bluuebunny/crossref_metadata_2025 huggingface dataset:
THE USE OF AN IRREVERSIBLE β‐ADRENORECEPTOR ANTAGONIST TO EXAMINE RESERPINE‐ AND HYPOTHERMIA‐INDUCED SUPERSENSITIVITY OF GUINEA‐PIG ATRIA
Authors: BROADLEY K. J. , NICHOLSON C. D.
Published: January 2008

Positive inotropic and chronotropic responses of guinea‐pig isolated left and right atria respectively to the sympathomimetic amine orciprenaline were recorded.

2 Pretreatment of animals with reserpine for 3 days produced supersensitivity of both the inotropic and chronotropic responses. Lowering the bath temperature from 38° to 30°C produced supersensitivity of untreated atria to the inotropic responses only.

Irreversible β‐adrenoreceptor antagonism of orciprenaline by Ro 03‐7894 was demonstrated by a persistent depression of the maximum inotropic and chronotropic responses after a prolonged washout from the bath (3 h).

The depression of the maximum rate and tension responses by Ro 03‐7894 was less in atria from reserpinepretreated animals.

The maxima were also depressed less at the lower bath temperature of 30°C. However, when atria were cooled during the incubation with Ro 03‐7894, the maxima were still depressed to the 38°C level.

That these results suggest either a receptor proliferation or change in efficacy as possible mechanisms for reserpine‐ and hypothermia‐induced supersensitivity is discussed.
RESPONSES TO NORADRENALINE OF PORTAL VEIN STRIPS FROM NORMOTENSIVE AND SPONTANEOUSLY HYPERTENSIVE RATS
Authors: HARRIS A. , SWAMY V. C. , TRIGGLE D. J. , WATERS D. H.
Published: January 2008

Responses to noradrenaline of isolated portal vein strips from 5–7 week and 15–17 week Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) have been examined.

15–17 week SHR tissues exhibited a greater sensitivity (lower ED50) to noradrenaline but only at reduced Ca2+EXT levels.

pA2 values for the α‐adrenoreceptor antagonists WB 4101 and prazosin were significantly lower in 5–7 week SHR consistent with some change at the adrenoreceptor level.

Veins from SHR relaxed more rapidly in Ca2+‐free saline following removal of noradrenaline than did veins from WKY.

D600 is a competitive antagonist of the Ca2+EXT‐dependent component of the noradrenaline response but K1 values were not significantly different in SHR and WKY.
DENERVATION AND β‐ADRENORECEPTORS OF THE CAT NICTITATING MEMBRANE
Authors: VARMA D. R. , NICKERSON M.
Published: January 2008

Dose‐response curves to the relaxant effects of isoprenaline, salbutamol, adrenaline and noradrenaline were determined on the partially contracted smooth muscles of the cat nictitating membrane following α‐adrenoreceptor blockade in order to test the hypothesis of a causal relationship between the inhibition of neuronal uptake and denervation super‐sensitivity.

Denervation did not produce super‐sensitivity of the nictitating membrane to the β‐adrenoreceptor‐mediated relaxant effects of any of the four agents studied.

The sensitivity of the inferior muscle was greater than that of the medial muscle to agents which were good substrates for neuronal uptake (adrenaline and noradrenaline) as well as to those which were not (isoprenaline and salbutamol).

Denervation did not alter the antagonist activity of β‐adrenoreceptor blockers propranolol (nonselective) and metoprolol (β1‐blocker) against isoprenaline or of H 35/25 (β2‐blocker) against salbutamol.

These results do not support the hypothesis of a causal relationship between inhibition of neuronal uptake and super‐sensitivity to sympathomimetic amines.
MUSCARINIC EFFECTS OF VARIOUS ISOARECAIDINE ESTERS IN SYMPATHETIC GANGLIA
Authors: PORSIUS A. J. , WILFFERT B. , LAMBRECHT G. , MOSER U. , MUTSCHLER E.
Published: January 2008

The pressor effects of various tertiary and quaternary isoarecaidine esters in both pithed and anaesthetized rats are reported. In order to elucidate the mechanism of action, various experiments were carried out with the quaternary isoarecaidine methyl ester (Q‐4‐Me).

Treatment with mecamylamine, dexetimide, reserpine and phentolamine abolished or reduced the pressor response to Q‐4‐Me, whereas pretreatment with cocaine gave rise to a prolonged pressor effect. Plasma noradrenaline levels were significantly increased after the infusion of Q‐4‐Me.

From the results it can be concluded that the pressor effects brought about by the quaternary compounds can be attributed to a stimulation of nicotinic and muscarinic receptors in sympathetic ganglia. The consequences of interaction with muscarinic receptors predominate over the effects due to minimal interference with nicotinic receptors by the drug.
THE RESPONSE OF THE COSTO‐UTERINE MUSCLE OF THE RAT TO ADRENORECEPTOR AGONISTS DURING THE OESTROUS CYCLE: A COMPARISON WITH THE UTERINE HORN
Authors: HARTLEY MARGARET L. , PENNEFATHER JOCELYN N.
Published: January 2008

Adrenoreceptors in the rat costo‐uterine muscle were compared with those in the uterine horn. The responses of electrically‐stimulated preparations of both tissues to isoprenaline and phenylephrine were investigated in the absence and presence of phentolamine and propranolol to block α‐ and β‐adrenoreceptors respectively. Preparations were taken from rats at known stages of the four‐day oestrous cycle.

Both adrenoreceptor agonists consistently inhibited contractions in both tissues; threshold sensitivity to isoprenaline was similar for both tissues and at all cycle stages. The same held true for phenylephrine, which was only approximately 1/400 as potent as isoprenaline. A generally similar pattern was observed when concentrations producing maximum inhibition were compared; however during proestrus, phenylephrine was more potent in producing maximal responses in uterine horns than in costo‐uterine muscles.

Phentolamine had no effect on inhibitory responses to isoprenaline in either tissue, nor to phenylephrine in costo‐uterine muscles, but slightly enhanced the inhibitory action of phenylephrine in uterine horns from proestrous rats. Propranolol blocked the inhibitory effects of both drugs, revealing an excitatory effect of phenylephrine in the uterine horns at proestrus.

These observations, and estimates of pA2 values for propranolol against both agonists, indicate that β‐adrenoreceptors insensitive to cyclical fluctuations in ovarian hormone levels, are predominant in the uterine horn and may be the exclusive adrenoreceptor present in the costo‐uterine muscle. In the uterine horn a small sub‐population of excitatory α‐adrenoreceptors, the presence of which is masked by β‐adrenoreceptors, can be demonstrated during proestrus. These receptors may be dependent upon the presence of the endometrium and/or the circular smooth muscle layer. The costo‐uterine muscle, which lacks excitatory α‐adrenoreceptors, could serve as a useful model of the longitudinal layer of the myometrium in investigations of drug actions at β‐adrenoreceptors.
A STUDY OF GASTRIC SECRETION IN DOGS USING PILOCARPINE
Authors: WISECARVER J. , ETZEL K. , MAGEE D. F.
Published: January 2008

Pilocarpine (40 μg/min i.v.) stimulated acid and pepsin secretion from Heidenhain pouches but did not stimulate secretion from the innervated stomach.

Pilocarpine significantly increased acid secretion from the innervated main stomach after the vagal nerves were bilaterally blocked with lidocaine.

The effect of pilocarpine on secretion from the Heidenhain pouch was depressed by ganglionic blockade (hexamethonium), by dopamine and by isoprenaline.

The stimulatory action of histamine on gastric secretion from either pouch or gastric fistulae was uninfluenced by dopamine.

The action of pilocarpine was augmented by the muscarinic ganglionic stimulant AHR 602. Considering this effect, as well as the secretory depression of isoprenaline, pilocarpine resembles pentagastrin rather than methacholine in its action.
NON‐ATROPINIC ANTICHOLINERGIC ACTION OF QUINIDINE ON THE FERRET STOMACH
Authors: GRUNDY D. , ANDREWS P. L. R. , MITCHELL H. W.
Published: January 2008

The effect of quinidine on the cholinergic response of the ferret gastric corpus was investigated in vivo and in vitro.

In vivo, the atropine sensitive contractions of the gastric corpus evoked by stimulation of the cervical vagus in the anaesthetized ferret were antagonized by quinidine (10–30 mg/kg).

In vitro, quinidine (10 μg/ml) antagonized the contractile response elicited by transmural stimulation (T.M.) of strips of corpus. At this dose of quinidine, the response to acetylcholine at doses adjusted to match the response to T.M. stimulation were unaffected. At higher doses of quinidine (50 μg/ml) the response to stimulation of the non‐cholinergic, non‐adrenergic inhibitory neurones was also antagonized.

These results indicate that, at low doses, quinidine has an inhibitory effect on the cholinergic neurones.
EXOGENOUSLY STIMULATED GASTRIC SECRETION IN DOGS AFTER GANGLION AND SYMPATHETIC BLOCKADE AND ANTRAL ACIDIFICATION
Authors: ETZEL K. , WISECARVER J. , MAGEE D. F.
Published: January 2008

In conscious dogs with gastric fistulae, Heidenhain pouches and in some cases, innervated pyloric pouches, ganglionic blockade augmented Heidenhain pouch acid secretion only if the gastric fistula remained closed in animals receiving pentagastrin.

Ganglionic blockade depressed methacholine‐stimulated acid and pepsin secretion from the Heidenhain pouch whether or not the fistula was open.

Acidification of the antral pouch consistently augmented the acid and pepsin secretion from the Heidenhain pouch when either pentagastrin or methacholine was the stimulus. Ganglionic blockade prevented this.
NON‐SPECIFIC SUPERSENSITVITY IN RAT PAROTID SALIVARY GLANDS FOLLOWING PARASYMPATHECTOMY
Authors: POAT JUDITH A. , TEMPLETON D.
Published: January 2008

The effect of parasympathetic denervation (Px) of the rat parotid salivary glands has been studied.

Px produced a significant reduction in wet and dry weight of the parotid gland compared with the intact contralateral control gland. The DNA content per gland was not reduced indicating that cell death had not occurred but that individual cells were smaller.

Supersensitivity to both cholinoreceptor and β‐adrenoreceptor stimulation resulted following Px and was observed as a decrease in the threshold dose and an increase in the maximum secretory response.

The supersensitivity to β‐adrenoreceptor stimulation was not accompanied by a change in cyclic AMP production but there was an increase in the density of β‐adrenoreceptor binding sites/mg membrane protein.

The relationship of this increased density of receptors to the observed supersensitivity is discussed.
HETEROGENEITY OF β‐ADRENORECEPTOR SUBTYPES IN THE HUMAN PLACENTA
Authors: BARNETT D. B. , COOK N. , NAHORSKI S. R.
Published: January 2008

The human placenta is a rich source of β‐adrenoreceptors. However, previous work has provided conflicting evidence as to the predominant receptor subtype present. This study was designed to clarify this situation.

The radioligand 3H‐dihydroalprenolol (3H‐DHA) was used to identify β‐adrenoreceptor binding sites in membranes prepared from human placentae obtained immediately post partum from normal full term pregnancies.

3H‐DHA binding to human placental membranes was saturable, of high affinity and exhibited the pharmacological characteristics of a β‐adrenoreceptor. Displacement by β‐adrenoreceptor agonists suggested a predominant β1‐subtype with a hierarchy of potency isoprenaline > adrenaline > noradrenaline. Analysis of the displacement of the specific binding of 3H‐DHA by β‐adrenoreceptor antagonists yielded Hill plots with an apparent slope (nH) of one for the non selective antagonist (−)propranolol, and of less than one for the highly selective antagonists practolol (β1), and ICI 118,551 (β2) indicating a possible heterogeneity of binding sites.

A direct comparison of the displacement of 3H‐DHA binding by selective antagonists in the placenta with that occurring in rat and rabbit lung, further established that a mixture of β1‐ and β2‐adrenoreceptor binding sites was present.

Graphical analysis by Hofstee plot and computer assisted iterative curve fitting was used to further evaluate the displacement by the selective agents and established the presence of an heterogeneous population of β‐adrenoreceptor subtypes in the human placenta with approximately 65%β1 and 35%β2.
VALIDATION OF INDIRECT SYSTOLIC BLOOD PRESSURE MEASUREMENT IN ETHER ANAESTHETISED RATS
Authors: BORKOWSKI K. R. , QUINN P.
Published: January 2008

Systolic blood pressures and plasma catecholamine concentrations were determined in conscious and ether‐anaesthetised male spontaneously hypertensive (SHR), Wistar‐Kyoto normotensive (WKY/N), Wistar (W) and Sprague‐Dawley (SD) rats.

When compared to conscious animals, plasma noradrenaline concentrations were significantly higher in all four strains of ether‐anaesthetised rats.

Only the SHR rats did not show an elevation in plasma adrenaline concentration when anaesthetised with ether.

A good correlation was obtained between systolic blood pressures measured indirectly, using a tailcuff method with two different sensors, in ether‐anaesthetised rats and pressures measured directly, via an indwelling carotid catheter, in conscious unrestrained animals.

It is concluded that, while ether anaesthesia elevates plasma catecholamine concentrations in rats, the increase in plasma catecholamines has little, if any, effect on indirect systolic blood pressure measurements.
β‐ADRENORECEPTOR ANTAGONISTS WITH MULTIPLE PHARMACOPHORES: PERSISTENT INHIBITION OF RAT HEART ADENYLATE CYCLASE
Authors: KUSIAK J. W. , PITHA J.
Published: January 2008

β‐Adrenoreceptor antagonists containing several pharmacophores, so called alprenolol‐Jeffamines, were studied. These compounds are derived from JeffamineR NH2‐CH‐(CH3)‐CH2‐[‐O‐CH2‐CH(CH3)‐]n‐ NH29n = 2.6 ave. by substitution of nitrogen with 3‐(2‐allylphenoxy)‐2‐hydroxypropyl groups, which are part of the AlprenololR pharmacophore.

Alprenolol‐Jeffamines inhibited (‐)isoprenaline stimulated adenylate cyclase activity; the derivative with one pharmacophore was about 4‐fold and the derivative with two pharmacophores was about 17‐fold less potent than (+)alprenolol; the trisubstituted derivative which has one complete and two partial pharmacophores was ineffective.

The ratio of Ki's for inhibition of (‐)3H‐DHA binding and for inhibition of adenylate cyclase were approximately one for each derivative.

When (+)alprenolol‐Jeffamine derivatives were injected intraperitoneally into rats and heart membranes or homogenates were prepared 18–20 h afterwards, the mono, di, and trisubstituted derivatives, but not (+)alprenolol, inhibited bindng of (‐)3H‐DHA. This persistency pattern is different from that observed in vitro, where only di and trisubstituted derivatives are persistent. Slow metabolism/slow excretion of the monosubstituted derivative may be a source of the increased persistency in vivo.

In similarly prepared animals, the dose‐response curve for (‐)isoprenaiine stimulated adenylate cyclase was shifted to the right 3‐to‐4 fold for mono and disubstituted derivatives but was unaffected by (+) alprenolol and the trisubstituted derivative.

The results suggest that these derivatives interact with physiologically important β‐adrenoreceptors in vitro, and that, in vivo, they persistently block β‐adrenoreceptors and inhibit isoprenaline stimulated adenylate cyclase.
AUTONOMIC NEUROPATHY IN THE ALLOXAN‐DIABETIC RAT
Authors: TOMLINSON D. R. , YUSOF A. P. M.
Published: January 2008

This study was designed to correlate functional and ultrastructural examination of the innervation of the atria and vas deferens of rats with long‐term alloxan‐induced diabetes mellitus.

After 7–8 months of diabetes the responses of preparations in vitro to nerve stimulation and to exogenous autonomic transmitter were compared with those from age‐matched controls.

Right atria from controls and diabetics were equally responsive to noradrenergic nerve stimulation and to exogenous noradrenaline. Left atria from diabetic rats were supersensitive to both noradrenaline and acetylcholine. The left atria gave normal inotropic responses to noradrenergic nerve stimulation but responses to cholinergic nerve stimulation were absent. The vasa deferentia from both groups gave similar responses to noradrenergic nerve stimulation and to noradrenaline.

The electron microscope revealed many abnormal, degenerate noradrenergic nerve profiles in both right atria and vas deferens. No cholinergic terminals were found in the right atria.

These findings indicate that this form of experimental diabetes causes parasympathetic denervation of the heart with some indications of degeneration of sympathetic nerves.
Comparison between the cardiovascular effects of 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) and clonidine in the conscious sino‐aortic denervated rat
Authors: Petty M. A. , Kintz J. , Di Francesco G. F. , Fozard J. R.
Published: January 2008

1 The purpose of this study was to investigate the role of an intact baroreceptor reflex mechanism in the expression of the cardiovascular response to 8‐OH‐DPAT and to determine whether there are any differences between the activation of central α2‐adrenoreceptors and 5‐HT1A receptors in this respect. To this end, the effects of 8‐OH‐DPAT and clonidine have been assessed on blood pressure, heart rate, ECG and cardiac contractility indices in conscious sino‐aortic baroreceptor denervated (SAD) rats and their sham‐operated controls.

2 In both sham‐operated and SAD rats, intravenous (i.v.) administration of 8‐OH‐DPAT (32 μg kg−1) and clonidine (8 μg kg−1) produced falls in systemic blood pressure, left ventricular systolic pressure and dP/dtmax.

3 8‐OH‐DPAT produced similar bradycardia in each group of rats; in contrast, clonidine had a greater effect in the SAD animals. Increases of the PQ interval mirrored the heart‐rate changes with both compounds.

4 No significant changes in end diastolic blood pressure or in the myocardial contractility indices dP/dtmas/P and Vmax: were evident.

5 This study provides support for the view that i.v. 8‐OH‐DPAT lowers blood pressure and heart rate through a central mechanism. The effects occur independently of an intact baroreceptor reflex and are not associated with effects on myocardial contractility. 8‐OH‐DPAT shows close qualitative similarities to clonidine in this model.
Comparison of the effects of phenoxybenzamine and uptake blockade on noradrenaline efflux from rabbit ear arteries evoked by field stimulation and propagated nerve impulses
Authors: Rand M. J. , Story D. F. , Sutton I.
Published: January 2008

1 A comparison has been made of the effects of blockade of prejunctional α‐adrenoreceptors and blockade of transmitter noradrenaline uptake in segments of rabbit ear arteries subjected to field stimulation or neuronally propagated impulses.

2 The relationship between evoked release and frequency of stimulation differed in artery segments subjected to field stimulation and those receiving propagated nerve impulses. However, the effectiveness of phenoxybenzamine in increasing stimulation‐induced efflux of radioactivity decreased as the frequency of stimulation increased in artery segments subjected to either field stimulation or neuronally propagated impulses.

3 Blockade of neuronal and extraneuronal uptake had no effect on evoked efflux from field‐stimulated artery segments but it did produce a marked and significant enhancement of release evoked by propagated nerve impulses.
No evidence for more than one type of α1‐adrenoreceptor in rabbit pulmonary artery
Authors: Docherty J. R.
Published: January 2008

1 The effects of the α‐adrenoreceptor antagonists, prazosin and yohimbine, have been examined on the isometric contraction of the rabbit pulmonary artery produced by α1‐adrenoreceptor agonists. Cocaine, corticosterone and propranolol were present throughout and either a single or two concentration‐response curve method was used.

2 Prazosin and yohimbine competitively antagonized the responses to agonists but did not reveal differences between agonists.

3 Using the single concentration‐response curve method, prazosin had pA2 values of 9.06 against clonidine and 8.76 against methoxamine.

4 Using the two concentration‐response curve method the absolute pA2 values of prazosin (8.65 against phenylephrine, 8.78 against clonidine) and yohimbine (5.73 against phenylephrine, 5.72 against clonidine), as well as the relative potencies of the two antagonists (prazosin approximately 1000 times more potent than yohimbine), suggest that both agonists act on α1‐adrenoreceptors.

5 There is no evidence from this study to support the suggestion that the rabbit pulmonary artery contains two subtypes of of α1‐adrenoreceptor.
Effect of longitudinal muscle‐myenteric plexus removal and indomethacin on the response to tachykinin NK‐2 and NK‐3 receptor agonists in the circular muscle of the guinea‐pig ileum
Authors: Maggi Carlo Alberto , Patacchini Riccardo , Meini Stefania , Giuliani Sandro
Published: January 2008

1 The effect of removal of the longitudinal muscle‐myenteric plexus (LM‐MP) and/ or indomethacin (10 ‐μM) on the response to the tachykinin NK‐2 receptor selective agonist, [βAla8]NKA(4–10), or to the NK‐3 receptor selective agonist, senktide, was investigated by measuring mechanical activity (isotonic recording) of circular muscle (ring preparation) of the guinea‐pig ileum.

2 Indomethacin (10 μM) increased the percentage of ileal rings displaying spontaneous activity, either intact or LM‐MP‐free. The response to senktide (10nM and 1 μM) was lower in LM‐MP‐free than in intact ileal rings, either in the absence or presence of indomethacin. The response to a low concentration (10 nM) of [βAla8] NKA (4–10) was enhanced in LM‐MP‐free rings and by indomethacin.

3 In intact ileal rings, the response to senktide was unaffected by atropine (3 μM) alone or by the tachykinin NK‐2 receptor antagonist MEN 10,376 (10 μM) alone while it was reduced by the combined administration of the two antagonists. The response to senktide was greatly reduced by tetrodotoxin (TTX, 1 μM). Senktide‐induced contractions (10 nM) were also reduced by the blocker of N‐type voltage‐sensitive calcium channels, ω‐conotoxin (CTX, 0.1 μM).

4 In about 30% of preparations tested, an inhibitory response (decrease in spontaneous activity) to 10 nM senktide, was disclosed in CTX‐treated intact ileal rings. This inhibitory effect was TTX‐sensitive.

5 In LM‐MP‐free ileal rings, the response to senktide was abolished or reduced by atropine and MEN 10,376, alone or in combination, and was also reduced or abolished by TTX and CTX.

6 The response to [βAla8]NKA (4–10) was inhibited by MEN 10,376, in both intact and LM‐MP‐free ileal rings while it was unaffected by atropine, TTX or CTX.

7 These results indicate that indomethacin pretreatment induces a regular background activity for studying the motor response to tachykinins in the circular muscle of the ileum, probably by blocking the formation of relaxant prostanoids. A further increase in sensitivity to direct smooth muscle stimulation (NK‐2 receptor agonist) can be obtained by removal of the LM‐MP. The response to NK‐3 receptor stimulation is diminished but not abolished by removal of the LM‐MP, suggesting that NK‐3 receptors are located on neuronal bodies of myenteric neurons, but possibly also at other sites (possibly, nerve terminals). Furthermore, the presence of NK‐3 receptors on myenteric plexus neurons, which inhibit circular muscle activity, is suggested.
Increased sensitivity of neonatal mouse myocardia to autonomic transmitters
Authors: Tanaka H. , Manita S. , Shigenobu K.
Published: January 2008

1 Chronotropic and inotropic responses to noradrenaline and acetylcholine were examined in isolated right atrial and ventricular preparations from neonatal and adult mice.

2 Noradrenaline and acetylcholine produced positive and negative chronotropic responses, respectively, in the atria from both ages. Noradrenaline produced positive inotropic responses in ventricular preparations from both ages. In all cases, the sensitivity, expressed in terms of pD2 values, was higher in neonatal preparations.

3 In the ventricle, desipramine produced a leftward shift of the concentration–response curve for noradrenaline in the adult, but no such shift was observed in the neonate. The sensitivity to isoprenaline of ventricular preparations was higher in the neonate than in the adult.

4 Our results demonstrated developmental decreases in sensitivities to autonomic transmitters in mouse myocardia. As for the inotropic response to noradrenaline of ventricular muscle, both pre‐ and postjunctional mechanisms were responsible for the developmental decrease in sensitivity.
Interactions between endothelin and the dihydropyridine‐type calcium antagonist nicardipine in the human renal artery: a radioligand and autoradiographic study
Authors: Amenta F. , Rossodivita I. , Ferrante F.
Published: January 2008

1 The interactions between dihydropyridine Ca2+ channels and endothelin were analysed using combined radioligand binding and autoradiographic techniques.

2 Endothelin is a potent constrictor peptide of arterial smooth muscle. Endothelin‐induced vasoconstriction is attenuated by dihydropyridine‐type Ca2+ antagonists such as nicardipine. However, the molecular mechanisms of this effect are not yet understood.

3 Sections of the human renal artery bound [3H]‐nicardipine in a manner consistent with the labelling of dihydropyridine‐type Ca2+ channels. The highest density of [3H]‐nicardipine binding sites occurred within the tunica media of the renal artery, probably over smooth muscle. A lower density of [3H]‐nicardipine binding sites was noticeable in the tunica adventitia, whereas no specific binding occurred in the tunica intima.

4 Endothelin‐1, from a concentration of 1 pm 1−1, reduced [3H]‐nicardipine binding as a function of concentration. A 10 nm endothelin concentration reduced [3H]‐nicardipine binding by about 85%. The isoform, endothelin‐3, had little effect on [3H]‐nicardipine binding.

5 The above findings suggest the occurrence of an interaction, probably at the receptor level, between [3H]‐nicardipine binding and endothelin‐1. This interaction probably accounts for the attenuation of endothelin‐1‐elicited vasoconstriction induced by nicardipine.
Inhibition of serotonin‐induced increase in canine external carotid blood flow by drugs that decrease the sympathetic outflow
Authors: Terrón José A. , Hong Enrique , López‐Muñoz Francisco J. , Villalón Carlos M.
Published: January 2008

1 The present study was designed to analyse the effect of the centrally‐acting sympatho‐inhibitory drugs, prazosin and ketanserin, on the increase in external carotid blood flow (external CBF) produced by 5‐hydroxytryptamine (5‐HT) in pentobarbital‐anaesthetized dogs.

2 Intracarotid (i.c.) infusions of 5‐HT (10 μ g min−1 during 1 min) produced an increase in external CBF without changes in mean arterial blood pressure or heart rate. This response to 5‐HT was dose‐dependently blocked by intravenous (i.v.) administration of prazosin (1, 3, 10, 30 and 100 μg kg−1) or ketanserin (10, 30, 100 and 300 μg kg−1).

3 Furthermore, 5‐HT‐induced increase in external CBF was inhibited by either the ganglionic blocking agent, mecamylamine (0.03, 0.1, 0.3, 1, 3 and 10 mg kg−1), the mixed 5‐HT1‐like and 5‐HT2 receptor antagonist, methiothepin (3, 10 and 30 μ g kg−1) or the 5‐HT1A ligand, spiroxatrine (10, 30, 100 and 300 μg kg−1). In contrast, the selective 5‐HT2 and 5‐HT1C receptor antagonist, ritanserin (30 and 100 μg kg−1, i.v.), was unable to block the above response to 5‐HT.

4 It is concluded that the inhibition of 5‐HT‐induced increase in external CBF by prazosin, ketanserin, mecamylamine and spiroxatrine is due to a reduction in the sympathetic tone and not to a blockade of 5‐HT receptors.
Muscle layer and regional differences in autonomic innervation and responsiveness to transmitter agents in swine myometrium
Authors: Taneike Tetsuro , Bando Shin‐Ichi , Takasaki Kumiko , Okumura Mayumi , Sato Hitomi , Teraoka Hiroki , Kitazawa Takio , Ohga Akira
Published: January 2008

1 To clarify possible regional and muscle layer differences in adrenergic innervation of swine myometrium, functional, biochemical and histochemical experiments were performed on longitudinal (LM) and circular (CM) muscle isolated from nonpregnant uteri of 84 gilts.

2 Transmural stimulation (TMS) in the presence of propranolol evoked tetrodotoxin‐sensitive contractions in a frequency‐dependent manner (2–20 Hz) in LM and CM. The cornual LM contractions were attenuated by phentolamine (1 μm) and by guanethidine (10 μm) though unaffected by atropine (1 μm). Contractions in cervical LM were diminished by atropine but not by phentolamine, and the corpus LM contractions were reduced incrementally by atropine and phentolamine when added sequentially. In CM, the TMS‐induced contractions were abolished by tetrodotoxin and atropine in all three regions.

3 In response to noradrenaline (NA) and acetylcholine (ACh), LM contractile intensity was the most potent in cornua, slightly weaker in the corpus and weakest in the cervix. CM was insensitive to NA, and contractile responses elicited by ACh indicated no regional variation.

4 NA content, significantly greater in LM than in CM, was most highly concentrated in cornual LM. Nerves exhibiting glyoxylic acid‐induced histofluorescence occurred in both LM and CM, though more abundantly in LM and with notable density in the cornual LM. Cholinesterase activity, distributed evenly throughout the three myometrial regions studied, was more intense in LM than in CM.

5 These results show that, in swine myometrium, innervation in cornual LM is predominantly noradrenergic, cervical LM is mostly cholinergic, and throughout the myometrium the CM layers are principally cholinergic.
Effect of chemical sympathectomy on (−)‐isoprenaline‐induced changes in cardiac β‐adrenoceptor subtypes in the guinea‐pig and rat
Authors: Kompa Andrew R. , Molenaar Peter , Summers Roger J.
Published: January 2008

1 Quantitative autoradiography was used to determine β‐adrenoceptor densities in cardiac regions of guinea‐pigs and rats after chemical sympathectomy with 6‐hydroxydopamine, and to examine how chemical sympathectomy affected β‐adrenoceptor changes following infusion of (‐)‐isoprenaline (400 μg kg−1 hr−1, 7 days).

2 Seven days after 6‐hydroxydopamine (100 mg kg−1, i.v.), cardiac tissue levels of noradrenaline were reduced by 94.0± 3.5% (guinea‐pig) and 86.0 ± 7.0% (rat). The blood pressure increase in rats to tyramine (0.5 mg, i.v.) was reduced from 118 mmHg in 6‐hydroxydopamine‐treated animals.

3 There were no changes 7 and 14 days after 6‐hydroxydopamine treatment in total, β1‐ and β2‐adrenoceptor density in the atrioventricular conducting system and atrial and ventricular myocardium in both species.

4 In control animals, (‐)‐isoprenaline infusion produced selective reductions in β2‐adrenoceptor density, whilst β1‐adrenoceptor density remained unchanged.

5 In 6‐hydroxydopamine treated guinea‐pigs or rats, (‐)‐isoprenaline infusion caused no change in β1‐radrenoceptors except in the right bundle branch whilst β2‐adrenoceptors were reduced in the atrioventricular conducting system (atrioventricular node, bundle of His, right and left bundle branches) and myocardium (interventricular septum and atria).

6 The differential effect of (‐)‐isoprenaline on β1‐and β2‐adrenoceptors is not therefore due to the occupation of β1‐adrenoceptors by noradrenaline or to prior down‐regulation of β1‐adrenoceptors by noradrenaline, since it persists after depletion of noradrenaline.
XV.:Investigations on Cutaneous Reaction in Scarlatina.
Authors: MALMBERG N. , JACOBSOHN G.
Published: January 2008

1. The Dick reaction taken on 1 200 children, 0–15 years, was positive in 66,8 %, negative in 24,2 % and of an uncertain character in 9 %.

2. Investigations of the frequency of positive Dick reaction at different ages gave results agreeing with those hitherto published.

3. Children with a history of scarlatina gave a positive Dick reaction in 11 %.

4. Pseudoreactions were more often found in children with increased sensitivity to tuberculine than in those without.

5. Investigations on 320 children of the variability (»Spontanschwankungen») of the Dick reaction, showed that a positive reaction gives practically no changes on retesting (occurred in only 1 % of our cases); a negative reaction on the other hand may in a certain percentage of cases (our figure was slightly less than 20 %) change to a positive one on retesting.

6. It thus seems permissible to regard a positive reaction as giving definite information, while a negative one should be judged more cautiously and under certain conditions occasion a retesting.

7. We have hitherto tested 16 foreign toxins derived from scarlatina streptococci and only 2 were found to compare in strength with the toxin which we ordinarily use. Ten toxins, among which were 2 derived from Dick strains, have plainly appeared considerably weaker, and 4 have shown themselves to be practically atoxic.

For further information, cf. Acta Pædiatrica, Vol. VI. p. 442; Svenska Läkaresällskapets Förhandlingar (Transactions of the Society of Swedish Physicians) 1927.
On acute Encephalitis as a Cause of Sudden Death.
Authors: MUHL GRETA
Published: January 2008

The author is relating five cases of acute encephalitis who died within the course of < 12–24 hours.

The age of the patiens was 91/2, 11/2, 41/2, 4 months and 8 years 8 months respectively.

The most prominent clinical symptoms were: peracute onset after previous perfect health or a few days of mild fever or, as in one case, sudden aggravation in connection with bronchitis.

Very rapid onset of unconsciousness.

High temperature.

Signs of circulatory disturbances.

In most cases spasms and vomiting.

In three cases symptoms indicating localised cerebral disease. In the two others no such symptoms.

Lumbar puncture, carried out in two cases, showed increased pressure and increased cell contents.

Patho‐anat. ex. In one case haemorrhagic encephalitis, in the four others there were no macroscopic pathological changes. Macroscopic examination is thus insufficient.

Microscopical examination of the brain: in four cases encephalitis of non‐specific type, in the fifth case signs of toxic influence: pseudoencephalitis. Since in this case, however, there was an increased number of cells in the cerebrospinal fluid with increased pressure there a commencing encephalitis was considered present.

In the differential diagnosis various kinds of meningitis have to be considered, besides poliomyelitis, sepsis, toxicosis and possibly pneumonia.
Some less common Lung Complications in asthmatic Conditions in Children
Authors: SÖDERLING BERTH
Published: January 2008

In children with asthmatic bronchitis or bronchial asthma we sometimes meet with the following complications, to which less attention seems to have been paid in the past.

Parenchymatous changes which, having regard also to the clinical examination, course of disease and radiological appearance, must be considered a condition of atelectasis. These conditions seem to have been fairly little observed in this relation and to have caused considerable difficulties in the differential diagnosis. They refer to children of 2, 3, 4, 5 and 6 years of age respectively.

Bronchiectasis. A couple of eases are related and their etiology discussed.

Pleural changes. These may cause one to suspect tuberculosis both in. the form of residual changes (fibrous bands) and of active pleurisy.

The author is finally referring to a tuberculin‐negative asthmatic patient with calcification of the parenchyma.

All the children have been tested with the Mantoux intracutaneous tuberculin method–most of them repeatedly–and most of them have been followed and after‐examined for a relatively long time.

To avoid a mistake in the diagnosis (tuberculosis is particularly liable) it is important to know of the above‐mentioned complications; several of the cases referred to have been regarded as tuberculous and even been under treatment in sanatoria.
Die Aetiologie des Pyloruspasmus (hypertrophische Pylorusstenose Typus Hirschsprung.)
Authors: HALBERTSMA T. J.
Published: January 2008

Der Krankheitsbild des Pyloruspasmus wird aufgefasst als Symtomkomplex Spasmus, Tumorbildung, Erbrechen, der zustande kommt als Folgeerscheinung einer angeborenen Missbildung: primär ist der Schleimhautkanal des Pylorus zu lang und zu eng angelegt.

In den ersten drei Lebenswochen genügt das Lumen noch für die Passage der relativ geringen Nahrungsmengen. Mit steigender Beanspruchung wird die Passage behindert. In wenigen Wochen kann als Reaktion auf die Passage‐Störung der Muskeltumor entstehen.

Diese Auffassung der Genese des Pyloruspasmus stützt sich auf röntgenologische und klinische Befunde verschiedener Autoren und folgende eigene Beobachtungen:

1. Bei einer Recidiv‐Operation wurde im Verlauf von 5 Wochen eine starke Zunahme eines Pylorus‐Tumors beobachtet.

2. Unter 32 eigenen Beobachtungen von Pyloruspasmus trat das Leiden in nicht weniger als drei Familien gehäuft auf bei insgesammt 7 Kindern. Da zwei dieser Familien ausserdem eng verwandt sind, lässt sich hier ein Stammbaum aufstellen, wobei wahrscheinlich gemacht wird, dass auch in der vorhergehenden Generation das Leiden vorkam.

3. Bei zweieiigen Zwilligen tritt die Krankheit ebenso häufig wie bei den übrigen Geschwisterschaften auf. Bei eineiigen Zwillingspaaren sind beide Pyloruspastilter.

Mit grösster Wahrscheinlichkeit handelt es sich also beim Pyloruspasmus um eine angeborene, familiäre vererbte Missbildung.
Über die Behandlung des kindlichen Diabetes ohne Diät
Authors: RÄIHÄ C.‐E.
Published: January 2008

Seit dem Herbst 1934 sind die Diabetiker auf der Kinderstation des Allgemeinen Krankenhauses zu Helsinki ohne Diät behandelt worden. Die Kranken haben frei essen dürfen, was sie wünschten, und die Insulindosen sind so gross bemessen worden, dass die Kranken säurefrei bleiben und der Harn dauernd Zucker enthält. Der letzterwähnte Umstand ist mit Rücksicht auf die Hypoglykämiegefahr als Massstab für die Insulindosierung betrachtet worden. Auf Grand unserer bisher gewonnenen Erfahrung ist diese Behandlungsmethode des kindlichen Diabetes der früher angewandten Diätbehandlung bedeutend überlegen. Unsere Ansicht gründet sich auf folgende Tatsachen:

Die Mortalität der Kinder an Diabetes ist nach der Einführung der neuen Behandlungsmethode erheblich gesunken. Früher starben über die Hälfte der an Diabetes erkrankten Kinder innerhalb der ersten zwei Jahre. Von den mit freier Kost Behandelten ist vorläufig nur knapp ein Sechstelgestorben.

Die bei freier Kost lebenden Kinder fühlen sich subjektiv und objektiv wohler als diejenigen, welche eine Diät einhalten; sie entwickeln sich normal und überstehen Infektionskrankheiten relativ gut.
Gourbe évolutive de la teneur leucocyiaire du sang pendant la première année de I'existence
Authors: MAGNUSSON Par J. HENNING
Published: January 2008

Le présent travail étudie la courbe évolutive de la teneur leucocytaire du sang dans une série formée de 52 enfants prématurés (la limite supérieure admise pour le poids à la naissance était 2 250 gr.) & âgés de 3 semaines à un an. L'au‐teur compare les résultats obtenus pour cette série avec ceux que donna L'examen, – aax mêmes âges, – d'une série de coniparaison formée de 47 enfants à terme (la limite inférieure admise pour le poids à la naissance était 3 000 gr.; la limite supérieure était 3 500 gr.)

Cette étude autorise la conclusion suivante:

Les enfants prématurés offrent une insuffisance dans la teneur leucocjtaire de leur sang. A un certain âge on constate, chez les prématurés, un niveau inférieur aussi Men pour le total général des globules blancs que pour les totaux partiels des gra‐nidocytes, des lymphocytes & des monocytes.

La série de comparaison montre que, durant la première année de l'existence des enfants à terme, les variations pré‐sentent une grande amplitude aussi bien pour le total général des leucocytes que pour les valeurs des différentes espèces de cellules. Cette observation est également applicable aux enfants prématurés
ÜBER MONGOLOIDE PARTIALSYMPTOME MIT BESONDERER BEACHTUNG DER SOG. VIERFINGERFURGHE.
Authors: BRANDER T.
Published: January 2008

Nach einer Übersicht der Literatur über mongoloide Partialsymptome, mit besonderer Beachtung der Vierfingerfurche (V. F. F.) wird über die Resultate einer Untersuchung an über 700 schwedischsprachigen Volksschulschülern in Helsingfors, von denen die meisten im Alter von 7–13 Jahren standen, berichtet. Der Prozentsatz für das Vorkommen des Epicanthus sank bei den Knaben von 7.7% bei einem Alter von 7 Jahren auf 4.2% bei 13 Jahren, bei den Mädchen waren die entsprechenden Werte 13.3 % resp. 5.9 % und für das gesamte Material 10.7% resp. 4.9%. Im ganzen Material wurde Epicanthus in 7.6 ± 1.0 % beobachtet. Schraggestellte Lidspalten wurden im Mittel bei Knaben in 31.3%, bei Madchen in 45.3% und im ganzen Material in 38.9 ± 1.8% vermerkt. Auch bei dieser Eigenheit ist eine leichte Tendenz für das Sinken der Prozentzahlen mit zunehmendem Alter festzustellen. Auch die allerleichtesten Fälle sind in diesen Zahlen mit einberechnet. Die V. F. F. mit ihren Übergangsformen war vollständig altersstabil. Übergangsform 1 nach Portius kam bei 5.8 ± 0.9 %, Übergangsform 2 nach demselben Autor bei 2.8 ± 0.6% und Typus 3 desselben Verfassers samt klassische V. F. F. bei 2.4 ± 0.6 % der Untersuchten vor. Die Häufigkeit des Vorkommens der V. F. F. war bei Kindern mit übrigen mongoloiden Stigmata nicht bewiesenermassen grösser; desgleichen spielt dabei auch das Geschlecht der Probanden keine wichtigere Rolle.
MICROCEPHALUS UND TETRAPLEGIE BEI EINEM KINDE NACH KOHL'ENMONOXYDVERGIFTUNG DER MUTTER WAHREND DER SCHWANGERSCHAFT.
Authors: BRANDER T.
Published: January 2008

Es handelt sich um einen Fall von Microcephalus, kompletter Idiotie und Tetraplegie (Littlesches Syndrom). Hereditär nichts von Interesse. Im 4. Schwangerschaftsmonat erlitt die Mutter eine Kohlenmonoxydvergiftung, wobei sie für 5 Stunden das Bewusstsein verloren hatte. Die Geburt des Kindes verlief ohne etwas Bemerkenswertes, und doch wurden sofort nach der Geburt schwere cerebrale Erscheinungen beobachtet. Im Alter von 4 Jahren weist das Kind, das weder ein Wort sprechen noch den Kopf heben kann, Symptome auf, die u. a. auf Hydromyelia cervicalis hinweisen.
The acute leukemia in children
Authors: RMS. JOHAN
Published: January 2008

Account of 24 cases of acute leukemia in children.

The acute leukemia in children as a rule is a myeloblast‐leuke‐mia (in at least 21 of 24 cases).

The initial symptoms are diffuse, – fatigue, fever, lack of appetite and pallor. In most cases (23 of 24) there is found either splenic or glandular enlargement and besides, in 13 cases also enlargement of the liver. These symptoms are considered as specially valuable in an early diagnosis.

3/4 of the cases commence in the first 5 years of life.

Anemia is a frequent symptom in an early stage of the disease, but in some cases it may be absent for weeks.

The red blood corpuscles show no characteristics. Index varies between 0.7 and 1.8. In 20 out of 23 cases index lies between 0.8 and 1.2.

Clinical bleeding‐tendency is found in 50 % of the patients in the more advanced stages of the disease. No connection between the bleeding‐tendency and the number of thrombocytes has been demonstrated.

The number of white blood cells varies within wide limits, from 1300 to 185 000 per mm3 of blood. It also varies highly from time to time in the individual patient. On admission to the department, 21 of 24 patients show values below 20 000 white blood cells per mm3 of blood, 17 below 10 000. 2 patients showed above 30 000 white blood cells per mm3 of blood.

Eoentgen picture of the bones have been taken in 17 patients. 5 show certain changes similar to those that sometimes are found in acute leukemia.

In 18 cases it has been made successful sternal puncture with findings of bone marrow rich in cells, with up to 99.4 % of myeloblasts. The pathological cellular type has in all cases been demonstrated in blood‐smear preparations, in 17 of 18 cases however, they have been recognised as myeloblasts only after successful sternal puncture having ascertained the diagnosis.
Massive Single‐Dose Chemotherapy in Pneumonia in Children
Authors: HESSELMAN B. H.
Published: January 2008

An account is given of 195 cases of pneumonia and bronchopneumonia in children from 0 15 years of age, treated in the medical wards of Kronprinsessan Lovisas Barnsjukhus during the period ½ 1941 ½ 1945.

In all the cases chemotherapy has been given in the form of a massive single dose. In 48 cases (24 %) the massive dose treatment has been supplemented by continuous chemotherapy. Sulphapyridine, sulphathiazole and sulfadimin have been used. The dosage has been 0.3 g per kg body weight for children under 3 years, and 0.2 g per kg body weight for the others, with 8 g as the maximal dose.

There have been few complications, and the toxic side‐effects have been extremely slight. 5.6 % fatal cases are recorded of all the cases observed, but if those cases where pneumonia has appeared as a complication of a serious congenital malformation or of a serious primary basic illness, are subtracted, the mortality is 2.1 %.

As the massive single‐dose treatment is technically easy to carry out, gives the patient more repose than does the continuous treatment during the period when the illness is most severe, lessens to a considerable degree the work of the hospital personnel, gives a result which can be compared favourably with that of continuous chemotherapy, gives rise to few complications and toxic side‐effects, this treatment can be recommended for pneumonia in children.

Satisfactory results have also been obtained with massive single‐dose treatment in eases of capillary bronchitis.
COW'S MILK IDIOSYNCRASY IN INFANTS
Authors: VENDEL STEPHAN , WALLGREN HEAD: PROFESSOR ARVID
Published: January 2008

In the period 1919—1947 a total of 23 clinically definite cases of cow's milk idiosyncrasy were treated at the 4 children's hospitals of Stockholm. This series of cases, supplemented by one case from private practice in Stockholm, is surveyed and attention is directed to an unusual symptom to which earlier authors have not attached any great significance, namely the very varying interval of time between exposure and allergic reaction.1 It is found that this allergic period of latency is as a rule individually constant and that therefore with this basis of classification it is possible to present the 24 cases so that their other clinical symptoms fall naturally into two distinct clinical types. These two types agree with the classification of cow's milk idiosyncrasy which von Sydow, on other grounds, has proposed.