLDH. CONCLUSIONS: In the absence of native or recombinant positive control antigens, well-standardized P. falciparum-infected dried blood samples can be used as positive control samples for monitoring RDT performance, particularly with HRP2-detecting tests.     

Bovine embryos cultured in serum-poor oviduct-conditioned medium need cooperation to reach the blastocyst stage

Immature bovine oocytes were matured and fertilized in vitro, and the resulting zygotes were cultured to the blastocyst stage in droplets of tissue culture medium 199 (TCM 199) conditioned by oviduct cells in the absence of serum. In Experiment 1, the effect of the number of zygotes in a constant culture volume was investigated by culturing 1, 4 or 40 zygotes in 40 mul of culture medium. The cleavage rate was low with a single embryo (36%) but increased with the number of embryos, to reach 50% with 4 embryos/40 mul and 59% with 40 embryos/40 mul. Blastocyst formation was nil with 1 embryo per 40 mul, reaching 2.5% with 4 embryos/40 mul and 18% with 40 embryos/40 mul. The effect of the size of the drop was assessed in Experiment 2, the concentration of embryos remaining constant (1 embryo/1 mul). The volumes tested were 10, 20, 30 and 40 mul. Development into blastocysts increased gradually from 12% in the 10 10 group to 20% in the 40 40 group. Experiment 3 was designed to find a minimal droplet volume able to support the development of a single embryo to the blastocyst stage. The minimum tested volume was 5 mul and was not successful. These results show that bovine embryos cultured in oviduct-conditioned TCM 199 need to cooperate to reach the blastocyst stage. The mechanism of this cooperation is not known, but some autocrine/paracrine factors, probably growth factors, could promote embryo development as was demonstrated in mice. From Experiment 2 we can hypothesize that the surface volume ratio of the droplets could play a role in the culture conditions by interfering with the exchanges between the culture medium and the surrounding environment.     

The role of oxygen limitation in the formation of poly-β-hydroxybutyrate during batch and continuous culture of Azotobacter beijerinckii

Azotobacter beijerinckii was grown in ammonia-free glucose-mineral salts media in batch culture and in chemostat cultures limited by the supply of glucose, oxygen or molecular nitrogen. In batch culture poly-beta-hydroxybutyrate was formed towards the end of exponential growth and accumulated to about 74% of the cell dry weight. In chemostat cultures little poly-beta-hydroxybutyrate accumulated in organisms that were nitrogen-limited, but when oxygen limited a much increased yield of cells per mol of glucose was observed, and the organisms contained up to 50% of their dry weight of poly-beta-hydroxybutyrate. In carbon-limited cultures (D, the dilution rate,=0.035-0.240h(-1)), the growth yield ranged from 13.1 to 19.8g/mol of glucose and the poly-beta-hydroxybutyrate content did not exceed 3.0% of the dry weight. In oxygen-limited cultures (D=0.049-0.252h(-1)) the growth yield ranged from 48.4 to 70.1g/mol of glucose and the poly-beta-hydroxybutyrate content was between 19.6 and 44.6% of dry weight. In nitrogen-limited cultures (D=0.053-0.255h(-1)) the growth yield ranged from 7.45 to 19.9g/mol of glucose and the poly-beta-hydroxybutyrate content was less than 1.5% of dry weight. The sudden imposition of oxygen limitation on a nitrogen-limited chemostat culture produced a rapid increase in poly-beta-hydroxybutyrate content and cell yield. Determinations on chemostat cultures revealed that during oxygen-limited steady states (D=0.1h(-1)) the oxygen uptake decreased to 100mul h(-1) per mg dry wt. compared with 675 for a glucose-limited culture (D=0.1h(-1)). Nitrogen-limited cultures had CO(2) production values in situ ranging from 660 to 1055mul h(-1) per mg dry wt. at growth rates of 0.053-0.234h(-1) and carbon-limited cultures exhibited a variation of CO(2) production between 185 and 1328mul h(-1) per mg dry wt. at growth rates between 0.035 and 0.240h(-1). These findings are discussed in relation to poly-beta-hydroxybutyrate formation, growth efficiency and growth yield during growth on glucose. We suggest that poly-beta-hydroxybutyrate is produced in response to oxygen limitation and represents not only a store of carbon and energy but also an electron sink into which excess of reducing power can be channelled.     

Carbon dioxide compensation points of flowering plants

Carbon dioxide compensation points of several hundred species of monocotyledons and dicotyledons have been measured during the course of various experiments in our laboratory over a period of several years. These have been classified into two groups: high, compensation points of 40 mul/l or greater; and low, compensation points of 10 mul/l or less. They are listed alphabetically both by families and species for monocotyledons and dicotyledons. Only two species did not unequivocally fit into the above established groups. These were Moricandia arvensis (L.) DC., which had an average compensation point of 26 mul/l and Panicum milioides Nees ex Trin., which was variable, but most often equilibrated between 12 to 20 mul/l CO(2).     

Contralateral but not systemic administration of bupivacaine reduces acute inflammation in the rat hindpaw

The effects of contralateral treatment with local anesthetics following acute hindpaw inflammation were investigated in rats. Inflammation was induced by unilateral injection of either 50 or 100 &#119 l of 1% carrageenan into the right paw. Contralateral injection of either bupivacaine or saline was given immediately before the carrageenan. Hindpaw edema and withdrawal responses to thermal and mechanical stimulation were evaluated after 3, 6 and 24 h. The results showed that the proinflammatory effects of carrageenan were strongest at 6 h after the injection of 100 mul carrageenan with bilaterally decreased withdrawal latencies and ipsilateral edema formation. Contralateral treatment with bupivacaine (1.25, 2.5 or 5 mg/ml) dosedependently reduced nociceptive behavior for 3-24 h. The edema was also reduced at 6 h. No effects on pain-related behavior were observed following systemic administration of bupivacaine. Sciatic nerve ligation on the contralateral side or intrathecal administration of saline significantly reduced the effects of bupivacaine when respectively compared with shamoperation and subcutaneous saline injection. Contralateral treatment with bupivacaine into the knee joint induced the same anti-nociceptive effect as administered into the paw. Our findings indicate that contralateral administration of bupivacaine induces long-lasting anti-nociceptive effects and may serve as a new or complementary treatment approach in acute inflammatory pain conditions.     

Urinary enzyme excretion during renal papillary necrosis induced in rats with ethyleneimine.

N-Acetyl-beta-glucosaminidase, beta-galactosidase, beta-glucosidase, acid and alkaline phosphatase were monitored in urine kidney homogenates and serum of rats with papillary damage induced with ethyleneimine. Serum urea levels, total protein in the urine and urine volume were monitored throughout the study. Histological studies showed that the injection of ethyleneimine caused immediate papillary necrosis, followed later by secondary cortical involvement. Minor papillary necrosis induced by a low dose (0.5 mul/kg) of ethyleneimine was characterised by a rise in urinary N-acetyl-beta-glucosaminidase activity which was followed later by an increase in the activity of the other enzymes monitored. More severe papillary necrosis induced with a higher dose of ethyleneimine (5.0 mul/kg) resulted in an immediate rise in the activities of all the urinary enzymes which then decreased only to rise again when cortical involvement occurred. Serum urea was unaltered but urine volume and protein were increased coincidentally with the urinary enzyme activities. The value of the assay of urinary enzymes in distinguishing papillary from glomerular and tubular damage is assessed. The possible relevance of the ethyleneimine model to the etiology of papillary nephropathy is discussed.     

Retinal degeneration from oxidative damage

Paraquat, a herbicide that generates reactive oxygen species, has been used to probe the oxidative defense systems of lung. In this study, we investigated the effects of paraquat in the retina. There was no significant decline in electroretinogram (ERG) a- or b-wave amplitudes after intravitreous injection of 1 mul of 0.5 mM paraquat in C57BL/6 mice, but loss of ERG function occurred after injection of 0.75 or 1 mM paraquat. Histology in paraquat-injected eyes showed condensation of chromatin and thinning of the inner and outer nuclear layers indicating cell death, and terminal deoxynucleotidyl transferase-mediated duTP-biotinide end labeling demonstrated that one mechanism of cell death was apoptosis. Fluorescence in the retina and retinal pigmented epithelium after intraocular injection of paraquat followed by perfusion with hydroethidine indicated high levels of superoxide radicals, and oxidative damage was demonstrated by staining for acrolein and enzyme-linked immunosorbent assay for carbonyl adducts. Paraquat-induced damage to the outer nuclear layer was greater in BALB/c mice than in C57BL/6 mice, suggesting strain differences in the oxidative defense system of photoreceptors and/or other modifier genes. Intravitreous injection of paraquat provides a new model of oxidative damage-induced retinal degeneration that is likely to be useful for testing new antioxidant treatments.     

Estradiol and neuropeptide Y (intra-lateral septal) reduce anxiety-like behavior in two animal models of anxiety

Anxiolytic-like effects of intra-lateral septal nuclei (LSN) infusions of the neuropeptide Y (NPY) alone or combined with estradiol benzoate were assessed in ovariectomized Wistar rats in two animal models of anxiety-like behavior. In a conflict test, immediately punished responses were assessed: 17-beta-estradiol (50.0microg/rat, P<0.05) plus vehicle (intra-LSN) or intra-LSN infusions of NPY (2.5microg/microl, P<0.05; 3.0microg/mul, P<0.05) plus vehicle (systemic route) or the combination of subthreshold doses of 17-beta-estradiol (25.0microg/kg) plus intra-LSN infusions of NPY (2.0microg/mul, P<0.05) increased the amount of immediately punished reinforcers. In the elevated plus-maze test several spatial-temporal variables were evaluated: 17-beta-estradiol (50.0microg/kg, P<0.05) plus vehicle (intra-LSN) or intra-LSN infusions of NPY (2.5microg/mul, P<0.05; 3.0microg/mul, P<0.05) plus vehicle (systemic route) or the combination of subthreshold doses of 17-beta-estradiol (25.0microg/kg) plus intra-LSN infusions of NPY (2.0microg/mul, P<0.05) produced anxiolytic-like actions without affecting locomotion. It is concluded that estradiol or NPY may produce anxiolytic-like actions and that subthreshold doses of estradiol and subthreshold doses of NPY when combined produced anxiolytic-like actions.     

Effect of silver iodide as an ice inducer on viability of frozen-thawed rabbit morulae

A new method was devised for inducing ice crystal formation in extracellular solution using silver iodide. A latent heat occurred immediately before temperature of sample reached -7 degrees C, when a column 70 mm high of 1.5M dimethyl sulfoxide (the freezing solution, FS) was aspirated into a plastic straw followed by 3 mm high of air and 10 mm high of 1% suspension of silver iodide in distilled water (1% AgI). To examine the effect of silver iodide as an inducer of ice crystal formation in extracellular solution on in vitro development of frozen-thawed rabbit morulae, the straws were filled by successive aspiration of the following fractions: 175 mul of FS containing the embryos, 7.5 mul of air, 25 mul of 1% AgI. The straws were cooled to -7 degrees C at 1 degrees C/min, and held at -7 degrees C for 10 min without initiating seeding; they were then cooled again to -30 degrees C at 1 degrees C/min and plunged into liquid nitrogen. After rapid thawing (>1000 degrees C/min), 100 of 109 (92%) embryos that were recovered developed into expanding blastocysts.     

Pressure-dependent PAH and creatinine transport from the brain ventricles.

The brain ventricular system of the adult dog was perfused with an artificial cerebrospinal fluid (CSF) containing inulin, creatinine and radioactively labeled p-aminohippuric acid (PAH) and mannitol. Inflow and outflow rates and concentrations of test molecules were measured at different intraventricular pressures, allowing calculation of their steady-state rates of removal from the ventricles. Clearance of inulin, a measure of CSF bulk absorption varied nearly with intraventricular pressure (- 15 to +12 cm H2O relative to the external auditory meatus). The efflux coefficient (Ko; representing clearance of a molecule by means other than bulk absorption) for mannitol was independent of intraventricular pressure. Ko's for PAH and creatinine were pressure dependent. PAH and creatinine efflux may be related to the amount of fourth ventricular choroid plexus surface exposed to the perfusion fluid. Ko's for creatinine and PAH (46 plus or minus 4 mul/min; 34 plus or minus 4mul/min, respectively) were significantly greater than mannitol (16 plus or minus 8 mul/min) at comparable intraventricular pressures, suggesting that both creatinine and PAH leave the CSF by an active process in addition to passive diffusion.     

Effect of glucagon on growth hormone secretion in rats

Gentled rats injected subcutaneously with glucagon (20 microgram/100 g body weight) showed a significant decrease in plasma growth hormone (GH) at 15 min after glucagon injection. A subcutaneous injection of 50% glucose did not cause the early suppression as shown at 15 min after glucagon injection, but at 30 min after glucose injection a tendency to decrease in plasma GH was observed. In urethane anesthetized rats, a subcutaneous administration of glucagon (1 microgram or 10 microgram/100 g body weight) failed to elicit an increase in plasma GH. In vitro incubation of anterior pituitary fragments with glucagon failed to decrease the release of GH, suggesting that glucagon does not act directly on the anterior pituitary.     

Effects of indomethacin and prostaglandins on ovulation of goldfish.

A technique is described whereby elevated temperature and HCG injection yield a high percentage of ovulation in gravid goldfish. Indomethacin (10 mug/g; i.p. injection) completely inhibits ovulation if given within 6 hours following HCG (4 IU/g); the unovulated oocytes develop rapidly into corpora atretica. PGE1, PGE2, and PGF2alpha (5 mug/g; i.p. injection) induce ovulation in fish treated with indomethacin and HCG; PGE2 was most effective when given 11 hours after HCG. The results suggest that the ovulatory action of prostaglandins following HCG stimulation is at the level of the ovary and that it is restricted to a period between 7 and 12 hours after the gonadotropin injection.     

LYSINE METABOLISM IN THE RAT BRAIN: BLOOD—BRAIN BARRIER TRANSPORT, FORMATION OF PIPECOLIC ACID AND HUMAN HYPERPIPECOLATEMIA

Through the use of intravenous pulse injection of L-[U-¹⁴C] lysine, the blood-brain barrier transport of L-lysine was studied. The uptake of L-lysine plus metabolites in the brain remained essentially unchanged at approx 0.002–0.005 nmol/g in the low dose (3μg per kg body weight) injection, and 20–40 nmol/g in the high dose (30 mg/kg) injection throughout the time intervals of up to 60 min. The uptake of L-lysine plus metabolites in the heart, however, decreased substantially from 0.03 to 0.003 nmol/g in the low dose injection and from 320 to 62 nmol/g in the high dose injection. The plasma to heart uptake ratio only decreased slightly through the 60 min period: from 6 to 2 in either the low or high dose L-lysine injection. The plasma to brain uptake ratio, however, decreased rapidly from a high of 62 to a low of about 4 in either the low or high dose injection throughout the 60-min time course. Study of labeled L-pipecolate formation in the plasma and individual organs indicates that this compound was formed only in the brain to a significant level within 0.5 min of ¹⁴C-L-lysine intravenous pulse injection. Labeled pipecolate was recovered from heart, liver, kidney and plasma in significant quantities only at 2 min or later after pulse-injection. It is concluded that the blood-brain barrier of L-lysine in the rat is not particularly strong and that the rat brain may be primarily responsible for L-pipecolate synthesis from L-lysine. The possible etiology of human hyperpipecolatemia is also discussed in light of the current findings.