bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changing utilization of Stavudine (d4T) in HIV‐positive people in 2006–2013 in the EuroSIDA study
Authors: Podlekareva D , Grint D , Karpov I , Rakmanova A , Mansinho K , Chentsova N , Zeltina I , Losso M , Parczewski M , Lundgren JD , Mocroft A , Kirk O ,   EuroSIDA in EuroCoord
Published: May 2015

ObjectivesThe long‐term side effects of stavudine (d4T) led to recommendations in 2009 to phase out use of this drug. We aimed to describe temporal patterns of d4T use across Europe.MethodsPatients taking combination antiretroviral therapy (cART) in EuroSIDA with follow‐up after 1 January 2006 were included in the study. cART was defined as d4T‐containing [d4T plus at least two other antiretrovirals (ARVs) from any class] or non‐d4T‐containing (at least three ARVs from any class, excluding d4T). Poisson regression was used to describe temporal changes in the prevalence of d4T use and factors associated with initiating d4T.ResultsA total of 5850 patients receiving cART on 1 January 2006 were included in the current analysis, rising to 7768 patients on January 1 2013. During this time, the prevalence of d4T use fell from 11.2% to 0.7%, with an overall decline of 19% per 6 months [95% confidence interval (CI) 19–20%]. d4T use declined fastest in Northern Europe [26% (95% CI 23–29%) per 6 months], and slowest in Eastern Europe [17% (95% CI 16–19%) per 6 months]. In multivariable Poisson regression models, new d4T initiations decreased by 14% per 6 months [adjusted incidence rate ratio (aIRR) 0.86; 95% CI 0.80–0.91]. Factors associated with initiating d4T were residence in Eastern Europe (aIRR 4.31; 95% CI 2.17–9.98) versus other European regions and HIV RNA > 400 copies/mL (aIRR 3.11; 95% CI 1.60–6.02) versus HIV RNA < 400 copies/mL.Conclusionsd4T use has declined sharply since 2006 to low levels in most regions; however, a low but persistent level of d4T use remains in Eastern Europe, where new d4T initiations post 2006 are also more common. The reasons for the regional differences may be multifactorial, but it is important to ensure that all clinicians treating HIV‐positive patients are aware of the potential harmful effects associated with d4T.
Digital radiographs displayed on different devices: effect on the detection of vertical root fractures
Authors: Vasconcelos T. V. , Santaella G. M. , Nascimento H. A. R. , Rovaris K. , Ambrosano G. M. B. , Freitas D. Q. 
Published: May 2015

AbstractAimTo evaluate whether the type of display device affects the detection of vertical root fractures (VRFs) on digital radiographs in unfilled canals and canals with fibreglass posts.MethodologyForty single‐rooted human teeth were decoronated, and the root canals were prepared. The teeth were divided into 2 groups: controls (20 teeth) and with VRF (20 teeth). The VRFs were induced using an universal testing machine. Periapical radiographs of all teeth, with canal unfilled or with a fibreglass post, were obtained using the parallel technique in 3 directions (ortho‐, mesio‐ and distoradial) on storage phosphor plates (VistaScan®). All images were evaluated and re‐evaluated after 30 days by 3 examiners on a 5‐point scale using 4 different devices (notebook display with full high definition resolution, desktop display with a standard resolution, 8‐inch Android™ tablet with high definition resolution and a 9.7‐inch iPad® tablet with Retina resolution). Areas under ROC curves, sensitivity, specificity and accuracy values were compared by anova.ResultsThe weighted kappa values for intra‐ and interobserver reproducibility were 0.55–0.88 and 0.31–0.65, respectively. There was a significant difference (P < 0.05) in relation to the area under the ROC curve, specificity and sensitivity when unfilled canals were compared with canals with a fibreglass post; however, no difference was observed for the different devices studied.ConclusionsThe type of display device did not affect the detection of VRFs. Thus, the detection of VRFs can be performed using different screen sizes and resolutions.
Maturation of somatomotor responses to strychnine in the albino rat
Authors: ENGELHARDT E. , ESBÉRARD C. A. 
Published: May 2015

The maturation of the convulsogenic activity of the caudal brainstem and spinal cord in the developing albino rat was studied by intraperitoneal injections of strychnine sulphate.
The observed responses were classed as hyperexcitability and hypertonic responses, graded 1 to 4. The complete tonic seizure (grade 4 hypertonic reaction, strychnine tetanus, maximal response) was obtained in all age groups, from birth to adulthood. The responses were grouped in sequences, and two patterns were distinguished: an infant one (from birth to 3 weeks) and an adult one (from 3 weeks on).
All doses varied according to age. The curve obtained for the median convulsive dose falls into two parts: descending, from birth to 3 weeks, and ascending, from 3 weeks on. Each part corresponded to a sequence pattern, the descending one to the infant pattern, and the ascending one to the adult pattern.
From these patterns and the corresponding median effective doses, three stages of the convulsogenic maturation of the spinal cord were distinguished: immaturity, pharmacological maturity and convulsogenic maturity.
It is suggested that the mechanism responsible for the complete tonic seizure is fully functional from birth, while that responsible for clonic seizure only reaches full maturity at 3 weeks of age.
Inhibition by antihistamines of the vascular permeability increase induced by bradykinin
Authors: BECKER E. L. , MOTA I. , WONG D. 
Published: May 2015

Mepyramine and triprolidine hydrochloride have a marked inhibitory effect on the local increase of vascular permeability induced by bradykinin.
The anti‐bradykinin effect of both antihistamines was species dependent, being evident in rabbits, rats and mice but not in guinea‐pigs.
The effects of bretylium on C fibre excitation and noradrenaline release by acetylcholine and electrical stimulation
Authors: DAVEY M. J. , HAYDEN M. L. , SCHOLFIELD P. C. 
Published: May 2015

The effects of bretylium on the excitation of postganglionic adrenergic C fibres by acetylcholine and the release of noradrenaline by acetylcholine and electrical stimulation of the splenic nerves have been studied using the in situ and cross perfused cat spleen.
Close arterial injections of acetylcholine (10–200 μg) evoked a brisk asynchronous discharge in fine filaments of the splenic nerve which reduced the height of the orthodromic C fibre compound action potential.
Hexamethonium abolished both the excitation of C fibres and release of noradrenaline by acetylcholine, whereas the liberation of noradrenaline by electrical stimulation of the splenic nerves remained unchanged.
Bretylium (0.5 and 1.0 mg) given close arterially blocked the output of noradrenaline and contractions of the spleen that occurred in response to nerve stimulation (30 c/s) but had much less effect on the responses to acetylcholine.
Bretylium (2–4 mg) given close arterially blocked the output of noradrenaline and contractions of the spleen caused by both nerve stimulation (30 c/s) and acetylcholine.
The close arterial injection of (+)‐amphetamine sulphate (100 μg) after bretylium (2–4 mg) partially restored the output of noradrenaline and contractions of the spleen to both nerve stimulation and acetylcholine.
The difference in the sensitivity to blockade by bretylium of the effects of nerve stimulation and the sympathomimetic effects of acetylcholine did not exist if the more “physiological” frequency of stimulation of 10 c/s was employed.
The close arterial injection of acetylcholine (100 μg) caused a mean average fibre discharge frequency of 5.4 spikes/sec.
Bretylium in amounts sufficient to completely block the sympathomimetic effects of acetylcholine did not alter the excitation of C fibres by acetylcholine.
The significance of these results is discussed both in relation to the mode of action of bretylium and to the use of these differential effects of bretylium as evidence for the “cholinergic link” hypothesis.
Procaine perfused into cerebral ventricles and subarachnoid space in conscious and anaesthetized dogs
Authors: HARANATH P. S. R. K. , VENKATAKRISHNA‐BHATT H. 
Published: May 2015

Perfusion of 1% procaine into the cerebral ventricles of conscious dogs produced mild paresis, defaecation, vomiting, jerky movements of eyelids, brisk nystagmus, increase in amplitude of respiration and sometimes loss of consciousness. Procaine 2% produced paralysis, loss of consciousness and sometimes respiratory depression.
Procaine 2% perfused into the cerebral ventricles of dogs under chloralose anaesthesia produced an initial increase in amplitude of respiration, which preceded its final depression, which is due primarily to procaine and only partly to a change in pH.
The site of action for the initial increase in amplitude of respiration was in the fourth ventricle, for it did not occur on perfusion of procaine into the cranial subarachnoid space.
Perfusion of spinal subarachnoid space with procaine is enough to cause respiratory failure even when the procaine does not reach the medulla.
The nature of the positive inotropic response of the isolated frog heart to theophylline and to iminazole
Authors: MASSINGHAM R. , NASMYTH P. A. 
Published: May 2015

Summary
The mechanism of the positive inotropic responses to theophylline and to iminazole has been examined in the frog heart.
Both theophylline and iminazole caused positive inotropic effects which declined to control amplitude with time despite continued exposure to the drugs. The duration of the response to iminazole was always longer than that to theophylline.
On washout of theophylline and iminazole the amplitude of heart beat slowly decreased to a value below that in the control period.
The theophylline response was not prevented by phentolamine or by propranolol given separately or in combination.
Theophylline potentiated the staircase and prolonged the post‐stimulation potentiation phenomena when its own inotropic activity had subsided but iminazole reduced the staircase effect at this time.
Theophylline, iminazole and 3 × [Ca2+]o all increased the influx of 45Ca into isolated ventricles. Theophylline increased but iminazole and 3 × [Ca2+]o slightly reduced 45Ca efflux.
Total cell calcium changes were only detected in ventricles exposed for 15 min to 3 × [Ca2+]o or theophylline (5 × 10−3M). After 60 min exposure to theophylline the total cell calcium was not significantly different from controls.
It is concluded that the positive inotropic responses to theophylline and iminazole can be interpreted in terms of the increased calcium influx which they produce and that interpretation of effects in terms of their action on phosphodiesterase should be treated with reservation.
Interaction in the cerebral metabolism of the biogenic amines. Effect of phenelzine on this interaction
Authors: MOIR A. T. B. , YATES CELIA M. 
Published: May 2015

Summary
Chronic administration of phenelzine to dogs caused the concentrations of homovanillic acid (HVA) in c.s.f. from both the lateral ventricle and cisterna magna to fall to new low levels at which they were maintained.
After 10–12 days treatment with phenelzine the caudate nucleus had elevated concentrations of dopamine and 3‐methoxytyramine and lowered concentrations of 3,4‐dihydroxyphenylacetic acid and HVA.
Intravenous administration of tryptophan to dogs pretreated with phenelzine caused in c.s.f. an increase in the concentrations of HVA and in the caudate nucleus a decrease in dopamine concentration and an increase in the concentrations of its metabolites, 3‐methoxytyramine, 3,4‐dihydroxyphenylacetic acid and HVA.
A model is proposed for the cerebral metabolism of dopamine and some of the points at which tryptophan and its metabolites may interact with dopamine metabolism are discussed.
The inactivation of bradykinin in the pulmonary circulation of isolated lungs
Authors: ALABASTER VALERIE A. , BAKHLE Y. S. 
Published: May 2015

Summary
The isolated lungs of guinea‐pigs, rats and dogs, perfused with Krebs bicarbonate solution via the pulmonary artery, inactivated 95, 98 and 99% respectively of the bradykinin infused through them.
This inactivation process was not inhibited by 2‐mercaptoethanol (1 mm) or EDTA (500 μm).
The inactivation was inhibited by 2:3‐dimercaptopropanol (100 μm), N‐ethylmaleimide (100 μm), and several of the bradykinin potentiating peptides from Bothrops jararaca, in both natural and synthetic forms.
The effect of these compounds, 2‐mercaptoethanol, EDTA, 2:3‐dimercaptopropanol, N‐ethylmaleimide and Bothrops peptides on the pulmonary bradykininase activity is the same as their effect on pulmonary angiotensin I converting enzyme.
Impairment of cognitive function associated with hydroxyamylobarbitone accumulation in patients with renal insufficiency
Authors: BALASUBRAMANIAM K. , MAWER G. E. , POHL J. E. F. , SIMONS P. J. G. 
Published: May 2015

Summary
Sodium amylobarbitone was given by intravenous infusion to six patients with chronic renal insufficiency and to six healthy volunteer subjects. Serum concentrations of amylobarbitone and its major metabolite hydroxyamylobarbitone were measured by a gas chromatograph method.
The serum concentrations of amylobarbitone were consistently lower in the patient group than in the control group and the concentration half time was shorter (0·10>P>0·05); the 48 h urinary excretion of hydroxyamylobarbitone was reduced (P<0·001) and the serum concentrations of hydroxyamylobarbitone were consistently raised.
When two patients were given 200 mg of sodium amylobarbitone daily over five consecutive days the serum concentration of hydroxyamylobarbitone rose steadily to a maximum of about 8 μg/ml. The serum concentrations in two healthy control subjects did not exceed 0·5 μg/ml.
Three parallel tests of cognitive function (Otis matched test forms A, B and C) were given to 16 control patients and to 12 amylobarbitone‐treated patients. Significant impairment of performance was observed in test B (P<0·001) at a time when amylobarbitone only could be detected in the patients' serum, and in test C (P<0·001) when amylobarbitone concentrations were very low (0·52±0·08 μg/ml±sem) but hydroxyamylobarbitone concentrations were still high (3·30±1·23, μg/ml±sem).
There was a strong (r = −0·71) and significant (P<0·01) negative correlation between the performance in test C and the serum concentration of hydroxyamylobarbitone. It is concluded that hydroxyamylobarbitone has cerebral depressant effects in man.
ACETYLCHOLINE‐SENSITIVE CELLS IN THE CAUDAL MEDULLA OF THE RAT: DISTRIBUTION, PHARMACOLOGY AND EFFECTS OF PENTOBARBITONE
Authors: DUGGAN A.W. , HEADLEY P.M. , LODGE D. 
Published: May 2015

The distribution of cholinoceptive and non‐cholinoceptive cells in various nuclei of the caudal medulla of the rat is described.
The nature of the responses of cells of the paramedian reticular nucleus and of the perihypoglossal nuclei to electrophoretically applied acetylcholine (ACh) was investigated.
In unanaesthetized decerebrate preparations ACh responses were usually of a ‘fast onset‐fast offset’ nature. Dihydro‐β‐erythroidine was a more effective antagonist than atropine.
In rats anaesthetized with barbiturate nearly all the ACh responses showed a slower onset and prolonged action. Atropine was the more effective antagonist.
The synaptic responses of cells of the paramedian reticular and perihypoglossal nuclei to stimulation of glossopharyngeal, superior laryngeal, lingual and hypoglossal nerves were investigated. It is concluded that ACh does not mediate the responses at the level of these nuclei.
A COMPARISON OF THE EFFECTS OF CYTOSINE ARABINOSIDE AND ADENINE ARABINOSIDE ON SOME ASPECTS OF BRAIN GROWTH AND DEVELOPMENT IN THE RAT
Authors: ADLARD B.P.F. , DOBBING J. , SANDS JEAN 
Published: May 2015

Treatment of pregnant rats with cytosine arabinoside (ara‐C, 50 mg/kg, i.p.) at 14 days of gestation severely impaired both prenatal and postnatal whole brain growth in their offspring, although the cerebellum was relatively less affected than whole brain.
Rats treated at 5 days of age with ara‐C (250 mg/kg, i.p.) showed an impairment in growth of the cerebellum relative to the rest of the brain.
Adenine arabinoside (ara‐A) treatment, either prenatally or postnatally, had negligible effect on brain growth, even at doses considerably higher than those of ara‐C.
Adult rats, previously treated with ara‐C (50 mg/kg, i.p.) at 14 days of gestation, showed an impairment in discrimination learning when tested in a water T‐maze.
These results are discussed in relation to the proposed use of ara‐C or ara‐A as antiviral agents, particularly against intrauterine infection with cytomegalovirus.
RENAL TUBULAR EXCRETION OF TRIETHYLCHOLINE (TEC) IN THE CHICKEN: ENHANCEMENT AND INHIBITION OF RENAL EXCRETION OF CHOLINE AND ACETYLCHOLINE BY TEC
Authors: ACARA MARGARET , KOWALSKI MARGARET , RENNICK BARBARA , HEMSWORTH B. 
Published: May 2015

[3H]‐triethylcholine (TEC) was actively transported by the renal tubule of the chicken at a rate 85% that of simultaneously administered p‐aminohippuric acid (PAH).
TEC was demonstrated to be transported by the organic cation transport system in the kidney through inhibition with quinine and the bio‐cation choline.
When the infusion of TEC was increased to 2 × 10−6 mol kg−1 min−1 reaching the infused kidney, the transport of [3H]‐TEC was inhibited, suggesting that an excretory transport maximum for TEC in the renal tubules had been reached.
The excretion of both choline and acetylcholine was enhanced by TEC loads as low as 1 × 10−18 mol kg−1 min−1. Enhancement continued as TEC infusion was increased up to approximately 1 × 10−7 mol kg−1 min−1 at which point this enhancement was converted to inhibition.
Possible mechanisms for the biphasic effect of TEC on organic cation transport are discussed.
STUDIES ON SOME para‐SUBSTITUTED CLONIDINE DERIVATIVES THAT EXHIBIT AN α‐ADRENOCEPTOR STIMULANT ACTIVITY
Authors: LECLERC G. , ROUOT B. , SCHWARTZ J. , VELLY J. , WERMUTH C.G. 
Published: May 2015

α‐Adrenoceptor stimulant activity was determined for noradrenaline (NA), clonidine and a series of para‐substituted derivatives of clonidine on rat aortic strips, a rat brain synaptosome preparation, and anaesthetized pithed rats. The effects on the blood pressure of intraventricular (i.c.v.) injections of para‐aminoclonidine were also determined in anaesthetized rats.
Para‐substituted derivatives of clonidine (amino‐, diethylamino‐, ethylamino‐, acetamido‐, bromoacetamido‐, N‐chloroethyl‐N‐methyl‐amino and N‐β‐chloroethyl‐N‐methylaminomethyl‐) retain α‐adrenoceptor stimulant activity.
pD2 values determined on rat aortic strips were 11.2, 7.67 and 9.05 respectively for para‐aminoclonidine, clonidine and noradrenaline. The Ki values of these agents, determined on a rat brain synaptosomal preparation with a radioreceptor assay using [3H]‐clonidine as ligand, were 1.3, 8.0 and 23 nm respectively for para‐aminoclonidine, clonidine and NA. When given by i.c.v. injection in rats, para‐aminoclonidine lowered the blood pressure.
N‐β‐chloroethyl‐N‐methylaminomethylclonidine is an alkylating agent with an unusual agonist activity. It elicits contractions of the rat aorta that persist despite repeated washing.
α‐Adrenoceptor affinities are discussed in relation to their structural features.
THE SIZE OF THE HYDROXYL GROUP AND ITS CONTRIBUTION TO THE AFFINITY OF ATROPINE FOR MUSCARINE‐SENSITIVE ACETYLCHOLINE RECEPTORS
Authors: BARLOW R.B. , RAMTOOLA SHENAZ 
Published: May 2015

From measurements of the affinity constants of hydratropyltropine and its methiodide for muscarine‐sensitive acetylcholine receptors in the guinea‐pig ileum, the increment in log K for the hydroxyl group in atropine is 2.06 and in the methiodide it is 2.16. These effects are slightly bigger than any so far recorded with these receptors.
The estimate of the increment in apparent molal volume for the hydroxyl group is 1.1 cm3/mol in atropine and 1.0 cm3/mol in the methobromide.
The large effect of the group on affinity may be linked to its small apparent size in water as suggested in the previous paper.
PHARMACOLOGICAL STUDY OF THE ANOCOCCYGEUS MUSCLE OF THE DOG
Authors: DEHPOUR A.R. , KHOYI M.A. , KOUTCHEKI H. , ZARRINDAST M.R. 
Published: May 2015

The response of the dog anococcygeus muscle to field stimulation and to some drugs has been studied. The results are compared with those reported previously in the rat, cat and rabbit.
Field stimulation produced frequency‐dependent contractions which were inhibited by guanethidine and phentolamine. When the tonus of the muscle was increased with guanethidine, field stimulation always produced frequency‐dependent relaxation. The relaxation was not prevented by propranolol.
The muscle was contracted by noradrenaline, tyramine, acetylcholine, histamine (H1), 5‐hydroxy‐tryptamine, prostaglandin E2 and vasopressin. Phentolamine, atropine, promethazine (but not cimetidine) and methysergide inhibited the effect of the respective agonists.
After increasing the tonus of the muscle, it was relaxed by low concentrations of isoprenaline. The relaxation was antagonized by propranolol.
The response to adenosine triphosphate (ATP) was variable. In some preparations, it relaxed the muscle, in others it contracted the muscle prior to relaxation, in others still it only contracted the muscle. Indomethacin did not prevent ATP‐induced contraction.
It is concluded that the anococcygeus of the dog, like that of rat, cat and rabbit, has an adrenergic motor innervation and an inhibitory innervation, the transmitter of which is not identified.
MECHANISM OF NORADRENALINE POTENTIATION BY PROSTAGLANDIN E2 IN RAT MESENTERIC ARTERY
Authors: ADEAGBO A.S.O. , OKPAKO D.T. 
Published: May 2015

Effects of prostaglandins E2 and F2α (PGE2 and PGF2α) on vasoconstrictor responses to noradrenaline (NA) and methoxamine in isolated mesenteric arteries of the rat were investigated.
PGE2 and to a lesser extent PGF2α potentiated vasoconstrictor responses to NA and methoxamine.
Prior treatment with reserpine increased, and bretylium reduced, the extent of potentiation significantly.
NA vasoconstriction persisted for 1 h after Ca2+ was removed from the perfusing Krebs solution. Prostaglandin‐induced potentiation was absent in Ca2+‐free Krebs, but increased proportionately with increase in external Ca2+ concentration.
Vasoconstriction induced by high potassium, was not potentiated by PGE2.
It is concluded that PGE2 potentiates NA vasoconstriction by facilitating Ca2+ influx.
INTERACTION BETWEEN ADENOSINE TRIPHOSPHATE AND NORADRENALINE IN THE ISOLATED VAS DEFERENS OF THE GUINEA‐PIG
Authors: KAŽIĆ TOMISLAV , MILOSAVLJEVIĆ DRAGICA 
Published: May 2015

An interaction between adenosine triphosphate (ATP) and noradrenaline (NA) was investigated in the isolated vas deferens of the guinea‐pig.
ATP (1.7 to 50 μm) enhanced contractions due to transmural electrical stimulation (ES; parameters: 30 Hz, 0.2 to 0.3 ms, 10 to 30 V; 1 s train duration). Responses to exogenous NA (12 μm) were also potentiated by ATP while contractions to acetylcholine (6 μm) were inhibited.
NA (1.2 μm) potentiated ATP‐induced contractions and prevented the development of tachyphylaxis to ATP (510 μm).
Phentolamine (12.5 μm) prevented the potentiation by NA of ATP‐induced contractions; these contractions were insensitive to phentolamine (up to 25 μm).
Removal of potassium chloride from the Tyrode solution for 10 min abolished the potentiating actions of both ATP and NA.
The present results suggest that the effect of ATP may be functionally closely related to that of NA at α‐adrenoceptors in the vas deferens of the guinea‐pig.