bluuebunny/crossref_metadata_2025_split huggingface dataset:
FELINE ENDOTOXIN SHOCK: EFFECTS OF METHYLPREDNISOLONE ON KININOGEN‐DEPLETION, ON THE PULMONARY CIRCULATION AND ON SURVIVAL
Authors: AL‐KAISI NAHLA , PARRATT J.R. , SIDDIQUI H.H. , ZEITLIN I.J. 
Published: July 2012

1 Escherichia coli endotoxin, administered intravenously in a dose of 2mg/kg to pentobarbitone‐anaesthetized, artificially ventilated cats resulted in pulmonary hypertension, systemic hypotension and an immediate (1‐2 min) 30‐40% reduction in plasma kininogen, an effect which probably indicates a release of plasma kinins.2 Methylprednisolone (30 mg/kg), when administered 30 min before endotoxin, did not influence the endotoxin‐induced pulmonary hypertension or systemic hypotension but completely prevented the depletion of plasma kininogen.3 In spontaneously breathing cats, methylprednisolone, administered 30 min after endotoxin, caused a rapid repletion of kininogen and prolonged survival (47% at 6 h compared to 10% in the endotoxinalone animals). Methylprednisolone did not appear to influence lactate production or the hyperventilation observed during the delayed endotoxin shock phase.4 It is concluded that methylprednisolone does not prevent the release, by endotoxin, of a pulmonary vasoconstrictor prostaglandin, or its effects, but that perhaps by preventing kinin release it may reduce endotoxin‐induced capillary leakage.
EFFECTS OF ASPIRIN‐LIKE DRUGS ON CANINE GASTRIC MUCOSAL BLOOD FLOW AND ACID SECRETION
Authors: BENNETT A. , CURWAIN B.P. 
Published: July 2012

1 The effects of aspirin, paracetamol and benorylate were studied on gastric mucosal blood flow (MBF) and acid secretion in canine denervated gastric pouches.2 Aspirin 20 mM in the unstimulated pouch had no effect; pentagastrin‐stimulated acid output, but not MBF, was reduced. Aspirin buffered to pH 6 was ineffective.3 Aspirin 3‐50 mg/kg reaching the pentagastrin‐stimulated pouch through the blood, increased acid secretion and MBF, but the MBF: secretion ratio was variably affected.4 Paracetamol (10 or 20 mg/kg i.v., or 20 mM in the pouch) or benorylate (280 mg/kg orally) mainly had little effect.5 Circular muscle strips from dog arteries were contracted by prostaglandins E2, F1α or F2α, and often slightly by indomethacin, but prostaglandin E1 produced variable effects.6 These results do not favour the view that aspirin causes gastric bleeding in dogs by breakdown of blood vessels due to ischaemia following mucosal vasoconstriction.
AN INVESTIGATION OF THE SEX DIFFERENCE IN THE DIURETIC RESPONSE TO ETHACRYNIC ACID IN MICE
Authors: COOLING M.J. , SIM M.F. 
Published: July 2012

1 Female mice of the Hough/Porton and Tuck/TO strains were found to be more sensitive than male mice to the diuretic effects of oral and intravenous doses of ethacrynic acid.2 The sensitivity of Hough/Porton male mice to ethacrynic acid was increased after pretreatment with stilboestrol and the sensitivity of female Hough/Porton mice decreased after pretreatment with testosterone.3 There were no significant sex differences in the diuretic response to frusemide, acetazolamide, aminophylline, bendrofluazide, and Su 15049A although a small, but significant, increase in the sensitivity of male Tuck/TO mice to triamterene was noted.4 The sex difference in diuretic response to ethacrynic acid may be related to an effect of sex hormone balance on its metabolism or on the sensitivity of its renal receptor.
ENZYMATIC HISTAMINE DEGRADATION BY HUMAN SKIN
Authors: FRANCIS D. , GREAVES M.W. , YAMAMOTO S. 
Published: July 2012

1 Degradation of histamine by homogenized human skin in vitro, in the presence of the cofactor S‐adenosyl methionine, indicates the presence of the histamine metabolizing enzyme histamine‐N‐methyl transferase in human skin. Under the experimental conditions described, no significant histamine degradation by diamine oxidase was observed.2 The enzyme activity is temperature‐sensitive with an optimum at 37°C. The enzyme is stable in intact excised skin at −20°C, but unstable in homogenized skin at this temperature.3 Little or no enzyme activity is present in mid‐ or deep dermis, but the distribution of the enzyme between superficial papillary dermis and epidermis is uncertain.4 The presence of a potent histamine degrading mechanism raises the possibility that histamine‐N‐methyl transferase activity may be an important modulating factor in histamine‐mediated skin disorders
THE EFFECT OF DIURETICS ON THE FAECAL EXCRETION OF WATER AND ELECTROLYTES IN HORSES
Authors: ALEXANDER F. 
Published: July 2012

1 The effect on plasma, urinary and faecal electrolytes of frusemide and hydrochlorthiazide was measured in ponies, mean weight 180 kg.2 The rapid loss in urine of large quantities of sodium had only a small effect on plasma sodium concentration.3 Faecal sodium excretion was increased substantially after the administration of frusemide.4 Frusemide increased faecal potassium during the 48 h following administration and faecal water in the 24/48 h period. It also produced a hypopotassaemia.5 Hydrochlorthiazide increased faecal chloride during the 24 h after administration.6 Frusemide increased the intestinal transit time of both liquid (polyethylene glycol) and particulate (Cr2O3) markers.
RENAL BLOOD FLOW AUTOREGULATION AND RENAL VENOUS PROSTAGLANDINS IN THE PUMP‐PERFUSED CANINE KIDNEY (In situ)
Authors: DIGHE K.K. , HALL JANET C. , SMITH G.W. , UNGAR A. 
Published: July 2012

Renal autoregulation of blood flow was re‐examined in the pump‐perfused canine kidney and concentrations of prostaglandins E and F in the renal venous plasma were measured by radioimmunoassay.
At low perfusion pressures, below the range of autoregulation, prostaglandin E and F concentrations rose and calculated prostaglandin E secretion rate fell.
Meclofenamate (10 mg/kg, i.v.) reduced renal blood flow and prostaglandin E and F secretion rates, but did not abolish autoregulation.
Renal prostaglandins do not appear to mediate autoregulation in the kidney but may affect the level at which flow is controlled.
EFFECTS OF SYMPATHETIC INNERVATION AND TEMPERATURE ON THE PROPERTIES OF RAT HEART ADRENOCEPTORS
Authors: KUNOS G. , NICKERSON M. 
Published: July 2012

The pharmacological characteristics of adrenoceptors at different temperatures were assessed on the basis of the effects of various α‐ and β‐adrenoceptor agonists and antagonists on electrically‐driven left atria and spontaneously‐beating pairs of atria from rats.
Phenoxybenzamine (Pbz) potentiated inotropic responses of left atria to noradrenaline (NA) at 31°C, produced significantly less potentiation at 24°C and inhibited responses at 17°C; it had little effect on responses to CaCl2. Both Pbz and phentolamine inhibited responses to phenylephrine more effectively at 17 than at 31°C. N‐cyclohexylmethyl‐N‐ethyl‐β‐chloroethylamine hydrochloride (GD‐131), a haloalkylamine with negligible α‐adrenoceptor blocking activity, caused only potentiation of responses to NA at 17°C.
The presence of phentolamine during incubation with Pbz eliminated block of responses to NA and revealed a potentiation that was equivalent at all three temperatures tested. Phentolamine did not alter the block of responses to 5‐hydroxytryptamine by Pbz. Protection of α‐adrenoceptors by phentolamine during exposure to [3H]‐Pbz significantly decreased the amount of label bound to the myocardium at 17°C, but did not alter binding at 31°C.
Inhibition of responses to NA by propranolol decreased with temperature, and the magnitude of the change increased with the concentration of propranolol. Compared to 31°C, the effect of the highest concentration of propranolol. (4.0 μM) was significantly decreased at 24°C, and the effects of all except the lowest concentration (0.04 μM) were significantly decreased at 17°C.
The potency of isoprenaline decreased and that of phenylephrine increased at low temperatures, and their potency ratio was much lower at 17 than at 31°C for both the inotropic and chronotropic responses of spontaneously‐beating atria. However, the ratio was unaffected by temperature in electrically‐driven left atria. A similar difference between spontaneously‐beating and driven preparations is apparent in the data of other workers, but its basis is not clear.
Atria from rats pretreated with 6‐hydroxydopamine (6‐OHDA) were sensitized to the effects of NA, and there was no increase in α‐adrenoceptor properties at low temperatures. Little α‐adrenoceptor activity could be demonstrated in chemically denervated atria at any temperature. 6‐OHDA pretreatment did not alter the binding of [3H]‐Pbz at 31°C, but decreased it significantly at 17°C. Pretreatment with reserpine caused some sensitization, but did not significantly alter the characteristics of the adrenoceptors or their responses to temperature.
It is concluded that the adrenoceptors of rat atria are affected by temperature in much the same way as those of frog hearts, although the transition from β‐ to α‐adrenoceptor properties may begin at a slightly higher temperature. α‐Adrenoceptor properties appear to require the presence of intact adrenergic nerves but not the presence of normal stores of neurotransmitter.
TIME COURSE OF LITHIUM‐INDUCED ALTERATIONS IN RENAL AND ENDOCRINE FUNCTION IN NORMAL AND BRATTLEBORO RATS WITH HYPOTHALAMIC DIABETES INSIPIDUS
Authors: BALMENT R.J. , JONES I. CHESTER , HENDERSON I.W. 
Published: July 2012

A lithium chloride (1.1 g/kg) supplemented diet was given to Long Evans (LE) and Brattleboro (DI) rats to investigate its actions in the presence (LE) and absence (DI) of vasopressin.
During the first 24 h, Li‐supplemented LE rats displayed an initial water deficit (drinking less than renal output), increased plasma antidiuretic (ADH) titres and slightly increased plasma renin activities (PRA) and plasma osmolarities. Such changes were qualitatively similar to those seen in rats fed a normal diet, but deprived of water for 24 hours. After 12 days, the Li‐supplemented rats had elevated plasma ADH titres, but reduced pituitary oxytocic and antidiuretic activities.
The urinary losses of Na, K and Cl exceeded dietary intakes in LE rats on the introduction of the Li‐supplement, and the urinary osmolarity fell by 50%. Electrolyte balances were gradually reestablished, although drinking and urine production increased in parallel to reach twice the control values by day 12 of the supplement.
Aldosterone and corticosterone secretory rates and their peripheral plasma concentrations were unchanged both after 24 h and 28 days of the Li‐supplement.
Li elicited no water deficit or saluresis in DI rats, and although the polyuria and polydipsia were exacerbated, urinary osmolarity did not change over the 12 day observation period.
Li increased Ca excretion in both rat types; after 12 days the PRA of DI but not LE animals was increased.
It is concluded that the overall renal actions of Li are tempered by vasopressin rather than adrenocorticosteroids.
THE EFFECT OF SULPHAMETHOXYPYRIDAZINE ON LIVER AND PLASMA LEVELS OF VITAMIN A IN RATS
Authors: BRAVO MARÍA E. , MONCKEBERG F. , URBINA J. 
Published: July 2012

Long‐acting sulphonamides are highly bound to plasma proteins; the present study deals with the effects of this binding property upon a vitamin A compound also transported by plasma proteins.
Sulphamethoxypyridazine was administered in rats either orally or by intraperitoneal injection.
A significant fall in plasma vitamin A level and an increase in hepatic vitamin A concentration were observed.
These results suggest an interference by sulphamethoxypyridazine with the transport of vitamin A, either through competition between the drug and vitamin A for binding sites of plasma proteins, or through altered secretion of the vitamin from the liver.
AN EXCITATORY ACTION OF IONTOPHORETICALLY ADMINISTERED LITHIUM ON MAMMALIAN CENTRAL NEURONES
Authors: HAAS H.L. , RYALL R.W. 
Published: July 2012

The action of iontophoretically administered lithium was studied on spinal Renshaw cells and interneurones and on supraspinal neurones in cerebral cortex, thalamus, hypothalamus and brain stem in anaesthetized cats and rats.
There was a correlation between the effects of Li+ and those of acetylcholine (ACh), although rather more cells were unaffected by Li+ than by ACh.
The usual effect was an excitation of rather slow onset, but occasionally effects were produced with time courses similar to those of ACh. The excitation was blocked by ACh antagonists and was best demonstrated with dihydro‐β‐erythroidine on Renshaw cells.
The postsynaptic excitant action of ACh on Renshaw cells was reduced by Li+.
Depressant actions of Li+ were encountered on cells also depressed by ACh.
It is concluded that Li+ may facilitate cholinergic transmission at some sites in the CNS by increasing the release of ACh by an unknown mechanism. Similar effects at non‐cholinergic synapses might also occur but would appear to be of less importance. Since facilitation of neuronal firing with Li+ was usually observed, the depressant effects on postsynaptic responses to ACh may be of little consequence.
CYCLIC ADENOSINE 3′, 5′‐MONOPHOSPHATE AND LEUCOCYTE CHEMOTAXIS in vivo
Authors: DEPORTER D.A. 
Published: July 2012

The effect of local elevation of leucocyte cyclic adenosine 3′, 5′‐monophosphate (cyclic AMP) content on the continued migration of leucocytes to a site of acute inflammation was studied in the pleural cavity of rats.
Leucocyte cyclic AMP levels were elevated by injecting with the irritant into the pleural cavity dibutyryl cyclic AMP alone or with theophylline.
The treatments both produced a marked reduction in leucocyte migration into a pleural reaction induced by immediate hypersensitivity, but had no effect on cell numbers in pleurisy induced either by pyrophosphate or urate crystals.
THE POSSIBLE ROLES OF HISTAMINE, 5‐HYDROXYTRYPTAMINE AND PROSTAGLANDIN F2α AS MEDIATORS OF THE ACUTE PULMONARY EFFECTS OF ENDOTOXIN
Authors: PARRATT J.R. , STURGESS R.M. 
Published: July 2012

In an attempt to investigate the possible role of released vasoactive substances in mediating the pulmonary pressor responses to E. coli endotoxin, cats were pretreated with histamine, 5‐hydroxytryptamine (5‐HT) or prostaglandin antagonists, with a histamine depleting agent (compound 48/80) or with an inhibitor of prostaglandin synthetase (sodium meclofenamate).
The administration of endotoxin (2 mg/kg) resulted in a rapidly developing pulmonary hypertension (pressure twice normal after 2–3 min), increases in right atrial and intratracheal pressures, systemic hypotension and bradycardia. These effects were unaffected by methysergide in a dose sufficient to prevent the effects of intravenously administered 5‐HT.
Endotoxin responses were also unaffected by a combination of mepyramine and burimamide in doses sufficient to reduce markedly the effects of intravenously‐administered histamine. In cats pretreated (chronically or acutely) with compound 48/80, endotoxin induced a transient pulmonary pressor response which was not maintained.
The pulmonary and systemic responses to endotoxin were prevented by the prior administration of the prostaglandin antagonist, polyphloretin phosphate and by pretreatment with the prostaglandin synthetase inhibitor, sodium meclofenamate.
It is concluded that a pulmonary vasoconstrictor prostaglandin is involved in the acute response to endotoxin in the cat.
THE USE OF FUNCTIONAL ANTAGONISM TO DETERMINE WHETHER β‐ADRENOCEPTOR AGONISTS MUST HAVE A LOWER EFFICACY THAN ISOPRENALINE TO BE TRACHEA‐ATRIA SELECTIVE in vitro IN GUINEA‐PIGS
Authors: O'DONNELL STELLA R. , WANSTALL JANET C. 
Published: July 2012

The relative efficacies of three trachea‐atria selective β‐adrenoceptor agonists, fenoterol, Me 506 and Me 454, compared to isoprenaline, were determined on both trachea and atria of guinea‐pigs.
On tracheal preparations the β‐adrenoceptor agonists were used as functional antagonists of carbachol and a comparison of the maximum shifts in the carbachol concentration‐response line produced by each of the β‐adrenoceptor agonists provided a comparison of their efficacies.
On atrial preparations carbachol was used as a functional antagonist of the β‐adrenoceptor agonists and comparison of the maximum responses to the β‐adrenoceptor agonists in the presence of carbachol provided a comparison of their efficacies.
On trachea and atria the order of efficacy of the compounds was Me 454 > Me 506 ≥ isoprenaline = fenoterol.
The results indicated that high efficacy in a non‐catechol β‐adrenoceptor agonist is possible provided there is a favourable N‐substituent group.
Since Me 454, Me 506 and fenoterol, which are trachea‐atria selective, have efficacies equal to or greater than that of isoprenaline, which is non‐selective, it is concluded that low efficacy in a compound is not essential for it to show trachea‐atria selectivity in vitro in guinea‐pigs.
EVALUATION OF THE UPTAKE OF VARIOUS AMINES INTO STORAGE VESICLES OF INTACT HUMAN PLATELETS
Authors: COSTA J.L. , MURPHY D.L. , REVEILLE J. 
Published: July 2012

The uptake of various 3H‐labelled amines into a thrombin‐releasable compartment of human platelets, thought to represent the platelet vesicular storage pool, has been evaluated. Measurable amounts of 5‐hydroxytryptamine (5‐HT), dopamine, tyramine, octopamine, and tryptamine accumulate in this pool, and also in a non‐thrombin‐releasable (cytoplasmic) pool during a 30 min incubation period with 10−5 M extracellular amine concentrations.
No differences in the accumulation of vesicular or cytoplasmic 5‐HT, dopamine, and tyramine are found in platelets treated with deprenyl to inhibit platelet monoamine oxidase as compared to controls.
Extracellular tyramine or dopamine in concentrations as high as 10−5 M does not alter the initial rate of 5‐HT uptake across the platelet plasma membrane. Similarly, sizable cytoplasmic pools of either amine do not alter the initial rate at which small amounts of 5‐HT enter platelet cytoplasm or storage vesicles. 5‐HT thus appears to be the preferred substrate for uptake into platelets and for movement from cytoplasm to vesicles.
THE EFFECTS OF ALLOXANATE, NICOTINIC ACID AND IMIDAZOLE ON SECRETORY PROCESSES AND THE ACTIVITIES OF ADENYLATE CYCLASE AND 3‘,5’‐AMP PHOSPHODIESTERASE IN CAT PANCREAS
Authors: BONTING S.L. , DE PONT J.J.H.H.M. , KEMPEN H.J.M. , CASE R.M. , SMITH PAMELA A. , SCRATCHERD T. 
Published: July 2012

Nicotinic acid and alloxanate inhibited water and electrolyte secretion in a dose‐dependent fashion when added to the perfusate of the isolated saline‐perfused pancreas of the cat stimulated by a supramaximal dose of secretin.
There were no changes in the concentration of sodium or potassium secreted into the juice, but the anions exhibited changes which were related to flow rate. As the flow rate declined the chloride concentration increased with a reciprocal decrease in bicarbonate concentration.
Nicotinic acid and alloxanate inhibited enzyme secretion stimulated by carbachol.
Imidazole inhibited pancreatic electrolyte secretion, but stimulated amylase secretion. Atropine (0.14 μM) reduced the secretion of amylase but did not abolish the effect.
Adenylate cyclase prepared from cat pancreas, was stimulated by the octapeptide of cholecystokinin‐pancreozymin, secretin and sodium fluoride.
Alloxanate strongly inhibited both basal and hormone‐stimulated adenylate cyclase activity. Nicotinic acid and imidazole stimulated basal adenylate cyclase activity but had little effect on secretin‐stimulated activity.
Alloxanate, nicotinic acid and imidazole were all without effect on phosphodiesterase when tested in the presence of micromolar concentrations of adenosine 3′,5′‐monophosphate (cyclic AMP). At higher cyclic AMP concentrations (2 mM) alloxanate and nicotinic acid were without effect, whereas imidazole had a slight stimulatory effect at 10 mM which was more marked at 50 mM.
Alloxanate (10 mM) strongly inhibited both basal and secretin‐stimulated adenylate cyclase activity.
It is concluded that the effects of nicotinic acid, alloxanate and imidazole on pancreatic secretion are not mediated entirely through their effects on the adenylate cyclase or phosphodiesterase enzyme systems.
RELAXATION OF ISOLATED AORTA OF THE RABBIT BY PICOLINIC ACIDS
Authors: ASANO M. , HIDAKA H. 
Published: July 2012

When the isolated thoracic aorta of the rabbit was contracted with prostaglandin F2α, 5‐alkylpicolinic acids produced dose‐dependent relaxations.
Picolinic acid, 2,5‐pyridinedicarboxylic acid and 5‐acetylpicolinic acid which do not have the 5‐alkyl residue failed to relax blood vessels.
The vascular relaxation was dependent on the number of carbon atoms in the 5‐alkyl compounds.
Relaxations which occurred with 5‐alkylpicolinic acids were not affected by pretreatment with either propranolol or atropine.
It is concluded that the 5‐alkyl residue is necessary for the vascular relaxation with 5‐alkylpicolinic acid and that it was not produced by stimulation of β‐adrenoceptors or cholinoceptors but rather through an activation of the basic process.
OPIATE BINDING AND EFFECT IN ILEUM PREPARATIONS FROM NORMAL AND MORPHINE PRETREATED GUINEA‐PIGS
Authors: COX B.M. , PADHYA REKHA 
Published: July 2012

Dose‐response curves for normorphine in the absence and presence of naloxone have been obtained from myenteric plexus‐longitudinal muscle strip preparations from normal and morphine pretreated guinea‐pigs. In addition, the high affinity stereospecific binding of [3H]‐etorphine has been measured in homogenates of the same tissue.
Higher concentrations of normorphine were required to produce 50% inhibition of the electrically stimulated contractions of strip preparations from morphine pretreated animals. There was also an increase in the slope of linearized dose‐response curves in opiate‐tolerant preparations. Maximum opiate effect was unchanged, and responses to exogenous acetylcholine were not affected by the pre‐treatment.
There was a slight increase in the apparent equilibrium constant for naloxone after morphine pre‐treatment.
Tolerance to opiate effect was not accompanied by a change in the affinity or number of stereo‐specific binding sites for [3H]‐etorphine. Hill plots of [3H]‐etorphine binding in both control and morphine pretreated preparations gave slopes close to unity.
Most of these results can be explained by the assumption that in tolerant preparations, a certain fractional opiate receptor occupation threshold must be exceeded before opiate effects become apparent. It is suggested that the tissue adapts toward a threshold equivalent to the mean receptor occupancy attained during the period of opiate drug pretreatment.
ALTERATIONS IN BRAIN 5‐HYDROXY‐TRYPTAMINE METABOLISM DURING THE ‘WITHDRAWAL’ PHASE AFTER CHRONIC TREATMENT WITH DIAZEPAM AND BROMAZEPAM
Authors: AGARWAL R.A. , LAPIERRE Y.D. , RASTOGI R.B. , SINGHAL R.L 
Published: July 2012

Daily administration of diazepam or bromazepam (10 mg/kg) for 22 days significantly increased the activity of mid‐brain tryptophan hydroxylase by 36% and 39%, respectively. The concentration of tryptophan was also enhanced in the mid‐brain region of rats subjected to benzodiazepine treatment.
Chronic therapy with either of the two anti‐anxiety agents enhanced the endogenous levels of 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid in cerebral cortex, hypothalamus, pons‐medulla, mid‐brain and striatum.
Whereas diazepam treatment decreased (13%) the activity of monoamine oxidase in mid‐brain, bromazepam failed to exert any effect, suggesting that the observed elevation in 5‐hydroxyindoleacetic acid levels is not associated with enhanced deamination of 5‐hydroxytryptamine.
Discontinuation of treatment for 48 h significantly decreased the activity of mid‐brain tryptophan hydroxylase to levels that were significantly lower than those seen for benzodiazepine‐treated and normal rats. The concentrations of mid‐brain tryptophan and 5‐hydroxytryptamine were also reduced in various brain regions examined.
Withdrawal from diazepam or bromazepam therapy further augmented the levels of brain 5‐hydroxyindoleacetic acid.
The results demonstrate that the depressant effects on behaviour of these agents are accompanied by increased metabolism of 5‐hydroxytryptamine in the brain. Withdrawal from these minor tranquillizers, on the other hand, reduces the synthesis of this indoleamine.