Evaluating in vitro and in vivo the interference of ascorbate and acetaminophen on glucose detection by a needle-type glucose sensor.

The aim of this work was to assess, in vitro and in vivo, the interference of ascorbate and acetaminophen on glucose measurements by a needle-type glucose sensor detecting hydrogen peroxide generated during the enzymatic oxidation of glucose, and to ascertain whether the protection against interference by the membranes used in the construction of the electrode is feasible. The oxidation of ascorbate and acetaminophen on a platinum electrode set at a 650 mV potential yielded a current representing 75 +/- 5% and 25 +/- 6% of that generated by the oxidation of an equimolar concentration of hydrogen peroxide, respectively. The bias introduced by the presence of 100 mumol l-1 ascorbate on the reading of 5 mmol l-1 glucose by the complete sensor (electrode + membranes) would be minimal (approximately 0.4 mmol l-1). By contrast, the bias introduced by 200 mumol l-1 of acetaminophen (a plasma concentration easily reached in clinical practice) was about 7 mmol l-1. The sensor was implanted subcutaneously in anaesthetized rats (n = 3). Using the current generated in the presence of a plasma acetaminophen concentration of about 200 mumol l-1 for glucose monitoring would lead to a major underestimation (approx. 6 mmol l-1) of subcutaneous glucose concentrations.     

Brain glutamate metabolism during hypoxia and peripheral chemodenervation

Glutamate stimulates resting ventilation by altering neural excitability centrally. Hypoxia increases central ventilatory drive through peripheral chemoreceptor stimulation and may also alter cerebral perfusion and glutamate metabolism locally. Therefore the effect of hypoxia and peripheral chemodenervation on cerebrospinal fluid (CSF) transfer rate of in vivo tracer amidated central nervous system glutamate was studied in intact and chemodenervated pentobarbital-anesthetized dogs during normoxia and after 1 h of hypoxia induced with 10 or 12% O2 in N2 breathing at constant expired ventilation and arterial CO2 tension. Chemodenervation was performed by bilateral sectioning of the carotid body nerves and cervical vagi. CSF transfer rates of radiotracer 13NH4+ and [13N]glutamine synthesized via the reaction, glutamate + NH4(+)----glutamine, in brain glia were measured during normoxia and after 1 h of hypoxia. At normoxia, maximal glial glutamine efflux rate jm = 103.3 +/- 11.2 (SE) mumol.l-1.min-1 in all animals. After 1 h of hypoxia in intact animals, jm = 78.4 +/- 10.0 mumol.l-1.min-1. In denervated animals, jm was decreased to 46.3 +/- 4.3 mumol.l-1.min-1. During hypoxia, mean cerebral cortical glutamate concentration was higher in denervated animals (9.98 +/- 1.43 mumol/g brain tissue) than in intact animals (7.63 +/- 1.82 mumol/g brain tissue) and corresponding medullary glutamate concentration tended to be higher in denervated animals. There were no differences between mean glutamine and gamma-aminobutyric acid concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Gluconeogenesis from lactate in the developing rat. Studies in vivo

1. The specific radioactivity of plasma l-lactate and the incorporation of (14)C into plasma d-glucose, liver glycogen and skeletal-muscle glycogen were measured as a function of time after the intraperitoneal injection of l-[U-(14)C]lactate into 2-, 10- and 30-day-old rats. 2. Between 15 and 60min after the injection of the l-[U-(14)C]lactate, the specific radioactivity of plasma lactate decreased with a half-life of 20-33min in animals at all three ages. 3. At all times after injection examined, the specific radioactivity of plasma glucose of the 2- and 10-day-old rats was at least fourfold greater than that of the 30-day-old rats. 4. Although (14)C was incorporated into liver glycogen the amount incorporated was always less than 5% of that present in plasma glucose. 5. The results are discussed with reference to the factors that may influence the rate of incorporation of (14)C into plasma glucose, and it is concluded that the rate of gluconeogenesis in the 2- and 10-day-old suckling rat is at least twice that of the weaned 30-day-old animal.     

The effect of citrate loading on exercise performance, acid-base balance and metabolism

Nine subjects (VO2max 65 +/- 2 ml.kg-1.min-1, mean +/- SEM) were studied on two occasions following ingestion of 500 ml solution containing either sodium citrate (C, 0.300 g.kg-1 body mass) or a sodium chloride placebo (P, 0.045 g.kg-1 body mass). Exercise began 60 min later and consisted of cycle ergometer exercise performed continuously for 20 min each at power outputs corresponding to 33% and 66% VO2max, followed by exercise to exhaustion at 95% VO2max. Pre-exercise arterialized-venous [H+] was lower in C (36.2 +/- 0.5 nmol.l-1; pH 7.44) than P (39.4 +/- 0.4 nmol.l-1; pH 7.40); the plasma [H+] remained lower and [HCO3-] remained higher in C than P throughout exercise and recovery. Exercise time to exhaustion at 95% VO2max was similar in C (310 +/- 69 s) and P (313 +/- 74 s). Cardiorespiratory variables (ventilation, VO2, VCO2, heart rate) measured during exercise were similar in the two conditions. The plasma [citrate] was higher in C at rest (C, 195 +/- 19 mumol.l-1; P, 81 +/- 7 mumol.l-1) and throughout exercise and recovery. The plasma [lactate] and [free fatty acid] were not affected by citrate loading but the plasma [glycerol] was lower during exercise in C than P. In conclusion, sodium citrate ingestion had an alkalinizing effect in the plasma but did not improve endurance time during exercise at 95% VO2max. Furthermore, citrate loading may have prevented the stimulation of lipolysis normally observed with exercise and prevented the stimulation of glycolysis in muscle normally observed in bicarbonate-induced alkalosis.     

Postnatal development of the hepatobiliary transport of phenolsulfonphthalein in rats

1. The postnatal development of the biliary excretion of phenolsulfonphthalein (PSP) was studied in male Wistar rats. 2. Following i.v. injection of PSP at 200 mumol/kg body wt, a maximal biliary excretion of 175 +/- 10 nmol/min/100 g body wt and 32 +/- 5 nmol/min/100 g body wt was reached for unconjugated and conjugated PSP, respectively, in the adult group. 3. The maximal biliary excretion of conjugated PSP was significantly lower in the 20-, 30- and 40-day-old groups as compared to the adults. The excretion of unconjugated dye was also significantly lower in 20- and 30-day-old rats. 4. The postnatal development of PSP excretion was unrelated to changes in the activity of UDP-glucuronosyltransferase. The importance of other factors is also discussed.     

Role of natriuretic factor in central nervous system (CNS)-induced natriuresis

The presence of a natriuretic factor in the plasma of rats in which a 350 mM Na (high Na) artificial cerebrospinal fluid (CSF) was infused into the lateral ventricle was tested. Blood was obtained from control rats and rats which received an infusion of high Na CSF intraventricular (IVT) for 15 min. The plasma was incubated for 30 min at room temperature, acidified, placed in a boiling-water bath, and then centrifuged. The plasma supernate was assayed for natriuretic activity in pentobarbital anesthetized bioassay rats. Sodium excretion increased 6.5 +/- 1.1 mueq/kg X min in rats which received an infusion of a control saline solution, 13.3 +/- 3.2 mueq/kg X min in rats which received infusion of control plasma supernates, and 32.1 +/- 8.3 mueq/kg X min in those rats which received plasma supernates from rats infused with high Na CSF IVT. Blood pressure was unchanged in all groups. The increment in sodium excretion elicited by plasma supernate from the high Na IVT group was significantly greater than that elicited by either control saline solution or control plasma extracts. Therefore, it is concluded that a heat-stable and nonpressor natriuretic factor is present in the plasma of rats infused IVT with high Na CSF.     

Influence of opioid peptides on release from vasopressin and oxytocin neurones of the hypothalamoneurohypophyseal system: effects of naloxone in the conscious rat

We examined the effects of acute and chronic treatments with naloxone on release of vasopressin and oxytocin from the hypothalamoneurohypophyseal system (HNS) in conscious, chronically instrumented Long-Evans rats. Plasma concentrations of vasopressin-associated neurophysin and oxytocin-associated neurophysin were evaluated before and during an intravenous infusion of 18% saline at 100 microL.kg-1 body weight.min-1 for 60 min. Acute treatment with naloxone (2.75 mumol/kg, intravenous) did not measurably alter basal plasma osmolality or vasopressin-associated neurophysin concentration, but it caused a three-fold rise in basal plasma oxytocin-associated neurophysin concentration (16 +/- 2 to 46 +/- 3 fmol/mL, p less than 0.005). Chronic treatment with naloxone (13.75 mumol/day, subcutaneous pellets) increased plasma osmolality (292 +/- 1 to 300 +/- 2 mosmol/kg H2O, p less than 0.01) by day 5, but it had no measurable effects on basal vasopressin- or oxytocin-associated neurophysin concentration. There were also no significant differences in plasma sodium concentration (144.8 +/- 1.1 vs. 142.2 +/- 1.4 mequiv./L) under both conditions. Acute and chronic treatments with naloxone accompanied by salt loading produced a five- and four-fold decrease in the rates that plasma concentration of vasopressin-associated neurophysin changed with plasma osmolality, compared with untreated salt-loaded control rats. For oxytocin secretion from the HNS, both treatments accompanied by salt loading substantially decreased the threshold for changes in relation to plasma osmolality; the rise in plasma concentration of oxytocin-associated neurophysin was similar at all levels of hyperosmotic stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carrier-Mediated Transport of Chloride Across the Blood-Brain Barrier

36Cl concentrations in each of eight brain regions and in cisternal cerebrospinal fluid (CSF) were determined 30 min after the intravenous injection of 36Cl in dialyzed-nephrectomized rats with plasma Cl concentrations between 14 and 120 mumol X ml-1. CSF 36Cl exceeded 36Cl concentrations in brain extracellular fluid. The calculated blood-to-brain transfer constants for Cl, kCl, ranged from 1.8 X 10(-5) S-1 at the parietal cortex to 3.8 X 10(-5) S-1 at the thalamus-hypothalamus. kCl fell by 42-62% when mean plasma [Cl] was elevated from 16 to 114 mumol X ml-1. Brain uptake of [14C]mannitol or of 22Na was independent of plasma [Cl], but 22Na influx into CSF fell when plasma [Cl] was reduced. Cl flux into brain and CSF could be represented by Michaelis-Menten saturation kinetics, where, for the parietal cortex, Km = 43 mumol X ml-1 and Vmax = 2.5 X 10(-3) mumol X S-1 X g-1, and for CSF Km = 68 mumol X ml-1. At least 80% of 36Cl influx into the parietal cortex was calculated to occur at the cerebrovascular endothelium, whereas the remainder was derived from tracer that first entered CSF. The CSF contribution was greater at brain regions adjacent to cerebral ventricles. The results show that Cl transport at the cerebrovascular endothelium as well as at the choroid plexus epithelium is a saturable concentration-dependent process, and that the CSF is a significant intermediate pathway for Cl passage from blood to brain.     

Progesterone secretion by adrenal glands of hamsters and comparison of ACTH influence in rats and hamsters.

Studies were designed to determine a) if adrenal glands of hamsters secrete progesterone (PROG), b) the effects of adrenocritocotropin (ACTH) administration on adrenocortial function of rats and hamsters under the surgical conditions necessary for collection of adrenal venous blood from the left renal vein, and c) the effects of blood loss during sample collection. PROG was quantitated by the competitive protein-binding method after extraction and separation by sephadex LH-20 column chromatography. The presence of interfering quantities of androstenedione necessitated two column chromatographic steps. Glucocorticoids (11-OHCS) were determined fluorometrically. PROG was detected in adrenal venous plasma of female hamsters. The PROG concentration and secretory rate were 91 +/- 12 ng/ml and 4 +/- 1 ng/min, respectively, while the peripheral plasma level of the same animals was 2 +/- 0.2 ng/ml, indicating that the adrenal glands of female hamsters are capable of secreting PROG. ACTH administration increased PROG secretory rates in both hamsters (3 +/- 1 to 14 +/- 3 ng/min) and rats (62 +/- 9 to 152 +/- 32 ng/min) on estrus, as well as increasing the 11-OHCS secretory rate of hamsters (16 +/- 1 to 33 +/- 4 ng/min), but not of rats. The greater increase in PRCC than in 11-OHCS secretion may be related to excess PROG formation relative to the capacity of the 17alpha- or 21-hydroxylating enzyme systems. The adrenal venous PROG concentration and secretory rate of female hamsters infused with 10% dextran while collecting adrenal venous blood did not differ significantly from those of the non-infused animals, suggesting that this amount of blood loss (1 ml) does not influence PROG secretion.     

Sex-hormone-binding globulin and albumin concentrations in human cerebrospinal fluid

Polyacrylamide gel electrophoresis of plasma and concentrated cerebrospinal fluid (CSF) preincubated with tritium labelled 5 alpha-dihydrotestosterone (DHT) showed identical migration of the radioactivity, indicating the presence of sex-hormone-binding globulin (SHBG) in human CSF. The concentrations of SHBG (measured as the binding capacity) and albumin were measured in concentrated CSF (12 women and 1 man) and samples of plasma of some patients (9 women). SHBG could not be detected in 6 of the CSF samples, and the mean value of the determinable samples was 42.3 +/- 13.4 pmol/l. The mean +/- SE of the SHBG concentration in plasma was 90.8 +/- 8.9 nmol/l and the mean albumin concentrations in CSF and plasma were 3.4 +/- 0.6 mumol/l and 670 +/- 107 mumol/l respectively. The distribution ratio for SHBG over the blood-CSF barrier was 10 times higher than for albumin. It was concluded that the SHBG-binding in the CSF is negligible but that the albumin-binding may contribute to the CSF concentrations of testosterone and estradiol, which are 10-25% above the plasma unbound concentrations.     

Plasma glutathione turnover in the rat: effect of fasting and buthionine sulfoximine

Hepatic glutathione (GSH) plays an important role in the detoxification of reactive molecular intermediates. Because of evidence that the intrahepatic turnover of glutathione in the rat may be largely accounted for by efflux from hepatocytes into the general circulation, the quantitation of plasma GSH turnover in vivo could provide a noninvasive index of hepatic glutathione metabolism. We developed a method to estimate plasma glutathione turnover and clearance in the intact, anesthetized rat using a 30-min unprimed, continuous infusion of 35S-labelled GSH. A steady state of free plasma glutathione specific radioactivity was achieved within 10 min, as determined by high-pressure liquid chromatography with fluorometric detection after precolumn derivatization of the plasma samples with monobromobimane. The method was tested after two treatments known to alter hepatic GSH metabolism: 90 min after intraperitoneal injection of 4 mmol/kg buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis, and after a 48-h fast. Liver glutathione concentration (mean +/- SEM) was 5.00 +/- 0.53 mumol/g wet weight in control rats. It decreased to 3.10 +/- 0.35 mumol/g wet weight after BSO injection and to 3.36 +/- 0.14 mumol/g wet weight after fasting (both p less than 0.05). Plasma glutathione turnover was 63.0 +/- 7.46 nmol.min-1.100 g-1 body weight in control rats, 35.0 +/- 2.92 nmol.min-1.g-1 body weight in BSO-treated rats, and 41.7 +/- 2.28 nmol.min-1.g-1 body weight after fasting (both p less than 0.05), thus reflecting the hepatic alterations. This approach might prove useful in the noninvasive assessment of liver glutathione status.     

Arachidonic acid-induced inhibition of (Na+K+)-stimulated ATPase in the cerebral cortex and medulla oblongata of young and adult rats

The effect of arachidonic acid in 5.10(-4) and 5.10(-5) mol.l-1 concentration (as the Na salt, SIGMA) on ouabain-sensitive ATPase (E. C. 3.6.1.3) activity was studied in the cerebral cortex and medulla oblongata of 5-day-old and adult rats. In adult rats, arachidonic acid significantly inhibited ouabain-sensitive ATPase activity in both the cerebral cortex and the medulla oblongata. In 5-day-old rats, only the higher concentration (5.10(-4) mol.l-1) inhibited the enzyme statistically significantly; use of the lower concentration was not followed by any significant changes in Na+-K+-ATPase activity.     

Nitric Oxide Synthase Activity in Retinas from Non-Insulin-Dependent Diabetic Goto-Kakizaki Rats: Correlation with Blood–Retinal Barrier Permeability

The aim of this work was to examine whether the non-insulin-dependent diabetic Goto-Kakizaki (GK) rats develop retinal changes with similar characteristics to those observed in insulin-dependent diabetic rats in what concerns blood-retinal barrier (BRB) permeability, nitric oxide (NO) production, and retinal IL-1beta level. BRB permeability was evaluated by vitreous fluorophotometry. NO synthase (NOS) activity was assessed by the production of l-[(3)H]-citrulline and retinal IL-1beta level was determined by ELISA. The expression of the inducible isoform of NOS (iNOS) protein was evaluated by Western blot analysis and immunohistochemistry. The in vivo studies indicated that in GK rats the BRB permeability to fluorescein was increased (787.81 +/- 68 min(-1)) in comparison to that in normal Wistar rats (646.6 +/- 55 min(-1)). The ex vivo studies showed that in retinas from GK rats the NOS activity was higher (207 +/- 28.9 pmol l-[(3)H]-citrulline/mg protein/30 min) than that in normal Wistar rats (125 +/- 32.3 pmol l-[(3)H]-citrulline/mg protein/30 min). These results were correlated with an increase in the protein level of iNOS in the retinas of GK rats, which was confirmed not only by the study of the iNOS protein expression but also by the use of NOS activity inhibitors. Indeed, the data about the effect of specific inhibitors on the NOS activity revealed that in retinas from GK rats the most effective inhibitor was aminoguanidine, which predominantly inhibits the iNOS isoform whereas in retinas from normal Wistar rats it was N(G) nitro l-arginine that predominantly inhibits the constitutive isoforms of NOS. In summary, in retinas from GK rats there is an increased production of NO which may contribute to the BRB breakdown.     

L-asparaginase activity in Aeromonas sp. isolated from freshwater mussel

Aeromonas sp. from Lamellidens marginalis produced L-asparaginase when grown at 37 degrees C. The optimum enzyme activity was at pH 9 when temperature was 45 degrees C. Half-life of partially purified enzyme at 50 degrees C and 55 degrees C was 35 and 20 min, respectively. Activation and deactivation energies of partially purified enzyme were 17.48 and 24.86 kcal mol-1 respectively. The enzyme exhibited a Km (L-asparagine) value of 4.9 x 10(-6) mol l-1 and a Vmax of 9.803 IU ml-1. Three metal ions inhibited the enzyme activity at 10-20 mumol l-1 concentrations. Catalytic activity was also inhibited by EDTA, iodoacetic acid, parachloromercuribenzoic acid and phenylmethylsulphonyl fluoride at 0.1 mumol l-1.     

Brain and cerebrospinal fluid uptake of zidovudine (AZT) in rats after intravenous injection

Uptake kinetics of zidovudine into cerebrospinal fluid (CSF) and brain tissue were determined in adult Sprague Dawley male rats after single intravenous injection of 6.7 mg/kg (25 mumol/kg). The drug kinetics in plasma followed biexponential disposition with an initial distribution half-life of approximately 11 minutes and an elimination half-life of 40 minutes. Over the plasma concentration range of 0.2 to 10 micrograms/ml, the cerebrospinal fluid to plasma ratio averaged 14.8 +/- 1.9% whereas the mean brain tissue to plasma ratio was 8.2 +/- 1.2% (uncorrected) or 2.3 +/- 1.8% (corrected) for the brain vascular space contribution. Simultaneous nonlinear regression analysis of brain, CSF and plasma concentration data indicate that the overall rate constant for efflux of drug from brain is approximately 75-fold higher and from CSF is 8-fold higher than the respective rate constants for influx. Thus, the ratio of the efflux to influx appears to be the predominant factor in determining the net accumulation of drug into CSF and brain parenchymal tissue.     

Inhibition of ovulation by tyrosine kinase inhibitors in the in vitro perfused rat ovary

Protein tyrosine kinase activity, leading to tyrosine phosphorylation of the intracellular domains of receptors or non-receptor proteins, is an important feature of downstream signalling after receptor binding of a variety factors, such as growth factors and cytokines. Since several members of these classes of paracrine-autocrine mediator may be involved in the intraovarian events of ovulation, the present study was designed to evaluate the effect of protein tyrosine kinase inhibition on the in vitro perfused rat ovary. Immature rats were primed with 20 iu pregnant mares' serum gonadotrophin 48 h before surgical isolation of the right ovary with connecting vasculature. The ovary was placed in a perfusion system for either 10 h, to examine ovarian concentrations of the established ovulatory mediators plasminogen activator, prostaglandins E2 and F2 alpha, or for 20 h, enabling a complete ovulatory process to occur in vitro. Ovulation was induced by ovine LH (0.2 microgram ml-1) in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (0.2 mmol l-1) and the effects of two different protein tyrosine kinase inhibitors, genistein and tyrphostin A25, were studied. Unstimulated control ovaries did not ovulate and showed low secretion of progesterone and oestradiol. Addition of LH + 3-isobutyl-1-methylxanthine resulted in a marked stimulation of steroid release, and ovulations occurred in all ovaries (9.0 +/- 0.9; mean +/- SEM). The protein tyrosine kinase inhibitors, genistein and tyrphostin A25, significantly inhibited ovulation at the higher concentrations tested (3.0 +/- 0.3 at 100 mumol genistein l-1; 5.8 +/- 1.0 at 500 mumol tyrphostin A25 l-1) but no effect was seen at lower concentrations. The presence of genistein and tyrphostin A25 at any concentration used did not significantly decrease the LH + 3-isobutyl-1-methylxanthine-induced progesterone or oestradiol concentrations. The intraovarian concentrations of plasminogen activator activity, and prostaglandin E2 and F2 alpha were not altered by the presence genistein (100 mumol l-1). In conclusion, the results of the present study indicate that protein tyrosine kinase signalling pathways are integral parts of the mammalian ovulatory process but do not involve actions on the synthesis of steroids, plasminogen activator or prostaglandins.     

Stimulation of the release of [32P]guanosine 5'-diphosphate from G proteins in the rat anterior pituitary lobe by gonadotrophin-releasing and thyrotrophin-releasing hormones.

Plasma membranes (1-2 mg protein) purified from the anterior pituitary lobes of adult male rats were incubated with 0.6 mumol [alpha-32P]guanosine 5'-triphosphate (GTP) l-1 in an ATP-regenerating buffer at 37 degrees C for 60 min; during this incubation the [32P]GTP was hydrolysed and the nucleotide that was predominantly bound to the membranes was [32P]GDP. The release of [32P]GDP from the membranes was monitored at 37 degrees C; the amount released was proportional to the protein concentration and increased as a function of time. 5'-Guanylylimidodiphosphate (Gpp(NH)p) increased [32P]GDP release by up to 30% at 0.1 mumol l-1. Although 10 nmol Gpp(NH)p l-1 had no effect on GDP release, it appeared to stabilize the hormonal effect by blocking further GDP-GTP exchange. Gonadotrophin-releasing hormone (GnRH) agonist and thyrotrophin-releasing hormone (TRH), at 0.1 mumol l-1 caused a maximum increase in the release of [32P]GDP of 31-38%. The GnRH agonist (0.1 mumol l-1) stimulated GDP release by 21%, 24%, 17% and 14% at 30 s, 1, 2 and 5 min, respectively. TRH (0.1 mumol l-1) stimulated GDP release by 38%, 30%, 17% and 16% at 30 s, 1, 2 and 5 min, respectively. A GnRH antagonist also stimulated [32P]GDP release, albeit less effectively than GnRH agonist; the antagonist did not inhibit agonist stimulation of GDP release. These results indicate that ligand binding to the GnRH and TRH receptors results in interaction of the receptor with a guanine-nucleotide-dependent transducer protein (G protein) and activation of GTP-GDP exchange.(ABSTRACT TRUNCATED AT 250 WORDS)     

Nucleoside and Oxypurine Homeostasis in Adult Rabbit Cerebrospinal Fluid and Plasma

Abstract: In adult New Zealand white rabbits, the effects of food deprivation and of massive elevations of plasma uridine or thymidine concentrations on CSF and plasma nucleoside and oxypurine concentrations were studied. Nucleoside and oxypurine levels were determined by high performance liquid chromatography using unequivocal methods of compound identification. After 48 and 96 h of food deprivation, the concentrations of uridine, cytidine, inosine, thymidine, deoxycytidine, deoxyuridine, hypoxanthine, xanthine, and uric acid in CSF and plasma were not different than in controls, except at 96 h, when the plasma uridine concentration was 35% lower (p < 0.05). After elevation of the plasma and CSF thymidine concentrations to ∼200 and 100 μM, respectively, with intravenous thymidine for 5 h, there was a large increase in CSF and plasma thymine to ∼100 μM and a smaller increase in plasma and CSF deoxyuridine concentrations. After elevation of the plasma and CSF uridine concentrations to 0.6 and 0.2 mM, respectively, there was a large increase in CSF and plasma uracil and a smaller increase in plasma and CSF deoxyuridine concentrations. Elevated plasma concentration of thymidine and uridine significantly decreased the CSF to plasma ratios of deoxyuridine and thymidine; however, only elevated plasma uridine concentrations decreased the CSF to plasma ratio of uridine. These results document the powerful homeostatic mechanisms that regulate the concentrations of the principal nucleosides and oxypurine bases in CSF.     

Growth hormone secretory pattern and somatomedin C plasma concentrations in newborn calves

Plasma growth hormone (GH) and somatomedin-C (IGF-1) concentrations were measured by radioimmunoassay in 16 dairy calves during the first 20 days of postnatal life. The lowest plasma GH concentration (0.07 +/- 0.01 nmols . l-1) occurred 4 h after birth. It increased gradually until the 3rd day, to reach values similar to those measured in adult males (0.15 +/- 0.05 nmoles . l-1) and remained stable until 20 days. The lowest plasma IGF-1 concentration (3.1 +/- 0.5 nmol . l-1) was measured at 3 days, then increased at 4 days (7.6 +/- 0.6 nmol . l-1) and remained stable until 20 days of age. In nine 2-10 days-old calves, the GH secretory profile observed in blood samples collected every 30 min over a 24-h period showed 8-13 secretory spikes, without periodicity. No relationship could be demonstrated between plasma GH and IGF1 concentrations. A marked increase in plasma GH concentrations followed every morning milk feeding.     

Effects of tiadenol and clofibrate on plasma post heparin lipolytic hepatic, extrahepatic and monoglyceride hydrolase activities in rats with hypertriglyceridemia induced by a sucrose rich diet

Normal rats fed an isocaloric sucrose-rich diet (SRD) for 3 weeks developed high levels of triacylglycerol in plasma (P) (mmol triacylglycerol I-1) heart (H) and liver (L) tissues (mumol triacylglycerol mg DNA-1) as compared to control rats fed the standard chow (STD) (X +/- SEM; P: SRD 1.32 +/- 0.06 vs STD 0.49 +/- 0.05, P less than 0.001; H: SRD 2.1 +/- 0.17 vs STD 0.94 +/- 0.01, P less than 0.001; L: SRD 8.48 +/- 1.47 vs STD 1.71 +/- 0.12, P less than 0.001). A simultaneous drop in the activities (mumol glycerol ml-1 hr-1) of several plasma post heparin lipolytic enzymes was observed; total triglyceride lipase (T-TGL): SRD 5.32 +/- 0.34 vs STD 7.48 +/- 0.64, P less than 0.01; lipoprotein lipase (LPL): SRD 1.61 +/- 0.26 vs STD 2.42 +/- 0.41, P less than 0.05; hepatictriglyceride lipase (H-TGL): SRD 3.71 +/- 0.28 vs STD 5.05 +/- 0.69, P less than 0.05 and monoglyceride hydrolase (MGH) (mumol glycerol I-1 min-1): SRD 558 +/- 108 vs STD 1165 +/- 45, P less than 0.001. Rats fed the SRD presented glucose intolerance after i.v. glucose (Kg X 10(-2); 1.06 +/- 0.09 vs 2.61 +/- 0.14 of STD, P less than 0.001) in spite of the presence of hyperinsulinism (sigma plasma IRI microU/ml from 0 to 30 min: 184.6 +/- 23.6 vs 100.5 +/- 9.7 of STD, P less than 0.01) suggesting that a state of insulin resistance had developed.(ABSTRACT TRUNCATED AT 250 WORDS)