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.     

Endothelial lipase is associated with inflammation in humans

The aim of this study was to investigate the extent to which inflammation is linked with plasma endothelial lipase (EL) concentrations among healthy sedentary men. Plasma C-reactive protein (CRP) concentrations were measured with a highly sensitive commercial immunoassay, plasma interleukin-6 (IL-6) concentrations were measured using a commercial ELISA, and plasma secretory phospholipase A(2) type IIA (sPLA(2)-IIA) concentrations were measured using a commercial assay in a sample of 74 moderately obese men (mean body mass index, 29.8 +/- 5.2 kg/m(2)). Plasma EL concentrations were positively correlated with various indices of obesity, fasting plasma insulin, and plasma CRP, IL-6, and sPLA(2)-IIA concentrations. Multiple regression analyses revealed that plasma CRP concentrations explained 14.5% (P = 0.0008) of the variance in EL concentrations. When entered into the model, LPL activity accounted for 16.1% (P < 0.0001) and plasma CRP concentrations accounted for 20.9% (P < 0.0001) of the variance in EL concentrations. The combined impact of visceral adipose tissue (VAT) and of an inflammation score on EL concentrations was investigated. Among subjects with high or low VAT, those having a high inflammation score based on plasma CRP, IL-6, and sPLA(2)-IIA concentrations had increased plasma EL concentrations (P = 0.0005). In conclusion, our data reveal a strong association between proinflammatory cytokines and plasma EL concentrations among healthy people with low or high VAT levels.     

Contribution of cholesterol 7alpha-hydroxylase to the regulation of lipoprotein metabolism.

Clinical studies have clearly established a relationship between bile acid synthesis and plasma LDL-cholesterol concentrations. Interruption of the enterohepatic circulation of bile acids leads to increased bile acid synthesis and a reduction in plasma LDL-cholesterol concentrations. New studies indicate that genetic variation in cholesterol 7alpha-hydroxylase activity accounts for a significant fraction of the inter-individual variation in plasma LDL-cholesterol concentrations in the general population, and a specific CYP7A1 allele associated with increased plasma LDL-cholesterol concentrations has been identified. Studies in which cholesterol 7alpha-hydroxylase was transiently overexpressed in hamsters and mice indicate that direct manipulation of cholesterol 7alpha-hydroxylase leads to changes in plasma LDL-cholesterol concentrations. Interestingly, targeted inactivation of the gene encoding cholesterol 7alpha-hydroxylase does not lead to increased plasma LDL-cholesterol concentrations in mice.     

Effects of gonadotropin-releasing hormone administration on the pituitary-gonadal axis in male and female dogs before and after gonadectomy

GnRH-stimulation tests were performed in 14 female and 14 male client-owned dogs of several breeds, before and 4 to 5 mo after gonadectomy. The aim of the study was to obtain more insight into the pituitary-gonadal axis in intact and neutered dogs and to establish reference values. Basal plasma luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were increased significantly after gonadectomy in both bitches and male dogs. In both males and females ranges of the basal plasma FSH concentrations, before and after gonadectomy, did not overlap as opposed to the overlap in ranges of the basal plasma LH concentrations. Before gonadectomy basal plasma LH concentrations were lower and basal plasma FSH concentrations were higher in bitches than in male dogs. After gonadectomy these basal values did not differ significantly. GnRH administration before gonadectomy resulted in an increase in plasma LH and FSH concentrations in both genders. GnRH administration after gonadectomy produced an increase only in plasma LH concentrations in both genders, and a just significant increase in plasma FSH in castrated male dogs. GnRH administration before gonadectomy resulted in a significant increase in plasma testosterone concentration in both genders. In males ranges of basal and GnRH-stimulated plasma testosterone concentrations before and after gonadectomy did not overlap. Basal plasma estradiol concentrations were significantly higher in intact males than in castrated males and their ranges did not overlap. The basal estradiol concentrations in bitches before and after ovariectomy were not significantly different. At 120 min after GnRH administration, ranges of plasma estradiol concentration of intact and ovariectomized bitches no longer overlapped. In conclusion, basal plasma FSH concentration appears to be more reliable than basal plasma LH concentration for verification of neuter status in both male and female dogs. The basal plasma testosterone concentration appears to be reliable for verification of neuter status in male dogs. The plasma estradiol concentration at 120 min after GnRH administration can be used to discriminate between bitches with and without functional ovarian tissue.     

Leptin acts peripherally to limit meal-induced increases in plasma insulin concentrations in mice: a brief communication

Leptin inhibits food intake and lowers plasma insulin concentrations. This study was designed to determine whether leptin acts independent of food-intake regulation to affect meal-induced increases in plasma insulin concentrations. Leptin-deficient, Lep(ob)/Lep(ob) mice were administered 1 microg leptin intracerebroventricularly (ICV) or intraperitoneally. Food intake and plasma insulin concentrations of mice administered leptin ICV before a meal were lower, as expected, than were intakes and plasma insulin concentrations of mice administered vehicle ICV. However when food intake was controlled, meal-induced increases in plasma insulin were unaffected by ICV administration of leptin. Intraperitoneal administration of 1 microg leptin before a meal lowered meal-induced increases in plasma insulin concentrations without influencing the size of the meal. We conclude that plasma leptin concentrations can affect meal-induced insulin secretion independent of the central nervous system actions of leptin associated with food-intake regulation.     

Mood changes in puerperium,and plasma tryptophan and cortisol concentrations.

Eighteen women aged 18-31 years were studied daily during the second to fifth postpartum days to assess mood changes and plasma tryptophan and cortisol concentrations. Psychiatric rating scales, clinical interviews, and published biochemical methods were used. Over the period plasma free tryptophan concentrations tended to rise and plasma cortisol concentrations to decline. There was a positive correlation between plasma free tryptophan concentrations and mood state.     

Plasma triiodothyronines in fetal sheep: effects of illness and thyroidectomy.

Plasma 3,5,3'-triiodothyronine (T3) and 3,3',5'-triiodothyronine concentrations were measured in fetal sheep prior to death in utero and after thyroidectomy. In six fetal sheep who subsequently died in utero, plasma rT3 concentrations were elevated in all for 2 to 13 days prior to death. There were no consistent changes in plasma T4 concentrations. In two thyroidectomized fetal sheep, plasma T4 and rT3 concentrations fell to low levels. Plasma T3 concentrations remained low and there was no increase in plasma T3 in the last week prior to parturition like that which occurs in normal fetal sheep. Parturition was preceded by the normal increase in fetal plasma cortisol concentrations and occurred at the normal time. These data indicate that plasma rT3 concentrations are increased as a result of illness in fetal sheep and that such measurements may be useful as an indicator of fetal distress. The normal increase in plasma T3 late in gestation is not necessary for the late gestational cortisol surge or for normal parturition.     

Should we measure serum or plasma lead concentrations?

ProjectSerum samples may not be appropriate to assess lead (Pb) concentrations because they may contain artificially higher Pb concentrations compared with those measured in plasma samples. Here, we compared Pb concentrations in serum versus heparin plasma separated from blood collected with or without vacuum. We have also examined the effects of sample standing time on Pb concentrations measured in serum, heparin plasma, and EDTA plasma.ProcedureWe studied plasma and serum samples from twelve healthy subjects. Blood samples were collected via venous drainage phlebotomy with and without vacuum into trace metal free tubes containing no anticoagulants (serum), or lithium heparin, or EDTA (to obtain plasma). Variable sample standing times (0, 5, and 30 min) prior to centrifugation were allowed. Plasma and serum Pb and iron concentrations were determined by inductively coupled plasma mass spectrometry. Plasma and serum cell-free hemoglobin concentrations were measured.ResultsPb concentrations in serum and in heparin plasma from blood samples collected with or without vacuum were similar and not associated with significant changes in iron or hemoglobin concentrations. The sample standing time (up to 30 min) did not affect Pb concentrations in serum or in heparin plasma, which were approximately 50% lower than those found in EDTA plasma.ConclusionsSerum or heparin plasma separated from blood samples collected via venous phlebotomy with or without vacuum are appropriate medium to assess Pb concentrations, independently of the sample standing time.     

Fetal and maternal endocrine changes associated with parturition in the goat

In 4 goats maternal jugular plasma concentrations of progesterone started to decline before labor commenced, but levels remained elevated above basal concentrations throughout parturition. Fetal and maternal plasma concentrations of estrogen rose before and during labor, increasing markedly just prior to fetal delivery. Fetal carotid plasma glucocorticoid concentrations appeared to rise over the 5 days prior to parturition, but a significant increase was only noted during labor. Maternal plasma concentrations of glucocorticoids were significantly lower than fetal plasma concentrations of glucocorticoids. Estradiol-17α was the predominant estrogen in both fetal and maternal plasma, less estrone was detected and apparently little estradiol-17β was present.No good correlation was found between plasma progesterone or estrogen and parturient uterine activity; the latter lasted from 22 to 78 hours, with the most dramatic increase occurring close to delivery. It is probable that other agents are involved in controlling uterine activity during parturition in the goat.     

Detection, analysis and interactions of plasma ghrelin, leptin and growth hormone in the mink (Mustela vison)

The aim of this study was to obtain basic knowledge of the plasma concentrations and interactions of weight regulatory hormones in juvenile minks (Mustela vison). Ghrelin, leptin, and growth hormone (GH) levels were validated and determined by radioimmunoassay methods from the plasma of 30 female and 30 male minks. The female minks had higher plasma ghrelin and GH levels than the males. The plasma ghrelin concentrations of the females correlated positively with their body masses (BMs). The plasma leptin levels did not differ between sexes, but there was a positive correlation between the plasma leptin concentrations and BMs in the male minks. When the data from the male and female minks were combined, the correlation between the leptin levels and the BMs was still clear, but this was not observed in the females alone. In the male minks, the plasma GH levels correlated positively with the BMs and with the plasma leptin concentrations. However, there was no correlation between the plasma ghrelin and GH or leptin concentrations. The hormone concentrations were quite similar to earlier measurements in other carnivores.     

The acute effects of central- and peripheral-acting dopamine antagonists on plasma HVA in schizophrenic patients

The short-term effects of fluphenazine on plasma HVA concentrations were compared with the effects of fluphenazine and concurrent administration of debrisoquin, a monoamine oxidase inhibitor which does not cross the blood brain barrier and is used to enhance the CNS contribution to circulating plasma HVA concentrations. Fluphenazine significantly increased plasma HVA with or without debrisoquin 24 hours following the initiation of treatment. Domperidone, a butyrophenone dopamine antagonist which acts only in the peripheral nervous system, failed to alter plasma HVA concentrations. These data suggest that the acute effects of neuroleptic drugs on plasma HVA concentrations are dependent upon interaction with CNS dopaminergic systems and provide additional support for the use of plasma HVA as a reflection of CNS dopamine system activity in clinical studies.     

Plasma noncholesterol sterols in male distance runners and sedentary men

Plasma lathosterol concentration is taken to be an index of the rate of cholesterol synthesis and plasma concentrations of plant sterols just as campesterol and betasitosterol are taken to be indeces of cholesterol absorption efficiency. These noncholesterol sterols were measured in plasma from 14 male distance runners and 10 sedentary men. Plasma lathosterol concentration was 30% lower (P less than 0.02) and plasma betasitosterol concentration was 33% higher (P less than 0.02) in the runners compared to the sedentary men. Plasma concentrations of lathosterol and plant sterols were inversely and significantly (P less than 0.05) correlated in both the runners and the sedentary men. Plasma plant sterol concentrations were correlated positively and significantly (P less than 0.01) with plasma high density lipoprotein cholesterol (HDL-C) concentrations in the runners and sedentary men combined. These findings suggest that more efficient cholesterol absorption may lead to higher plasma plant sterol concentrations and may contribute to lower cholesterol synthesis rates, reduced concentrations of plasma lathosterol and higher plasma HDL-C concentration in distance runners.     

Plasma lipid concentrations in professional cyclists after competitive cycle races

Plasma lipid concentrations were measured in professional cyclists at the beginning of the training season and both before the start and at the end of two cycle races of similar length (800 and 900 km in 6 days). Plasma concentrations of triglyceride, total and low density lipoprotein-cholesterol (LDL-C) and total cholesterol: high density lipoprotein-cholesterol (HDL-C) ratio were significantly lower and HDL-C concentrations significantly higher in cyclists compared to values in matched sedentary controls. At the end of the races, plasma concentrations of triglyceride and LDL-C were further reduced and HDL-C concentrations had increased compared to values at the start. At the end of the races, plasma concentrations of HDL-C were inversely correlated (r = -0.28, n = 45, P less than 0005) with triglyceride plasma concentrations. Body fat content, assessed as the sum of skinfold thicknesses was slightly reduced at the end of the race compared to the starting values. There was no significant correlation between skinfold thickness and plasma concentrations of HDL-C. Total plasma fatty acid concentrations were reduced and nonesterified fatty acids concentrations were increased at the end of the race compared to resting values. Consequently, the plasma concentrations of esterified fatty acids were significantly reduced after the race and there was a redistribution of the nonesterified fatty acids. The relative amounts of single fatty acids in the total fatty acid pool remained, however, remarkably constant. In conclusion, the results presented suggested that physical exercise, performed at the level of professional cyclists in a race, was an independent modifier of plasma lipid concentrations.     

Effects of dehydration on plasma osmolality, thirst-related behavior, and plasma and brain angiotensin concentrations in Couch's spadefoot toad, Scaphiopus couchii

Under dehydrating conditions, many terrestrial vertebrates species exhibit increases in plasma osmolality and their drinking behavior. Under some circumstances, this behavioral change is accompanied by changes in plasma and central angiotensin concentrations, and it has been proposed that these changes in angiotensin levels induce the thirst-related behaviors. In response to dehydration, the spadefoot toad, Scaphiopus couchii, exhibits thirst-related behavior in the form of cutaneous drinking. This behavior has been termed water absorption response (WR) behavior. Spadefoot toads live in harsh desert environments and are subject annually to dehydrating conditions that may induce thirst-related behavior. We tested the hypothesis that an increase in WR behavior is associated with both an increase in plasma osmolality and an increase in plasma and brain angiotensin concentrations. First, we determined the degree of dehydration that was necessary to initiate WR behavior. Animals dehydrated to 85% of their standard bladder-empty weight via deprivation of water exhibited WR behavior more frequently than control toads left in home containers with water available. Next, using the same dehydration methods, we determined the plasma osmolality and sodium concentrations of dehydrated toads. Toads dehydrated to 85% standard weight also had a significant increase in plasma osmolality, but exhibited no overall change in plasma sodium concentrations, indicating that while an overall increase in plasma osmolality appears to be associated with WR behavior in S. couchii, changes in sodium concentrations alone are not sufficient to induce the behavior. Finally, plasma and brain angiotensin concentrations were measured in control toads and toads dehydrated to 85% standard weight. Plasma and brain angiotensin concentrations did not increase in dehydrated toads, indicating that dehydration-induced WR behavior that is associated with changes in plasma osmolality may not be induced by changes in endogenous angiotensin concentrations in S. couchii.     

Variations in the distribution of calcium, magnesium and inorganic phosphorus within chronically catheterized sheep conceptuses during the last eight weeks of pregnancy

The concentrations of calcium, magnesium and inorganic phosphorus were higher in foetal arterial plasma than in maternal jugular plasma in sheep examined between 90 and 145 days of gestation. During the same period the calcium and magnesium concentrations of foetal urine were usually less than amniotic fluid values which in turn were less than maternal plasma concentrations. In allantoic fluid, calcium concentrations were usually less and magnesium concentrations greater than maternal and foetal plasma values. A 2-5 fold increase in the calcium concentrations of allantoic fluid after superfical uterine surgery and in amniotic fluid from a group of foetuses that were exposed during operation, were considered to be artefacts of technique. Inorganic phosphorus concentrations in foetal urine, amniotic fluid and allantoic fluid were variable.     

24-hour cerebrospinal fluid levels of vasopressin in hydrocephalic patients

The variation in vasopressin concentrations of ventricular cerebrospinal fluid and plasma throughout a 24-h period was studied in 10 patients with hydrocephalus. In 6 control patients, the diurnal variation in plasma vasopressin concentrations was studied. Vasopressin concentrations were determined by radioimmunoassay in plasma and in extracted and unextracted cerebrospinal fluid. Cortisol and osmolality in plasma were also measured. Vasopressin concentrations measured in extracted cerebrospinal fluid showed only small intra- and interindividual variation, while the corresponding values for unextracted cerebrospinal fluid were 2-5-fold higher and showed more variation. Plasma vasopressin concentrations varied considerably throughout the 24-h period in the individual hydrocephalic patient and between the patients. The pattern of variation was inconstant with no circadian rhythm, and the variation was not related to any changes in plasma osmolality, blood pressure or intracranial pressure. In some of the patients, the normal diurnal pattern of variation in plasma cortisol was broken, however, without a relation to the observed fluctuations in vasopressin concentrations. The abnormal variation of plasma vasopressin and cortisol was considered to reflect stress in connection with the intracranial pressure monitoring procedure. In the control patients, plasma vasopressin showed only small variations and plasma cortisol showed a normal diurnal rhythm. It is concluded that cerebrospinal fluid vasopressin concentration in patients with hydrocephalus is very constant throughout the day, even when plasma vasopressin concentrations show marked episodic increases. Thus, a circadian rhythm in the cerebrospinal fluid vasopressin concentration, as reported in several animal species, could not be confirmed in these patients.     

Free Amino-acid Concentrations in Fetal Fluids

The pattern of free amino-acid concentrations in maternal venous plasma, fetal umbilical arterial plasma, fetal urine, and amniotic fluid at 15 to 20 weeks'' gestation has been determined. Free amino-acid concentrations were greater in fetal plasma than in maternal plasma, amniotic fluid, or fetal urine.The ratios of amino-acid concentrations in fetal umbilical arterial plasma and urine indicate that the fetal kidney can effectively conserve amino-acids, possibly reaching an adult level of competence in this respect.There was little correlation between amino-acid concentrations in the fluids analysed with the exception of that between amniotic fluid and fetal urine.     

Comparison of Active Drug Concentrations in the Pulmonary Epithelial Lining Fluid and Interstitial Fluid of Calves Injected with Enrofloxacin,Florfenicol, Ceftiofur,or Tulathromycin

Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC₉₀ of 0.06 μg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 μg/mL), and the MIC₉₀ for Mannheimia haemolytica (1.0 μg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 μg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points.     

Relationship Between Plasma and Brain Large Neutral Amino Acids in Rats Fed Diets with Different Compositions at Different Times of the Day

Large neutral amino acids (LNAAs) compete with each other for carrier-mediated transport through the blood-brain barrier into the brain. The relative plasma concentration, expressed as the ratio of each LNAA to the sum of LNAAs, is considered the main regulator of brain LNAA concentrations. In order to investigate the consistency of this assumption throughout a 24-h period, we have compared the relationship of plasma LNAAs to brain LNAAs among groups of rats fed diets containing various amounts of protein (in order to obtain a wide range of plasma LNAA levels) at two different phases of the light/dark cycle (0900 and 2100 hours). The relationship between plasma and brain LNAAs was found to be dependent on both diet and the time of day. Similar plasma amino acid concentrations in the morning and in the evening contrasted with different brain concentrations. Furthermore, previous findings that brain LNAA concentrations are influenced by plasma amino acid concentrations were confirmed.     

Effects of weaning on concentrations of inhibin in follicular fluid and plasma of sows.

Changes in plasma and follicular fluid concentrations of inhibin were examined in sows after weaning at 28-32 days post partum. From 0 to 48 h after weaning, inhibin concentrations were 200-300 times higher in follicular fluid from small (less than 4 mm) and medium-large (greater than or equal to 4 mm) follicles than in ovarian venous plasma. Inhibin concentrations increased in follicular fluid from medium-large follicles at 24 and 48 h after weaning; concentrations in ovarian venous plasma were positively correlated with the number of medium-large follicles (r = 0.40) and with ovarian venous plasma concentrations of oestradiol (r = 0.61). Blood samples were collected for 30 days from sows (n = 6) that exhibited oestrus within 5 days after weaning and from sows (n = 5) that remained anoestrous for 11 days after weaning. Plasma inhibin concentrations rose in oestrous and anoestrous sows by 12 h and continued to rise for 60 h after weaning. Plasma inhibin concentrations rose further and were higher at 3.5-4.5 days after weaning in oestrous sows than in sows that remained anoestrous. After oestrus, plasma inhibin concentrations declined. At weaning, plasma concentrations of follicle-stimulating hormone (FSH) were higher in sows that subsequently exhibited oestrus than in sows that remained anoestrous. After weaning, plasma concentrations of FSH declined in both groups, reached a nadir at 2.5 days, and increased gradually in anoestrous sows; oestrous sows exhibited an FSH surge at oestrus. Plasma FSH returned to preweaning concentrations in both groups of sows at Days 7-8.(ABSTRACT TRUNCATED AT 250 WORDS)