Cholinergic system of rats treated with vincristine sulphate and nandrolone decanoate

This study aimed to detect brain and red blood cell acetylcholinesterase activity (AChE and RBC-AChE, respectively) of rats treated with vincristine sulphate and different doses of nandrolone decanoate. Thirty rats were divided into six groups (n = 5). The treatments were applied once a week for 2 weeks. Sample collection was performed in the third week. The groups were divided in: G1, physiologic solution (PS) (first and second week); G2, vincristine sulphate (4 mg/m²) in the first week and PS in the second week; G3, PS in the first week and nandrolone decanoate (1.8 mg/kg⁻¹) in the second week; G4, PS in the first week and nandrolone decanoate (10 mg/kg⁻¹) in the second week; G5, vincristine sulphate (4 mg/m²) in the first week and nandrolone decanoate (1.8 mg/kg⁻¹) in the second week; and G6, vincristine sulphate (4 mg/m²) in the first week and nandrolone decanoate (10 mg/kg⁻¹) in the second week. The isolated use of nandrolone decanoate and its use in association with vincristine sulphate altered brain AChE and RBC-AChE activity. These results suggest that there is interference in cholinergic neurotransmission, which could cause an alteration of its neurotransmitter, as well as a low or high stimulation of post-synaptic receptors. The serum RBC-AChE activity results presented in this study are similar to those exhibited by brain tissue.     

Enzyme activity of rat tibialis anterior muscle differs between treatment with triamcinolone and prednisolone and nutritional deprivation

The maximal activity of a selection of enzymes involved in muscle carbohydrate handling, citric acid cycle and fatty acyl β-oxidation were studied after treatment with the fluorinated corticosteroid triamcinolone and compared to a similar treatment of the non-fluorinated corticosteroid prednisolone in an equipotent anti-inflammatory dose. Furthermore, because triamcinolone causes loss of body mass and muscle wasting, the effects of triamcinolone were investigated relative to a control group, with the same loss of body mass, due to nutritional deprivation. The study was performed in male Wistar rats in the following treatment groups: TR, triamcinolone treatment (0.25?mg?·?kg^?1?· day^?1 for 2 weeks), which resulted in a reduction of body mass (24%); ND, nutritional deprivation (30% of normal daily food intake for 2 weeks) resulting in a similar (24%) decrease of body mass as TR; PR, prednisolone treatment (0.31?mg?·?kg^?1?·?day^?1 for 2 weeks), with a 10% increase in body mass; FF, free-fed control group, with a 12% increase in body mass in 2 weeks. Compared to FF, TR induced an increase in phosphofructokinase (PFK) activity (P?P?P?P?P?P?P?P?P?P?P?相似文献   

Effects of combined β-adrenergic and cholinergic blockade on the initial ventilatory response to exercise in humans

To elucidate whether combined adrenergic and parasympathetic blockade would affect the ventilatory response to exercise, especially at the initial stage (phase I), six healthy subjects performed a brief and light voluntary bilateral leg extension exercise and passive movements under the conditions of control (before the blockade) and after intravenous administration of combined β-adrenergic (propranolol, 0.2 mg?·?kg^?1) and muscarinic (atropine, 0.04 mg?·?kg^?1) receptor antagonists. The movements were continued only within two breaths after the onset of the motion. Ventilation increased immediately and significantly (P<0.05) within the first breath at the onset of voluntary exercise in all conditions as compared with at rest. However, the magnitude of increase in mean ventilation within two breaths at the start of exercise as against the resting value (delta ventilation) was significantly less (P<0.05) after the combined blockades (2.5 l?·?min^?1) than in the control condition (3.7 l?·?min^?1). Passive movements showed a similar but smaller change as compared with voluntary exercise. The heart rate response to exercise was attenuated by the combined blockade while cardiac output showed a slight change at the onset of exercise. It is concluded that phase I should occur despite the inhibited activity of the β-adrenergic and the cholinergic systems; nevertheless, the response was attenuated by the combined blockade. These results suggest a possible role of the β-adrenergic and/or cholinergic systems in the rapid increase in ventilation that occurs at the start of exercise.     

Integration of Pig-a, micronucleus, chromosome aberration, and Comet assay endpoints in a 28-day rodent toxicity study with 4-nitroquinoline-1-oxide

As part of the Stage III Pig‐a multilaboratory validation trial, we examined the induction of CD59‐negative reticulocytes and total red blood cells (RET^CD59? and RBC^CD59?, respectively) in male Sprague Dawley® rats treated with 4‐nitroquinoline‐1‐oxide (4NQO), for 28 consecutive days by oral gavage, at doses of 1.25, 2.50, 3.75, 5.00, and 7.50 mg kg^?1 day^?1 (the high dose group was sacrificed on Day 15 due to excessive morbidity/mortality). Animals also were evaluated for: micronucleated reticulocytes (mnRET) by flow cytometry; DNA damage in peripheral blood, liver, and stomach using the Comet assay; and chromosome aberrations (CAb) in peripheral blood lymphocytes (PBL). All endpoints were analyzed at two or more timepoints where possible. Mortality, body and organ weights, food consumption, and clinical pathology also were evaluated, and demonstrated that the maximum tolerated dose was achieved at 5.00 mg kg^?1 day^?1. The largest increases observed for the genetic toxicology endpoints (fold‐increase compared to control, where significant; all at 5.00 mg kg^?1 day^?1 on Day 29) were: RET^CD59? (21X), RBC^CD59? (9.0X), and mnRET (2.0X). In contrast, no significant increases were observed for the CAb or Comet response, in any tissue analyzed, at any timepoint. Because 4NQO is a well known mutagen, clastogen, and carcinogen, the lack of response for these latter endpoints was unexpected. These results emphasize the extreme care that must betaken in dose and endpoint selection when incorporating genotoxicity endpoints into routine toxicity studies as has been recommended or is under consideration by various regulatory and industrial bodies. Environ. Mol. Mutagen., 2011. © 2011 Wiley‐Liss, Inc.     

Beta-endorphin infusion alters pancreatic hormone and glucose levels during exercise in rats

β-Endorphin (BE) infusion at rest can influence insulin and glucagon levels and thus may affect glucose availability during exercise. To clarify the effect of BE on levels of insulin, glucagon and glucose during exercise, 72 untrained male Sprague-Dawley rats were infused i.v. with either: (1) BE (bolus 0.05?mg?·?kg^?1 +0.05?mg?·?kg^?1?·?h^?1, n?=?24); (2) naloxone (N, bolus 0.8?mg?·?kg^?1?+?0.4?mg?·?kg^?1, n?=?24); or (3) volume-matched saline (S, n?=?24). Six rats from each group were killed after 0, 60, 90 or 120 min of running at 22?m?·?min^?1, at 0% gradient. BE infusion resulted in higher plasma glucose levels at 60?min [5.93 (0.32)?mM] and 90?min [4.16 (0.29)?mM] of exercise compared to S [4.62 (0.27) and 3.41 (0.26?mM] and N [4.97 (0.38) and 3.44 (0.25)?mM]. Insulin levels decreased to a greater extent with BE [21.5 (0.9) and 18.3 (0.6) uIU?·?ml^?1] at 60 and 90?min compared to S [24.5 (0.5) and 20.6 (0.6)?uIU?·?ml^?1] and N [24.5 (0.4) and 21.6 (0.7)?uIU?· ml^?1] groups. Plasma C-peptide declined to a greater extent at 60 and 90?min of exercise with BE infusion compared to both S and N. BE infusion increased glucagon at all times during exercise compared to S and N. These data suggest that BE infusion during exercise influences plasma glucose by augmenting glucagon levels and attenuating insulin release.     

Comparison of immunofluorescence method with histochemical and ELISA methods focusing on wheat protein detection in meat products

Gliadin is a major allergen causing allergies occurring also in meat products. Since wheat protein is used as a meat substitute to reduce cost of meat products. Sensitive consumers of these products are really threatened by food allergies in different allergic reaction. The objective of the study was to compare the histochemical, immunochemical (ALERT gliadin screening test) and immunofluorescence methods for the detection of wheat protein in model meat samples and meat products. The limit of detection for the ALERT gliadin screening test was 10?×?10⁴?mg?kg^?1 of addition, while the histochemical method demonstrated concentration of wheat protein already from 10?×?10³?mg?kg^?1, and the immunofluorescence method from the concentration of 20?mg?kg^?1. Comparison of the methods using McNemar’s test shows a statistically highly significant difference (p?=?.01) between the immunofluorescence method and ELISA and a statistically highly significant difference (p?=?.01) between the immunofluorescence and histochemical methods.     

Systemic effects of angiotensin III in conscious dogs during acute double blockade of the renin-angiotensin-aldosterone-system

Aims: The study was designed to determine (i) whether the effects of angiotensin III (AngIII) are similar to those of angiotensin II (AngII) at identical plasma concentrations and (ii) whether AngIII operates solely through AT₁‐ receptors. Methods: Angiotensin II (3 pmol kg^?1 min^?1–3.1 ng kg^?1 min^?1) or AngIII (15 pmol kg^?1 min^?1–14 ng kg^?1 min^?1) was infused i.v. during acute inhibition of angiotensin converting enzyme (enalaprilate; 2 mg kg^?1) and of aldosterone (canrenoate; 6 mg kg^?1 plus 1 mg kg^?1 h^?1). Arterial plasma concentrations of angiotensins were determined by radioimmunoassay using a cross‐reacting antibody to AngII. During ongoing peptide infusion, candesartan (2 mg kg^?1) was administered to block the AT₁‐receptors. Results: Angiotensin immunoactivity in plasma increased to 60 ± 10 pg mL^?1 during infusion of AngII or infusion of AngIII. AngII significantly increased mean arterial blood pressure (+14 ± 4 mmHg) and plasma aldosterone by 79% (+149 ± 17 pg mL^?1) and reduced plasma renin activity and sodium excretion (?41 ± 16 mIU L^?1 and ?46 ± 6 μmol min^?1 respectively). AngIII mimicked these effects and the magnitude of AngIII responses was statistically indistinguishable from those of AngII. All measured effects of both peptides were blocked by candesartan. Conclusion: At the present arterial plasma concentrations, AngIII is equipotent to AngII with regard to effects on blood pressure, aldosterone secretion and renal functions, and these AngIII effects are mediated through AT₁‐ receptors. The metabolic clearance rate of AngIII is five times that of AngII.     

Heme oxygenase-1/biliverdin/carbon monoxide pathway downregulates hypernociception in rats by a mechanism dependent on cGMP/ATP-sensitive K<Superscript>+</Superscript> channels

Objective and design

To investigate the role of heme oxygenase-1 (HO-1), carbon monoxide (CO), and biliverdin (BVD) in the zymosan-induced TMJ arthritis in rats.

Materials and Methods

Mechanical threshold was assessed before and 4 h after TMJ arthritis induction in rats. Cell influx, myeloperoxidase activity, and histological changes were measured in the TMJ lavages and tissues. Trigeminal ganglion and periarticular tissues were used for HO-1, TNF-α, and IL-1β mRNA time course expression and immunohistochemical analyses. Hemin (0.1, 0.3, or 1 mg kg^?1), DMDC (0.025, 0.25, or 2.5 µmol kg^?1), biliverdin (1, 3, or 10 mg kg^?1), or ZnPP-IX (1, 3 or 9 mg kg^?1) were injected (s.c.) 60 min before zymosan. ODQ (12.5 µmol kg^?1; s.c.) or glibenclamide (10 mg kg^?1; i.p.) was administered 1 h and 30 min prior to DMDC (2.5 µmol kg^?1; s.c), respectively.

Results

Hemin (1 mg kg^?1), DMDC (2.5 µmol kg^?1), and BVD (10 mg kg^?1) reduced hypernociception and leukocyte migration, which ZnPP (3 mg kg^?1) enhanced. The effects of DMDC were counteracted by ODQ and glibenclamide. The HO-1, TNF-α, and IL-1β mRNA expression and immunolabelling increased.

Conclusions

HO-1/BVD/CO pathway activation provides anti-nociceptive and anti-inflammatory effects on the zymosan-induced TMJ hypernociception in rats.

     

Pancreatic secretory response to cholecystokinin-pancreozymin and caerulein in the conscious rat

1. The effects of graded intravenous doses of cholecystokinin (CCK) and caerulein on exocrine pancreatic secretion have, been assessed in conscious rats. Bile and pancreatic juice were separately returned to the duodenum between and during tests.
2. Low doses of CCK (from 417 to 3,335 ng kg^?1 h^?1) or caerulein (from 37.5 to 150 ng kg^?1 h^?1) slightly increased flow rate but increased K⁺ and HCO ₃ ^? outputs to a greater extent, without altering Cl^? output. The sum of the anion concentrations (Cl^?+HCO ₃ ^? ) stayed constant, which explains the decrease in Cl^? concentration when the HCO ₃ ^? concentration increased.
3. High doses of CCK (6,670 and 13,335 ng kg^?1 h^?1) and of caerulein (600 ng kg^?1 h^?1 strongly inhibited volume flow and outputs of all the ions, and the sum of the concentrations of anions fell.
4. Protein concentration and output increased with the same time course in response to both CCK and caerulein, i. e. course in response to both CCK and caerulein, i. e. a sustained stimulation during infusion, without any delayed inhibitory effect afterwards. The increase followed a linear dose-response relation to both CCK and caerulein. D50 was approximately 1,000 ng kg^?1 h^?1 for CCK and 95 ng kg^?1 h^?1 for caerulein. The maximal secretory rate of protein in our experiments was obtained with 300 ng kg^?1 h^?1 caerulein (20.27 mg 30 min^?1) and was almost twice that obtained with CCK (10.6 mg 30 min^?1) which suggests that the most potent agonist is a shorter derivative of CCK. Finally, both hormones decreased protein output at supramaximal levels.
5. It is concluded that both CCK and caerulein have similar effects on pancreatic secretion in the conscious rat and in other species. However, the conscious rat differs from other species in that water, HCO ₃ ^? and K⁺ secretions are stimulated by low doses of agonists. In contrast, high doses of agonists inhibited all components of secretion.

     

Angiogenic and Tissue Remodeling Factors in the Prostate of Elderly Rats Submitted to Hormonal Replacement

The influence of senescence and hormone replacement on the onset of pathologic processes in the prostate is not yet fully understood. The aim was to identify the immunoreactivity and protein levels of molecules involved in cell proliferation, tissue remodeling and angiogenesis in the ventral prostate of elderly rodents following hormonal replacement. Male Sprague–Dawley rats were separated into one Young group (4‐months old), treated with peanut oil (5 mL kg^?1, s.c.), and six Senile groups. The senile rats (10‐months old) were subdivided into: Senile group (SEN) (5 mL kg^?1 peanut oil, s.c.); Testosterone group (TEST) (5 mg kg^?1 testosterone cipionate, s.c.); Estrogen group (EST) (25 µg kg^?1 17β‐estradiol, s.c.); castrated group (CAS) (surgical castration); castrated‐testosterone group (CT) (same treatment as CAS and TEST groups); and castrated‐estrogen group (CE) (same treatment as CAS and EST groups). After 30 days, samples of the ventral prostate were harvested for analyses of insulin‐like growth factor‐1 receptor (IGFR‐1), matrix metalloproteinase‐9 (MMP‐9), vascular endothelial growth factor (VEGF) and endostatin features. IGFR‐1 and MMP‐9 showed increased protein levels and epithelial immunolabeling both after hormonal replacement and castration. Increased VEGF levels and reduced endostatin were verified in the SEN group. Hormonal therapy and castration led to a higher increase of VEGF, especially in the EST, CAS, and CE groups. Endostatin increased mainly in the TEST and CT groups. Hormonal therapy in senescence generated a reactive microenvironment characterized by the increase of mitogenic and tissue remodeling factors and by the imbalance of angiogenesis, which possibly compromised organ function and predisposed toward glandular disorders. Anat Rec, 296:1758–1767, 2013. © 2013 Wiley Periodicals, Inc.     

Honey and quercetin reduce ochratoxin A-induced DNA damage in the liver and the kidney through the modulation of intestinal microflora

This study was conducted to evaluate the interactions between the gut microbiota, ochratoxin A and functional food such as honey and quercetin, and the consequences of these interactions on ochratoxin-induced DNA damage in blood, liver and kidney cells. Honey (2?g?kg^?1) or Quercetin (50?mg?kg^?1) was applied to mice by intragastric application every day for 15 days, immediately before ochratoxin treatment (100?µg?kg^?1). We investigated colonic probiotic bacteria count, β-glucuronidase activity, the alkaline comet assay in blood, liver and kidney, the number of cells in the peritoneal cavity, macrophage spreading index and hematological and biochemical parameters. Honey and QU may reduce ochratoxin-induced DNA damage in the liver and kidney, β-glucuronidase activity and inflammation, partly through increasing the colon Bifidobacteria and Lactobacilli counts. The obtained results suggest that honey and QU counteracted the OTA-induced toxicity due to their bifidogenic activity and antigenotoxic activity.     

Development and Validation of Enzyme‐Linked Immunosorbent Assays for Quantification of Anti‐Methotrexate IgG and Fab in Mouse and Rat Plasma

Abstract

This laboratory is investigating the use of anti‐methotrexate IgG (AMI) and anti‐methotrexate Fab fragments (AMF) within an inverse targeting strategy that is designed to enhance the pharmacokinetic selectivity of intraperitoneal (i.p.) chemotherapy. The goal of this study was to develop enzyme‐linked immunosorbent assays (ELISAs) to determine concentrations of AMI and AMF in mouse and rat plasma. An antigen‐specific ELISA was developed for AMI and AMF in mouse and rat plasma. The assay was validated with respect to precision and accuracy by evaluating the recovery of AMI and AMF from mouse and rat plasma samples. Preliminary pharmacokinetic studies of AMI and AMF were performed in Sprague‐Dawley rats and Swiss Webster mice. The animals were instrumented with a jugular vein cannula and administered AMI or AMF, 15?mg?kg^?1 via the cannula. Plasma samples were taken at various time points and analyzed using the ELISA, and the observed concentration vs. time profiles were subjected to non‐compartmental pharmacokinetic analyses. Standard curves for the ELISAs were found to be linear over concentration ranges of 0–250 and 0–350?ng?mL^?1 for AMI and AMF, respectively. Intra‐assay and inter‐assay recovery of AMI and AMF from plasma samples were found to be within 15% of theoretical values. Preliminary pharmacokinetic investigations of AMI allowed estimation of AMI clearance to be 0.017?mL?kg^?1?min^?1 in the rat and 0.043?mL?kg^?1?min^?1 in the mouse. AMF clearance was estimated to be 0.038 and 1.93?mL?kg^?1?min^?1 in the mouse and rat, respectively. In conclusion, ELISAs have been developed and validated for quantitation of AMI and AMF in rat and mouse plasma. The assays will allow further investigations of AMI and AMF pharmacokinetics.     

Sex-related differences in thermoregulatory responses while wearing protective clothing

This study examined the thermoregulatory responses of men (group M) and women (group F) to uncompensable heat stress. In total, 13?M [mean (SD) age 31.8 (4.7) years, mass 82.7 (12.5)?kg, height?1.79?(0.06)?m, surface area to mass ratio 2.46?(0.18)?m²?·?kg^?1?·?10^?2, Dubois surface area 2.01 (0.16)?m², %body fatness 14.6 (3.9)%, V˙O_2peak 49.0?(4.8)?ml?·?kg^?1?·?min^?1] and 17 F [23.2 (4.2) years, 62.4 (7.7)?kg, 1.65 (0.07)?m, 2.71 (0.14)?m²?·?kg^?1?·?10^?2, 1.68 (0.13)?m², 20.2 (4.8)%, 43.2 (6.6)?ml?·?kg^?1?·?min^?1, respectively] performed light intermittent exercise (repeated intervals of 15?min of walking at 4.0?km?·?h^?1 followed by 15?min of seated rest) in the heat (40°C, 30% relative humidity) while wearing nuclear, biological, and chemical protective clothing (0.29?m²?·°C · W^?1 or 1.88 clo, Woodcock vapour permeability coefficient 0.33?i _m). Group F consisted of eight non-users and nine users of oral contraceptives tested during the early follicular phase of their menstrual cycle. Heart rates were higher for F throughout the session reaching 166.7 (15.9) beats?·?min^?1 at 105?min (n?=?13) compared with 145.1 (14.4)?beats?·?min^?1 for M. Sweat rates and evaporation rates from the clothing were lower and average skin temperature ( ) was higher for F. The increase in rectal temperature (T _re) was significantly faster for the F, increasing 1.52 (0.29)°C after 105?min compared with an increase of 1.37?(0.29)°C for M. Tolerance times were significantly longer for M [142.9?(24.5)?min] than for F [119.3?(17.3)?min]. Partitional calorimetric estimates of heat storage (S) revealed that although the rate of S was similar between genders [42.1?(6.6) and 46.1?(9.7) W?·?m^?2 for F and M, respectively], S expressed per unit of total mass was significantly lower for F [7.76?(1.44)?kJ?·?kg^?1] compared with M [9.45?(1.26) kJ?·?kg^?1]. When subjects were matched for body fatness (n?=?8?F and 8?M), tolerance times [124.5?(14.7) and 140.3?(27.4)?min for F and M, respectively] and S [8.67?(1.44) and 9.39?(1.05)?kJ?·?kg^?1 for F and M, respectively] were not different between the genders. It was concluded that females are at a thermoregulatory disadvantage compared with males when wearing protective clothing and exercising in a hot environment. This disadvantage can be attributed to the lower specific heat of adipose versus non-adipose tissue and a higher percentage body fatness.     

Effect of muscle glycogen availability on maximal exercise performance

This investigation determined the influence of pre-exercise muscle glycogen availability on performance during high intensity exercise. Nine trained male cyclists were studied during 75 s of all-out exercise on an air-braked cycle ergometer following muscle glycogen-lowering exercise and consumption of diets (energy content approximately 14 MJ) that were either high (HCHO – 80% CHO) or low (LCHO – 25% CHO) in carbohydrate content. The exercise-diet regimen was successful in producing differences in pre-exercise muscle glycogen contents [HCHO: 578(SEM?55) mmol?·?kg^?1 dry mass; LCHO: 364 (SEM 58) P??1 dry mass]. Despite this difference in muscle glycogen availability, there were no between trial differences for peak power [HCHO 1185 (SEM 50)W, LCHO 1179 (SEM?48)W], mean power [HCHO 547 (SEM?5)W, LCHO 554 (SEM ?8)W] and maximal accumulated oxygen deficit [HCHO 54.4 (SEM?2.3)?ml?·?kg^?1, LCHO 54.6 (SEM?2.0) ml?·?kg^?1]. Postexercise muscle lactate contents (HCHO 95.9 (SEM?4.6)?mmol?·?kg^?1 dry mass, LCHO 82.7 (SEM?12.3) mmol?·?kg^?1 dry mass, n?=?8] were no different between the two trials, nor were venous blood lactate concentrations immediately after and during recovery from exercise. These results would indicate that increased muscle glycogen availability has no direct effect on performance during all-out high intensity exercise.     

Testicular morphology and antispermatogenic effects of 2,4-dichlorophenoxyacetic acid (2,4-D) in male West African Dwarf (WAD) goats

This study investigated the testicular morphology as well as the gonadal and extra-gonadal sperm reserves of West African Dwarf (WAD) goats exposed to graded levels of 2,4-dichlorophenoxyacetic acid (2,4-D). Twenty male WAD goats of five goats per group were used for this study. Goats in groups A, B and C received low [75?mg/kg body weight (BW)], medium (100?mg/kg BW) and high (125?mg/kg BW) dose levels of 2,4-D, respectively. The group D goats served as the control. On day?112, goats in the four groups were sacrificed and the testicular and epididymal sperm reserves were determined. Histopathologic changes in the testis of the 2,4-D-exposed and control goats were also assessed. The mean number of spermatozoa in the testes and the various segments of the epididymides decreased significantly (p?<?0.05) in all the treatment groups relative to the control. Combined testicular sperm reserve per millilitre for the treatment groups (group A—19.61?±?2.63?×?10⁸, group B—12.02?±?1.02?×?10⁸ and group C—9.95?±?0.97?×?10⁸) reduced significantly (p?<?0.05) relative to the mean value (23.52?±?4.43?×?10⁸) of the control—group D. The total epididymal sperm reserve per millilitre in the treatment groups (group A—24.25?±?4.19?×?10⁸, group B—17.18?±?2.57?×?10⁸ and group C—17.88?±?2.89?×?10⁸) was also found to be significantly (p?<?0.05) lower than the mean value (40.85?±?11.24?×?10⁸) for the control—group D. This reduction in the testicular and epididymal sperm counts of the 2,4-D-exposed WAD goats in this study suggest disruption in spermatogenic activity, which may lead to low productivity. Variable degrees of circulatory disturbances were observed in the testis sections of 2,4-D-exposed goats.     

N-methyl-d-aspartate receptor antagonists potentiate morphine's antinociceptive effect in the rat

The interaction between morphine and three antagonists of the N-methyl-d -aspartate (NMDA) receptor, MK-801 (non-competitive channel blocker), dextromethorphan (clinically available non-competitive antagonist) and CGS19755 (competitive receptor antagonist), was examined in rats with the hot plate test. The NMDA antagonists were administered intraperitoneally and none of them caused antinociception at doses that did not produce motor deficits (0.1 mg kg^-1 MK-801, 30 mg kg^-1 dextromethorphan and 5 mg kg^-1 CGS19755). However, pretreatment with the NMDA antagonists at these doses 30 min prior to subcutaneous injection of 5 mg kg^-1 morphine significantly potentiated the antinociceptive effect of morphine, with strongest effect observed with dextromethorphan. It is suggested that blockade of NMDA receptors enhances the antinociceptive effect of morphine and NMDA antagonists may improve the analgesic efficacy of morphine in the clinic.     

Competitive sustained exercise in humans, lymphokine activated killer cell activity, and glutamine – an intervention study

This study examined whether oral glutamine supplementation abolishes some of the exercise-induced changes in lymphocyte functions following long-term intense exercise. A group of 16 marathon runners participating in The Copenhagen Marathon 1996 were placed randomly in either a placebo (n?=?7) or a glutamine receiving group (n?=?9). Each subject received four doses of either placebo or glutamine (100?mg?·?kg^?1) administered at 0, 30, 60, and 90-min post-race. In the placebo group the plasma glutamine concentrations were lower than pre-race values during the post-exercise period [mean 647 (SEM 32) compared to 470 (SEM 22)?μmol?·?l^?1 90-min post-race, P??1). Glutamine supplementation in vivo had no effect on the lymphokine activated killer (LAK) cell activity, the proliferative responses or the exercise-induced changes in concentrations or percentages of any of the leucocyte subpopulations examined. Glutamine addition in in vitro studies enhanced the proliferative response in both groups. These data would suggest that decreased plasma glutamine concentrations post-exercise are not responsible for exercise-induced decrease in LAK activity and that the influence of glutamine in vitro is not dependent on the plasma glutamine concentration at the time of sampling.     

Adenosine triphosphate treatment for meconium aspiration-induced pulmonary hypertension in pigs

To investigate the pulmonary haemodynamic effects of meconium aspiration and subsequent adenosine triphosphate (ATP) treatment, 12 anaesthetized and ventilated pigs (wt 24-28 kg) received either ATP or an equal volume of saline into the right heart in doses of 0.02 to 0.80 lmol kg^-1 min^?1 after intratracheal administration of 2 mL kg^?1 of human meconium. Meconium instillation induced significant increases in pulmonary vascular pressures and total and postarterial resistances calculated from pulmonary artery occlusion studies, but did not affect the systemic haemodynamics, except for a fall in heart rate and increase in central venous pressure. Infusion of ATP at the lowest doses (0.02 and 0.08 µmol kg^?1 min^?1) selectively decreased the pulmonary arterial pressure and vascular resistance and at 0.32 and 0.80 µmol kg^?1 min^?1 reduced both the pulmonary and systemic resistances. In the lung circulation the increasing doses of ATP reduced preferably the arterial, but also the postarterial resistance. Withdrawal of ATP infusion led to a significant rebound effect especially in the postarterial segment of the lung circulation. Meconium aspiration thus induces an acute, predominantly postarterial obstruction in the lung circulation and infusion of ATP at low doses selectively dilates the pulmonary vascular bed and may help to preclude elevation of capillary pressures in meconium aspiration-induced pulmonary hypertension.     

An alternative method to determine maximal accumulated O2 deficit in runners

An accepted measure of anaerobic capacity is the maximal O₂ deficit. But it is not feasible to use O₂ deficit if ≥10 submaximal runs are needed to extrapolate the O₂ demand of high velocity running (Medbø et al. 1988). Recently, an alternative method to determine O₂ deficit was proposed (Hill 1996) using only results of supramaximal cycle ergometer tests. The purpose of this study was to evaluate this alternative method with data from treadmill tests. Twenty-six runners ran at 95%, 100%, 105%, and 110% of their velocity at VO₂max. Times to exhaustion, velocity, and accumulated oxygen uptake (VO₂) from each individual's four tests were fit to the following equation using iterative nonlinear regression: The mean values derived for O₂ demand and O₂ deficit were 0.198?±?0.031?ml?·?kg^?1?·?m^?1 and 42?±?22?ml?· kg^?1. SEE for the parameters were 0.007?±?0.007?ml?· kg^?1?·?m^?1 and 8?±?10?ml?·?kg^?1, respectively. Mean R² was 0.998?±?0.003. It was concluded that O₂ deficit can be determined from all-out treadmill tests without the need to perform submaximal tests.     

Melatonin and behavioral thermoregulation in the turtle, Terrapene carolina triunguis

Intraperitoneal injections of melatonin (4.0 and 8.0 mg kg^?1) significantly decreased mean selected temperatures (MST) of the three-toed box turtle (Terrapene carolina triunguis) when compared with control animals over 24-hour periods. Chlorpromazine (25.0 mg kg^?1), which may block the breakdown of endogenous melatonin, also caused a significant decline in MST. Both exogenous and endogenous melatonin appear to play a role in behavioral and physiological thermoregulation of vertebrates.