bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular signatures of long‐lived proteins: autolytic cleavage adjacent to serine residues
Authors: Su Shih‐Ping , Lyons Brian , Friedrich Michael , McArthur Jason D. , Song Xiaomin , Xavier Dylan , Truscott Roger J. W. , Aquilina John A. 
Published: July 2012

SummaryThe centre of the human lens, which is composed of proteins that were synthesized prior to birth, is an ideal model for the evaluation of long‐term protein stability and processes responsible for the degradation of macromolecules. By analysing the sequences of peptides present in human lens nuclei, characteristic features of intrinsic protein instability were determined. Prominent was the cleavage on the N‐terminal side of serine residues. Despite accounting for just 9% of the amino acid composition of crystallins, peptides with N‐terminal Ser represented one‐quarter of all peptides. Nonenzymatic cleavage at Ser could be reproduced by incubating peptides at elevated temperatures. Serine residues may thus represent susceptible sites for autolysis in polypeptides exposed to physiological conditions over a period of years. Once these sites are cleaved, other chemical processes result in progressive removal or ‘laddering’ of amino acid residues from newly exposed N‐ and C‐termini. As N‐terminal Ser peptides originated from several crystallins with unrelated sequences, this may represent a general feature of long‐lived proteins.
The effects of rock fragmentation and / or deep tillage on soil skeletal material and chemical properties in a Mediterranean climate
Authors: FERRARA G. , FARRAG K. , BRUNETTI G. 
Published: July 2012

AbstractIn Puglia, Italy, deep tillage and rock fragmentation are common agricultural practices to prepare land for vineyards or orchards. Unfortunately, little is known about how these practices influence soil structure and quality. There is a lack of information on the consequences of these practices on the soil fractions coarser than 2 mm, which are known as rock fragments or skeletal material, the focus of this study. Soil samples were obtained from depths of 0‐20 and 20–40 cm and analysed for pH, electrical conductivity, total organic carbon, total nitrogen, available phosphorus, and total and active calcium carbonate. For each soil depth, we determined the amount of fine earth and skeletal material by volume. The results indicate that rock fragmentation and/or deep ploughing cause a major change in soils, leading to the progressive reduction in total organic carbon and nitrogen, and to an increase in total and active calcium carbonate. In addition, there was a marked increase in skeletal material compared to undisturbed soil. The results confirm that rock fragmentation causes significant changes in soil physical properties and increases greatly the amount of skeletal material.
The biological properties of the optical isomers of propranolol and their effects on cardiac arrhythmias
Authors: BARRETT A. M. , CULLUM VALERIE A. 
Published: July 2012

The optical isomers of propranolol have been compared for their β‐blocking and antiarrhythmic activities.In blocking the positive inotropic and chronotropic responses to isoprenaline, (+)‐propranolol had less than one hundredth the potency of (–)‐propranolol. At dose levels of (+)‐propranolol which attenuated the responses to isoprenaline, there was a significant prolongation of thePRinterval of the electrocardiogram.The metabolic responses to isoprenaline in dogs (an increase in circulating glucose, lactate and free fatty acids) were all blocked by (–)‐propranolol. (+)‐Propranolol had no effect on fatty acid mobilization but significantly reduced the increments in both lactate and glucose.Both isomers of propranolol possessed similar depressant potency on isolated atrial muscle taken from guinea‐pigs.The isomers of propranolol exhibited similar local anaesthetic potencies on an isolated frog nerve preparation at a level approximately three times that of procaine. The racemic compound was significantly less potent than either isomer.Both isomers of propranolol were capable of preventing adrenaline‐induced cardiac arrhythmias in cats anaesthetized with halothane, but the mean dose of (–)‐propranolol was 0.09 ± 0.02 mg/kg whereas that of (+)‐propranolol was 4.2 ± 1.2 mg/kg. At the effective dose level of (+)‐propranolol there was a significant prolongation of thePRinterval of the electrocardiogram. Blockade of arrhythmias with both isomers was surmountable by increasing the dose of adrenaline.Both isomers of propranolol were also capable of reversing ventricular tachycardia caused by ouabain in anaesthetized cats and dogs. The dose of (–)‐propranolol was significantly smaller than that of (+)‐propranolol in both species but much higher than that required to produce evidence of β‐blockade.The implications of these results are discussed.
Restoration of the chronotropic effect of tyramine on rat atria after reserpine
Authors: MURNAGHAN M. F. 
Published: July 2012

The restoration by various sympathomimetic amines of the chronotropic response to tyramine was studied on the isolated atria of rats pretreated with reserpine. The atria were exposed to the “restorative” sympathomimetic amine for 10 min, washed over a period of 1 hr and then tested with 10 μm tyramine. The effect of noradrenaline, dopamine and norphenylephrine before and after inhibition of monoamine oxidase by 0.5 mm iproniazid were compared with their α‐methyl and N‐alkyl analogues in their ability to restore the chronotropic response to tyramine.
Noradrenaline and adrenaline restored the chronotropic response to tyramine, the degree of restoration depending on the concentration of the restorative amine used. Noradrenaline after iproniazid and α‐methylnoradrenaline were equipotent and were about 1,000 times more active than noradrenaline where monoamine oxidase was not inhibited. Dopamine, epinine, norphenylephrine, phenylephrine, octopamine, synephrine and isoprenaline in the absence of monoamine oxidase inhibition had no effect. Dopamine after iproniazid and α‐methyldopamine were equipotent and were about 1/10 as active as α‐methylnoradrenaline. Norphenylephrine after iproniazid and metaraminol were equipotent and were about 1/500 as active as α‐methylnoradrenaline. Octopamine after iproniazid was even less active. The N‐methylated analogues were about 1/10 as active as their nor‐compounds but the N‐isopropyl analogue, isoprenaline, was devoid of activity.
Dopamine after iproniazid and α‐methyldopamine were inactive if a dopamine‐β‐hydroxylase inhibitor, disulphiram or sodium diethyldithio‐carbamate, was present.
It is concluded that, in atria of reserpinized rats, (a) protection from monoamine oxidase increases; (b) N‐substitution decreases; and (c) hydroxyl groups at the β‐carbon and ring positions 3 and 4 increase the capabilities of a sympathomimetic amine to restore the chronotropic response to tyramine.
A study of the role of noradrenaline in behavioural changes produced in the rat by psychotomimetic drugs
Authors: SUGRUE M. F. 
Published: July 2012

LSD‐25, psilocybin and JB‐329 reduced the noradrenaline content of the rat hypothalamus.
All three drugs affected the acquisition of a conditioned avoidance response, LSD‐25 and psilocybin retarding and JB‐329 enhancing the acquisition. With the exception of JB‐329, doses affecting the acquisition of a conditioned avoidance response were lower than those required to decide hypothalamic noradrenaline concentrations. The time of peak drug effect on the acquisition of a conditioned avoidance response occurred approximately 1.5 hr after injection as opposed to 3 hr in the case of noradrenaline content.
The amount of LSD‐25, psilocybin and JB‐329 necessary to elicit gross behavioural excitation was similar to the dose producing noradrenaline depletion. Here also the peak behavioural effect was detected earlier.
Pretreatment with reserpine and α‐MT had no effect on the intensity of gross behavioural excitation induced by LSD‐25 and psilocybin but shortened the duration of the response. The excitation induced by JB‐329 was abolished by reserpine pretreatment and was markedly reduced both in intensity and duration by the prior injection of α‐MT.
Brain monoamines and adrenocortical activation
Authors: DE SCHAEPDRYVER A. , PREZIOSI P. , SCAPAGNINI U. 
Published: July 2012

The effect of a pharmacologically induced increase or depletion of brain monoamines (5‐hydroxytryptamine, noradrenaline, dopamine) was investigated with respect to adrenocortical function.
No strict correlation was found between the depletion of brain amine stores induced by prenylamine or p‐chlorophenylalanine and adrenocortical activation, even at times in which the peak effect of brain amine depletion occurs.
Restraint stress causes a manifest increase in brain 5‐hydroxytryptamine while decreasing the cerebral noradrenaline and dopamine content. This stress strongly stimulates corticosterone secretion by the adrenals.
A monoamine oxidase inhibitor, nialamide, at a dose which causes an evident increase in brain amine concentrations, does not modify plasma corticosterone. At the same dose it was, furthermore, unable to prevent the adrenocortical stimulation induced by restraint stress.
Brain amine content does not seem to play an important part in the control of corticotrophin releasing factor in corticotrophin secretion by the pituitary gland. The relationship between hypothalamic monoamines and other neuro‐humours is discussed.
Anti‐arrhythmic, local anaesthetic, and adrenergic blocking activity of some β‐receptor antagonists
Authors: HERMANSEN KELD 
Published: July 2012

The antagonistic effect of the β‐receptor blocking compounds propranolol, Ph QA 33 and INPEA on ouabain‐induced cardiac fibrillations in guinea‐pigs was compared with their local anaesthetic and β‐receptor blocking properties.
All three compounds were found capable of increasing the tolerance to ouabain and of reversing ouabain‐induced fibrillations, the ED50 being 0.3 mg/kg intravenously, 0.5 mg/kg intravenously, and 1.5 mg/kg intravenously, respectively for propranolol, Ph QA 33 and INPEA.
Propranolol and Ph QA 33 were found to be moderate to strong local anaesthetics while INPEA had a considerably weaker though significant effect.
The order of potency as β‐receptor blocking compounds was propranolol ≥ Ph QA 33 > INPEA, the latter compound being less than 1% as active as propranolol.
Despite the surprising finding that INPEA was effective against non‐catecholamine‐induced arrhythmias, the results support the general assumption that the anti‐arrhythmic effect of β‐receptor blocking compounds is related to their local anaesthetic action rather than to their β‐blocking ability.
A pharmacological study of the toxin of a Cnidarian, Chironex fleckeri Southcott
Authors: FREEMAN SHIRLEY E. , TURNER R. J. 
Published: July 2012

A study has been made of the pharmacological actions of toxic preparations obtained from the box jellyfish Chironex fleckeri Southcott. Two toxin preparations were used. One was a tentacle extract which was partially purified by Sephadex gel filtration; the second was obtained by a process analogous to snake milking, and is probably similar in composition to the material injected into victims.
All preparations were extremely toxic; death in animals, following minimally lethal doses, occurred in minutes. Respiratory arrest of central origin appeared to be the terminal event in all species tested. This was accompanied by marked signs of cardiotoxicity. The heart was slowed, irregular, and showed varying degrees of conduction delay. Terminally it showed atrioventricular block.
Blood pressure changes were biphasic. An initial rise in carotid pressure was followed by a profound fall; a second rise to an above normal level frequently followed this. These blood pressure oscillations were damped down by prior treatment with hexamethonium but the hypertensive response remained.
Blood samples taken before terminal apnoea showed a variable degree of haemolysis and a raised K+ level.
Experiments with isolated organ preparations suggested that the toxin had a non‐specific lytic effect on cells, but did not contain pharmacologically active substances of small molecular weight such as 5‐hydroxytryptamine.
It is suggested that the toxin(s) act by altering membrane permeability; the signs at death may reflect the sensitivity of the target organs to such a change.
Uptake of dopamine by platelets in vivo
Authors: Boullin D. J. , McMahon E. M. , O'Brien R. A. 
Published: July 2012

Circulating platelets of cats infused with 141C‐dopamine take up the amine against a concentration gradient, with maximal concen‐tration occurring 10 min after infusion. 58%, of the platelet‐bound radioactive dopamine was localized in a subcellular fraction rich in 5‐hydroxytryptamine (5‐HT) storage organ‐elles. The results support earlier work with human platelets showing in vitro dopamineuptake by normal platelets, and in vivo accumulation in parkinsonian patients treated with l‐dopa.
The effects of adrenaline, noradrenaline and isoprenaline on inhibitory α‐ and β‐adrenoceptors in the longitudinal muscle of the guinea‐pig ileum
Authors: KOSTERLITZ H. W. , LYDON R. J. , WATT A. J. 
Published: July 2012

Summary
Two preparations, a segment of the ileum and the myenteric plexus‐longitudinal muscle preparation, have been used for an analysis of the inhibitory effects of adrenaline, noradrenaline and isoprenaline on the contractor responses of the longitudinal muscle to acetylcholine or to electrical, coaxial or field, stimulation.
Since the inhibitory effects of adrenaline, noradrenaline and isoprenaline on the acetylcholine‐induced contractions were not affected by phenoxybenzamine but were antagonized by propranolol, it is concluded that β‐adrenoceptors are present on the muscle cells.
The responses to electrical stimulation were suppressed by adrenaline or noradrenaline but only partly inhibited by isoprenaline. Propranolol antagonized the effect of isoprenaline and, to some extent, that of noradrenaline, but scarcely affected the action of adrenaline. Phenoxybenzamine, on the other hand, antagonized most of the effect of adrenaline and, to some extent, that of noradrenaline; it usually potentiated the effect of isoprenaline.
The output of acetylcholine evoked by electrical stimulation was diminished by adrenaline or noradrenaline but was not affected by isoprenaline. The depressant effect on acetylcholine release was antagonized by phenoxybenzamine but not affected by propranolol; therefore these effects of adrenaline and noradrenaline are mediated by α‐adrenoceptors.
It may be assumed that α‐adrenoceptors in situ are stimulated mainly by circulating adrenaline and possibly noradrenaline and thus cause a prejunctional inhibition at the nerve‐smooth muscle junction.
Interaction of atropine‐like drugs with dopamine‐containing neurones in rat brain
Authors: BOWERS M. B. , ROTH R. H. 
Published: July 2012

Summary
A variety of atropine‐like drugs effective in the treatment of drug‐induced extrapyramidal syndromes have been investigated with regard to their interaction with dopamine‐containing neurones in rat brain.
Under some conditions benztropine, trihexyphenidyl, atropine and ethopropazine significantly antagonized the chlorpromazine‐induced increase in subcortical concentrations of homovanillic acid.
Most of the atropine‐like drugs investigated also decreased the turnover of dopamine in the subcortex as measured by following the disappearance of dopamine after administration of α‐methyl‐p‐tyrosine.
These findings are suggestive that an imbalance between a dopaminergic and cholinergic system might be closely linked to the pathogenesis of extrapyramidal movement disorders.
Effect of physostigmine on ventricular fibrillation and myocardial glycogen in hypothermic dogs
Authors: DAS P. K. , SINHA P. S. 
Published: July 2012

Summary
Physostigmine (0·1 mg/kg i.v.) given at 37° C and 25° C rectal temperatures, completely protected the hypothermic dog heart against ventricular fibrillation.
Pentolinium, atropine, vagotomy and reserpine did not significantly alter the incidence of ventricular fibrillation.
The incidence of ventricular fibrillation under hypothermia could be significantly increased by ligating the anterior descending branch of the left coronary artery. The incidence of ventricular fibrillation in coronary ligated hypothermic dogs was reduced to half by physostigmine pretreatment.
Hypothermia produced ventricular glycogen depletion and physostigmine prevented ventricular glycogenolysis under hypothermia. However, in the normothermic state physostigmine itself produced a significant decrease in cardiac glycogen.
The relation between the antifibrillatory and antiglycogenolytic effects of physostigmine under hypothermia are discussed.
Evaluation of mechanisms controlling the release and inactivation of the adrenergic transmitter in the rabbit portal vein and vas deferens
Authors: HUGHES J. 
Published: July 2012

Summary
A method is described for the detection and assay of picogramme quantities of noradrenaline. This involves transferring Krebs solution containing noradrenaline to a cascade system where the catecholamine may be bioassayed on superfused preparations of the rabbit aorta and iliac artery.
Electrical field stimulation of the rabbit vas deferens and portal vein caused the release, into the bathing medium, of a material which was identified by pharmacological and chemical tests as noradrenaline.
Cocaine (0·3–5 μg/ml) caused a marked increase in noradrenaline output after electrical stimulation of the portal vein and vas deferens. This effect appeared to be maximal at a concentration of 2·4 μg/ml; when the cocaine concentration was increased above 10 μg/ml the noradrenaline output was greatly reduced.
Phenoxybenzamine (5 μg/ml) caused a 4–8 times greater increase in noradrenaline output than cocaine; however, the increase in output due to phenoxybenzamine was much smaller in tissues pretreated with cocaine.
Corticosterone (20 μg/ml) increased noradrenaline output by 30–40% in untreated vas deferentia, but caused a 300% increase in output in tissues pretreated with cocaine. Cocaine also caused a much greater increase in output in tissues pretreated with corticosterone than in untreated tissues.
Treatment with pargyline plus tropolone caused a 100–200% increase in noradrenaline output; this effect was not modified by cocaine, but was abolished when the tissues were pretreated with either phenoxybenzamine or corticosterone.
When tissues were stimulated for 240 pulses at 1–16 Hz, the output per pulse of noradrenaline increased linearly with the logarithm of the frequency of stimulation. This relationship between frequency and output was seen in both untreated tissues, and in tissues treated with cocaine, phenoxybenzamine, corticosterone or pargyline plus tropolone.
It is concluded that cocaine enhances output by blocking the neuronal reuptake of noradrenaline, and corticosterone by blocking the extraneuronal uptake and subsequent metabolism of noradrenaline. Phenoxybenzamine acts by blocking both neuronal and extraneuronal uptake mechanisms. There appears to be a dynamic balance in the distribution of noradrenaline between the two uptake mechanisms after the release of the transmitter from the nerve endings.
It is calculated that more than 90% of the noradrenaline released by nerve stimulation (240 pulses at 2–16 Hz) is inactivated by neuronal and extraneuronal uptake mechanisms.
It is calculated that the fraction of the total noradrenaline store that is released by one pulse at 2 Hz is 6·6 × 10−5 in the portal vein and 5·6 × 10−5 in the vas deferens; the corresponding values at 16 Hz were 15·9 × 10−5 and 16·2 × 10−5.
Evaluation of cryogenine on rat paw thermal oedema and rat isolated uterus
Authors: MALONE M. H. , TROTTIER R. W. 
Published: July 2012

Summary
. Significant inhibition of oedema formation caused by thermal injury was observed for calcium carbaspirin, phenylbutazone, hydrocortisone, cryogenine and indomethacin when given daily beginning 2 days prior to thermal exposure and afterwards. Several anti‐inflammatory drugs, including cryogenine, failed to reduce thermal oedema significantly when given as single doses 1 h prior to the thermal injury.
. Kinetic experiments on the rat isolated uterus demonstrated that cryogenine, chlorpromazine, and flufenamic acid were, in part, competitive inhibitors of synthetic bradykinin, while indomethacin and tetrabenazine showed only non‐competitive antagonism.
The bradykininase activities of extracts of dog lung
Authors: ALABASTER VALERIE A. , BAKHLE Y. S. 
Published: July 2012

Summary
Homogenates of dog lungs freed from blood inactivate bradykinin. The bradykininase activity is present in soluble and particulate subcellular fractions.
The fraction with the highest relative specific activity is that sedimenting between 8,700 g and 78,000 g. This fraction has been studied in more detail.
There is evidence for two bradykinin inactivating enzymes in this fraction with apparent Km values of 7·5 μm and 120 μm.
The bradykininase activity is not dependent on the concentration of chloride ion.
The bradykininase activity is inhibited by EDTA, 2:3‐dimercaptopropanol, nickel ions and some of the peptides from the venom of Bothrops jararaca and of Agkistrodon halys blomhoffii but not by 2‐mercaptoethanol or N‐ethylmaleimide.
Angiotensin II in either 15 or 170 mm chloride ion is not an inhibitor of bradykininase activity but angiotensin I at either chloride concentration is an inhibitor. It is proposed that chloride is not necessary for binding of angiotensin I to converting enzyme but is necessary to ensure the correct orientation of substrate for hydrolysis to proceed.
EFFECT OF SELECTIVE DESTRUCTION OF CENTRAL AND PERIPHERAL CATECHOLAMINE‐CONTAINING NEURONES WITH 6‐HYDROXYDOPAMINE ON CATECHOLAMINE EXCRETION IN THE RAT
Authors: HOELDTKE R. , ROGAWSKI M. , WURTMAN R.J. 
Published: July 2012

The contribution of various tissues to some of the pools of catecholamine metabolites in urine has been estimated by measuring the excretion of these compounds by rats given DOPA‐free diets and intravenous, intraventricular, or intracisternal 6‐hydroxydopamine.
Destruction of peripheral sympathetic neurones by repeated intravenous doses of 6‐hydroxy dopamine led to a 34% decrease in noradrenaline excretion, and a 38% decrease in 4‐hydroxy‐3‐methoxyphenylglycol sulphate excretion. Depletion of brain noradrenaline (by 67%), after intracisternal 6‐hydroxydopamine, was unassociated with changes in the excretion of noradrenaline or of 4‐hydroxy‐3‐methoxyphenylglycol sulphate. This suggests that these compounds in rat urine are derived mainly from peripheral tissues.
Depletion of brain dopamine (by 80%) by intraventricular 6‐hydroxydopamine was associated with a 27% decrease in the excretion of homovanillic acid. Destruction of peripheral sympathetic neurones with intravenous 6‐hydroxydopamine led to a 25% decrease in homovanillic acid excretion. The data suggest that the homovanillic acid in rat urine derives partially from brain dopamine and partially from dopamine released from or metabolized within sympathetic neurones.
Neither depletion of brain dopamine, nor destruction of sympathetic neurones, caused alterations in the excretion of dopamine or dihydroxyphenylacetic acid.