Min In Relation Research Articles

San Min and its Spencerian origin

PurposeThe aim of this article is two-fold. First, it offers a unique account of San Min, the prototype of the current Chinese educational principle proposed by Yan Fu (1854–1921) that aimed at improving people’s physical, intellectual and moral capacities. This system of educational thinking has received only marginal attention in Anglophone research literature. Second, given the influence of Yan Fu’s interpretation and promulgation of Herbert Spencer’s educational philosophy during that period, it investigates the extent to which San Min is derived from Spencer’s educational thought (the “Spencerian Triad”). This article focusses on how Yan Fu adapted the ideas of San Min from Spencer’s account.Design/methodology/approachThis article considers Yan Fu’s principle of San Min in relation to Spencer’s educational triad through a close reading and comparison of key primary texts (including Yan Fu’s original writing). It explores the similarities and differences between each account of education’s goals and its proposed means of attainment.FindingsYan Fu’s principle of San Min is shown to have been adapted from the Spencerian Triad. However, using the theory of Social Organism, Yan Fu re-interpreted Spencer’s individual liberty as liberty for the nation. While Spencer’s goal was to empower individuals, Yan Fu aimed to serve collective independence, wealth and power.Originality/valueThis article addresses oversights concerning San Min’s Western origins in the Spencerian Triad and its influence on Chinese education under Yan Fu’s sway. It is significant because San Min is still at the core of the current Chinese educational policy.

Pesticide residues in sauce manufactured from agricultural products

In this study, pesticide residues in sauce manufactured from agricultural products were examined. A simultaneous multiresidue analysis for 260 pesticides in sauce samples was performed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). The QuEChERS AOAC 2007.01 (quick, easy, cheap, effective, rugged, and safe) was selected as the most suitable protocol for routine determination of pesticide residues. In line with the SANTE/11312/2021 guideline two parameters were used as identification criteria: retention time (RT) with a tolerance of ± 0.1 min in relation to the RT of the analyte in matrix-matched calibration standard and ion ratio tolerance below 30%. The RT deviation in positive samples was always < 0.1 min, and the ion ratio tolerance was < 30%. A total 4 different pesticides were detected in 20 sauce samples. No active ingredient was found in 16 samples. The residue levels were between 10 and 94 µg kg. The residues of acetamiprid, ametoctradin, imazalil sulfate, and metalaxyl-M were below the European Union Maximum Residue Limits (EU-MRLs).

Determination of glycaemic response to the consumption of two specialised formulas for glycaemic control.

To assess the glycaemic response after ingestion of two specialised oral and enteral nutrition formulas for glycaemic control. The participants were sixteen healthy volunteers, aged 21-49 years, with normal glucose tolerance. The volunteers attended the tests fasting for 10 h, for 5 weeks, and consumed the reference food - glucose solution - for 3 weeks, and the two formulas DiamaxO and DiamaxIG in the following weeks, in amounts equivalent to 25 g of available carbohydrates. During the period of 120 min, seven blood samples were taken through capillary blood sampling to determine the glycaemic response. The glycaemic index (GI) was calculated according to the trapezoidal rule, ignoring areas below the fasting line. The glycaemic load (GL) was determined by the formula GL = ((GI(glucose = reference) × 'g' of available carbohydrate per serving]/100. The formulas showed low GI and GL. GI = 37·8 and GL = 6·6 for DiamaxO and GI = 21·5 and GL = 3·5 for DiamaxIG. The peak of the glycaemic response occurred 30 min after ingestion, with a marked difference in blood glucose between the Diamax products in relation to glucose. Differences were also significant at times 15, 45, 60 and 90 min in relation to glucose (ANOVA with post hoc Bonferroni, P < 0·005), but not between the two products. However, the AUC and the GI of DiamaxIG are significantly smaller than that of the DiamaxO second t test (P = 0·0059). The glycaemic response to the products is quite reduced, presenting a curve with a little accentuated shape, without high peak, especially in the modified product.

СРАВНИТЕЛЬНАЯ ОЦЕНКА ПРОТИВОЛУЧЕВОЙ ЭФФЕКТИВНОСТИ ФЛАГЕЛЛИНА ПО ВЫЖИВАЕМОСТИ И МИКРОЯДЕРНОМУ ТЕСТУ

Purpose: Comparative evaluation of the effectiveness of the domestic drug flagellin (development of the State Research Institute of High-Purity Biological Products, St. Petersburg) in an extended range of drug administration periods before and after irradiation, as well as evaluation of the possibility of using the micronucleus test as a biomarker of its effectiveness.&#x0D; Material and methods: The work was performed on male ICR CD1 mice weighing 20–22g. The radioprotective effectiveness of flagellin was evaluated by the 30-day survival rate of experimental animals in comparison with control groups. The cytogenetic effect was evaluated by a micronucleus test in polychromatophilic erythrocytes (MJ-PCE) of mouse bone marrow. Irradiation was performed on the RUST M1 X-unit at a dose rate of 1.1 Gy/min in the dose range from 7 to 10 Gy for survival assessment and at a dose of 1 Gy for the micronucleus test. Flagellin was administered intraperitoneally at 0.2 mg/kg for 18 h and 30 min before irradiation, 10 and 30 min after irradiation. The animals of the control groups were injected with a solvent – phosphate-albumin buffer at the same time and in the same volume.&#x0D; Results: The most effective was the use of flagellin for 30 min and 10 min in relation to radiation (survival at 8.5 Gy 92 % and 78 %, at 9 Gy 81 % and 55 %, respectively) with survival in the control 29 % and 0. In the most studied version of the introduction of flagellin 30 minutes before exposure, the FID values at the level of generally accepted estimates LD16, LD50, LD84, were 1.3; 1.2 and 1.2, respectively.&#x0D; Conclusions: It is of interest to further expand the time range of the use of flagellin, especially after irradiation. The use of the method of estimating the proportion of polychromatophilic erythrocytes with micronuclei in the bone marrow allowed us to identify the optimal timing of drug administration much faster than in terms of survival (MJ-PCR test was performed 24 hours after irradiation). The MJ-PHE indicator can be considered as a potential biomarker of drug-induced increased radioresistance (this was previously shown in our studies for betaleukin, indralin, and riboxin).

Electrospun (Nickel and palladium) tin(IV) oxide/polyaniline/polyhydroxy-3-butyrate biodegradable nanocomposite fibers for low temperature ethanol gas sensing

Tin (IV) oxide (SnO2) nanostructures are regarded as one of the most popular materials for conventional gas sensors, due to their high surface area and fast response in regard to most reducing and oxidizing gases. However, their high operating temperature (>200 °C) leads to high power consumption and limits their applications. Here, a new nanocomposite fiber materials, consisting of undoped and doped (nickel and palladium) SnO2 nanorods, polyaniline (PANI), and polyhydroxy-3-butyrate (P3HB) are synthesized via the hydrothermal method,followed by an in situ polymerization and electrospinning technique. The as-synthesized nanocomposites are tested using ethanol gas at different operating temperatures: 25 °C (room temperature), 60 °C, and 80 °C. The results reveal that all samples began to show a response at 80 °C. Pd:SnO2/PANI/P3HB nanocomposite fiber sensors demonstrate a relatively higher response than that of SnO2/PANI/P3HB and Ni:SnO2/PANI/P3HB nanocomposite sensors. At 80 °C , the Pd:SnO2/PANI/P3HB nanocomposite sensor records a response (R0/Rg) of 1610, with a response time (Tres) of 90 s and a recovery time (Trec) of 9 min in relation to 1000 ppm ethanol gas in N2. The sensor also displays a good level of response (R0/Rg = 200) at a low concentration level (50 ppm) of ethanol gas. Structural and chemical characterizations indicate that the ethanol gas sensing performance of Pd:SnO2/PANI/P3HB nanocomposite fibers can mainly be attributed to the p-n heterojunction, fiber geometry, and one-dimensional structure of SnO2 and to the presence of the Pd catalyst. This bio-nanocomposite fiber has the potential to be a breakthrough material in biodegradable low temperature ethanol sensing applications.

Evaluation of Analgesic Activities of 80% Methanol Leaf Extract of Solanum incanum L. (Solanaceae) in Mice

Solanum incanum Linnaeus is traditionally used for treatment of pain and other ailments. But there is no scientific evidence on its analgesic activity to-date. Thus the aim of this study was to evaluate the analgesic activities of 80% methanol leaf extract of S.incanum in mice. After extraction of the crude using 80% methanol, S.incanum extract was evaluated for analgesic activity in hot plate test and acetic-acid induced writhing test. Mice were randomly assigned to different groups and treated with 100, 200 and 400 mg/kg doses of the extract and reference control groups (morphine 5mg/kg and Aspirin 150 mg/kg) and negative control were treated with 2% tween 80. In the hot-plate method, all doses of the extract and the standard drug of morphine prolonged the reaction time significantly (p&lt;0.05, or p&lt;0.01 or p&lt;0.001) as compared to negative control throughout the observation period. Prolongation of reaction time produced by 100mg/kg of the extract was lower (p&lt;0.01) compared to morphine, 200mg/kg, and 400mg/kg at 90 and 120 min. However, middle and higher dose exerts comparable result at 30, 60 and 90and 120 min in relation to the standard drug. In addition 80% methanol extract of S.incanum showed a significant protection (p&lt;0.05) against acetic acid induced writhing compared to negative control. The extract produced a significant analgesic activity with 55.6, 38.2 and 44.8% inhibition of number of writhing at 100, 200 and 400 mg/kg dose levels, respectively. In conclusion, this study clearly suggests that 80% methanol leaf extract of S. incanum is endowed with central and peripheral analgesic activity. Hence, the findings collectively uphold the traditional use of the plant for pain treatment.&#x0D; Keywords: Analgesic, S.incanum , Hot plate, Acetic acid

Purification of biodiesel by dry washing and the use of starch and cellulose as natural adsorbents: Part II – study of purification times

This work describes the use of adsorbents as starch from different sources (corn, potato, cassava and rice), cellulose and Select 450® and compared to conventional wet washing with hot water in biodiesel purification, varying the time: 1, 2.5, 5, 7.5, 10, and 15 min in relation to weight/volume fixed at 5%. The adsorbents were characterised by SEM and BET analysis. For the acidity index, all purification processes resulted values in agreement with the specifications of the ANP in Brazil. The levels of free glycerin with the use of Select 450® (at all times, except 10 min), cassava starch (at all times, except 5 min), and cellulose (at all times, except 1 and 10 min) were also in agreement with ANP specifications. In relation to a combined alkalinity test, the best results were obtained with the use of Select 450® and potato and cassava starches. The turbidity was satisfactorily reduced with the use of potato (10 and 15 min), cassava (15 min), and rice (2.5 min) starches as well as Select 450® (at all times). In terms of water content, there was a decrease compared with crude biodiesel and biodiesel purified by conventional wet washing.

High hydrostatic pressure processing affects the phenolic profile, preserves sensory attributes and ensures microbial quality of jabuticaba (Myrciaria jaboticaba) juice.

Jabuticaba (Myrciaria jaboticaba) is a Brazilian fruit rich in phenolic compounds and much appreciated for its sweet and slightly tangy taste. However, the high perishability of this fruit impairs its economic exploitation, creating an opportunity for the development of innovative products, such as high hydrostatic pressure (HHP) processed juices. We investigated the effect of HHP (200, 350 and 500 MPa for 5, 7.5 and 10 min) on phenolic compounds, antioxidant activity and microbiological quality of jabuticaba juice and the effect of the most effective HHP condition on its sensory acceptance. Pressurization increased total phenolic compound content (up to 38%) and antioxidant activity by FRAP assay (up to 46%), probably by increasing phenolic compound extractability due to tissue damage. Pressurization progressively decreased microbial counts, and colony growth was undetectable at pressures of 350 MPa or 500 MPa. With the exception of aroma, which was 10% lower in pressurized juice at 350 MPa for 7.5 min in relation to unprocessed juice, HHP did not affect sensory acceptance scores. Our results show that HHP was effective in ensuring microbiological quality, increasing bioactive potential and maintaining overall acceptance of jabuticaba juice, reinforcing the potential application of this processing technology in bioactive-rich foods. © 2017 Society of Chemical Industry.

Vertical migration of Daphnia galeata – Evidence for the use of an alternative resource from a lethal environment

Metazoans normally avoid anaerobic environments, at least when they are combined with toxic stress due to hydrogen sulfide. In Lake Speldrop, a small but deep gravel pit lake at the Lower Rhine, Daphnia galeata was found not only to dominate the zooplankton community, but was also regularly found in anoxic and even sulfidic layers during summer. We conducted field experiments with a newly developed “Zooplankton In-situ Incubator”, simulating vertical migrations of D. galeata . When daphnids were exposed to sulfidic conditions, mortality increased with exposure time, revealing LT 50 -values between 129 and 42 min in relation to increasing concentrations of sulfide. Additionally, those experimental individuals originating from 12.5 m depth showed significantly higher mortality rates than those from 7.5 m depth. Further migration experiments showed that an interruption period of sulfidic exposition in less stressful environments reduced mortality rates significantly. Daphnids found in the hypolimnion belonged partly to moribund parts of the population; however, the majority of daphnids showed regular mowing activity and was able to withstand sulfidic conditions in the hypolimnion for a limited time. It is so far unclear what maybe the major ultimate factor for this type of short term migratory behavior, to seek for shelter or to use high amounts of sulfur bacteria as an alternative food resource.

Glucagon-like peptide-2 stimulates mucosal microcirculation measured by laser Doppler flowmetry in end-jejunostomy short bowel syndrome patients

BackgroundIn animal and human studies glucagon-like peptide-2 (GLP-2) has been shown to increase blood flow in the superior mesenteric artery and the portal vein. This study describes the effect of GLP-2 measured directly on the intestinal mucosal blood flow by laser Doppler flowmetry (LDF) in end-jejunostomy short bowel syndrome (SBS) patients. MethodsIn five SBS patients with end-jejunostomy a specially designed laser Doppler probe was inserted into the stoma nipple, and blood flow measured directly on the jejunal mucosa for 105min in relation to no treatment, systemic saline infusion, topical adrenaline application and a subcutaneous injection of 800μg native GLP-2. ResultsThe GLP-2 injection increased jejunal mucosal blood flow by 79±37% compared to conditions, where no treatment was given (p<0.001). The significant effect was present at least 105min. Systemic saline infusion and topical, mucosal adrenaline application did not affect mucosal microcirculation. ConclusionsGLP-2 raises jejunal microcirculation in SBS patients with end-jejunostomy. This may explain the redness and increase in the end-jejunostomy nipple size imminently after commencing GLP-2 injections. The potential beneficial effects of this GLP-2-mediated increase of blood flow in the mesenteric bed should be investigated in clinical conditions other than the short bowel syndrome.

Effects of P2Y1 receptor antagonism on the reactivity of platelets from patients with stable coronary artery disease using aspirin and clopidogrel

P2Y(1) is a purine receptor that triggers platelet aggregation. Its inhibition was studied in patients with stable coronary artery disease (CAD) receiving standard anti-platelet therapy. Blood samples from 10 patients on aspirin therapy (ASA, 80 mg·day(-1) ) were withdrawn before and 24 h after the administration of 450 mg clopidogrel (ASA/C) and were anti-coagulated with citrate or hirudin/PPACK in the presence or absence of the P2Y(1 ) inhibitor MRS2179 (M, 100 µM). Platelet responses to ADP (2.5 µM) and TRAP (2.5 µM), and collagen-induced thrombosis under flow conditions were analysed. Compared with ASA, ASA + M strongly inhibited ADP-induced peak platelet aggregation (88%), late aggregation (84%), P-selectin expression (85%) and α(IIb) β(3) activation (62%) (28%, 65%, 70% and 51% inhibition, respectively, for ASA/C vs. ASA). ASA + M also inhibited platelet/monocyte and platelet/neutrophil conjugate formation by 69% and 71% (57% and 59% for ASA/C vs. ASA). In TRAP-activated blood, ASA + M unexpectedly inhibited α(IIb) b(3) activation by 30%. In blood perfused in collagen-coated glass capillaries (shear rate of 1500 s(-1) ), ASA/C prevented thrombus growth beyond 5 min in relation to thrombus fragments embolization. ASA + M with or without clopidogrel completely prevented thrombus formation. Finally, ex vivo addition of MRS2179 and ASA to the blood of healthy donors markedly blocked thrombus formation on collagen in flow conditions, in contrast to ASA plus the P2Y(12) inhibitor 2-MeSAMP. Through particularly efficient complementarities with ASA to inhibit platelet activation and thrombus formation, the inhibition of P2Y(1) in the blood of patients with CAD appears to play a more important role than previously anticipated.

Effects of edible coatings based on ultrasound-treated whey proteins in quality attributes of frozen Atlantic salmon (Salmo salar)

Abstract The effects of ultrasound-treated whey protein coatings on frozen Atlantic salmon quality parameters were evaluated. The experiment was performed using an ultrasonic bath at a frequency of 35 kHz and three sonication times (1, 15 and 60 min). The yield, the thaw yield, the drip loss in thawing, the drip loss after chilled storage and the cooking loss of fish samples were not influenced by the ultrasound treatment of coatings when compared to fish samples with untreated whey protein coatings. Decreases in yield, drip loss in thawing and drip loss after chilled storage were observed in samples from whey proteins sonicated 60 min in relation to those sonicated 15 min. The ultrasound treatment of whey proteins did not modify the colour of frozen and thawed fillets but increased L* and whiteness of cooked samples in comparison with untreated whey protein coated samples. All whey protein coatings decreased the lipid oxidation of fish fillets. However, the ultrasound treatment of coatings significantly delayed the lipid oxidation of salmon pieces in comparison with those coated with untreated proteins. The sensory properties of salmon samples were not negatively affected by these coatings. Industrial relevance Freezing is a very usual method of fish preservation; some changes during frozen storage that decrease product quality can occur, such as lipid oxidation. The results obtained in this investigation show that ultrasound applied to whey protein coatings could be useful for the reduction of the lipid oxidation of frozen salmon. These treated coatings could be a good alternative to conventional packaging and, at least, they could partially substitute plastic packaging. The edible coatings can contribute to reduce the plastic packaging residues of frozen seafood industry and the environmental contamination.

Ovarian function in cows submitted to acute stress during proestrus

Studies in which ACTH was administrated in heifers after the occurrence of luteolysis showed a delay in the onset of estrus and the estrus duration was shortened. This study evaluated the effect of acute stress by road transportation on estrous behavior and ovulation, monitored by serum progesterone and cortisol concentrations in cows at the periovulatory period, using a crossover design. Eleven crossbred cows, divided into Control and Transport groups had their estrus cycle synchronized with GnRH, an intravaginal progesterone device, and cloprostenol. Thirty hours after withdrawal of the device, the animals of the Transport group were transported for 60 min by truck and those from the Control group remained at pasture. Ovarian ultrasound examination was performed every 12 h from device withdrawal until ovulation in every cow. From the day after removal of the device until ovulation estrous behavior was monitored 24 h a day. Blood samples for serum cortisol and progesterone concentrations were taken at − 90, − 60, 0, 30, 60 and 180 min in relation to the end of transportation. Transportation during the estrous period induced stress in cows as reflected by changes in serum concentrations of progesterone and cortisol. However, we did not detect impairment in estrus expression, estrus duration or ovulation (P > 0.05).

Anionic linear aliphatic surfactants activate TRPV1: A possible endpoint for estimation of detergent induced eye nociception?

The transient receptor potential vanilloid type 1 (TRPV1) has been reported as one of the key components in the pain pathway. Activation of the receptor causes a Ca 2+ influx in sensory C-fibres with secondary effects leading to neurogenic inflammation in the surrounding tissue. We have earlier reported specific activation of TRPV1 by surfactant-containing hygiene products. We have continued this project by investigating activation of the TRPV1 by shampoo and soap ingredients in low concentrations measured as intracellular Ca 2+ influxes in stably TRPV1-expressing neuroblastoma SH-SY5Y cells. As a TRPV1 specific control, the TRPV1 antagonist capsazepine was used. The response was quantified as the product induced Ca 2+ influx during 2 min in relation to the maximum response induced by the TRPV1 agonist capsaicin. The results show that anionic alkyl linear surfactant ingredients such as sodium lauryl sulphate, sodium laureth sulphate, ammonium lauryl sulphate, sodium C12-15 pareth sulphate and N-lauroylsarcosine concentration-dependently induced Ca 2+ influx that could be addressed to TRPV1. The cationic surfactants benzalkonium chloride and cetylpyridinium chloride induced a Ca 2+ influx that was not TRPV1 mediated as well as the zwitterionic surfactant cocamidopropyl betaine, the non-linear anionic surfactant sodium deoxycholate and the non-ionic surfactant Triton-X. These results reveal a new mechanistic pathway for surfactant-induced nociception.

Change in hunger, fullness, ghrelin, PYY and GLP-1 in relation to a fixed test meal pre and post Rou-en-Y gastric bypass (RYGBS).

Bariatric surgery is the most effective treatment for achieving long-term weight loss in clinically severe obese patients. This study examines changes in hunger, fullness and appetite hormones in relation to a fixed meal in patients pre and 5 months post-RYGBS. There were 10 severely obese, otherwise healthy premenopausal women, BMI=45.3±6.8 SD, % body fat (BODPOD)=53.6±6.0, age=35±9.3. Ratings of hunger and fullness immediately preceded blood draws at 0, 15, 30, 60 min in relation to a fixed complete liquid meal of Glytrol, 250 ml, 1kcal/ml, consumed at 0–10 min. The meal was presented at 2 pm following an overnight 18-h fast. Results revealed a decline in hunger prior to the meal ( p =.013) and an increase ( p =.009) in area under the curve (AUC) for fullness from pre to post 5 months. However, fasting ghrelin and AUC for ghrelin did not change from pre to post-5 months. AUC for PYY ( p =.009) and GLP-1 ( p =.004) increased from pre- to 5 months post-surgery. However, the change in hunger did not correlate with the change in fasting ghrelin and the change in fullness AUC did not correlate with the changes in AUC for GLP-1 or PYY. Moreover, the reduction in stomach capacity itself would not be able to help explain the reduction in premeal hunger post-surgery. Thus, other biological mechanisms to explain the changes in hunger and fullness post-RYGBS should be explored. Supported by NIH DK 61519 and MO1 RROO64529.

Lactulose and mannitol intestinal permeability detected by capillary electrophoresis

Aim of this study was to set up a method by capillary electrophoresis to detect lactulose and mannitol in urine after an oral load, and to estimate the intestinal permeability in controls and in type I diabetes patients. The underivatized carbohydrates were monitored by indirect UV detection using sorbate, cetyltrimethylammonium bromide and LiOH as background electrolyte. Urines were purified by solid phase extraction, shaken with cation exchange resin, filtered and analysed. Carbohydrates migrated in <10 min in relation to their pK(a) and M(r). Controls (n = 33) and patients (n = 23) had an excretion ratio lactulose/mannitol 0.025 (0.018-0.051) and 0.067 (0.050-0.127), respectively (p < 0.01, median, interquartile range).

Inhaled Beclomethasone Dipropionate Acutely Stimulates Dose-Dependent Growth Hormone Secretion in Healthy Subjects

It is well known that systemic administration of corticosteroids has a dual effect on growth hormone (GH) secretion in man: acute systemic administration stimulates GH release, whereas chronic administration consistently blocks it. In this study, we evaluate whether administration of inhaled corticosteroids could acutely stimulate GH secretion, and whether this effect could be dose related. Double-blind, placebo-controlled, crossover study. Eight normal male volunteers all recruited at our institution. Administration of increasing doses of inhaled beclomethasone dipropionate (BDP; range, 50 to 1,500 mug) or placebo. Blood samples for GH determinations were collected at - 15, 0, 60, 120, 180, 240, 300, and 360 min in relation to BDP or placebo administration. The results of this study show a peak GH secretion at 240 min after the administration of BDP at doses > 100 microg. The comparisons among the peaks obtained with increasing doses showed a dose-response effect on GH secretion, starting from 100 to 1,000 microg. BDP 1,500 microg did not induce a peak significantly different from that obtained with 1,000 microg. When we calculated the GH response to BDP as an area under the curve (micrograms per liter x 6 h), the data confirmed that GH secretion was elicited in a dose-related manner. Our data show that inhaled BDP at dose > 100 microg acutely stimulates GH secretion in a strictly dose-dependent manner. We propose this test as a surrogate for systemic absorption and as a valuable test to compare systemic effects among different inhaled steroids.

Cortisol Responses to the Insulin Hypoglycaemia Test in Children

Aim: To determine the timing of the peak cortisol response to the insulin hypoglycaemia (IH) test in children and to establish paediatric reference data. Methods: We retrospectively reviewed all IH tests in a tertiary paediatric endocrine referral centre over a 6-year period. Inclusion criteria were age <16 years and adequate hypoglycaemia (glucose ≤2.0 mmol/l). Patients with an impaired hypothalamic-pituitary-adrenal axis or receiving glucocorticoid medication were excluded. Fifty-four subjects (35 males) met the criteria. Blood samples were collected at –30, 0, 20, 30, 60, 90, 120, and 150 min in relation to insulin bolus injection (0.15 U/kg) at 0 min. Glucose, cortisol, and growth hormone (GH) were measured in all samples. Results: Peak cortisol and GH responses occurred by 90 min in all subjects. Peak cortisol was inversely correlated with age (r_s –0.65, p < 0.0001). The median (5th centile) peak cortisol value was 689 nmol/l (547 nmol/l) in children younger than 10 years as compared with 555 nmol/l (468 nmol/l) in those older than 10 years (p < 0.0001). Peak cortisol was not related to peak GH (r_s –0.20, p = 0.15). Conclusions: Blood sampling in the IH test may be curtailed 90 min after injection. The peak cortisol response to IH is age related.

Nitric oxide regulates ovarian blood flow in the rat during the periovulatory period.

The aim of this study was to characterize the roles of nitric oxide (NO) on the rat ovarian blood flow (OBF) during the preovulatory period. Immature Sprague-Dawley rats were primed with pregnant mares' serum gonadotrophin (PMSG, 15 IU) and given hCG (15 IU) 48 h later. The ovary was exposed 48-56 h after PMSG, a laser Doppler probe was attached to the ovarian surface and OBF was measured at two time periods: preovulatory (PO) 48 h after PMSG and ovulatory (OV) 6-8 h after hCG. A non-selective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), was injected i.v. (4 and 10 mg/kg) or intrabursally (1 mg/kg). Intravenous administration of L-NAME to OV rats rapidly increased blood pressure and reduced OBF by 30%, which returned to the pretreatment level within 30 min. L-NAME given into the ovarian bursa of both PO and OV rats did not affect blood pressure and reduced OBF by nearly 40%, which remained low throughout the experiment. Intravenous injection of hCG to PO rats increased OBF to 116.1% at 5 min and 133.5% at 30 min in relation to the pretreatment level. When L-NAME was given intrabursally, subsequent hCG injection was without effect. These results indicate that locally produced NO is important for the maintenance and increase of rat OBF during the preovulatory period.

Blood-brain barrier transport and brain distribution of morphine-6-glucuronide in relation to the antinociceptive effect in rats--pharmacokinetic/pharmacodynamic modelling.

1. The objective of this study was to investigate the contribution of the blood-brain barrier (BBB) transport to the delay in antinociceptive effect of morphine-6-glucuronide (M6G), and to study the equilibration of M6G in vivo across the BBB with microdialysis measuring unbound concentrations. 2. On two consecutive days, rats received an exponential infusion of M6G for 4 h aiming at a target concentration of 3000 ng ml(-1) (6.5 microM) in blood. Concentrations of unbound M6G were determined in brain extracellular fluid (ECF) and venous blood using microdialysis and in arterial blood by regular sampling. MD probes were calibrated in vivo using retrodialysis by drug prior to drug administration. 3. The half-life of M6G was 23+/-5 min in arterial blood, 26+/-10 min in venous blood and 58+/-17 min in brain ECF (P<0.05; brain vs blood). The BBB equilibration, expressed as the unbound steady-state concentration ratio, was 0.22+/-0.09, indicating active efflux in the BBB transport of M6G. A two-compartment model best described the brain distribution of M6G. The unbound volume of distribution was 0.20+/-0.02 ml g brain(-1). The concentration-antinociceptive effect relationships exhibited a clear hysteresis, resulting in an effect delay half-life of 103 min in relation to blood concentrations and a remaining effect delay half-life of 53 min in relation to brain ECF concentrations. 4. Half the effect delay of M6G can be explained by transport across the BBB, suggesting that the remaining effect delay of 53 min is a result of drug distribution within the brain tissue or rate-limiting mechanisms at the receptor level.