bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance status as a significant prognostic predictor in patients with urothelial carcinoma of the bladder who underwent radical cystectomy
Authors: Hinata Nobuyuki , Miyake Hideaki , Miyazaki Akira , Nishikawa Masatomo , Tei Hiromoto , Fujisawa Masato 
Published: May 2015

ObjectivesTo assess the significance of performance status as a prognostic factor after radical cystectomy for urothelial carcinoma of the bladder.MethodsThe present study included 730 consecutive patients with urothelial carcinoma of the bladder who underwent radical cystectomy. Clinicopathological outcomes in these patients were analyzed focusing on the impact of performance status, which was assessed using the Karnofsky Performance Status scale before surgery. Patients were classified into groups with Karnofsky Performance Status ≥90 and ≤80.ResultsA total of 561 (76.8%) and 169 (23.2%) patients were judged to have Karnofsky Performance Status ≥90 and ≤80, respectively. During a mean of 52.0 months, disease recurrence and mortality occurred in 257 (35.2%) and 249 (34.1%) patients, respectively, and the 5‐year recurrence‐free and overall survival rates were 64.1 and 65.3%, respectively. There were significant differences in age, hemoglobin, albumin, estimated glomerular filtration rate, pathological T stage and nodal involvement between the Karnofsky Performance Status ≥90 and ≤80 groups. Multivariate analysis showed independent impacts of Karnofsky Performance Status, pathological T stage, nodal involvement and lymphovascular invasion on recurrence‐free survival, as well as independent impacts of Karnofsky Performance Status, age, body mass index, hemoglobin, pathological T stage, nodal involvement and lymphovascular invasion on overall survival.ConclusionsThe results suggest a significant association between impaired performance status and unfavorable prognosis in patients with urothelial carcinoma of the bladder undergoing radical cystectomy.
Rosai–Dorfman disease with atypical intrascrotal involvement
Authors: Rodríguez Torres Cristina , Riazuelo Fantova Gema , Escartín Martínez Irene , Castillo Escudero Juan José , del Agua Arias Celia 
Published: May 2015

AbstractWe describe two new cases of Rosai–Dorfman disease with intrascrotal involvement. Also known as sinus histiocytosis with massive lymphadenopathy, this is a rare entity, usually presenting with massive bilateral cervical lymphadenopathy. It is associated with extranodal involvement in up to 40% of cases, commonly in the face and neck area. Isolated intrascrotal involvement with no lymphadenopathies is extremely rare, and its definitive diagnosis is histopathological. Although they are the most frequent type, not all intrascrotal lesions are neoplastic; therefore, it is important to know other possible etiologies and their radiogical features that might help in the diagnosis. We also review other cases of intrascrotal involvement reported in the literature, as well as a review clinical features, treatment and prognosis of this entity, and a differential diagnosis of solid intrascrotal lesions.
Antagonism of reserpine‐induced emesis in pigeons: a screening method for antidepressant activity
Authors: DHAWAN K. N. , GUPTA G. P. , JAJU B. P. 
Published: May 2015

Various antidepressant drugs and procedures have been studied against reserpine‐induced emesis in pigeons.
Electroconvulsions, pentylenetetrazol and a non‐hydrazide monoamine oxidase inhibitor (pargyline) block reserpine emesis.
It is suggested that reserpine‐induced emesis in pigeons provides a simple and reliable method for studying anti‐reserpine activity, and the compounds effective in antagonizing this emetic response are likely to have antidepressant property.
The effect of drugs on the constriction of isolated depolarized blood vessels in response to calcium or barium
Authors: NORTHOVER B. J. 
Published: May 2015

The rat isolated anterior mesenteric artery was perfused at a constant rate with a calcium‐free depolarizing solution. Injection close to the cannula of 0.05–0.1 ml. of solutions of CaCl2(117 mm) or BaCl2(100 mm) caused a rise in perfusion pressure.The responses to injected CaCl2solution could be obtained repeatedly but those to successive injections of BaCl2solution slowly declined. When the responsiveness to barium had almost disappeared, it could be restored by the addition to the perfusing fluid of a small amount of calcium (0.05 mm).The contractile effects of calcium or barium were antagonized by the addition to the perfusing fluid of several anti‐inflammatory substances, certain local anaesthetics and certain spasmolytic drugs.Perfusion of the mesenteric artery with a depolarizing solution containing 0.2 mm‐CaCl2caused a persistent rise of the perfusion pressure. This was rapidly and completely reversed by the addition of indomethacin (4 mg/100 ml.) or cinchocaine hydrochloride (2 mg/100 ml.) to the perfusing fluid.The uptake of45Ca by rat aorta depleted of calcium was reduced by amethocaine hydrochloride (10 mg/100 ml.) or cinchocaine hydrochloride (2 mg/100 ml.) but not by indomethacin (10 mg/100 ml.) or desipramine hydrochloride (1 mg/100 ml.).
The influence of β‐adrenoceptive receptor blocking agents on urinary function in the rat
Authors: LEES P. 
Published: May 2015

Intramuscular or subcutaneous injections of isoprenaline and dichloroisoprenaline and subcutaneous injection of pronethalol reduced the rates of excretion of water, sodium, potassium and chloride in the urine of conscious, hydrated rats. Inulin excretion usually fell at high, but not at low, dose levels. These changes were attributed to direct stimulant actions on β‐adrenoceptors in the kidney.
A reduction in perfusion pressure to the kidney may also have contributed to these urinary changes, because isoprenaline produced a transient fall in mean arterial blood pressure when given subcutaneously to anaesthetized rats.
Intramuscular injection of pronethalol and subcutaneous injection of antidiuretic hormone both reduced the rate of urine flow without modifying other parameters of urinary function (excretion of inulin and electrolytes were not diminished).
This latter action of pronethalol could not be ascribed to an increased secretion of antidiuretic hormone, for it also occurred in hypophysectomized rats.
Propranolol increased the renal excretion of sodium and chloride. A small rise in urinary potassium levels also occurred but urine volume and inulin excretion were not modified. Some possible modes of action of propranolol are discussed.
Assessment of the effectiveness of β‐adrenoceptor blocking agents towards cardiac and bronchiolar responses of the pithed guinea‐pig to electrical stimulation of the spinal outflow
Authors: BURDEN D. T. , PARKES M. W. 
Published: May 2015

Summary
The responses of heart rate and resistance to lung inflation of the pithed guinea‐pig on electrical stimulation of the thoracic spinal roots could be related to similar responses to injected catecholamines, such that dose‐stimulus frequency relations could be plotted.
The range of frequency of stimulation that was equi‐effective with a dose range of injected catecholamines was higher for effects on air overflow than for heart rate. The slope of the relations for heart rate also differed from that for air overflow. These features may reflect a difference in effectiveness of the sympathetic innervation of heart and bronchial tree.
Propranolol was equally effective in reducing the responses of heart rate and air overflow to injected noradrenaline. Practolol was somewhat more active against the effects of noradrenaline on air overflow than on heart rate, though equally active against the effects of isoprenaline.
For the assessment of equivalent blockade of the effects of cord stimulation on heart rate and air overflow, frequency‐ratios corresponding to a noradrenaline dose‐ratio of 2 were derived from the slopes of the dose‐frequency relations; for air overflow this value was approximately 2 and for heart rate approximately 1·4.
When the doses required to produce these degrees of blockade were computed from the dose‐response relations for blockade of the effects of cord stimulation by propranolol, they were found to be similar for effects on heart rate and air overflow. For practolol, the effective dose for block of heart rate increase was found to be lower than that for air overflow.
A dual action of histamine on guinea‐pig lung vessels
Authors: OKPAKO D. T. 
Published: May 2015

Summary
In isolated guinea‐pig lungs perfused through the pulmonary artery, histamine caused a rise in perfusion pressure which was converted to a fall by a prior injection of mepyramine.
Evidence is provided to show that at least part of the histamine effect was due to its direct action on pulmonary vascular tissue, and was largely independent of bronchomotor tone.
Neither the pressor nor the depressor effects were modified by adrenoceptor blocking agents, phentolamine and propranolol, in doses which reversed or blocked the effects of noradrenaline, adrenaline or isoprenaline. The actions of histamine could therefore not be attributed to catecholamine release. The involvement of cholinergic mechanisms was also excluded since atropine failed to influence the histamine effects.
It is suggested that the mepyramine‐sensitive pressor, and the mepyramine‐resistant depressor effects of histamine, were mediated by different receptors.
It is proposed that a vasodilator action of histamine leading to a partial obstruction of the pulmonary airways could be part of the explanation for the relative ineffectiveness of mepyramine in blocking anaphylactic bronchoconstriction in the guinea‐pig.
The anti‐inflammatory effect of catecholamines in the peritoneal cavity and hind paw of the mouse
Authors: GREEN K. L. 
Published: May 2015

Summary
Carrageenin or 5‐hydroxytryptamine‐induced oedema of the mouse hind paw was antagonized by catecholamines acting on both α‐ and β‐adrenoceptors.
Increased permeability of the mouse peritoneum induced by the local injection of acetic acid or pro‐inflammatory mediators was antagonized by catecholamines acting predominantly on β‐adrenoceptors.
The anti‐inflammatory effect of catecholamines was due neither to hyper‐glycaemia nor to the release of adrenal cortical hormones.
Occurrence of bombesin and alytesin in extracts of the skin of three European discoglossid frogs and pharmacological actions of bombesin on extravascular smooth muscle
Authors: ERSPAMER V. , ERSPAMER G. FALCONIERI , INSELVINI M. , NEGRI L. 
Published: May 2015

Summary
Methanol extracts of the skin of Bombina bombina and Bombina variegata variegaia, two European discoglossid frogs, contain an active tetradecapeptide, bombesin. Alytesin, a tetradecapeptide strictly related to bombesin is present in extracts of the skin of Alytes obstetricans, another European discoglossid frog. The American frog Rana pipiens, contains in its skin ranatensin, an endecapeptide related to bombesin and alytesin.
Passage of crude skin extracts of Bombina through a column of alumina yields eluates which may be considered free of other peptide contaminants and are suitable for the isolation of bombesin in a pure form.
Bombesin has a stimulant action on several preparations of intestinal, uterine and urinary tract smooth muscle. Sometimes the effect is easily repeatable and shows a fair proportionality to the dose, but at other times a prompt and intense tachyphylaxis is observed. Other smooth muscle preparations are poorly sensitive or insensitive to bombesin. The rat uterus, the kitten small intestine, the guinea‐pig colon and the rat urinary bladder may be used for the quantitative bioassay of bombesin.
Bombesin‐like peptides may easily be distinguished from all other naturally occurring peptides by parallel assay. They constitute a new group of active peptides possessing a peculiar spectrum of activity.
Time course of acetylcholinesterase inhibition in the medulla oblongata of the rat by O‐ethyl S‐(2‐dimethylaminoethyl) methylphosphonothioate in vivo
Authors: BAJGAR J. 
Published: May 2015

Summary
The time course of acetylcholinesterase inhibition in three parts of the medulla oblongata of the rat following intramuscular injection of O‐ethyl S‐(2‐dimethylaminoethyl) methylphosphonothioate was studied.
The inhibition in the three parts of the medulla oblongata proceeded at different rates and this indicates that penetration of the inhibitor through various parts of the blood‐brain barrier is not uniform.
EFFECT OF CLONIDINE ON THE EXCITABILITY OF VASOMOTOR LOCI IN THE CAT
Authors: DHAWAN B.N. , JOHRI M.B. , SINGH G.B. , SRIMAL R.C. , VISWESARAM D. 
Published: May 2015

The effect of clonidine on the direct excitability of hypothalamic, medullary and spinal vasomotor loci has been investigated in cats anaesthetized with chloralose.
Clonidine inhibited the excitability of these loci when it was localized to the central sites by intracerebroventricular, intravertebral arterial or intrathecal injection in very low doses (1‐2 μg).
Topical application of clonidine (0.01% and 1.0%) to the floor of the fourth ventricle inhibited pressor responses evoked either by stimulation of medullary or hypothalamic vasomotor areas. Inhibition of the pressor responses was accompanied by hypotension and bradycardia in many experiments.
It appears that effects of clonidine on the vasomotor loci of the medulla oblongata and the spinal cord contribute to its hypotensive action.
CARDIOTONIC STEROIDS: CORRELATION OF SODIUM‐POTASSIUM ADENOSINE TRIPHOSPHATE INHIBITION AND ION TRANSPORT in vitro WITH INOTROPIC ACTIVITY AND TOXICITY IN DOGS
Authors: BEARD NICOL A. , ROUSE W. , SOMERVILLE A.R. 
Published: May 2015

A new series of cardiotonics based on five steroid nuclei has been evaluated for inhibition of Na+/K+‐ATPase and Rb uptake by red blood cells, and for inotropic activity and toxicity in dogs. Structure‐activity relationships are discussed.
The in vitro tests can be used satisfactorily to predict inotropic activity, but not toxicity or therapeutic ratio.
Although compounds with greatly improved therapeutic ratios relative to ouabain and tolusin have been obtained, they proved to be strongly emetic in the conscious dog.
STUDIES ON THE POSITIVE INOTROPIC EFFECT OF PHENYLEPHRINE: A COMPARISON WITH ISOPRENALINE
Authors: LEDDA F. , MARCHETTI P. , MUGELLI A. 
Published: May 2015

The effects of phenylephrine and isoprenaline on the isometric contraction of guinea‐pig ventricle were compared over the whole range of their respective dose‐response curves.
In preparations driven at 2.5 Hz the increase in contractile force induced by either isoprenaline or phenylephrine was linearly correlated to an increase in maximum velocity of force development. The relaxation time was shortened by isoprenaline but not by phenylephrine.
The negative inotropic effect induced by δ[N‐(3,4‐dimethoxyphenethyl)‐N‐methyl‐amino]‐α‐(3,4,5‐trimethoxyphenyl)α‐isopropylvaleronitrile hydrochloride (D600) was reversed by isoprenaline, but little influenced by phenylephrine.
The study of the interval‐force relationship shows that the increase in contractile force induced by phenylephrine (3 × 10−5 M) was relatively greater at low frequencies of stimulation, and that the maximum effect was reached at the frequency of 1 Hz.
The positive inotropic effect of phenylephrine (10−4 M) was significantly higher at a frequency of 1 Hz than at 2.5 Hz; the effect of isoprenaline (3 × 10−8 M) was not significantly different at the two driving frequencies.
In preparations driven at 1 Hz the inotropic effect of the lower concentrations of phenylephrine was due to an increase in the time to peak tension without any change of the maximum velocity of force development; however an increase of this parameter became evident only after higher concentrations of the amine (10−5 M or more), associated with a progressive shortening of the time to peak.
A correlation between mechanical and electro physiological effects of phenylephrine is attempted; the suggestion is advanced that the prolongation of the action potential and of the active state duration may be an important factor in the inotropic effect of phenylephrine.
STUDIES ON THE BEHAVIOURAL PHARMACOLOGY OF A CYCLIC ANALOGUE OF DOPAMINE FOLLOWING ITS INJECTION INTO THE BRAINS OF CONSCIOUS RATS
Authors: ELKHAWAD A.O. , WOODRUFF G.N. 
Published: May 2015

The cyclic analogue of dopamine, 2‐amino‐6,7‐dihydroxy‐1,2,3,4‐tetrahydronaphthalene (ADTN) was injected into the lateral ventricle or bilaterally into the nucleus accumbens or caudate nucleus of conscious rats and its effect on locomotor activity was investigated.
When given intraventricularly, ADTN produced some stereotyped responses which were followed by a strong and long lasting stimulation of locomotor activity. When administered bilaterally into the nucleus accumbens a similar stimulation of locomotor activity was observed. ADTN had no effect on locomotor activity when injected bilaterally into the caudate nucleus.
The ADTN‐induced locomotor stimulation following its intraventricular injection was completely abolished by a low dose of pimozide (0.01 mg/kg, i.p.) or haloperidol (0.5 mg/kg, i.p.). Pimozide (1 mg/kg, i.p.) given 30 min before ADTN injected bilaterally into the nucleus accumbens completely blocked locomotor stimulation.
Unilateral injections of ADTN (5 μg) into the nucleus accumbens caused locomotor stimulation but no turning.
Bilateral injections into the nucleus accumbens of 2‐amino‐6,7‐dimethoxy‐1,2,3,4‐tetrahydronaphthalene or 0.9% w/v NaCl solution had no effect on locomotor activity.
It is concluded that the central stimulant action of ADTN is due to an effect on the dopamine receptors in the nucleus accumbens.
MECHANISM OF ACTION OF DOPAMINE ON THE GUINEA‐PIG GASTRO‐OESOPHAGEAL JUNCTION in vitro
Authors: COX BARRY , ENNIS CHRISTINE 
Published: May 2015

The effect of dopamine on longitudinal muscle strips of the guinea‐pig isolated gastro‐oesophageal junction was compared with the response obtained to phenylephrine, isoprenaline and clonidine. Phenylephrine (5 × 10−7 to 5 × 10−5 m) produced a dose‐related contraction, whilst dopamine (10−6 to 10−4 m) and isoprenaline (5 × 10−7 to 2 × 10−5 m) produced dose‐related relaxations. Clonidine was ineffective in doses up to 10−5 m. 5‐Hydroxytryptamine (5‐HT) produced a contraction.
Phenylephrine was antagonized by α1‐adrenoceptor antagonists but unaffected by β‐adrenoceptor antagonists, whilst the opposite was the case for isoprenaline. A mixture of α‐ and β‐adrenoceptor antagonists was required to inhibit completely dopamine‐induced relaxations. 5‐HT (3 × 10−7 m) was specifically antagonized by methysergide (3 × 10−6 m).
pA2 values for a range of α‐adrenoceptor and dopamine receptor antagonists were determined against dopamine and phenylephrine. The relative order of potency of the antagonists was the same for both antagonists and was prazosin > spiroperidol > phentolamine > domperidone > haloperidol, with pimozide and metoclopramide being inactive.
Tyramine caused dose‐related relaxations of the gastro‐oesophageal strips which were susceptible to the same range of antagonists as dopamine.
Cocaine (6 × 10−6 m) and desmethylimipramine (3 × 10−7 and 10−6 m) reduced the relaxations induced by dopamine and tyramine but there were quantitative differences in the antagonism.
Tissue from reserpine pretreated guinea‐pigs was insensitive to tyramine but the response to dopamine was only partly reduced.
Histological examination of the strips revealed the presence of smooth muscle but only a sparse adrenergic innervation.
The results suggest that dopamine acts partly indirectly and partly directly on postjunctional α‐and β‐adrenoceptors. There is no evidence for an action on specific dopamine receptors.
THE OCCURRENCE OF POSTSYNAPTIC α‐ AND β‐ADRENOCEPTORS IN THE GUINEA‐PIG GALL BLADDER
Authors: DOGGRELL SHEILA A. , SCOTT G.W. 
Published: May 2015

Guinea‐pig gall bladder strips were contracted by (–)‐noradrenaline, 10−5 m, and by field stimulation at 5 Hz (in the absence or presence of 10−6 m atropine) and relaxed to 10−5 m (–)‐isoprenaline. (–)‐Adrenaline, 10−5 m, predominantly contracted, but sometimes relaxed, this preparation.
In the presence of 10−6 m phentolamine, contractions to (–)‐noradrenaline and to (–)‐adrenaline were reversed to relaxations. The relaxations produced by (–)‐isoprenaline were unaltered. In the presence of 10−6 m propranolol, contractions to (–)‐noradrenaline increased in magnitude, relaxations to (–)‐adrenaline were reversed to contractions, and relaxations to (–)‐isoprenaline were abolished. These results demonstrate the presence of postsynaptic α‐adrenoceptors which mediate contractions, and postsynaptic β‐adrenoceptors which initiate relaxations, in the guinea‐pig gall bladder.
The contractile responses to continuous field stimulation for 5 min at 5 Hz in Krebs solution alone were reduced in magnitude by propranolol, 10−6 m. In the presence of 10−6 m atropine (added to eliminate the cholinergic component of the response), propranolol, 10−6 m, had no effect on responses to stimulation at 5 Hz. Thus propranolol reduced the response to cholinergic stimulation in this tissue; the basis of this effect is unclear. In the absence or presence or atropine (10−6 m), the responses to 5 Hz were smaller in magnitude in the presence than absence of phentolamine, 10−6 m. This suggests that the responses to field stimulation of the guinea‐pig gall bladder may, in part, be due to the release of endogenous noradrenaline which acts at postsynaptic α‐adrenoceptors.
ACTION OF ENKEPHALIN ANALOGUES AND MORPHINE ON BRAIN ACETYLCHOLINE RELEASE: DIFFERENTIAL REVERSAL BY NALOXONE AND AN OPIATE PENTAPEPTIDE
Authors: JHAMANDAS KHEM , SUTAK MAAJA 
Published: May 2015

Methionine (Met)‐enkephalin, leucine (Leu)‐enkephalin and their synthetic analogues were tested for effects on the spontaneous release of cortical acetylcholine (ACh) in vivo. The ability of naloxone to reverse the action of enkephalins on ACh release was compared with its action against morphine. An enkephalin analogue, structurally related to Met‐enkephalin, was tested for opiate antagonistic activity in ACh release experiments.
Intraventricular administration of Met‐enkephalin, Leu‐enkephalin, d‐Ala2‐Met5‐enkephalinamide (DALA) and d‐Ala2‐d‐Leu5‐enkephalin (DALEU) produced a dose‐related inhibition of cortical ACh release. Met‐ and Leu‐enkephalin were very similar both in their potency and the time course of their action on ACh release. Both DALA and DALEU were more potent and had a longer duration of action than Leu‐enkephalin. Systemic injections of two pentapeptides, d‐Met2‐Pro5‐enkephalinamide and d‐Ala2‐MePhe4‐Met5(O)‐ol‐enkephalin (33,824), produced a sustained inhibition of cortical ACh release.
Naloxone, administered systemically following the depression of ACh release induced by either intraventricular injections of enkephalins (DALA or DALEU), or systemic injections of enkephalins (d‐Met2‐Pro5‐enkephalinamide or 33,824), reversed this depression and restored the release to baseline levels. The effect of d‐Met2‐Pro5‐enkephalinamide on the release of ACh was reversed by naloxone with difficulty. Naloxone also reversed the inhibitory effect of systemic morphine and this reversal was associated with a large overshoot of ACh release. The latter was never observed in the enkephalin experiments.
Intraventricular injection of the pentapeptide, d‐Ala2‐d‐Ala3‐Met5‐enkephalinamide (TAAPM), at doses that did not influence the basal ACh release, blocked or reversed the inhibitory effect of morphine on this release. This peptide did not block the effect of the non‐opiate, chlorpromazine, under similar conditions. In two experiments TAAPM failed to reverse the inhibition of ACh release produced by systemically injected enkephalin, D‐Met2‐Pro5‐ enkephalinamide.
Effects of morphine and enkephalin on ACh release are discussed in terms of their action on different opiate receptors.