bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antidiabetic sulphonylureas activate mitochondrial permeability transition in rat skeletal muscle
Authors: Skalska Jolanta , Debska Grazyna , Kunz Wolfram S , Szewczyk Adam 
Published: May 2005

Antidiabetic sulphonylureas can bind to various intracellular organelles including mitochondria. The aim of this study was to monitor the influence of antidiabetic sulphonylureas on membrane permeability in mitochondria isolated from rat skeletal muscle.
The effects of glibenclamide (and other sulphonylurea derivatives) on mitochondrial function were studied by measuring mitochondrial swelling, mitochondrial membrane potential, respiration rate and Ca2+ transport into mitochondria.
We observed that glibenclamide induced mitochondrial swelling (EC50=8.2±2.5 μM), decreased the mitochondrial membrane potential and evoked Ca2+ efflux from the mitochondrial matrix. These effects were blocked by 2 μM cyclosporin A, an inhibitor of the mitochondrial permeability transition.
Moreover, 30 μM glibenclamide accelerated the respiratory rate in the presence of glutamate/malate, substrates of complex I of the mitochondrial respiratory chain.
In conclusion, we postulate that the antidiabetic sulphonylureas activate the mitochondrial permeability transition in skeletal muscle by increasing its sensitivity to Ca2+.

British Journal of Pharmacology (2005) 145, 785–791. doi:10.1038/sj.bjp.0706214
The ventral tegmental area as a putative target for tachykinins in cardiovascular regulation
Authors: Deschamps Kathleen , Couture Réjean 
Published: May 2005

Tachykinin receptor agonists and antagonists were microinjected into the ventral tegmental area (VTA) to study the relative participation of the three tachykinin receptors in cardiovascular regulation in freely behaving rat.
Selective agonists (1–100 pmol) for NK1 ([Sar9, Met (O2)11]SP), NK2 ([β‐Ala8]NKA (4–10)) and NK3 (senktide) receptors evoked increases in blood pressure, heart rate (HR) along with behavioural manifestations (face washing, sniffing, head scratching, rearing, wet dog shake). At 1 pmol, NK1 and NK3 agonists did not affect behaviour and blood pressure but only HR.
Tachykinin agonists‐induced cardiovascular responses were selectively and reversibly blocked by the prior injection of antagonists for NK1 receptors (LY 303870 ((R)‐1‐[N‐(2‐methoxybenzyl)acetylamino]‐3‐(1H‐indol‐3‐yl)‐2‐[N‐(2‐(4‐(piperidin‐1‐yl)piperidin‐1‐yl)acetyl)amino]propane), 5 nmol), NK2 receptors (SR 48968 ([(S)‐N‐methyl‐N‐[4‐acetylamino‐4‐phenylpiperidino‐2‐(3,4‐dichlorophenyl)butyl]benzamide]), 250 pmol) and NK3 receptors (SB 235375 ((−)‐(S)‐N‐(α‐ethylbenzyl)‐3‐(carboxymethoxy)‐2‐phenylquinoline‐4‐carboxamide), 25 nmol). With the exception of the NK2 agonist, most behavioural effects were also blocked by antagonists.
Tachykinin agonists‐induced cardiovascular responses were inhibited by intravenous (i.v.) treatments with antagonists for D1 dopamine receptor (SCH23390, 0.2 mg kg−1) and β1‐adrenoceptor (atenolol, 5 mg kg−1) but not for D2 dopamine receptor (raclopride, 0.16 mg kg−1). Behavioural responses were blocked by SCH23390 only.
The present study provides the first pharmacological evidence that the three tachykinin receptors in the rat VTA can affect the autonomic control of blood pressure and HR by increasing midbrain dopaminergic transmission. This mechanism may be involved in the coordination of behavioural and cardiovascular responses to stress and noxious stimulation.

British Journal of Pharmacology (2005) 145, 712–727. doi:10.1038/sj.bjp.0706249
Inhibition of fatty acid amide hydrolase and monoacylglycerol lipase by the anandamide uptake inhibitor VDM11: evidence that VDM11 acts as an FAAH substrate
Authors: Vandevoorde Séverine , Fowler Christopher J 
Published: May 2005

There is some dispute concerning the extent to which the uptake inhibitor VDM11 (N‐(4‐hydroxy‐2‐methylphenyl) arachidonoyl amide) is capable of inhibiting the metabolism of the endocannabinoid anandamide (AEA) by fatty acid amide hydrolase (FAAH). In view of a recent study demonstrating that the closely related compound AM404 (N‐(4‐hydroxyphenyl)arachidonylamide) is a substrate for FAAH, we re‐examined the interaction of VDM11 with FAAH.
In the presence of fatty acid‐free bovine serum albumin (BSA, 0.125% w v−1), both AM404 and VDM11 inhibited the metabolism of AEA by rat brain FAAH with similar potencies (IC50 values of 2.1 and 2.6 μM, respectively). The compounds were about 10‐fold less potent as inhibitors of the metabolism of 2‐oleoylglycerol (2‐OG) by cytosolic monoacylglycerol lipase (MAGL).
The potency of VDM11 towards FAAH was dependent upon the assay concentration of fatty acid‐free bovine serum albumin (BSA). Thus, in the absence of fatty acid‐free BSA, the IC50 value for inhibition of FAAH was reduced by a factor of about two (from 2.9 to 1.6 μM). A similar reduction in the IC50 value for the inhibition of membrane bound MAGL by both this compound (from 14 to 6 μM) and by arachidonoyl serinol (from 24 to 13 μM) was seen.
An HPLC assay was set up to measure 4‐amino‐m‐cresol, the hypothesised product of FAAH‐catalysed VDM11 hydrolysis. 4‐Amino‐m‐cresol was eluted with a retention time of ∼2.4 min, but showed a time‐dependent degradation to compounds eluting at peaks of ∼5.6 and ∼8 min. Peaks with the same retention times were also found following incubation of the membranes with VDM11, but were not seen when the membranes were preincubated with the FAAH inhibitors URB597 (3′‐carbamoyl‐biphenyl‐3‐yl‐cyclohexylcarbamate) and CAY10401 (1‐oxazolo[4,5‐b]pyridin‐2‐yl‐9‐octadecyn‐1‐one) prior to addition of VDM11. The rate of metabolism of VDM11 was estimated to be roughly 15–20% of that for anandamide.
It is concluded that VDM11 is an inhibitor of FAAH under the assay conditions used here, and that the inhibition may at least in part be a consequence of the compound acting as an alternative substrate.

British Journal of Pharmacology (2005) 145, 885–893. doi:10.1038/sj.bjp.0706253
Heteroactivation of cytochrome P450 1A1 by teas and tea polyphenols
Authors: Anger Dana L , Petre Maria‐Alexandra , Crankshaw Denis J 
Published: May 2005

We studied 7‐ethoxyresorufin deethylase as an index of cytochrome P4501A1 (CYP1A1) activity in liver microsomes from rats pretreated with 3‐methylcholanthrene. The enzyme had complex kinetics compatible with a multisite model.
At 1 μM substrate, brewed black, green and white teas had complex effects on enzyme activity consisting of activation at low concentrations and inhibition at higher concentrations.
Data fit well to a two‐site model that allowed us to determine maximal activation (% increase above control), pEC50 for activation (g ml−1) and pIC50 for inhibition (g ml−1). These parameters were 190±40, 5.9±0.1 and 4.51±0.09 for green tea, 350±40, 5.43±0.05 and 5.43±0.05 for black tea and 230±80, 5.3±0.3 and 4.7±0.2 for white tea, respectively.
The effects of the brewed teas were mimicked to different degrees by the green tea polyphenols. Maximal activation, pEC50 (M) and pIC50 (M) were: (−)‐epicatechin, 55±9, 5.4±0.3, 2±1; (−)‐epicatechin gallate, 160±60, 6.2±0.3, 5.28±0.06; (−)‐epigallocatechin 30±10, 6.5±0.5, 3.37±0.08; and (−)‐epigallocatechin gallate 130±40, 6.7±0.3, 5.0±0.1. A crude extract of black tea polyphenols inhibited 7‐ethoxyresorufin deethylase, but did not cause enzyme activation consistently.
Enzyme activation was dependent upon substrate concentration.
Heteroactivation of CYP1A1 may partially explain the lack of agreement between biological and epidemiological evidence of a role for tea in cancer prevention.

British Journal of Pharmacology (2005) 145, 926–933. doi:10.1038/sj.bjp.0706255
Intravenous adenosine protects the myocardium primarily by activation of a neurogenic pathway
Authors: Manintveld Olivier C , te Lintel Hekkert Maaike , Keijzer Elisabeth , Verdouw Pieter D , Duncker Dirk J 
Published: May 2005

Endogenous adenosine is a trigger for ischemic myocardial preconditioning (IPC). Although intravascular administration of adenosine has been used to further unravel the mechanism of protection by IPC, it is questionable whether adenosine and IPC employ the same signaling pathways to exert cardioprotection.
We therefore investigated whether the active metabolic barrier of the endothelium prevents an increase in myocardial interstitial adenosine concentrations by intravenous adenosine, using microdialysis, and also the role of NO and activation of a neurogenic pathway in the cardioprotection by adenosine.
In pentobarbital‐anesthetized rats, area at risk and infarct size (IS) were determined 120 min after a 60‐min coronary artery occlusion (CAO), using trypan blue and nitro‐blue‐tetrazolium staining, respectively.
IPC with a single 15‐min CAO and a 15‐min adenosine infusion (ADO, 200 μg min−1 i.v.) limited IS to the same extent (IS=41±6% and IS=40±4%, respectively) compared to control rats (IS=63±3%, both P<0.05). However, IPC increased myocardial interstitial adenosine levels seven‐fold from 4.3±0.7 to 27.1±10.0 μM (P<0.05), while ADO had no effect on interstitial adenosine (4.1±1.2 μM), or any of the other purines.
The NO synthase inhibitor Nω‐nitro‐L‐arginine (LNNA), which did not affect IS (IS=62±3%), attenuated the protection by ADO (IS=56±3%; P<0.05 vs ADO, P=NS vs LNNA). The ganglion blocker hexamethonium, which had also no effect on IS (IS=66±3%), blunted the protection by ADO (IS=55±4%; P<0.05 vs ADO and vs hexamethonium).
These observations demonstrate that cardioprotection by ADO is dependent on NO, and is primarily mediated by activation of a neurogenic pathway.

British Journal of Pharmacology (2005) 145, 703–711. doi:10.1038/sj.bjp.0706258
Cardioprotection with adenosine: ‘a riddle wrapped in a mystery’
Authors: Przyklenk Karin , Whittaker Peter 
Published: May 2005

Review of the published literature on adenosine and cardioprotection could lead one to paraphrase the famous words of Sir Winston Churchill (Radio broadcast, 1 October 1939 (in reference to Russia)) and conclude: ‘I cannot forecast to you the action of adenosine. It is a riddle wrapped in a mystery inside an enigma’. That is, although it is well‐established that adenosine can render cardiomyocytes resistant to lethal ischemia/reperfusion‐induced injury, new and intriguing insights continue to emerge as to the mechanisms by which adenosine might limit myocardial infarct size.British Journal of Pharmacology (2005) 145, 699–700. doi:10.1038/sj.bjp.0706261
Field evaluation of two biochemical tests which may reflect nutritional status in three areas of Uganda
Authors: Rutishauser I. H. E. , Whitehead R. G. 
Published: May 2005

1. Serum amino acid ratios and urinary hydroxyproline indices have been studied in three groups of children from different parts of Uganda. The results of these biochemical investigations are compared with clinical assessments and anthropometric measurements made at the same time.2. In Buganda, an area where protein deficiency is prevalent, a high incidence of both abnormal hydroxyproline indices and amino acid ratios was found. In Karamoja, where a drought had caused a widespread shortage of food, the hydroxyproline indices were particularly low but the amino acid ratios were relatively normal. In Bukedi the dietary pattern was changing and becoming more like that in Buganda; this was reflected by the biochemical results obtained which were similar in the two areas.3. The biochemical results confirmed earlier investigations, carried out in more severely ill children in a metabolic ward, which had indicated that these two tests can differentiate between primary protein deficiency and total calorie deficiency.4. The biochemical tests confirmed the anthropometric measurements in a quantitative way, and also indicated the reason for the nutritional difficulties which could otherwise only have been surmised from the food habits of the area.
Studies on intestinal digestion in the sheep
Authors: MacRae J. C , Armstrong D. G. 
Published: May 2005

1. The use of chromic oxide (Cr2O3) as an indigestible marker for studies on intestinal digestion in sheep has been examined. The sheep used were equipped with a cannula into the rumen and a re-entrant cannula in the proximal duodenum; some also had a re-entrant cannula in the terminal ileum. The marker was administered twice daily in the form of Cr2O3-impregnated paper, through the rumen cannula.2. Recovery of Cr2O3 in the faeces, based on 7-day collection periods, was satisfactory, the mean recovery for all seven experiments being 99.6 ± 0.7%. In seventeen 24 h collections of digesta entering the proximal duodenum, the mean recovery of the daily dose of marker was 83.7% (range 63.6-148.4%); in eleven such collections at the terminal ileum the mean recovery was 77.3% (54.0-90.0%).3. Detailed examination of the concentrations of Cr2O3 in dry matter was made with individual samples taken during single 24 h periods for five duodenal and three ileal collection periods. There were always marked variations in these concentrations. It is concluded that use of short collection periods to give mean values for the flow of digesta throughout the 24 h, at particular points along the tract, may lead to large errors.
Vitamin A status and the metabolism of cholesterol in the rat
Authors: Lakshmanan M. R. , Phillips W. E. J. , Brien R. L. 
Published: May 2005

1. The interrelationship between cholesterol and vitamin A metabolism has been studied in rats.2. The effect of cholesterol feeding in increasing the liver storage of cholesterol w-as enhanced during vitamin A deficiency.3. This effect was due to an increased rate of absorption of cholesterol and not due to a decreased turnover rate.4. Feeding of high levels of vitamin A markedly depressed the cholesterol absorption; however, its turnover was unaffected.
The effect of copper deficiency on reproduction in the female rat
Authors: Hall G. A. , Howell J. McC. 
Published: May 2005

1. Eighty-seven rats were fed a diet of milk treated with hydrogen sulphide together with copper-free mineral and vitamin supplements. Forty-three of the eighty-seven rats were used controls and given Cu supplements varying from 50 to 500 μg/week. In addition to the eighty-seven rats, twenty-eight rats were fed a commercial diet.2. Rats which did not receive Cu supplements developed signs of Cu deficiency and their liver Cu levels were significantly lower than those of control and stock animals. Oestrous cycles were normal and the majority of the rats were successfully mated.3. Litters developed to full term in stock rats and in those given Cu supplements but the Cu- deficient rats did not produce litters.
Histological observations on foetal resorption in copper-deficient rats
Authors: Howell J. McC. , Hall G. A. 
Published: May 2005

1. Twenty-six rats were fed a diet of milk treated with hydrogen sulphide together with copper-free mineral and vitamin supplements; fourteen of these rats were used as controls and were given 500 μg Cu per rat per week. Seven other rats were fed a commercial diet.2. Mating to stock males commenced when the rats had been fed the diets for 6 weeks, and they were killed from the 10th to the 16th days of pregnancy.3. The average number of placental sites was 17.9 in stock, 10.4 in control and 11.8 in deficient rats. Spontaneously resorbing sites were seen in three stock, seven control and six deficient animals.4. The foetuses of the stock and control animals grew normally but in the Cu-deficient rats normal development ceased on the 13th day of pregnancy when the foetal tissues were seen to be disintegrating. Necrosis of the placenta was seen on the 15th day of pregnancy and until then blood islands were present.5. Lesions were not seen in the maternal mammary glands, ovaries or pituitary glands.
The effect of oxygen on fermentation of sucrose by rumen micro-organisms in vitro
Authors: Czerkawski J. W. , Breckenridge Grace 
Published: May 2005

1. The effect of oxygen on the fermentation of sucrose by mixed rumen micro-organisms in vitro was studied by adding oxygen to the gas phase in three ways: at the beginning of incubation, at two hourly intervals during incubation and continuously.2. The additions of oxygen had no measurable effect on the utilization of sucrose or on the production of carbon dioxide, steam-volatile acids and particulate organic matter by the micro-organisms. The addition of oxygen at the beginning of incubation inhibited methane production and increased the accumulation of hydrogen. Similar but much less pronounced changes occurred when the oxygen was infused continuously.3. In all the experiments there was a net uptake of oxygen by micro-organisms. When large amounts of oxygen were present in the gas phase the rates of uptake were proportional to these amounts. When small amounts of oxygen were added, the rates of uptake were independent of the amount added and had a value of approximately 5 ml/h when 100 ml of strained rumen contents were incubated.
Volatile fatty acid production in the rumen of the grazing sheep: its use as an indicator of pasture value
Authors: Weller R. A. , Pilgrim A. F. , Gray F. V. 
Published: May 2005

1. An isotope dilution method, known to be satisfactory for measurement of volatile fatty acid (VFA) production in the rumen under steady-state conditions, was tested for its applicability where the VFA pool in the rumen could vary irregularly. The method indicated mean production rates closely similar to those obtained when the pool size was virtually constant. Tests carried out in a model rumen confirmed this finding and the method was accepted as suitable for measurement of VFA production in grazing sheep.2. The method, modified to allow continuous sampling of rumen acids by dialysis, was applied to sheep grazing a mixed pasture. Mean rates of VFA production determined in seven sheep during fourteen 3-day periods throughout winter, spring and summer months ranged from 3.4 to 5.3 moles daily, production increasing during the period of growth of the pasture, and declining again with its drying-off.3. The pasture was at all times abundant; the findings are therefore considered to represent the pasture's full potential yield of VFA to the sheep and so to indicate its changing value in this respect as the seasons progressed.4. Results from sheep given roughages and from the grazing sheep indicated that, despite irregular intake, good predictions of mean VFA production rates could be made from mean VFA concentrations in the rumen fluid.
Biological evaluation of rapeseed meal, soya-bean meal and casein fed to the weanling and the mature rat
Authors: Drouliscos N. J. , Bowland J. P. 
Published: May 2005

1. The biological evaluation of solvent and prepress-solvent processed rapeseed meals RM(S) and RM(PS) was carried out with the weanling (phase 1) and the mature (phase 2) rat. The nutritional indices measured were compared with those for diets containing soyabean meal SM and casein CS.2. The true nitrogen digestibility (td(N)) for RM(S), RM(PS), SM and CS in the weanling rat was (%) 78.9 f±1.2, 77.9±2.7, 90.4±0.9 and 96.0±0.6 (P < 0.01) respectively. Net protein utilization was (%) 68.9±10.1, 65.6±3.5, 80.6±4.8 and 81.7±3.1 (P < 0.05) respectively. Biological value was (%) 83.0±7.9, 84.1±5.6, 8.90±5.1 and 85.0±3.4 (P < 0.05) respectively. The same indices when measured in the mature rat showed an increase over those obtained in the weanling rat.3. The growth-promoting effects of the test diets were evaluated over a period of 8 weeks withad lib. feeding between phases 1 and 2. Protein efficiency ratio averaged 2.0±0.14, 1.9±0.35, 2.4±0.39 and 2.3±0.25 for the RM(S), RM(PS), SM and CS treatments respectively.4. The daily endogenous urinary N excretion was 1.58±0.14 mg N/basal kcal or 254 mg N/kg body-weight for the weanling rat and 0.16 mg N/basal kcal or 18 mg N/kg body-weight for the mature rat. Metabolic faecal N excretion was 98.0±9.3 mg N/kg body-weight, or 27.9% of the total N output for the weanling rat, and 37.9±7.2 mg N/kg body-weight, or 67.3% of the total N output for the mature rat during the ‘protein-free’ feeding periods.5. The fresh weight of the thyroid gland per kg metabolic body size was 70, 90, 40 and 40 mg respectively for the RM(S), RM(PS), SM and CS dietary treatments.6. The moisture content of the carcasses was 66.9±3.1, 63.6±2.3 and 64.2±2.2 and the protein content on a dry-matter basis was 55.9±9.6, 50.2±6.4 and 53.1±4.9 for the RM (S and PS), SM and CS diets respectively. The results suggest an increased lean body mass in the rats receiving the rapeseed meal treatments.7. Under the conditions of this experiment solvent-extracted rapeseed meal was superior to prepress-solvent meal on the basis of rat growth response and of results for nutritional indices. Both rapeseed meals were inferior to soya-bean meal and casein.
The effect of diets containing different proportions of butterfat and maize oil on plasma lipids and aortic atherosis in rabbits
Authors: Moore J. H. 
Published: May 2005

1. Seven groups of male rabbits (thirteen to fifteen per group) were givenad lib. a diet consisting of 80 parts of a low-fat basal ration to which were added 20 parts of fat in the form of butterfat, maize oil or various mixtures of the two.2. After 40 weeks, samples of blood were taken and the animals were killed. The concentrations of total cholesterol and phospholipid in the plasma and the fatty acid compositions of the plasma cholesteryl esters and phospholipids were determined. The degree of atheromatous degeneration was determined in the aortas.3. Little aortic atherosis was observed in the rabbits given the diets containing 0, 10 and 12% butterfat, but as the butterfat content of the diet was increased above 12%, pronounced increases occurred in the extent of atheromatous degeneration of the aorta. The concentration of cholesterol in the plasma increased progressively as the butterfat content of the diet was increased and the maize oil content was decreased. There was an inverse curvilinear relationship between the degree of aortic atherosis and the phospholipid: cholesterol ratio in the plasma.4. The concentration of linoleic acid in the plasma cholesteryl esters was inversely related to the concentration of cholesterol in the plasma, and the concentration of linoleic acid in the plasma phospholipids was inversely related to the concentration of phospholipids in the plasma. There was a positive linear relationship between the stearic: palmitic acid ratio and the linoleic: oleic acid ratio in the plasma phospholipids.
The metabolism and biological activity of esterified vitamin D in the rat
Authors: Fraser D. R. , Kodicek E. 
Published: May 2005

1. [I-3H]Cholecalciferol and [I-3H]cholecalciferol palmitate in amounts equivalent to 2 μg cholecalciferol were injected into rachitic rats as aqueous preparations (intravenously) or in arachis oil (intramuscularly).2. The radioactive faecal metabolites collected for up to 17 days were fractionated according to their polarity. The same pattern of excreted radioactivity was seen with intravenous and intramuscular cholecalciferol and intravenous cholecalciferol palmitate. Intramuscular chole-calciferol palmitate produced a higher proportion of the most polar metabolites in faeces.3. Parenterally administered cholecalciferol palmitate in a rickets-healing biological assay had activity equivalent to unesterified cholecalciferol.4. Vitamin D ester synthesized in vivo is considered to be eventually metabolized as vita- min D alcohol and to be available to vitamin D-requiring processes.