bluuebunny/crossref_metadata_2025 huggingface dataset:
Fellow‐eye neovascularization in unilateral retinal angiomatous proliferation in a Korean population
Authors: Chang Young Suk , Kim Jae Hui , Yoo Su Jin , Lew Young Ju , Kim Jooyeon
Published: May 2015

Purpose

To evaluate the incidence of fellow‐eye neovascularization in retinal angiomatous proliferation (RAP) in a Korean population and associated risk factors.

Method

This retrospective, observational study included 81 eyes (81 patients) diagnosed with unilateral RAP who were followed up for ≥12 months. The RAP diagnosis was based on an indocyanine green angiography reviewed by two retinal specialists. In fellow eyes experiencing neovascularization, the period between RAP diagnosis and neovascularization was compared between eyes with and without reticular pseudodrusen.

Results

The mean age (±standard deviation) of the 81 patients was 74.7 ± 6.1 years. The mean follow‐up period was 27.8 ± 12.4 months. Fellow‐eye neovascularization was noted in 31 patients (38.3%), and 24 of these (77.4%) was a RAP subtype. Fellow‐eye involvement was noted within 12 months in 13 eyes (16.0%). The period between diagnosis and fellow‐eye neovascularization was significantly shorter in eyes with reticular pseudodrusen (mean 13.8 ± 8.5 months) than in eyes without reticular pseudodrusen (mean 21.2 ± 9.1 months; p = 0.031).

Conclusion

In our cohort of unilateral RAP patients, fellow‐eye neovascularization was noted in 38.3% in 27.8 months. The presence of reticular pseudodrusen in the fellow eye was closely associated with relatively early onset.
Norah Fry – what can we learn from history?
Authors: Russell Oliver
Published: May 2015

Accessible Summary

The Norah Fry Research Centre is named after Norah Fry who was one of the first women to stand up for people with learning disabilities.

Over a 100 years ago Norah Fry visited people with learning disabilities and their families in Bristol and Somerset to find out what they needed to enjoy better lives.

She wrote reports about what she had found and people wrote down what she said should be done to make life better.

When she died she left money to the university to be used for teaching and for finding out more about the needs of people with learning disabilities and those who were mentally ill.

We can now look back on the changes that she wanted to make and the problems she faced in trying to bring about change.

This paper explores how Norah Fry's concerns of 100 years ago have been relevant to the work of the Norah Fry Research Centre. In 1898, Norah Fry began to investigate the social conditions and educational needs of people with learning disabilities living in Bristol and Somerset. In reporting her findings to a Royal Commission in 1905, she set out her vision for the future. For over 50 years, she was a champion for people with learning disabilities. She canvassed support for schools for those excluded from education; she led campaigns to close the parish workhouses; and she sought to establish new patterns of residential support. This account of Norah Fry's life and legacy explores the results of the social investigations which she carried out, the policies that emerged from her work and the resistances she encountered in working for change.
Being researchers for the first time: reflections on the development of an inclusive research group
Authors: Tilly Liz ,   Money, Friends and Making Ends Meet' Research Group
Published: May 2015

Accessible summary

A group of people with a learning disability joined a group to talk about their lives

Being part of it was important, and they have continued as a research group

The group gives the members a voice and it helps them to know other people have similar issues to deal with.

It has also shaped their identity – how they feel about their lives and themselves.

Money, Friends and Making Ends Meet was an inclusive research project; it enabled a group of people with a learning disability who do not receive specialist support services to explore their own lives. This group are often labelled as having a mild learning disability. The research project focused on the strategies they used to cope with day to day living, their experiences of poverty and the support received from their social networks and social capital. The group members found participation in the research project enabled them to have a voice, identify the social barriers in their lives and gave them support and confidence to take action about them and so resolve some of their difficulties. They also embraced the label of learning disability and wanted staff in front‐line services to be aware of this, so they had greater understanding and support. This article is written by the instigator of the research group, but with a central part written by the group members in their own words. It focusses on how participation in the research project had a major impact on the group members as they moved from individuals involved in a short term research project to an established research group with its own motivation and direction. The group has since received further grant funding to research the effects of the welfare reform on their lives, and some have completed a bespoke accredited course on doing inclusive research.
Identification of two novel mutations in SLC12A3 gene in two Chinese pedigrees with Gitelman syndrome and review of literature
Authors: Li Congcong , Zhou Xinli , Han Wenxia , Jiang Xiuyun , Liu Jia , Fang Li , Wang Hai , Guan Qingbo , Gao Ling , Zhao Jiajun , Xu Jin , Xu Chao
Published: May 2015

Objective

Gitelman syndrome (GS) is one of the most common causes of inherited hypokalaemia. As it was caused by mutations in the SLC12A3 gene, GS is a highly heterogeneous disease. Here, we aimed to investigate the clinical and genetic characteristics of two Chinese pedigrees and summarize the advance in GS genetics, diagnosis and management.

Subjects and methods

Two three‐generation families with GS were identified and screened for mutations in the SLC12A3 gene. Genotype–phenotype correlations were analysed.

Results

The two probands (A and B) were characterized by hypokalaemia, hypomagnesaemia and hypocalciuria without hypertension. Complete DNA sequencing of the SLC12A3 gene revealed two novel compound heterozygous mutations (c.179C>T and c.234delG; c.486‐490delTACGGinsA and c.1925G>A), which are predicted to drastically affect normal protein structure. The female members of the pedigrees showed mild‐to‐no phenotype, although they carried the same mutations as the probands. Moreover, proband B presented with more severe symptoms than did proband A, which might be related to a lower serum magnesium level. During the 1‐year follow‐up, both probands showed satisfactory symptom improvement following the use of potassium and magnesium supplements.

Conclusion

Our findings strongly suggested that the two novel mutations in the SLC12A3 gene are the causative agents of GS, which may provide further insights into the function of this gene and help clinicians better understand this disorder.
Rhabdomyomatous mesenchymal hamartoma presenting as a sacral skin tag in two neonates with spinal dysraphism
Authors: McKinnon Elizabeth L. , Rand Andrew J. , Selim M. Angelica , Fuchs Herbert E. , Buckley Anne F. , Cummings Thomas J.
Published: May 2015

Rhabdomyomatous mesenchymal hamartoma (RMH) is a rare congenital malformation involving the dermis and subcutaneous tissue, of which there were 62 reported cases through 2014. We report RMH in two neonates presenting as a sacral skin tag. In both cases, magnetic resonance imaging (MRI) of the spine showed evidence of spinal dysraphism, including a lipomyelomeningocele and a tethered cord. Surgical repair of the defects was performed. Histopathologic examination of the skin tags showed a haphazard arrangement of mature skeletal muscle fibers and adnexal elements, consistent with RMH. The second patient also had a hemangioma on the sacrum and was diagnosed with LUMBAR (lower body hemangioma and other cutaneous defects, urogenital anomalies/ulceration, myelopathy, bony deformities, anorectal/arterial anomalies, and renal anomalies) syndrome, an association between cutaneous infantile hemangiomas of the lower body and regional congenital anomalies. The apparent association of paraspinal RMH with spinal dysraphism suggests that aberrant migration of mesodermally derived tissues (including skeletal muscle fibers) during neural tube development may be responsible for the pathologic findings in the skin. Additional study of patients with spinal dysraphism and congenital cutaneous lesions may further support this hypothesis.
Lethal 1080 baiting continues to reduce European Red Fox (Vulpes vulpes) abundance after more than 25 years of continuous use in south‐west Western Australia
Authors: Marlow Nicola J. , Thomas Neil D. , Williams Andrew A. E. , Macmahon Brian , Lawson John , Hitchen Yvette , Angus John , Berry Oliver
Published: May 2015

European Red Fox (Vulpes vulpes) baiting with 1080 poison (sodium fluoroacetate) is undertaken in many Australian sites to reduce fox abundance and to protect vulnerable native species from predation. The longest continuous use of fox baiting for fauna conservation commenced in south‐west Western Australia in the 1980s and includes baiting Dryandra Woodland and Tutanning Nature Reserve. The trap success of the Woylie (Bettongia penicillata) in these two reserves initially increased more than 20‐fold after the commencement of baiting and was maintained until 2000. Woylie captures then decreased rapidly, despite ongoing fox baiting, so the long‐term efficacy of 1080 baiting was questioned. Here, fox density and probabilities of detection, re‐detection and survival between replicated baited and unbaited sites were compared by modelling capture–recapture of individual foxes. These were identified from microsatellite DNA genotypes obtained non‐invasively from hair, scat and saliva samples. The frequency and duration of fox residencies were also quantified. Remote cameras were used to determine the fate of baits but uptake by foxes was low, whereas nontarget species' bait uptake was high. Nevertheless, foxes inhabiting baited reserves had significantly higher mortality, shorter residency times, and 80% lower density than foxes inhabiting unbaited reserves. Baiting continues to significantly reduce fox abundance after more than 25 years of continuous use. This has positive implications for fox control programmes throughout Australia but reduced fox abundance may facilitate increased predation by feral Cats (Felis catus).
Preliminary data on the effect of osseous anatomy on ex vivo joint mobility in the equine thoracolumbar region
Authors: Jones K. E.
Published: May 2015

Reasons for performing study

The thoracolumbar region is clinically important in horses; however, the link between joint mobility and bony joint morphology has not been tested quantitatively.

Objectives

To establish which aspects of vertebral morphology correlate with ex vivo range of motion in the thoracolumbar region of Equus caballus, and demonstrate methodologies for linking vertebral form and function.

Study design

Morphometric study of osteological specimens.

Methods

A digital model was created of a disarticulated thoracolumbar region to examine bone‐to‐bone interactions during in silico bending. Linear measurements and geometric morphometric landmarks were taken from 6 vertebrae per specimen (specimens n = 5, vertebrae n = 30), and compared with experimental range of motion in dorsiflexion, ventroflexion, lateroflexion and axial rotation data using Spearman's rank correlation, to test a priori hypotheses regarding thoracolumbar functional anatomy.

Results

Decreased sagittal mobility correlates with a tall, heart‐shaped vertebral body, although bony interactions restrict dorsiflexion more than ventroflexion. Lateroflexion correlates with a narrow vertebral body, a short transverse process lever arm, and narrowly placed horizontally oriented zygapophyses. Lateral joints also restrict lateroflexion in the posterior lumbar region. Axial rotation is related to the shape of the zygapophyseal joint.

Conclusions

These preliminary data suggest that vertebral joint morphology does determine experimentally measured range of motion, but patterns depend upon the type of motion. These methods are useful for identifying functionally relevant morphological variation and suggest osteological features are important in determining motion.
Complementary and alternative medicine for the prevention and treatment of migraine headache: an overview of systematic reviews
Authors: Posadzki Paul , AlBedah Abdullah MN , Khalil Mohamed MK , AlQaed Meshari S , Lee Myeong S , Ernst Edzard , Car Josip
Published: May 2015

Background

Complementary and alternative medicine (CAM) is very popular among migraineurs.

Objectives

The aim of this article is to summarise and critically evaluate the evidence from systematic reviews (SRs) of CAM for the prevention and treatment of migraine headache.

Method

Ten electronic databases were searched from 1946 to August 2014. Retrieved papers were also hand‐searched for relevant references. Systematic reviews were eligible for inclusion if they reported the prevention and treatment of migraine headache using any type of CAM. Oxman criteria were used to appraise the methodological quality of the included SRs.

Results

Thirty‐three SRs, with a total of 45 886 migraine sufferers, were included in the analyses. The majority (64%) of the SRs were of high methodological quality (mean Oxman score=4.87, SD=3.96). Most (60.6%) SRs arrived at positive conclusions (16 of which were of high quality); two (6.0%) SRs arrived at negative conclusions (of which one was of high quality), and 11 (33.3%) arrived at equivocal conclusions (of which four were of high quality). The majority of the high‐quality SRs (Oxman score=6–9) were based on moderate‐quality RCTs. For multiple SRs, unanimously positive conclusions were reached for acupuncture and biofeedback. There was conflicting evidence regarding the effectiveness of homeopathy, herbal medicines such as Petasites hybridus and Tanacetum parthenium L., and spinal manipulative therapy.

Conclusion

The evidence from SRs evaluating the effectiveness of CAM for the prevention or treatment of migraine headache is mostly positive. However, several caveats should be taken into account, and only for acupuncture and biofeedback are the conclusions unanimously positive.
New Zealand's turbulent waters: the use of forced labour in the fishing industry
Authors: STRINGER CHRISTINA , WHITTAKER D. HUGH , SIMMONS GLENN
Published: May 2015

In this article, we make an empirical and conceptual contribution to the emerging debate on unfree labour in the context of labour chains and global value chains. We recast an historical view of poor labour practices aboard some foreign charter vessels fishing in New Zealand's waters as something more nefarious. Applying the International Labour Organization (ILO) and European Commission (EC) operational indicators of human trafficking for forced labour to 293 interviews, we evaluate the extent to which we can consider migrant fishing crew aboard South Korean vessels as victims of forced labour. We find that they are indeed victims of forced labour and that there is a need to extend the ILO/EC operational indicators to take into account exit strategies. Specifically, there is insufficient recognition of deception, exploitation and coercion at the point of exit, which can prevent a trafficked victim from exiting the employment relationship. Thus, it is crucial to take account of all stages, from recruitment to exit, to understand fully unfree labour in labour and global value chains.
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

Objectives

The 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.

Methods

Patients 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.

Results

A 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.

Conclusions

d4T 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

Aim

To 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.

Methodology

Forty 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.

Results

The 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.

Conclusions

The 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.
Structural Features of LiPON Glasses Determined by 1D and 2D 31P MAS NMR
Authors: Mascaraque Nerea , Durán Alicia , Muñoz Francisco , Tricot Gregory
Published: May 2015

The relationships between structure and electrical properties of nitrided lithium phosphate glasses (LiPON) used as electrolytes for lithium batteries are key issues for better understanding and design of these materials. For the first time, the effect of nitrogen introduction in the structure of lithium phosphorus oxynitride glasses, formulated over a wide range of composition 38–55 mol.% of Li2O, has been studied through 31P 1D/2D MAS NMR experiments. Information obtained from 2D 31P/31P correlation maps has been used to deconvolute the 1D 31P NMR spectra and allowed establishing the percentage of oxide phosphate groups (PO4) and phosphorus species with nitrogen (P(O,N)4) as well as the connectivity scheme of the phosphate network. Finally, it has been demonstrated that the lithium content affects the structural changes induced by the introduction of nitrogen. In particular, the lower the lithium content is, the lower the total percentage of nitrided P(O,N)4 species is.
Comparison of the residual effects of two benzodiazepines (nitrazepam and flurazepam hydrochloride) and pentobarbitone sodium on human performance.
Authors: Borland RG , Nicholson AN
Published: May 2015

1 The residual effects of two benzodiazepines, nitrazepam (10 mg) and flurazepam hydrochloride (30 mg), and pentobarbitone sodium (200 mg) were studied by adaptive tracking and by reaction time. Performance was measured at 10 h, 13 h, 16 h, 19 h and 34 h after ingestion of each drug. Impaired performance on adaptive tracking was observed at 10 h, 13 h, 16 h and 19 h after nitrazepam and pentobarbitone sodium and at 10 h, 13 h and 16 h after flurazepam hydrochloride. Enhanced performance was observed at 34 h after nitrazepam and pentobarbitone sodium. 2 Increased reaction time persisted to 16 h after nitrazepam, flurazepam hydrochloride and pentobarbitone sodium and reaction time was also increased at 34 h after nitrazepam and pentobarbitone sodium. 3 During the morning immediately after ingestion, the subjects as a group were able to differentiate correctly between placebo and drugs, but they were not able to assess accurately the persistence of the residual effects of nitrazepam and pentobarbitone sodium. 4 Flurazepam hydrochloride would appear to be a more promising benzodiazepine than nitrazepam for use as a hypnotic by persons involved in skilled activity. There was a rapid recovery of performance during the afternoon and, unlike pentobarbitone sodium and nitrazepam, subjects retained the ability to recognize impaired skill.
A single dose study of trazodone with an assessment of its effect on mood and arousal.
Authors: Munday B , Kendall MJ , Mitchard M
Published: May 2015

1 A pharmacokinetic study of a single oral dose of a new antidepressant (trazodone) is described, linked to an attempt to measure changes in mood and arousal induced by the drug in normal subjects. 2 The drug had a measurable effect on arousal, but not on mood. It caused bradycardia (compared with placebo) and this persisted through the following night's sleep. This effect has not been completely explained. 3 The technique of mood and arousal measurement employed in this study seems potentially useful.
Plasma levels and beta‐adrenoceptor blockade with acebutolol, practolol and propranolol in man.
Authors: Cuthbert MF , Collins RF
Published: May 2015

1 The degree of beta‐adrenoceptor blockade of isoprenaline‐induced tachycardia has been determined in three healthy volunteers after the administration of single oral doses of acebutolol, practolol or propranolol. 2 Plasma levels of these drugs were determined either colorimetrically (acebutolol and practolol) or fluorimetrically (propranolol). The colorimetric assay of acebutolol in plasma is fully described but the other drugs were assayed by published methods. 3 The degree of beta‐adrenoceptor blockade and the plasma level for acebutolol and practolol were well correlated, whereas in the case of propranolol correlation was poor, due in part to the presence in plasma of active metabolites not detected by the fluorimetric assay. The plasma levels of practolol and propranolol are in agreement with those previously reported. 4 The maximum cardiac beta‐adrenoceptor blockade achieved in this study with the respective single oral doses of acebutolol (300 mg), practolol (400 mg) or propranolol (40 mg) were similar in each of the three subjects. Therefore the beta‐adrenoceptor blocking potencies of these drugs against isoprenaline‐induced tachycardia are inversely related to these doses; indicating that propranolol is 7‐8 times more potent than acebutolol and the latter slightly more potent than practolol.
The effect of codeine phosphate on the absorption of ethyl alcohol.
Authors: Cudworth AG , Barber HE , Calvey TN
Published: May 2015

The effect of syrup, B.P. and codeine phosphate syrup, B.P.C. on blood alcohol levels was determined in six normal subjects. 2 Treatment with syrup alone had little or no influence on the concentration of ethanol in blood. 3 In contrast, pretreatment with codeine phosphate syrup significantly reduced alcohol absorption, as assessed by the maximum blood levels achieved or the area subtended by the blood concentration‐ time curve. It is suggested that the diminished absorption of ethanol is related to the pharmacological action of codeine on the stomach. 4 It was considered that the concentration of ethanol in linctuses or syrups containing codeine was unlikely to have any significant effect on the central nervous system.
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

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

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

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

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.
THE MECHANISM OF α‐ADRENERGIC INHIBITION OF CATECHOLAMINE RELEASE
Authors: COHEN JACKIE , ECKSTEIN LEAH , GUTMAN YEHUDA
Published: May 2015

The effect of α‐adrenoceptor agonists on membrane adenosine triphosphatase (ATPase) activity was studied in membranes from the bovine adrenal medulla and the rat submaxillary gland.

α‐Adrenoceptor agonists (10−7 to 10−5 m) enhanced significantly Na,K‐ATPase activity but not Mg‐ATPase activity in adrenal medulla. This effect was not observed in membranes from phaeochromocytoma. Phenylephrine (10−5 m), naphazoline (10−5 m) and clonidine (10−5 m) caused a significant increase of the activity of Na,K‐ATPase (but not of Mg‐ATPase) in the submaxillary gland. The enhancement became more prominent after ligature of the submaxillary duct but disappeared completely after superior cervical ganglionectomy. Thus, the effect of the α‐adrenoceptor agonists was due to an action on adrenergic nerve terminals in the submaxillary gland.

Phenylephrine and naphazoline did not affect 45Ca uptake but enhanced the rate of 45Ca efflux from adrenal medullary slices in vitro.

Phenylephrine enhanced the rate of 45Ca efflux from slices of submaxillary gland (with previous ligation of the duct); this was blocked by phentolamine and sympathetic denervation. Therefore phenylephrine was acting on the adrenergic nerve terminals.

It is suggested that the inhibition by α‐adrenoceptor agonists of the exocytotic release of catecholamines from adrenergic nerve terminals and from chromaffin cells may be due to activation of the sodium pump, which results in enhancement of calcium efflux, causing a reduction of free intracellular Ca2+.
INHIBITION OF NEUROEFFECTOR TRANSMISSION BY MORPHINE IN THE VAS DEFERENS OF NAIVE AND MORPHINE‐TREATED MICE
Authors: ILLES P. , SCHULZ R.
Published: May 2015

The amplitude of excitatory junction potentials (e.j.ps) recorded intracellularly from smooth muscle cells of the mouse vas deferens varied with the strength of stimulation. Normorphine (0.4, 2 and 10 μm) shifted the stimulus‐response curve to the right, without any change in slope. This shift of the curve was proportional to the concentration of the opiate in the bath. Naloxone (0.4 and 2 μm) antagonized this effect of normorphine.

The action of normorphine (2 and 10 μm) was studied in vasa deferentia prepared from control mice and mice that had been implanted with morphine pellets. Both groups of tissues were continuously exposed to a low concentration of normorphine (0.4 μm), to simulate the plasma concentration in the morphine‐treated mice. Addition of 10 μm normorphine produced a parallel displacement of the curve in vasa deferentia from control animals, and a non‐parallel displacement in tissues from morphine pellet‐implanted mice. In the preparations from morphine‐treated mice a pronounced degree of tolerance to normorphine was observed at a low stimulus strength.

Naloxone (0.4 and 2 μm) had a greater effect on vasa deferentia prepared from morphine‐treated animals than on tissues from control mice, when both organs were continuously exposed to 0.4 μm normorphine. The difference in the effect of the antagonist in the two groups of preparations was absent when the incubating solution contained 2 μm normorphine.

It is concluded that at a low intensity of stimulation the e.j.ps are more readily depressed by normorphine and also the degree of tolerance displayed is larger than at a high intensity of stimulation.