Jugular Vein Plasma Research Articles

Pituitary adenylate cyclase activating polypeptide concentrations in the sheep mammary gland, milk, and in the lamb blood plasma after suckling.

Pituitary adenylate cyclase activating polypeptide (PACAP) is involved in development and reproduction. We previously described elevated PACAP levels in the milk compared to the plasma, and the presence of its specific PAC1 receptor in the mammary gland. This study aimed to determine PACAP and vasoactive intestinal peptide (VIP) levels in female suckling lambs compared to ewe plasma and mammary gland, as well as their age-dependent alterations. mRNA expressions of PACAP, VIP, PAC1 receptor and brain-derived neurotrophic factor (BDNF) were quantified in the milk whey and mammary gland. PACAP38-like immunoreactivity (PACAP38-LI) was measured in plasma, milk whey and mammary gland by radioimmunoassay, VIP-LI by enzyme-linked immunoassay. PACAP38-LI was 5, 6 times higher in the milk compared to the plasma of lactating sheep. It significantly increased in the lamb plasma 1 h, but returned to basal level 2 h after suckling. However, VIP mRNA was not present in the mammary gland, we detected the VIP protein in the milk whey. BDNF mRNA significantly decreased with age to approximately 60% and 25% in the 3- and 10-year-old sheep respectively, compared to the 3-month-old lambs. No differences were found between mammary and jugular vein plasma PACAP and VIP concentrations, or during the daily cycle. We propose a rapid absorption of PACAP38 from the milk and/or its release in suckling lambs. PACAP accumulated in the milk might be synthesized in the mammary gland or secreted from the plasma of the mothers. PACAP is suggested to have differentiation/proliferation promoting and immunomodulatory effects in the newborns and/or a local function in the mammary gland.

Changes in expression profiles of internal jugular vein wall and plasma protein levels in multiple sclerosis

BackgroundMultiple sclerosis (MS) is an inflammatory, demyelinating and degenerative disorder of the central nervous system (CNS). Several observations support interactions between vascular and neurodegenerative mechanisms in multiple sclerosis (MS). To investigate the contribution of the extracranial venous compartment, we analysed expression profiles of internal jugular vein (IJV), which drains blood from CNS, and related plasma protein levels.MethodsWe studied a group of MS patients (n = 19), screened by echo-color Doppler and magnetic resonance venography, who underwent surgical reconstruction of IJV for chronic cerebrospinal venous insufficiency (CCSVI). Microarray-based transcriptome analysis was conducted on specimens of IJV wall from MS patients and from subjects undergoing carotid endarterectomy, as controls. Protein levels were determined by multiplex assay in: i) jugular and peripheral plasma from 17 MS/CCSVI patients; ii) peripheral plasma from 60 progressive MS patients, after repeated sampling and iii) healthy individuals.ResultsOf the differentially expressed genes (≥ 2 fold-change, multiple testing correction, P < 0.05), the immune-related CD86 (8.5 fold-change, P = 0.002) emerged among the up regulated genes (N = 409). Several genes encoding HOX transcription factors and histones potentially regulated by blood flow, were overexpressed. Smooth muscle contraction and cell adhesion processes emerged among down regulated genes (N = 515), including the neuronal cell adhesion L1CAM as top scorer (5 fold-change, P = 5 × 10− 4).Repeated measurements in jugular/peripheral plasma and overtime in peripheral plasma showed conserved individual plasma patterns for immune-inflammatory (CCL13, CCL18) and adhesion (NCAM1, VAP1, SELL) proteins, despite significant variations overtime (SELL P < 0.0001). Both age and MS disease phenotypes were determinants of VAP1 plasma levels.Data supported cerebral related-mechanisms regulating ANGPT1 levels, which were remarkably lower in jugular plasma and correlated in repeated assays but not between jugular/peripheral compartments.ConclusionsThis study provides for the first time expression patterns of the IJV wall, suggesting signatures of altered vascular mRNA profiles in MS disease also independently from CCSVI. The combined transcriptome-protein analysis provides intriguing links between IJV wall transcript alteration and plasma protein expression, thus highlighting proteins of interest for MS pathophysiology.

An integrated study for the utilization of anthraquinone compounds extract “Heshouwu” In vivo and their comparative metabolism in liver microsomes using UPLC-ESI-Q-TOF/MSn

Objective: Anthraquinone (AQ), a major bioactive component of the traditional Chinese medicine HeShouWu, has widespread applications in industry and medicine. The objective of the current study is to explore the differences in the bioavailability of anthraquinones in vivo and the metabolism in liver microsomes. Materials and Methods: In vivo, we used a reliable UPLC-ESI-QqQ-MS/MS method to measure seven AQ compounds in the jugular vein plasma of rats following oral administration of HeShouWu. Furthermore, in order to quantify the bioavailability of AQs in vivo and to further understand the metabolism of these compounds, we compared the in vitro metabolism of AQ in different species with respect to metabolic profiles, the enzymes involved, and catalytic efficiency using liver microsomes from human (HLM), mouse (MLM), rat (RLM), and beagle dog (DLM). Results: We identified two metabolic pathways, including the hydroxylation and glucuronidation of AQ, in the liver microsomes of humans and other species using UPLC-ESI-Q-TOF. We found that substitutions on the AQ ring were crucial to the activity and regioselectivity of its hydroxylation. In general, hydroxylation activity decreased greatly with β-COOH (rhein) and enhanced dramatically with β-OH (emodin). We also found that glucuronidation of the compound emodin-8-O-β-D-glucoside acts as the main isoform in AQ hydroxylation in HLM and DLM. Total microsomal intrinsic clearance values for AQ were greatest in mouse microsomes, followed by those in dog, human, and rat microsomes. Conclusion: The absorption of different anthrquinone compounds varied based on the compound structure, the metabolism types and products of anthraquinones in liver microsomes were different in different species. These findings provide vital information for a deeper unuunderstanding of the metabolism of AQs.

One should avoid retro-orbital pharmacokinetic sample collections for intranasal dosing in rats: Illustration of spurious pharmacokinetics generated for anti-migraine drugs zolmitriptan and eletriptan

Because of the avoidance of first pass metabolic effects due to direct and rapid absorption with improved permeability, intranasal route represents a good alternative for extravascular drug administration. The aim of the study was to investigate the intranasal pharmacokinetics of two anti-migraine drugs (zolmitriptan and eletriptan), using retro-orbital sinus and jugular vein sites sampling. In a parallel study design, healthy male Sprague–Dawley (SD) rats aged between 8 and 12weeks were divided into groups (n=4 or 5/group). The animals of individual groups were dosed intranasal (~1.0mg/kg) and oral doses of 2.1mg/kg of either zolmitriptan or eletriptan. Serial blood sampling was performed from jugular vein or retro-orbital site and plasma samples were analyzed for drug concentrations using LC-MS/MS assay. Standard pharmacokinetics parameters such as Tmax, Cmax, AUClast, AUC0-inf and T1/2 were calculated and statistics of derived parameters was performed using unpaired t-test. After intranasal dosing, the mean pharmacokinetic parameters Cmax and AUCinf of zolmitriptan/eletriptan showed about 17-fold and 3-5-fold higher values for retro-orbital sampling as compared to the jugular vein sampling site. Whereas after oral administration such parameters derived for both drugs were largely comparable between the two sampling sites and statistically non-significant. In conclusion, the assessment of plasma levels after intranasal administration with retro-orbital sampling would result in spurious and misleading pharmacokinetics.

Effects of continuous low dose infusion of lipopolysaccharide on inflammatory responses, milk production and milk quality in dairy cows.

The objective of this study was to evaluate the effects of continuous low dose infusion of lipopolysaccharide (LPS) on inflammatory responses and milk production and quality in lactating dairy cows. Eight Holstein cows were assigned to two treatments in a cross-over experimental design. Cows were infused intravenously either with saline solution or with saline solution containing LPS from Escherichia coli O111:B4 at a dose of 0.01μg LPS/kg body weight for approximately 6hr each day during a seven-day trial. The clinical symptoms and milk production performance were observed. Milk samples were analysed for conventional components, fatty acids and amino acids. And jugular vein and mammary vein plasma samples were analysed for concentrations of cytokines and acute phase proteins. LPS infusion decreased feed intake and milk yield. An increase in body temperature was observed after LPS infusion. LPS infusion also increased plasma concentrations of interleukin-1β, serum amyloid A, LPS-binding protein, C-reactive protein and haptoglobin. LPS infusion decreased the contents of some fatty acids, such as C17:1, C18:0, C18:1n9 (trans) and C18:2n6 (trans), and most amino acids except for methionine, threonine, histidine, cysteine, tyrosine and proline in the milk. The results indicated that a continued low dose infusion of LPS can induce an inflammatory response, decrease milk production and reduce milk quality.

The short chain fatty acid propionate stimulates GLP-1 and PYY secretion via free fatty acid receptor 2 in rodents.

Background and Objectives:The gut hormones peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) acutely suppress appetite. The short chain fatty acid (SCFA) receptor, free fatty acid receptor 2 (FFA2) is present on colonic enteroendocrine L cells, and a role has been suggested for SCFAs in appetite regulation. Here, we characterise the in vitro and in vivo effects of colonic propionate on PYY and GLP-1 release in rodents, and investigate the role of FFA2 in mediating these effects using FFA2 knockout mice.Methods:We used Wistar rats, C57BL6 mice and free fatty acid receptor 2 knockout (FFA−/−) mice on a C57BL6 background to explore the impact of the SCFA propionate on PYY and GLP-1 release. Isolated colonic crypt cultures were used to assess the effects of propionate on gut hormone release in vitro. We subsequently developed an in vivo technique to assess gut hormone release into the portal vein following colonic infusion of propionate.Results:Propionate stimulated the secretion of both PYY and GLP-1 from wild-type primary murine colonic crypt cultures. This effect was significantly attenuated in cultures from FFA2−/− mice. Intra-colonic infusion of propionate elevated PYY and GLP-1 levels in jugular vein plasma in rats and in portal vein plasma in both rats and mice. However, propionate did not significantly stimulate gut hormone release in FFA2−/− mice.Conclusions:Intra-colonic administration of propionate stimulates the concurrent release of both GLP-1 and PYY in rats and mice. These data demonstrate that FFA2 deficiency impairs SCFA-induced gut hormone secretion both in vitro and in vivo.

Growth Hormone and the Lipolysis of Exercise

From a dissertation read before the Society on January 22nd. 1969.Growth hormone (GH) is secreted by the acidophil cells of the anterior pituitary. It is a protein, partially α-helix in structure, of molecular weight 29,000 in man (1 ). In addition to its effect in promoting growth several metabolic effects follow its administration, one of which, the mobilisation of free fatty acid (FFA) from adipose tissue, will be discussed in some detail.The radio-immunoassay methods for estimating GH (2, 3) which are the most sensitive and accurate now available, depend on the fact that radio-iodinated GH of high specific activity (4) competes with standard or test GH in plasma for binding sites on a γ-globulin in antiserum prepared in rabbits. The competition results in ‘bound’ and ‘free’ 131I-GH which are separable electrophoretically and counted for radio-activity. Inhibition curves relating bound: free ratios to standards are drawn and test samples assayed against them.There is good evidence that the assay is specific (5). Reactive material is elevated in acromegaly and is absent after hypophysectomy: jugular vein plasma contains more than inferior vena cava plasma: cross-reaction occurs between plasma samples only from species whose pituitaries contain cross-reactive material: acromegalic plasma acts just as a plasma dilution of pituitary extract.

Intravenous glucagon like peptide-1 infusion does not affect dry matter intake or hypothalamic mRNA expression of neuropeptide Y, agouti related peptide and proopiomelatnocortin in wethers

Relling, A. E., Loerch, S. C. and Reynolds, C. K. 2014. Intravenous glucagon like peptide-1 infusion does not affect dry matter intake or hypothalamic mRNA expression of neuropeptide Y, agouti related peptide and proopiomelanocortin in wethers. Can. J. Anim. Sci. 94: 357–362. The objectives of the present study were to determine the effects of jugular vein infusions of glucagon like peptide-1 (GLP-1) and dietary fat inclusion on dry matter intake, nutrient digestibility and hypothalamic mRNA concentration of neuropeptide Y, agouti related peptide, and proopiomelanocortin in growing sheep. Thirty-six wethers were used (40.7±3.3 kg BW). Treatments were a control diet (n=11), dietary addition (6% of dry matter) of Ca salts of palm oil fatty acids (n=12), or 6-d jugular vein infusions of 0.155 µg kg−1 body weight/day of GLP-1 (n=11). Hormone concentrations were measured in jugular vein plasma from samples taken on days 1, 4 and 6. On day 7, the wethers were slaughtered for hypothalamus collection to measure mRNA concentration. The dietary addition of 6% of Ca salts of palm oil increased plasma GLP-1 concentration (P&lt;0.01) and decreased dry matter intake on day 1, but not on day 6 (time×treatment interaction, P&lt;0.05). The infusion of GLP-1 did not change dry matter intake (P&gt;0.20), but increased neutral detergent fibre digestibility (P&lt;0.01). In conclusion, glucagon like peptide-1 infusion or feeding fat did not decrease dry matter intake or affect hypothalamic neuropeptide mRNA concentrations of sheep.

Effects of the rate of insulin infusion during isoglycemic, hyperinsulinemic clamp procedures on measures of insulin action in healthy, mature thoroughbred mares

The objective of this study was to determine whether the rate of insulin infusion during isoglycemic hyperinsulinemic clamp procedures affected measures of insulin action, including glucose disposal and plasma non-esterified fatty acid, endothelin-1, and nitric oxide concentrations, in mature, healthy horses. Eight thoroughbred mares were studied during a 2-h hyperinsulinemic clamp procedure, conducted at each of 4 rates of insulin infusion: 0 (CON), 1.2 (LOWINS), 3 (MEDINS), and 6 (HIGHINS) mU·kg−1·min−1. The infusion rate of a dextrose solution was adjusted throughout the clamp procedures to maintain blood glucose levels within 10% of baseline glucose concentrations. Plasma insulin concentrations were measured throughout the clamp procedures, and used with the rate of glucose infusion to calculate the plasma insulin concentration-to-rate of glucose infusion ratio, a measure of insulin action on glucose disposal. The rate of glucose infusion increased with rate of insulin infusion (P < 0.05). The plasma insulin concentration-to-rate of glucose infusion ratio was highest for the LOWINS treatment (P < 0.05) and decreased by 62% (P < 0.05) and 84% (P < 0.05) for the MEDINS and HIGHINS treatments, respectively. Although plasma non-esterified fatty acid concentrations were lower than baseline by t = 30 min of the clamp procedures in the LOWINS, MEDINS, and HIGHINS treatments (P < 0.05), the decline was similar for all 3 rates of insulin infusion. Jugular vein plasma nitric oxide and endothelin-1 concentrations were not affected by insulin infusion rate (P > 0.05). The data indicate that it is important to standardize insulin infusion rate if data are to be compared between hyperinsulinemic clamp studies.

Possible Mechanisms of Circulating PYY-Induced Satiation in Male Rats

Peptide tyrosine-tyrosine (PYY) is implicated in eating control, but the site(s) and mechanism(s) of its action remain uncertain. We tested acute effects of intrameal hepatic portal vein (HPV) PYY(3-36) infusions on eating in adult, male rats and measured HPV and jugular vein (JV) plasma levels of PYY in response to a solid, mixed-nutrient meal. We also examined the effects of HPV PYY(3-36) infusions on JV plasma levels, flavor acceptance, and neuronal activation. Intrameal HPV PYY(3-36) infusions [1 and 3 nmol/kg body weight (BW)] selectively reduced (P < 0.05) ongoing meal size. HPV PYY levels increased (P < 0.05) during a chow (12.5 kcal) or an isocaloric high-fat meal. JV PYY levels were generally lower than HPV levels but also increased in response to the chow meal. HPV PYY(3-36) infusion (1 nmol/kg BW) caused a greater increase in JV PYY than a meal, but neither 1 nor 3 nmol/kg BW PYY(3-36) caused conditioned flavor avoidance. HPV PYY(3-36) (1 nmol/kg BW) increased the number of c-Fos-expressing cells in the nucleus tractus solitarii, the hypothalamic arcuate and paraventricular nuclei, the central area of the amygdala, and the nucleus accumbens but not in the area postrema and parabrachial nucleus. These data show that HPV infusions of PYY(3-36) inhibit eating in rats without causing avoidance, and they identify some brain areas that might be involved. Endogenous PYY may induce satiation by acting directly in the brain, but further studies should examine whether PYY(3-36) administrations that mimic the meal-induced increase in plasma PYY are sufficient to inhibit eating.

Acute Changes in the Concentrations of Prostaglandin F2α (PGF) and Cortisol in Uterine and Ovarian Venous Blood During PGF‐induced Luteolysis in Cows

Prostaglandin F2α (PGF) is considered to be the main luteolysin in cattle. We have previously demonstrated that cortisol (Cr) suppresses PGF production in non-pregnant bovine endometrium. This study was carried out to test whether exogenous PGF increases ovarian and/or uterine PGF production and to determine the temporal relationship between PGF and Cr in ovarian and uterine circulations during PGF-induced luteolysis in cows. Catheters were inserted into the ovarian vein (OV), uterine vein (UV) and jugular vein (JV) of 10 cows on Day 9 of the oestrous cycle (Ovulation = Day 0) for frequent blood collection. On Day 10, the cows were divided randomly into two groups and treated with a luteolytic dose of a PGF analogue (cloprostenol) or saline solution. Blood samples were collected at -0.25, 0, 0.25, 0.5, 1 and 2 h and then at 2-h intervals until 12 h after treatment (0 h). The basal concentrations of PGF and Cr in OV and UV plasma were not significantly different. Injection of a PGF analogue induced more than twofold increases in the levels of PGF between 0.25 and 1 h in UV plasma, but not in OV plasma. PGF increased (p < 0.05) the concentrations of Cr in OV, UV and JV plasma between 0.5 and 1 h. The Cr levels in OV, UV and JV plasma were similar. The PGF levels in UV plasma decreased after Cr reached its highest levels. The overall results suggest that the uterus rather than the ovary increases PGF production in response to PGF injection. Based on the temporal changes of PGF and Cr in the ovarian and uterine circulations, Cr may act to reduce uterine PGF production in non-pregnant cows in vivo.

PATHOPHYSIOLOGY OF DEPRESSION: DO WE HAVE ANY SOLID EVIDENCE OF INTEREST TO CLINICIANS?

Due to the clinical and etiological heterogeneity of major depressive disorder, it has been difficult to elucidate its pathophysiology. Current neurobiological theories with the most valid empirical foundation and the highest clinical relevance are reviewed with respect to their strengths and weaknesses. The selected theories are based on studies investigating psychosocial stress and stress hormones, neurotransmitters such as serotonin, norepinephrine, dopamine, glutamate and gamma-aminobutyric acid (GABA), neurocircuitry, neurotrophic factors, and circadian rhythms. Because all theories of depression apply to only some types of depressed patients but not others, and because depressive pathophysiology may vary considerably across the course of illness, the current extant knowledge argues against a unified hypothesis of depression. As a consequence, antidepressant treatments, including psychological and biological approaches, should be tailored for individual patients and disease states. Individual depression hypotheses based on neurobiological knowledge are discussed in terms of their interest to both clinicians in daily practice and clinical researchers developing novel therapies.

Plasma ghrelin and oxyntomodulin concentrations in lactating dairy cows receiving abomasal soybean oil, corn starch, and casein infusions

The effects of increased postruminal supply of casein, corn starch, and soybean oil on plasma concentrations of the gastrointestinal hormones ghrelin and oxyntomodulin (OXM) were investigated. Four mid-lactation Holstein cows were used in a 4 × 4 Latin square. Treatments were continuous abomasal infusions (23 h/d) for 7 d of water, soybean oil (500 g/d), corn starch (1100 g/d), or casein (800 g/d). Jugular vein plasma was obtained every 30 min for 7 h on days 1 and 7. Soybean oil and casein infusion decreased preprandial plasma ghrelin concentration by approximately 20% on both d (time-by-treatment P < 0.10); however, dry matter intake (DMI) was depressed only after 7 d of oil infusion. Infusion of soybean oil, corn starch, or casein did not change the plasma OXM concentration ( P > 0.20 ). The present data indicate that plasma ghrelin concentration is depressed immediately before feeding by the postruminal infusion of soybean oil and casein, but it is not affected during the postprandial period. Plasma ghrelin concentration was not altered ( P > 0.20), pre- or postfeeding, by increased postruminal supply of corn starch. In addition, plasma OXM concentration did not respond ( P > 0.20 ) to postruminal nutrient infusion. In conclusion, a decrease in DMI when fat is infused could be partially explained by the decrease in prefeeding plasma ghrelin concentration, but a decrease in prefeeding plasma ghrelin concentration is not always associated with a decrease in DMI, as observed for the infusion of casein. Plasma OXM concentration was not affected by postruminal infusion of macronutrients.

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

Cardiopulmonary Bypass in 2009: Achieving and Circulating Best Practices

A novel system allowing long-term simultaneous video-electroencephalography recording, drug infusion and blood sampling in rats

Introduction Electroencephalography (EEG) recording and drug administration is commonly used for neurological experiments in rats, but is typically cumbersome due the use of multiple lines. We have developed a unique system, which allows long-term simultaneous video-electroencephalography recording, drug infusion and blood sampling in rats. Methods The vEEG/drug infusion system was designed and tested on two contrasting animal models of epilepsy. Animals were implanted with EEG-electrodes and a jugular vein cannula fixed in a head cap, avoiding an additional cable for tethering. In an acute infusion study ( n = 16), repeated blood samples were taken after i.v. bolus injection of valproate. In a subset of these rats ( n = 10), paired blood samples were removed from the jugular vein and the heart after valproate administration. In a chronic infusion study ( n = 38), heparinised (4 IU/h) saline or valproate (42 mg/kg/h) was infused continuously for up to 17 days. Results In the acute study, repeated blood samples showed a decrease in plasma valproate levels over time following bolus injection. In the chronic study, high quality continuous EEG was achieved and 79% of animals were successfully infused throughout the planned infusion period (13–17 days), with 66% of projected blood samples able to be taken during the infusion. There was a high correlation between the jugular vein and cardiac plasma levels of valproate (Spearman test, r = 0.69; p < 0.05). Conclusion This system is ideal for pharmacokinetic/dynamic studies and long-term drug infusion where simultaneous EEG and/or frequent blood sampling are desired.

The Oxidative Response in the Chronic Constriction Injury Model of Neuropathic Pain

In the chronic constriction injury model of rat neuropathic pain, oxidative stress as well as antioxidants superoxide dismutase and reduced glutathione (GSH) are important determinants of neuropathological and behavioral consequences. Studies of the chronic constriction injury model observed (indirect) signs of inflammation. We, therefore, investigated the level of oxidative stress and antioxidant enzymes in skeletal muscle tissue of the rat hind paw and (jugular vein) plasma at d 7 after nerve injury. The level of reactive oxygen and nitrogen species (RONS) was determined as a measure of oxidative stress. Reduced GSH levels and the ceruloplasmin/transferrin ratio were determined as measures of overall antioxidant activity. RONS and overall antioxidant activity were measured in skeletal muscle tissue of the hind paw and jugular vein plasma. The level of RONS in muscle was determined using spin trapping combined with electron paramagnetic resonance spectroscopy. Using electron paramagnetic resonance spectroscopy, we also determined plasma levels of transferrin and ceruloplasmin. GSH levels were determined using high-performance liquid chromatography. In skeletal muscle tissue, the level of RONS was lower in nerve-injured hind paws than in controls. The plasma level (jugular vein) of RONS did not differ between nerve-injured and control rats. In skeletal muscle tissue, the level of GSH was higher in nerve-injured hind paws than in controls. The ceruloplasmin/transferrin ratio tended to be higher in (jugular vein) plasma of nerve-injured rats as compared to controls. This study shows that, at d 7 after nerve injury, oxidative stress-induced changes are present also in skeletal muscle tissue of the rat hind paw. Our findings of a decreased level of RONS in combination with an increased level of the antioxidant GSH suggest that an overshoot of antioxidant activity overrules initial oxidative stress.

Abomasal infusion of casein, starch and soybean oil differentially affect plasma concentrations of gut peptides and feed intake in lactating dairy cows

The effects of specific nutrients on secretion and plasma concentrations of gut peptides (glucagon-like peptide-1 (7–36) amide (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin-8 (CCK)) differ across species, but are not reported for cattle. Our objective was to determine acute (hours) and chronic (1 week) effects of increased abomasal supply of protein, carbohydrate, or fat to the small intestine on dry matter intake (DMI) and plasma concentrations of GLP-1, GIP, CCK, and insulin. Four mid-lactation Holstein cows were used in a 4 × 4 Latin square design experiment. Treatments were 7-day abomasal infusions of water, soybean oil (500 g/d), corn starch (1100 g/d), or casein (800 g/d). Jugular vein plasma was obtained over 7 h at the end of the first and last day of infusions. Oil infusion decreased DMI on day 7, but total metabolizable energy (ME) supply (diet plus infusate) did not differ from water infusion. Casein and starch infusion had no effect on feed DMI; thus, ME supply increased. Decreased DMI on day 7 of oil infusion was accompanied by increased plasma GLP-1 concentration, but decreased plasma CCK concentration. Increased plasma GIP concentration was associated with increased ME supply on day 7 of casein and starch infusion. Casein infusion tended to increase plasma CCK concentration on both days of sampling, and increased plasma GLP-1 and insulin concentration on day 1 of infusion. The present data indicate a sustained elevation of plasma concentration of GLP-1, but not CCK, may contribute to the reduced DMI observed in dairy cows provided supplemental fat.

Prevalence of Endotoxemia in Healthy Postparturient Dairy Cows and Cows with Abomasal Volvulus or Left Displaced Abomasum

Left displaced abomasum (LDA) and abomasal volvulus (AV) occur most commonly in postparturient dairy cows. Our main hypothesis was that endotoxemia occurred more frequently in the peripheral blood of cows with LDA or AV than in healthy cows because increased luminal pressure in AV or LDA, or the presence of a hemorrhagic strangulating obstruction in AV, may have injured the abomasal mucosa, thereby facilitating translocation of luminal endotoxin into the circulation. Therefore, our main objective was to compare the prevalence and magnitude of endotoxemia in healthy postparturient cows with the prevalence and magnitude of endotoxemia in cows with AV and LDA. We examined 60 adult dairy cows in early lactation that were diagnosed with AV (n = 15) or LDA (n = 15) or were healthy on physical examination (control group, n = 30). Jugular venous blood was obtained from cows in all 3 groups, and right gastroepiploic venous blood was obtained during surgical correction of AV and LDA immediately after repositioning of the abomasum. Platelet‐rich plasma endotoxin concentrations were measured with a chromogenic limulus amoebocyte lysate assay. Endotoxin was detected in jugular vein plasma in 50% (15/30) of control cows; however, the prevalence of endotoxemia was significantly lower (P&lt; .05) in cows with AV (7%, 1/15) or LDA (20%, 3/15). Endotoxin was detected simultaneously in right gastroepiploic and jugular vein plasma in only 1 cow with LDA and 0 cows with AV. Contrary to our hypothesis, we conclude that endotoxemia is infrequently present in postparturient dairy cows with AV or LDA.

Blood-brain barrier produces significant efflux of L-aspartic acid but not D-aspartic acid: in vivo evidence using the brain efflux index method.

The brain efflux index method has been used to clarify the mechanism of efflux transport of acidic amino acids such as L-aspartic acid (L-Asp), L-glutamic acid (L-Glu), and D-aspartic acid (D-Asp) across the blood-brain barrier (BBB). About 85% of L-[3H]Asp and 40% of L-[3H]Glu was eliminated from the ipsilateral cerebrum within, respectively, 10 and 20 min of microinjection into the brain. The efflux rate constant of L-[3H]Asp and L-[3H]Glu was 0.207 and 0.0346 min(-1), respectively. However, D-[3H]Asp was not eliminated from brain over a 20-min period. The efflux of L-[3H]Asp and L-[3H]Glu was inhibited in the presence of excess unlabeled L-Asp and L-Glu, whereas D-Asp did not inhibit either form of efflux transport. Aspartic acid efflux across the BBB appears to be stereospecific. Using a combination of TLC and the bioimaging analysis, attempts were made to detect the metabolites of L-[3H]Asp and L-[3H]Glu in the ipsilateral cerebrum and jugular vein plasma following a microinjection into parietal cortex, area 2. Significant amounts of intact L-[3H]Asp and L-[3H]Glu were found in all samples examined, including jugular vein plasma, providing direct evidence that at least a part of the L-Asp and L-Glu in the brain interstitial fluid is transported across the BBB in the intact form. To compare the transport of acidic amino acids using brain parenchymal cells, brain slice uptake studies were performed. Although the slice-to-medium ratio of D-[3H]Asp was the highest, followed by L-[3H]Glu and L-[3H]Asp, the initial uptake rate did not differ for both L-[3H]Asp and D-[3H]Asp, suggesting that the uptake of aspartic acid in brain parenchymal cells is not stereospecific. These results provide evidence that the BBB may act as an efflux pump for L-Asp and L-Glu to reduce the brain interstitial fluid concentration and act as a static wall for D-Asp.

Morphometric and endocrine analyses of the effects of nutrition on the testis of mature Merino rams.

The effects of nutrition on the testis were investigated in groups of five mature Merino rams that were fed either a sub-maintenance (low) diet or a supra-maintenance (high) diet for 69 days. Testosterone, oestradiol and inhibin were measured in blood plasma sampled simultaneously from jugular and testicular veins after an i.v. injection of 200 ng ovine LH kg-1. Plasma concentrations of testosterone, inhibin and oestradiol were higher in testicular than in jugular vein plasma for both diets (P < 0.01). After the LH injection, jugular plasma testosterone increased more rapidly (P < 0.01) in rams fed the high diet than in rams fed the low diet. This was not seen in the testicular vein. Oestradiol concentrations were higher in rams on the high diet than in those on the low diet, in both the testicular (P < 0.0001) and the jugular vein (P < 0.02). Diet did not affect inhibin concentrations. Testes were surgically removed and processed for light microscopy. Testicular mass and seminiferous tubule length and diameter were higher with the high diet than the low diet (P < 0.01). The number of Sertoli cell nuclei per testis was also affected (high diet: 120 +/- 6 x 10(8); low diet: 77 +/- 7 x 10(8); P < 0.001), whereas the proportion of testis occupied by Sertoli cell nuclei was not affected. The number of Leydig cells per testis was not affected by diet, but Leydig cells occupied a greater volume of testis in rams on the high diet than in those on the low diet (P < 0.001). The effects of nutrition on Leydig and Sertoli cells are consistent with changes in the endocrine and exocrine functions of the testis. The finding that Sertoli cell population was altered in adult rams may be explained by the GnRH-independent effects of nutrition.