bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein phosphatase‐1M and Rho‐kinase affect exocytosis from cortical synaptosomes and influence neurotransmission at a glutamatergic giant synapse of the rat auditory system
Authors: Lontay Beáta , Pál Balázs , Serfőző Zoltán , Kőszeghy Áron , Szücs Géza , Rusznák Zoltán , Erdődi Ferenc 
Published: July 2012

AbstractProtein phosphatase‐1M (PP1M, myosin phosphatase) consists of a PP1 catalytic subunit (PP1c) and the myosin phosphatase target subunit‐1 (MYPT1). RhoA‐activated kinase (ROK) regulates PP1M via inhibitory phosphorylation of MYPT1. Using multidisciplinary approaches, we have studied the roles of PP1M and ROK in neurotransmission. Electron microscopy demonstrated the presence of MYPT1 and ROK in both pre‐ and post‐synaptic terminals. Tautomycetin (TMC), a PP1‐specific inhibitor, decreased the depolarization‐induced exocytosis from cortical synaptosomes. trans‐4‐[(1R)‐1‐aminoethyl]‐N‐4‐pyridinylcyclohexanecarboxamide dihydrochloride, a ROK‐specific inhibitor, had the opposite effect. Mass spectrometry analysis identified several MYPT1‐bound synaptosomal proteins, of which interactions of synapsin‐I, syntaxin‐1, calcineurin‐A subunit, and Ca2+/calmodulin‐dependent kinase II with MYPT1 were confirmed. In intact synaptosomes, TMC increased, whereas Y27632 decreased the phosphorylation levels of MYPT1Thr696, myosin‐II light chainSer19, synapsin‐ISer9, and syntaxin‐1Ser14, indicating that PP1M and ROK influence their phosphorylation status. Confocal microscopy indicated that MYPT1 and ROK are present in the rat ventral cochlear nucleus both pre‐ and post‐synaptically. Analysis of the neurotransmission in an auditory glutamatergic giant synapse demonstrated that PP1M and ROK affect neurotransmission via both pre‐ and post‐synaptic mechanisms. Our data suggest that both PP1M and ROK influence synaptic transmission, but further studies are needed to give a full account of their mechanism of action.
Innovations in Practice: MICHI, a brief cognitive‐behavioural group therapy for adolescents with depression – a pilot study of feasibility in an inpatient setting
Authors: Straub Joana , Koelch Michael , Fegert Joerg , Plener Paul , Gonzalez‐Aracil Inma , Voit Anja , Sproeber Nina 
Published: July 2012

BackgroundGroup therapy is an economic intervention, allowing for fast access, for the treatment of several depressed adolescents simultaneously; evaluated manualised programs, however, are scarce.MethodNine depressive adolescent inpatients (M = 16.33 years;
SD
= 1.92) participated between October 2009 and March 2010 in a brief manualised group therapy programme (MICHI), which was evaluated with respect to feasibility and trends of efficacy.Results
MICHI demonstrated good feasibility, was positively evaluated by the participants by means of an evaluation questionnaire ranging from 1 (very bad) to 10 (very good) (M = 7.22;
SD
= 1.79), and showed significant reduction of depressive symptoms (z = −2.66, p = .008) assessed by means of a clinical interview.ConclusionsFeasibility of MICHI was demonstrated and larger trials for efficacy will follow.
Meaningful Use of Electronic Health Record Systems and Process Quality of Care: Evidence from a Panel Data Analysis of U.S. Acute‐Care Hospitals
Authors: Appari Ajit , Eric Johnson M. , Anthony Denise L. 
Published: July 2012

ObjectiveTo estimate the incremental effects of transitions in electronic health record (EHR) system capabilities on hospital process quality.Data SourceHospital Compare (process quality), Health Information and Management Systems Society Analytics (EHR use), and Inpatient Prospective Payment System (hospital characteristics) for 2006–2010.Study SettingHospital EHR systems were categorized into five levels (Level_0 to Level_4) based on use of eight clinical applications. Level_3 systems can meet 2011 EHR “meaningful use” objectives. Process quality was measured as composite scores on a 100‐point scale for heart attack, heart failure, pneumonia, and surgical care infection prevention. Statistical analyses were conducted using fixed effects linear panel regression model for all hospitals, hospitals stratified on condition‐specific baseline quality, and for large hospitals.Principal FindingsAmong all hospitals, implementing Level_3 systems yielded an incremental 0.35–0.49 percentage point increase in quality (over Level_2) across three conditions. Hospitals in bottom quartile of baseline quality increased 1.16–1.61 percentage points across three conditions for reaching Level_3. However, transitioning to Level_4 yielded an incremental decrease of 0.90–1.0 points for three conditions among all hospitals and 0.65–1.78 for bottom quartile hospitals.ConclusionsHospitals transitioning to EHR systems capable of meeting 2011 meaningful use objectives improved process quality, and lower quality hospitals experienced even higher gains. However, hospitals that transitioned to more advanced systems saw quality declines.
THE EFFECT OF DIURETICS ON THE WATER EXCRETION OF PROTEIN DEFICIENT RATS
Authors: BLACKMORE K. E. , SCHNIEDEN H. 
Published: July 2012

Adult rats kept for eleven weeks on a diet deficient in protein lost weight and some developed scrotal oedema. The retention of bromsulphthalein was increased, but the thymol turbidity test was unaffected; the apparent plasma volume was increased.Water diuresis in the protein deficient animals was impaired. There was no apparent delay in the mean rate of water absorption from the whole gastro‐intestinal tract although a delayed absorption of water from the intestine was found in some animals. The concentrations of total plasma proteins and plasma albumin were low as compared with normal animals, but the plasma sodium levels were within normal limits. The inulin clearance (glomerular filtration rate) of the animals on the protein‐deficient diet was significantly lower than that of the controls.In normal rats, aminophylline and acetazolamide were diuretic. Caffeine and sodium benzoate did not increase the urine output and mersalyl was antidiuretic. In the protein deficient rats, cortisone acetate increased the water diuresis. Caffeine and sodium benzoate, aminophylline and acetazolamide did not significantly increase this response, mersalyl had an antidiuretic effect. Cortisone acetate increased the food and water intake of the protein deficient rats; it also increased the glomerular filtration rate.
THE TOXICITY OF DIAMINODIPHENOXYALKANES
Authors: GOODWIN L. G. , RICHARDS W. H. G. , UDALL V. 
Published: July 2012

Representative members of a series of schistosomicidal diaminodiphenoxyalkanes were examined for their toxic effects in laboratory animals. Primary amino‐derivatives were, in general, more toxic than secondary methylamino‐compounds; tertiary compounds were less toxic than either. Large doses given by mouth or by injection to mice or rabbits produced intravascular haemolysis; the haemoglobin and erythrocyte counts began to increase again about a week after the dose. Mice which had been given large doses of diaminodiphenoxyalkanes developed symmetrical bald patches 2 to 3 weeks after treatment. The exposed skin appeared normal and new fur grew to cover the hairless areas in about 6 weeks. Large doses of drug delayed water diuresis in mice.Many compounds of the series caused visual impairment when given to cats. In order to obtain a quantitative assessment of retinotoxic potency, a method was devised in which the ability of the retina of the frog to resynthesize rhodopsin was measured in treated and control animals. Compounds that produced blindness in cats also inhibited rhodopsin synthesis in frogs; the most toxic compounds were primary amines. Treatment with some tertiary amines caused retinal damage if the drugs were given for long periods. Diaminodiphenoxyalkanes may perhaps interfere in some way with the biological activity of vitamin A. However, toxic effects on the hair and retina were not prevented by supplements of synthetic or natural vitamin A.
SENSITIZATION OF THE HEART AND NICTITATING MEMBRANE OF THE CAT TO SYMPATHOMIMETIC AMINES BY ANTIHISTAMINE DRUGS
Authors: INNES I. R. 
Published: July 2012

Sensitization to the cardio‐accelerator action of adrenaline and noradrenaline by five antihistamines was examined on the acutely denervated heart of the cat. Antazoline (Antistin), chlorcyclizine and promethazine (Phenergan) increased the cardio‐accelerator responses to both amines equally. Mepyramine (Anthisan) increased noradrenaline more than adrenaline action. Diphenhydramine (Benadryl) resembled cocaine in potentiating the responses to noradrenaline but not to adrenaline.On the nictitating membrane mepyramine caused sensitization to the actions of adrenaline, noradrenaline and tyramine, an effect similar to that of chronic preganglionic denervation. Diphenhydramine enhanced the action of noradrenaline more than that of adrenaline and had little effect on tyramine action, giving a sensitization which bears a greater resemblance to the type caused by cocaine or chronic postganglionic denervation.It is suggested that two distinct mechanisms are required to account for the phenomena of sensitization.
OBSERVATIONS CONCERNING THE ACTION OF 5‐HYDROXYTRYPTAMINE ON THE PERISTALTIC REFLEX
Authors: BÜLBRING EDITH , CREMA A. 
Published: July 2012

In isolated guinea‐pig intestine 5‐hydroxytryptamine increased the longitudinal muscle contractions in response to acetylcholine while the ganglionic action of nicotine was first facilitated and then blocked. Phenyldiguanide, veratrine, veratridine and protoveratrine, like 5‐hydroxytryptamine, depressed the response to nicotine, leaving that to acetylcholine unaffected.The sensory stimulants, like 5‐hydroxytryptamine, facilitated the peristaltic reflex when applied to the mucosa, and abolished it when applied to the serosa. Preceding the block, the initial effect of low concentrations of 5‐hydroxytryptamine applied to the serosa was a short stimulation of peristalsis.Concentrations of 5‐hydroxytryptamine which had an approximately equal stimulant action (mucosal 1 to 4 × 10−6, serosal 2 to 8 × 10−8were tested when various parts of the reflex arc were blocked. During block by procaine introduced into the lumen, mucosal application of 5‐hydroxytryptamine re‐established peristalsis, but serosal application of 5‐hydroxytryptamine had no effect. During block by hexamethonium or atropine present in the bath, 5‐hydroxytryptamine restored peristalsis more effectively by serosal application than by mucosal application. During block by serosal application of 5‐hydroxytryptamine, morphine, phenoxybenzamine or dihydroergotamine, mucosal application of 5‐hydroxytryptamine restored the peristaltic reflex while serosal application had no effect. During block by 2‐bromo‐lysergic acid diethylamide or lysergic acid diethylamide acting from the serosal surface, 5‐hydroxytryptamine had no effect whether acting on the mucosal or on the serosal surface.It is concluded that 5‐hydroxytryptamine facilitates the peristaltic reflex at two sites: when introduced into the lumen it stimulates mucosal sensory receptors; when acting from the serosal surface it sensitizes the muscle to the transmitter acetylcholine. There is also a transient stimulant action on the ganglia which is soon followed by inhibition; this indicates that 5‐hydroxytryptamine applied to the serosa abolishes peristalsis by ganglion block.
Effects of metabolic inhibitors on contraction of rabbit detrusor muscle
Authors: PATON D. M. 
Published: July 2012

. The contractile responses of rabbit detrusor muscle strips to acetylcholine are reversibly depressed but not abolished by 2,4‐dinitrophenol (0.1–1.0 mm) provided that d‐glucose or d‐mannose is present. l‐glucose, d‐2‐deoxyglucose, d‐galactose, d‐fructose, d‐xylose, maltose, lactose and sucrose are ineffective in this respect.
. The contractile responses are greatly reduced by iodoacetic acid (0.1–1.0 mm) in 30–60 min and eventually abolished. The depressant effect of iodoacetic acid (0.25 mm) can be partially reversed or retarded by pyruvate (20 mm).
. It is concluded that the energy for contraction of the detrusor muscle can be supplied by glycolysis alone. Because both d‐glucose and pyruvate can be utilized, it is assumed that the glycolytic route and Krebs cycle are available in the detrusor muscle cells.
Pharmacological modifications of sympathetic responses elicited by hypothalamic stimulation in the rat
Authors: MORPURGO CLARA 
Published: July 2012

. The rise in blood pressure and the eyelid contractions elicited by electrical stimulation of the posterior hypothalamus in anaesthetized rats were studied for the assessment of drug effects on the sympathetic system. They were compared with the noradrenaline pressor effect and eyelid responses to cervical sympathetic nerve stimulation.
. Phentolamine caused a similar reduction of the pressor responses induced by hypothalamic stimulation and by noradrenaline. It also reduced the eyelid contractions elicited by central and by peripheral electrical stimulation.
. Guanethidine caused an immediate inhibition of the pressor response to hypothalamic stimulation, while it potentiated noradrenaline effects. Eyelid contractions elicited both by central and by peripheral electrical stimulation were inhibited.
. Chlorpromazine inhibited the pressor responses both to hypothalamic stimulation and to noradrenaline, but it caused a much greater reduction in the centrally evoked eyelid responses than in those due to peripheral stimulation.
. Diazepam caused a reduction of sympathetic responses to central stimulation but not to peripherally elicited responses.
. In unanaesthetized rats the rise in blood pressure induced by hypothalamic stimulation was accompanied by increased locomotor activity culminating in a flight reaction. In contrast to the pressor effect, which was reduced by all four of the above‐mentioned drugs, the flight reaction was not affected by phentolamine and guanethidine and only delayed by chlorpromazine and diazepam at dose levels which impaired the spontaneous locomotor activity.
Some studies on peripheral actions of mephenesin, methocarbamol and diazepam
Authors: CRANKSHAW D. P. , RAPER C. 
Published: July 2012

. Mephenesin, methocarbamol and diazepam abolished polysynaptic reflex contractions of the cat tibialis anterior muscle elicited by stimulation of the homolateral femoral nerve.
. Mephenesin and methocarbamol caused a prolongation of the mean refractory period of directly or indirectly stimulated skeletal muscle. These effects were due to a direct action on the muscle fibres. There was no effect on responses to single stimuli.
. The increase in refractory period produced by mephenesin was greater in indirectly than in directly stimulated rat diaphragms. Experiments using the isolated phrenic nerve suggest that this difference is due to the local anaesthetic action of mephenesin.
. In the indirectly stimulated cat tibialis anterior muscle high frequency stimulation resulted in a non‐maintained tetanus in the presence of mephenesin and methocarbamol.
. Diazepam was without peripheral effects on the responses of skeletal muscle.
. The results with mephenesin and methocarbamol are discussed in relation to their mode of action in reducing muscle spasm.
The action of antidiuretic hormone on cell membranes. Voltage transient studies
Authors: CUTHBERT A. W. , PAINTER ELISABETH 
Published: July 2012

The instantaneous impedance method has been used to study the effects of antidiuretic hormone (ADH) on frog skin.
The resting skin may be represented by a parallel RC network with a single time constant.
Antidiuretic hormone causes an increase in conductance and capacitance and in some cases the appearance of a polarization angle.
The structures in the skin responsible for the transients are located in the outermost membranes.
The effects of ADH have been interpreted in terms of the formation of water‐filled sodium‐permselective pores in the outer facing membranes which occupy, at most, 0.3% of the skin surface. These pores constitute a parallel, and hence additive, capacitance with that of the normally ion impermeable parts of the cell surface, and in addition are responsible for the increase in conductance. The polarization angle is due to the polydisperse nature of the skin after hormone treatment.
Salbutamol: a new, selective β‐adrenoceptive receptor stimulant
Authors: CULLUM VALERIE A. , FARMER J. B. , JACK D. , LEVY G. P. 
Published: July 2012

Salbutamol is a β‐adrenoceptive receptor stimulant. Its pharmacological actions are reduced or abolished by β‐receptor antagonists.
In anaesthetized animals, salbutamol, given intravenously, was slightly less active than isoprenaline in preventing spasm of bronchial smooth muscle but was considerably less active as a cardiac stimulant and vasodepressor substance. Its duration of action was about 2 to 3 times that of isoprenaline.
Salbutamol given by mouth or aerosol to conscious guinea‐pigs, greatly diminished bronchospasm caused by inhalation of acetylcholine. By mouth, salbutamol was more active and had a longer duration than isoprenaline or orciprenaline without affecting heart rate. By aerosol, salbutamol was approximately 10 times as active as isoprenaline and 100 times as active as orciprenaline. Its duration of action was much longer than that of isoprenaline or orciprenaline. Only isoprenaline produced an increase in heart rate by the aerosol route.
On isolated guinea‐pig trachea salbutamol had about 1/10 the activity of isoprenaline, on isolated atria about 1/2000.
The effect of catecholamines and sympathetic stimulation on the release of acetylcholine from the guinea‐pig colon
Authors: BEANI L. , BIANCHI CLEMENTINA , CREMA A. 
Published: July 2012

In isolated guinea‐pig terminal colon, the effect of sympathetic stimulation on contraction and acetylcholine release elicited by pelvic and transmural stimulation was investigated.
Sympathetic stimulation reduced the nerve‐mediated contractile responses more than those produced by added acetylcholine.
Sympathetic stimulation also reduced the acetylcholine released during pelvic and transmural stimulation at low frequency. The inhibitory effect on acetylcholine released from resting colons is concealed by the simultaneous release of acetylcholine in considerable amounts from stimulated periarterial nerves which probably contain parasympathetic fibres.
The inhibitory effect of endogenous and exogenous catecholamines prevails when cholinergic neurones fire at low rates. It was confirmed that adrenaline is more active than noradrenaline.
The release of acetylcholine from unstimulated colons was for the most part maintained by nerve‐conducted activity, because tetrodotoxin was able to reduce it to about one‐tenth.
It is suggested that the sympathetic control of gastrointestinal tone and motility is exerted through two different routes: inhibition of intramural cholinergic plexuses and direct relaxation of smooth muscle cells.
The possible site and mechanism of action of catecholamines on intramural cholinergic structures is briefly discussed.
Effect of a new series of bicyclic compounds with potential thymoleptic properties on the reserpine‐resistant uptake mechanism of central and peripheral monoamine neuronesin vivoandin vitro
Authors: CARLSSON A. , FUXE K. , HAMBERGER B. , MALMFORS T. 
Published: July 2012

Bicyclic compounds with potential thymoleptic properties (Lu‐compounds) have recently become available, and their effects on the membrane pumps of the central and peripheral monoamine neurones have now been tested and compared with those of the tricyclic antidepressant drugs.Biochemical and histochemicalin vivostudies have been performed. The possible blocking action of Lu‐compounds on the noradrenaline (NA) and 5‐hydroxytryptamine (5‐HT) displacement caused by 4,α‐dimethyl‐meta‐tyramine (H 77/77) and 4‐methyl‐α‐ethyl‐meta‐tyramine (H 75/12), respectively, has been studied, and a positive result has been taken as evidence for membrane pump blocking activity. No certain effects were obtained on the 5‐HT displacement induced by H 75/12, whereas a partial blockade of the NA displacement by H 77/77 in central NA neurones was obtained after most of the Lu‐compounds (Lu‐3–010, 3–049, 3–092, 4–012) and especially after the thiophthalane derivative Lu 5–003. The ED50 of the latter drug was around 8 mg/kg, that is, somewhere between protriptyline (ED50 4 mg/kg) and desipramine (ED50 15 mg/kg) in potency.Histochemicalin vivostudies on the rat iris revealed that Lu 5–003 and especially the corresponding phthalane derivative Lu 3–010 were potent in blocking the uptake of α‐methyl‐NA in the adrenergic nerve terminals of the iris. The other Lu‐compounds were less active. The releasing effects of the Lu‐compounds on the extragranular accumulation of α‐methyl‐NA in the adrenergic terminals were weak compared with membrane blocking activity.In vitrostudies on the central and peripheral catecholamine (CA) neurones have also been performed. In the same way as, for example, protriptyline the Lu‐compounds only blocked accumulation of α‐methyl‐NA in the NA terminals but not in the dopamine (DA) nerve terminals. Lu 5–003 and Lu 3–010 were the most potent of the Lu‐drugs when addedin vitro. The Lu‐drugs were also injectedin vivoafter which the effect on the α‐methyl‐NA accumulation was studiedin vitro.In isotope experiments with labelled α‐methyl‐NA it was found that desipramine, Lu‐3–010, Lu 3–092 and Lu 4–012 were equally potent in blocking uptake in the central nervous system.In general the results obtained with the various models are in agreement. The high activity of Lu 5–003 on the central NA neurones may be related to its high heptane/H2O distribution coefficient.It is concluded that the Lu‐compounds have a selective action on the membrane pump mechanism of the central and peripheral NA neurones. In these respects they behave like desipramine and protriptyline.
The effect of tropolone on the formation of 3,4‐dihydroxyphenylacetic acid and 4‐hydroxy‐3‐methoxyphenylacetic acid in the brain of the mouse
Authors: MURPHY G. F. , ROBINSON D. , SHARMAN D. F. 
Published: July 2012

The development of a very sensitive and specific fluorimetric assay for 3,4‐dihydroxyphenylacetic acid has made it possible to measure how inhibitors of the enzyme catechol‐O‐methyl transferase affect the relative concentrations of this acid and its O‐methylated derivative 4‐hydroxy‐3‐methoxyphenylacetic acid (homovanillic acid) in the brains of mice treated with l‐3,4‐dihydroxy‐phenylalanine or probenecid.
It was found that tropolone and tropolone‐4‐acetamide reduce the concentration of homovanillic acid in the brains of the treated mice to an extent dependent on the dose.
The concentration of 3,4‐dihydroxyphenylacetic acid in the brain was increased by the administration of tropolone or tropolone‐4‐acetamide but the dose and response were not simply related to one another.
The results suggest that, in vivo, the formation of 3,4‐dihydroxyphenylacetic acid is not always a simple alternative to the formation of homovanillic acid when the enzyme catechol‐O‐methyl transferase is inhibited.