bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon, fire and seed addition favour native over exotic species in a grassy woodland
Authors: MORRIS E. CHARLES , DE BARSE MONIQUE
Published: July 2012

Cumberland Plain grassy woodland in western Sydney has been reduced to less than 12% of its pre‐settlement distribution; efforts to restore it on cleared and grazed sites within its former distribution have met with mixed success. Elevated soil nitrate levels, coupled with propagule and establishment limitation, have been identified as barriers to restoration in other grasslands. Our study used a factorial combination of carbon addition, fire and native seed addition to test whether these barriers operated on a former Cumberland plain woodland site dominated by exotic perennial grasses. Replicate field plots were established in November 2004; fire plots were burnt in December 2004; carbon was then added as sugar every 3 months until September 2005; and seeds of five native grasses were added in January 2005. Carbon addition significantly reduced soil nitrate, the effect appearing in October 2005. Carbon addition and fire each reduced the total abundance of exotics; when combined, they halved the abundance of the two dominant exotic grasses. Total abundance of native species responded positively to carbon and seed addition, but significant responses to carbon were not detected for individual species. Abundance of two native grasses responded positively to fire; after treatment the native proportion of total abundance rose from 26% on controls to 44–65% on carbon and/or fire plots. Exotic species richness was decreased independently by carbon addition and fire. Native species richness was increased independently by fire and seed addition. All five native grasses established sporadically, but only on carbon and/or fire plots. The three treatments each significantly and independently affected species composition, which showed the greatest change when all three were applied. The three treatments collectively increased the proportion of natives in measures of both plant abundance and species richness. The study confirmed that elevated soil nitrate, plus propagule and recruitment limitation are barriers to restoring this grassy woodland on cleared and grazed sites.
Presentation and outcome of idiopathic thrombocytopenic purpura in a single Australian centre
Authors: Choi P. Y‐I. , Gordon J. E. A. , Harvey M. , Chong B. H.
Published: July 2012

Immune thrombocytopenia can be a therapeutic challenge with multiple first‐ and second‐line treatment options. A change in idiopathic thrombocytopenic purpura (ITP) definition and classification in recent consensus guidelines suggests that past descriptions of ITP presentation and outcome may be outdated.

In this single centre retrospective analysis of patients with thrombocytopenia from 1 January 2005 to 1 June 2010, 139 patients met current ITP diagnostic criteria. About 54/139 were new presentations of primary ITP. Six‐ and 24‐month response rates were 39% and 30% respectively. About 26/54 patients did not require treatment at presentation: 15 were followed up for at least 6 months and none required treatment subsequently. These results suggest that almost half of all new primary ITP do not need treatment.
Australian resident doctors want more palliative medicine education: a survey of attitudes and perceived needs
Authors: Weil J. , Gold M. , McIver S. , Rotstein L. , Philip J.
Published: July 2012

Most expected deaths occur in acute hospitals, and medical staff providing end‐of‐life care are generally not palliative medicine specialists. Through a voluntary self‐administered survey, this study explored resident doctors' attitudes to palliative medicine and their perceived educational needs. Fifty‐two resident doctors participated (response rate 39%), mostly acknowledging the importance of palliative medicine to their practice and emphasising that further postgraduate education is necessary.
Lingual kinematics during rapid syllable repetition in Parkinson's disease
Authors: Wong Min Ney , Murdoch Bruce E. , Whelan Brooke‐Mai
Published: July 2012

Background: Rapid syllable repetition tasks are commonly used in the assessment of motor speech disorders. However, little is known about the articulatory kinematics during rapid syllable repetition in individuals with Parkinson's disease (PD).

Aims: To investigate and compare lingual kinematics during rapid syllable repetition in dysarthric speakers with PD (DPD), non‐dysarthric speakers with PD (NDPD) and a group of healthy controls.

Methods & Procedures: Electromagnetic articulography was used to record tongue‐tip and tongue‐back movement in five DPD and five NDPD participants during rapid repetition of /ta/and /ka/syllables, and matched with six healthy controls.

Outcomes & Results: Results revealed significant between‐group differences for most of the kinematic parameters measured but comparable rapid syllable repetition rates. Post‐hoc analyses indicated that the DPD participants, when compared with the NDPD participants, had similar range but prolonged duration of lingual movement. The DPD and NDPD participants had primarily increased range and prolonged duration of lingual movement accompanied by increased speed parameters, when compared with healthy controls.

Conclusions & Implications: The findings of the present study contradict theories that suggest that the clinical features of hypokinetic dysarthria, including articulatory imprecision, are the outcome of restrictions in the range of movement of the muscles of the articulators. The observed prolonged duration of lingual movement in PD may plausibly be due to the observed increased range of lingual movement rather than slowness of lingual movement.
Spatiotemporal visualization of deep brain stimulation‐induced effects in the subthalamic nucleus
Authors: Yousif Nada , Borisyuk Roman , Pavese Nicola , Nandi Dipankar , Bain Peter
Published: July 2012

Deep brain stimulation (DBS) is a successful surgical therapy used to treat the disabling symptoms of movement disorders such as Parkinson’s disease. It involves the chronic stimulation of disorder‐specific nuclei. However, the mechanisms that lead to clinical improvements remain unclear. Consequently, this slows the optimization of present‐day DBS therapy and hinders its future development and application. We used a computational model to calculate the distribution of electric potential induced by DBS and study the effect of stimulation on the spiking activity of a subthalamic nucleus (STN) projection neuron. We previously showed that such a model can reveal detailed spatial effects of stimulation in the vicinity of the electrode. However, this multi‐compartmental STN neuron model can fire in either a burst or tonic mode and, in this study, we hypothesized that the firing mode of the cell will have a major impact on the DBS‐induced effects. Our simulations showed that the bursting model exhibits behaviour observed in studies of high‐frequency stimulation of STN neurons, such as the presence of a silent period at stimulation offset and frequency‐dependent stimulation effects. We validated the model by simulating the clinical parameter settings used for a Parkinsonian patient and showed, in a patient‐specific anatomical model, that the region of affected tissue is consistent with clinical observations of the optimal DBS site. Our results demonstrated a method of quantitatively assessing neuronal changes induced by DBS, to maximize therapeutic benefit and minimize unwanted side effects.
Improved conditions for the generation of beta oscillations in the subthalamic nucleus–globus pallidus network
Authors: Pavlides Alex , John Hogan S. , Bogacz Rafal
Published: July 2012

A key pathology in the development of Parkinson’s disease is the occurrence of persistent beta oscillations, which are correlated with difficulty in movement initiation. We investigated the network model composed of the subthalamic nucleus (STN) and globus pallidus (GP) developed by A. Nevado Holgado et al. [(2010) Journal of Neuroscience, 30, 12340–12352], who identified the conditions under which this circuit could generate beta oscillations. Our work extended their analysis by deriving improved analytic stability conditions for realistic values of the synaptic transmission delay between STN and GP neurons. The improved conditions were significantly closer to the results of simulations for the range of synaptic transmission delays measured experimentally. Furthermore, our analysis explained how changes in cortical and striatal input to the STN–GP network influenced oscillations generated by the circuit. As we have identified when a system of mutually connected populations of excitatory and inhibitory neurons can generate oscillations, our results may also find applications in the study of neural oscillations produced by assemblies of excitatory and inhibitory neurons in other brain regions.
The role of inhibition in oscillatory wave dynamics in the cortex
Authors: Xiao Ying , Huang Xiao‐ying , Van Wert Stephen , Barreto Ernest , Wu Jian‐young , Gluckman Bruce J. , Schiff Steven J.
Published: July 2012

Cortical oscillations arise during behavioral and mental tasks, and all temporal oscillations have particular spatial patterns. Studying the mechanisms that generate and modulate the spatiotemporal characteristics of oscillations is important for understanding neural information processing and the signs and symptoms of dynamical diseases of the brain. Nevertheless, it remains unclear how GABAergic inhibition modulates these oscillation dynamics. Using voltage‐sensitive dye imaging, pharmacological methods, and tangentially cut occipital neocortical brain slices (including layers 3–5) of Sprague‐Dawley rat, we found that GABAa disinhibition with bicuculline can progressively simplify oscillation dynamics in the presence of carbachol in a concentration‐dependent manner. Additionally, GABAb disinhibition can further simplify oscillation dynamics after GABAa receptors are blocked. Both GABAa and GABAb disinhibition increase the synchronization of the neural network. Theta frequency (5–15‐Hz) oscillations are reliably generated by using a combination of GABAa and GABAb antagonists alone. These theta oscillations have basic spatiotemporal patterns similar to those generated by carbachol/bicuculline. These results are illustrative of how GABAergic inhibition increases the complexity of patterns of activity and contributes to the regulation of the cortex.
Metabolic adaptations of Pseudomonas aeruginosa during cystic fibrosis chronic lung infections
Authors: Behrends V. , Ryall B. , Zlosnik J. E. A. , Speert D. P. , Bundy J. G. , Williams H. D.
Published: July 2012

Pseudomonas aeruginosa forms chronic infections in the lungs of cystic fibrosis (CF) patients, and is the leading cause of morbidity and mortality in patients with CF. Understanding how this opportunistic pathogen adapts to the CF lung during chronic infections is important to increase the efficacy of treatment and is likely to increase insight into other long‐term infections. Previous studies of P. aeruginosa adaptation and divergence in CF infections have focused on the genetic level, both identifying characteristic mutations and patterns of gene expression. However, these approaches are not sufficient to fully understand the metabolic changes that occur during long‐term infection, as metabolic regulation is complex and takes place on different biological levels. We used untargeted metabolic profiling (metabolomics) of cell supernatants (exometabolome analysis, or metabolic footprinting) to compare 179 strains, collected over time periods ranging from 4 to 24 years for the individual patients, representing a series of mostly clonal lineages from 18 individual patients. There was clear evidence of metabolic adaptation to the CF lung environment: acetate production was highly significantly negatively associated with length of infection. For amino acids, which are available to the bacterium in the lung environment, the tendency of isolates to evolve more efficient uptake was related to the biosynthetic cost of producing each metabolite; conversely, for the non‐mammalian metabolite trehalose, isolates had significantly reduced tendency to utilize this compound with length of infection. However, as well as adaptation across patients, there was also a striking degree of metabolic variation between the different clonal lineages: in fact, the patient the strains were isolated from was a greater source of variance than length of infection for all metabolites observed. Our data highlight the potential for metabolomic investigation of complex phenotypic adaptations during infection.
Multifactorial risk factor intervention in patients with Type 2 diabetes improves arginine bioavailability ratios
Authors: Tripolt N. J. , Meinitzer A. , Eder M. , Wascher T. C. , Pieber T. R. , Sourij H.
Published: July 2012

Diabet. Med. 29, e365–e368 (2012)

Aim  Endothelial dysfunction is defined by reduced bioavailability of nitric oxide and has been shown to be associated with cardiovascular risk. The global arginine bioavailability ratio and the arginine to ornithine ratio have recently been shown to be associated with cardiovascular outcome in patients with coronary artery disease. The aim of our study was to investigate the impact of a multifactorial risk factor intervention in subjects with Type 2 diabetes on these two potential new cardiovascular surrogate parameters.

Methods  In a single‐centre and prospective study, we investigated 41 patients with Type 2 diabetes not reaching treatment targets according to current local diabetes guidelines in two out of three of the following measurements: HbA1c LDL cholesterol 2.6 or blood pressure. Within 3 months, therapy was intensified according to current guidelines aiming to reach the treatment targets. At baseline and 3 months, arginine, ornithine and citrulline were chromatographically determined after pre‐column‐derivatization followed by fluorescent detection, and arginine bioavailability ratios were calculated.

Results  Intensified risk factor management significantly improved the global arginine bioavailability ratio (0.33 ± 0.12 at baseline vs. 0.38 ± 0.14 after 3 months; P = 0.018). A significant improvement was only seen in patients with short diabetes duration (< 5 years), whereas in patients with longer diabetes duration improvement did not reach statistical significance.

Conclusion  In patients with Type 2 diabetes, intensified risk factor management improves arginine bioavailability ratios. Duration of diabetes seems to be an important factor influencing the capacity of the global arginine bioavailability ratio improvement.
Potential role of non‐insulin adjunct therapy in Type 1 diabetes
Authors: George P. , McCrimmon R. J.
Published: July 2012

Diabet. Med. 30, 179–188 (2013)

Despite improvements in the pharmacodynamics of injectable insulin and better insulin delivery systems, glucose control remains suboptimal in the majority of individuals with Type 1 diabetes. Profound defects in the physiological processes that normally maintain glucose homeostasis contribute to the difficulty in achieving glycaemic targets. Non‐insulin‐based adjunct treatments offer a potential means of complementing intensive insulin therapy in Type 1 diabetes through addressing some of the physiological disturbances that result from endogenous β‐cell destruction, particularly through preservation of β‐cell mass and prevention of apoptosis, and suppression of α‐cell glucagon release in the postprandial state. The former approach applies most readily to newly diagnosed C‐peptide‐positive Type 1 diabetes, while the latter to established C‐peptide‐negative Type 1 diabetes. This review focuses primarily on the clinical trial data available on the use of non‐insulin‐based therapies in longer‐duration Type 1 diabetes. We conclude that metformin may prove useful in macrovascular disease reduction, while pramlintide, glucagon‐like peptide‐1 agonists, dipeptidyl peptidase‐4 inhibitors and leptin co‐therapies may reduce HbA1c, glucose variability, postprandial glucose excursions and body weight. These early studies are encouraging and offer novel and potentially very effective approaches to the treatment of Type 1 diabetes, but the evidence is largely restricted to small, often uncontrolled trials. As such, these therapies cannot be currently recommended for routine clinical practice. There is a clear need to support large, multi‐centre randomized controlled trials designed to establish whether adjunct insulin therapy has a place in the modern management of Type 1 diabetes.
Are Global Imbalances Sustainable? Shedding Further Light on the Causes of Current Account Reversals
Authors: de Mello Luiz , Padoan Pier Carlo , Rousová Linda
Published: July 2012

Large shifts in countries' external current account positions can be disruptive, often reflecting sudden stops in the flows of external finance and leading to exchange rate and banking crises. As a result, an empirical literature has emerged on the sustainability of, and the determinants of large swings in, current account positions. Further light is shed on this issue by testing for the presence of unit roots in the current account balance‐to‐gross domestic product (GDP) ratios of a large set of mature and emerging‐market economies using a methodology that allows for structural breaks in levels and trends. A chronology is constructed of current account reversals that is consistent with sustainability of external positions and it is used to estimate the factors explaining the likelihood and magnitude of such reversals by utilising a selection model with ordered probit in the selection stage. It is found that most of the factors that explain the probability of reversals, such as trends in capital flows, in the budget balance and in external positions, also influence their magnitude, but there are a few exceptions. For instance, the stance of monetary policy and the magnitude of external imbalances prior to a reversal seem to be more powerful predictors of the probability of reversals than of their magnitude.
Share Repurchase Reasons and the Market Reaction to Actual Share Repurchases: Evidence from Australia
Authors: Akyol Ali C. , Foo Chi Chong
Published: July 2012

Using repurchase reasons provided by Australian companies for their stock repurchase programs, we ask if the market's response is different across repurchase motivations by examining actual daily share repurchases. We find that firms with the undervaluation motive experience a more positive stock price reaction when they report their repurchases to the market. We show that undervaluation motive firms repurchase fewer shares and have a lower program completion rate than other motives firms. During the 1‐year period following the repurchases, undervaluation motive firms do better than their control sample firms whereas other motive firms do not perform better or worse than their control sample firms. Overall, our results suggest that the undervaluation motive is a stronger signal than other repurchase motives, and contrary to the predictions of the standard signaling theories, management statements carry some value for the market. We also present some evidence suggesting that a costly action may not be needed for a signal to be credible.
Development and evolution of the vertebrate primary mouth
Authors: Soukup Vladimír , Horácek Ivan , Cerny Robert
Published: July 2012

The vertebrate oral region represents a key interface between outer and inner environments, and its structural and functional design is among the limiting factors for survival of its owners. Both formation of the respective oral opening (primary mouth) and establishment of the food‐processing apparatus (secondary mouth) require interplay between several embryonic tissues and complex embryonic rearrangements. Although many aspects of the secondary mouth formation, including development of the jaws, teeth or taste buds, are known in considerable detail, general knowledge about primary mouth formation is regrettably low. In this paper, primary mouth formation is reviewed from a comparative point of view in order to reveal its underestimated morphogenetic diversity among, and also within, particular vertebrate clades. In general, three main developmental modes were identified. The most common is characterized by primary mouth formation via a deeply invaginated ectodermal stomodeum and subsequent rupture of the bilaminar oral membrane. However, in salamander, lungfish and also in some frog species, the mouth develops alternatively via stomodeal collar formation contributed both by the ecto‐ and endoderm. In ray‐finned fishes, on the other hand, the mouth forms via an ectoderm wedge and later horizontal detachment of the initially compressed oral epithelia with probably a mixed germ‐layer derivation. A very intriguing situation can be seen in agnathan fishes: whereas lampreys develop their primary mouth in a manner similar to the most common gnathostome pattern, hagfishes seem to undergo a unique oropharyngeal morphogenesis when compared with other vertebrates. In discussing the early formative embryonic correlates of primary mouth formation likely to be responsible for evolutionary–developmental modifications of this area, we stress an essential role of four factors: first, positioning and amount of yolk tissue; closely related to, second, endoderm formation during gastrulation, which initiates the process and constrains possible evolutionary changes within this area; third, incipient structure of the stomodeal primordium at the anterior neural plate border, where the ectoderm component of the prospective primary mouth is formed; and fourth, the prime role of Pitx genes for establishment and later morphogenesis of oral region both in vertebrates and non‐vertebrate chordates.
Lactate production as a response to intrapartum hypoxia in the growth‐restricted fetus
Authors: Holzmann M , Cnattingius S , Nordström L
Published: July 2012

Please cite this paper as: Holzmann M, Cnattingius S, Nordström L. Lactate production as a response to intrapartum hypoxia in the growth‐restricted fetus. BJOG 2012;119:1265–1269.

Objective  To analyse whether the increase in lactate in response to intrapartum hypoxia differs between small‐ (SGA), appropriate‐ (AGA) and large‐for‐gestational‐age (LGA) fetuses.

Design  Observational cohort study.

Setting  Ten obstetric units in Sweden.

Population  A cohort of 1496 women.

Methods  A secondary analysis of a randomised controlled trial, in which 1496 women with fetal heart rate abnormalities, indicating fetal scalp blood sampling, were randomised to lactate analyses. After delivery, the neonates were divided according to birthweight for gestational age into SGA, AGA and LGA groups.

Main outcome measure  Lactate concentration in fetal scalp blood.

Secondary outcome measures  Acid–base balance in cord artery blood and Apgar score <7 at 5 minutes.

Results  Median lactate concentrations in the SGA, AGA and LGA groups were 3.8, 3.0 and 2.2 mmol/l, respectively (SGA versus AGA, P = 0.017; LGA versus AGA, P = 0.009). In the subgroups with scalp lactate >4.8 mmol/l (lactacidaemia), the corresponding median (range) values were 6.2 (4.9–14.6), 5.9 (4.9–15.9) and 5.7 mmol/l (5.0–7.9 mmol/l), respectively (no significant differences between the groups). The proportions of neonates with cord artery pH < 7.00, metabolic acidaemia or Apgar score <7 at 5 minutes were similar in all weight groups.

Conclusion  SGA fetuses with fetal heart rate abnormalities have the same ability to produce lactate as a response to intrapartum hypoxia as AGA and LGA fetuses. The risk of a poor outcome associated with high lactate concentration is the same in SGA, AGA and LGA fetuses. Scalp blood lactate analysis is therefore a reliable method for intrapartum fetal surveillance of suspected growth‐restricted fetuses scheduled for vaginal delivery at ≥34 weeks of gestation.
A comparative assessment of univariate longevity measures using zoological animal records
Authors: Moorad Jacob A. , Promislow Daniel E. L. , Flesness Nate , Miller Richard A.
Published: July 2012

Comparative biogerontology evaluates cellular, molecular, physiological, and genomic properties that distinguish short‐lived from long‐lived species. These studies typically use maximum reported lifespan (MRLS) as the index with which to compare traits, but there is a general awareness that MRLS is not ideal owing to statistical shortcomings that include bias resulting from small sample sizes. Nevertheless, MRLS has enough species‐specific information to show strong associations with many other species‐specific traits, such as body mass, stress resistance, and codon usage. The major goal of this study was to see if we could identify surrogate measures with better statistical properties than MRLS but that still capture inter‐species differences in extreme lifespan. Using zoological records of 181 bird and mammal species, we evaluated 16 univariate metrics of aging and longevity, including nonparametric quantile‐based measures and parameters derived from demographic models of aging, for three desirable statistical properties. We wished to identify those measures that: (i) correlated well with MRLS when the biasing effects of sample size were removed; (ii) correlated weakly with population size; and (iii) were highly robust to the effects of sampling error. Nonparametric univariate descriptors of the distribution of lifespans clearly outperformed the measures derived from demographic analyses. Mean adult lifespan and quantile‐based measures, and in particular the 90th quantile of longevity, performed particularly well, demonstrating far less sensitivity to small sample size effects than MRLS while preserving much of the information contained in the maximum lifespan measure. These measures should take the place of MRLS in comparative studies of lifespan.
The effects of some β‐adrenoreceptor blocking drugs on the uptake and release of noradrenaline by the heart
Authors: FOO J. W. , JOWETT ALISON , STAFFORD ANNE
Published: July 2012

The potencies of some β‐adrenoreceptor blocking drugs in reducing noradrenaline uptake by the isolated heart were compared with their potencies in reducing the release of noradrenaline from the heart by tyramine.

Of the drugs tested, propranolol, pronethalol and dichloroisoprenaline were the most potent in blocking uptake and release of noradrenaline, although none was at potent as cocaine; MJ 1999 and I.C.I. 50172 were only weakly effective.

Pronethalol and dichloroisoprenaline each reduced release of noradrenaline by tyramine in the concentration range (10−7–10−6M) where blockade of responses to tyramine was apparent; with these drugs both reduction of noradrenaline release and β‐receptor blockade contribute to the reduction in responses to tyramine.

Potency of β‐receptor blocking drugs in reducing noradrenaline uptake is unrelated to potency in blocking β‐receptors; Kö 592 blocks β‐receptors without affecting noradrenaline uptake.
Effects of quaternary ammonium compounds on choline transport in red cells
Authors: MARTIN K.
Published: July 2012

Neuromuscular blocking agents have been shown to be powerful inhibitors of choline transport in human erythrocytes. Ganglionic blocking agents were weaker inhibitors.

The affinity of the choline transport site for alkyltrimethylammonium compounds was considerably higher than its affinity for alkyl‐bis‐(trimethylammonium) compounds of similar chain length. The affinity increases with increasing length of the alkyl chain in both series.

Tetramethylammonium (TMA), ethyl‐ and propyltrimethylammonium appear to enter the cells on the choline carrier while the larger monoquaternary compounds, and the bisquaternary compounds, bind to the carrier but are unable to cross the cell membrane.

Radioactively labelled carbachol, acetylcholine and decamethonium do not enter the cells on the choline carrier.

Choline transport in erythrocytes from patients with myasthenia gravis is normal, suggesting that this disorder is not associated with a generalized defect of choline transport.
Some hepatotoxic actions of hexachloroethane and its metabolites in sheep
Authors: FOWLER J. S. L.
Published: July 2012

Pentachloroethane and tetrachloroethylene were major metabolites of hexachloroethane in sheep.

Concentrations of hexachloroethane, pentachloroethane and tetrachloroethylene were determined by gas‐liquid chromatography in blood, bile, faeces, urine and tissues after oral administration of hexachloroethane emulsions to sheep.

Increased blood concentrations of sorbitol dehydrogenase, glutamate dehydrogenase, and ornithine carbamoyl transferase were found to follow oral administration of hexachloroethane or pentachloroethane.

The rate of bromsulphthalein transfer from liver cells to bile was found to decrease after oral administration of hexachloroethane.
Partial purification of the anti‐inflammatory factor(s) in inflammatory exudate
Authors: BILLINGHAM M. E. J. , ROBINSON B. V. , ROBSON J. M.
Published: July 2012

The carrageenin foot test was established as a sensitive and reliable assay procedure for determining the anti‐inflammatory activity of inflammatory exudates.

Incubation alone at a temperature above 70° C or with pronase at 37° C destroyed the anti‐inflammatory activity of exudate.

The anti‐inflammatory component of exudate was partially precipitated by 50% ammonium sulphate.

A partial purification process was devised using Sephadex G‐150 gel filtration and DEAE and CM cellulose ion exchange chromatography to obtain at least a 24 fold purification.

Measurements of 11‐hydroxycorticosteroid levels indicated that steroids were not involved in the mechanism by which the exudate produced its antiinflammatory effects.
The effects of iproniazid and reserpine on the accumulation of granular vesicles and noradrenaline in constricted adrenergic nerves
Authors: BANKS P. , KAPELLER K. , MAYOR D.
Published: July 2012

. The accumulation of granular vesicles proximal to a constriction applied to hypogastric nerves has been investigated with the electron microscope in cats treated with reserpine and/or iproniazid.

. The ultrastructural changes have been correlated with the accumulation of noradrenaline at the same site in similarly treated animals.

. The findings give further support to the view that granular vesicles constitute a major storage site for intraneuronal noradrenaline.
The strychnine‐like action of curare and related compounds on the somatosensory evoked response of the rat cortex
Authors: BHARGAVA V. K. , MELDRUM B. S.
Published: July 2012

. Drugs were applied to the cerebral cortex of rats anaesthetized with pentobarbitone and changes measured in the somatosensory primary evoked response.

. Computer‐derived averages of thirty‐two consecutive responses yielded stable and consistent measurements of the potential changes comprising the evoked response, and comparable records from the opposite (non‐drug treated) cortex provided an essential control for systemic actions of the drug.

. The modifications produced by curare and strychnine were indistinguishable. The first positive wave (peak latency 7 msec) was unaltered; the second positive wave (peak latency 11.5 msec) was variably enhanced, and the first and second negative waves (peak latencies 16 and 40 msec) were replaced by a much larger negative wave (peak latency 22 msec).

. The time of onset of the effect on the negative waves and the maximal amplitude attained by the abnormal negative wave were related to the log concentration of the drug used. Curare is approximately 10 times more potent than strychnine.

. Toxiferine I, di‐allylnortoxiferine and atropine also produced this effect but were less potent than strychnine.

. Succinylcholine, dihydro‐β‐erythroidine and gallamine triethiodide did not produce this effect (in concentrations up to 10−3M).

. The observations are consistent with an action of curare and strychnine on an intracortical cholinergic inhibitory system, but other possibilities including a “non‐specific excitatory action” cannot be excluded.
The effects of oestrogens and progestins on the response of mice to barbiturates
Authors: BLACKHAM A. , SPENCER P. S. J.
Published: July 2012

. Mestranol (oestrogen) prolonged, whilst lynestrenol (progestin) reduced, the duration of pentobarbitone and hexobarbitone sleep in mice, whilst the effects of barbitone were not altered.

. The effects of these steroids on pentobarbitone sleep were dose‐related, did not show tachyphylaxis, and produced optimal effects after only 4 days pretreatment.

. The effects of lynestrenol were abolished by SKF 525A, whilst those of mestranol were markedly potentiated, suggesting a different mechanism and/or locus of action for mestranol and SKF 525A.

. Examination of plasma levels of pentobarbitone in mice pretreated with mestranol, lynestrenol or SKF 525A showed that lynestrenol increased whilst mestranol and SKF 525A reduced the rate of clearance of barbiturate from the plasma.

. The effects of lynestrenol disappeared when pentobarbitone was prevented from inducing hypothermia, whilst some significant prolongation of pentobarbitone sleep persisted in mestranol treated mice. This suggested that the ability to potentiate hypothermia was not the sole mechanism by which the effects of pentobarbitone were enhanced by mestranol.

. It is concluded these steroids alter the duration of action of pentobarbitone (and hexobarbitone) by changing the rate of barbiturate metabolism. In the case of mestranol, this might be a combination of an effect upon basal metabolic rate (enhancing hypothermia) and a direct effect on the liver. An effect upon renal clearance cannot be excluded by these results.
Further evidence for the involvement of kinin in anaphylactic shock in the rat
Authors: STARR M. S. , WEST G. B.
Published: July 2012

. Sodium phenylbutazone, soya bean trypsin inhibitor, or the concomitant administration of ascorbic acid and mepyramine protected rats against anaphylactic shock at 10 days after sensitization but gave no protection against anaphylaxis at 20 days.

. During anaphylactic shock in rats at 10 days after sensitization, the plasma bradykinin and bradykininogen levels, as well as those in the intestinal lumen and peritoneal cavity, were markedly raised.

. The results support the hypothesis that there are two phases in anaphylaxis in the rat—an early phase in which bradykinin is a mediator and against which phenylbutazone or soya bean trypsin inhibitor or the mixture of ascorbic acid and mepyramine, give protection, and a late phase which does not involve bradykinin.
Hydrolysis of suxamethonium by different types of plasma
Authors: HOBBIGER F. , PECK A. W.
Published: July 2012

. A method, based on the use of the isolated frog rectus abdominis preparation, is described for studying quantitatively the hydrolysis of suxamethonium at low concentrations.

. Rates of hydrolysis of butyrylcholine, 10 mM, benzoylcholine, 0.05 mM, and suxamethonium, 0.025 mM, by plasma from different species and human plasma with genetic variants of cholinesterase were measured.

. The rates of hydrolysis of suxamethonium by different types of plasma vary widely. Human plasma with usual cholinesterase and monkey plasma hydrolyse suxamethonium more speedily than do the plasma of cats, dogs and rats, and human plasma with either atypical or fluoride resistant cholinesterase. This is only to a small extent attributable to differences in enzyme concentration and not explained by the presence of an inhibitor.

. The Km values for butyrylcholine are very similar for different types of plasma but the KI values for suxamethonium in the system plasma‐butyryl‐choline‐suxamethonium vary greatly.

. These results and observations on the inhibition by decamethonium of the hydrolysis of butyrylcholine are consistent with the interpretation that the rates of hydrolysis of suxamethonium, 0.025 mM, obtained with different types of plasma vary because they are a function of two variables, the affinity of the ester for cholinesterase and the stability of the monosuccinyl derivative of the cholinesterase. It seems that human plasma with atypical cholinesterase hydrolyses suxamethonium much slower than does human plasma with usual cholinesterase mainly or solely because of differences in affinity of the ester for the two enzymes. On the other hand, cat plasma appears to hydrolyse suxamethonium much slower than does human plasma with usual cholinesterase mainly because the monosuccinyl derivative of cholinesterase in cat plasma is much more stable than that in human plasma. The reverse might apply for monkey plasma.

. Inhibition by dibucaine or sodium fluoride of the hydrolysis of benzoylcholine is not a general guide to rates of hydrolysis of suxamethonium by different types of plasma.
The effect of bretylium on intracellular cardiac action potentials in relation to its anti‐arrhythmic and local anaesthetic activity
Authors: PAPP J. GY. , WILLIAMS E. M. VAUGHAN
Published: July 2012

. The initial effect of bretylium tosylate on isolated rabbit atria was to increase conduction velocity, contraction heights, spontaneous frequency and maximum driven frequency, and to reduce electrical threshold. At concentrations of 200 mg/l. or less, these were the only effects, and were consistent with the known sympathomimetic actions of bretylium.

. At extremely high concentrations, 1,200 and 2,400 mg/l., the initial actions were succeeded by weak quinidine‐like effects; reduced conduction velocity, spontaneous and maximum driven frequencies, and rate of rise of action potential. The electrical threshold was raised, but contraction heights were not reduced.

. The local anaesthetic activity of bretylium, measured by reductions in the frog nerve action potential, was 1/90 that of procaine and 1/300 that of propranolol, on a molar basis.

. Acute pretreatment with bretylium, 20 mg/kg intravenously, significantly increased the amount of infused ouabain required before the appearance of the first signs of atrial arrhythmia in anaesthetized guinea‐pigs, but did not prevent ventricular arrhythmias.

. Pretreatment with bretylium 30 mg/kg subcutaneously 24 hr, and again 4 hr before ouabain infusion, increased the dose of ouabain inducing atrial irregularity and slightly but significantly reduced the incidence of ventricular fibrillation.
The influence of psychotropic drugs on aldolase, mitochondrial malic dehydrogenase and Mg++Na+K+ adenosine triphosphatase
Authors: CHOWDHURY A. K. , ROGERS H. , SKINNER A. , SPECTOR R. G. , WATTS D. C.
Published: July 2012

. The experiment investigated the effects of psychotropic drugs on enzymes in vitro.

. Chlorpromazine inhibits mitochondrial malate dehydrogenase in concentrations of 1·4 × 10−4m and above. No effect was observed below this concentration.

. A sharp inflection in the 1/V/drug plot was also seen with chlorpromazine (1·4 × 10−4m), trifluoperazine (1 × 10−5m), prochlorperazine (1 × 10−4m), and amylobarbitone (8 × 10−3m) acting on rat brain (Na+‐K+‐) Mg++‐ATPase and with chlorpromazine (10−4m) and imipramine (3 × 10−4m) acting on aldolase.
Quantitative studies on the antagonism by naloxone of some narcotic and narcotic‐antagonist analgesics
Authors: SMITS S. E. , TAKEMORI A. E.
Published: July 2012

Naloxone was used to study the antagonism of the analgesic effects of some narcotics (morphine sulphate, levorphanol tartrate, and methadone hydrochloride) and narcotic antagonists (pentazocine, cyclazocine, and nalorphine hydrochloride). The analgesic assay used was the mouse phenylbenzoquinone stretching test.

The in vivo equivalent of a pA2 value (apparent pA2) for naloxone was determined with each agonist. These values were found to be significantly larger with the narcotics than with the narcotic antagonists.

The slopes in the apparent pA2 plots were also found to be significantly different. It was concluded that this difference in slopes was probably not due to a lack of equilibrium in one of the two groups of analgesics.

The results suggest that the narcotic and the narcotic‐antagonist analgesics may inhibit stretching in this assay by interacting either with two different receptors or with the same receptor in a different manner.
The effect of reserpine on the pressor responses to angiotensin in the conscious cat
Authors: DAY M. D. , OWEN D. A. A.
Published: July 2012

Blood pressure recordings have been made in conscious cats in an attempt to reveal a possible indirect component to the angiotensin pressor response.

Reserpine (50 to 250 μg/kg per day) caused a maximal reduction of about 50% in the pressor response to angiotensin whilst virtually abolishing the responses to tyramine and McN‐A‐343. Responses to noradrenaline were only slightly and transiently reduced.

Syrosingopine (0.5 mg/kg) and reserpine (250 μg/kg) reduced the responses to angiotensin, McN‐A‐343 and tyramine to much the same extent, but tetrabenazine only reduced the responses to all these agents in a dose (25 mg/kg) which probably had effects on the catecholamine stores of smooth muscle.

The reduction in the responses to angiotensin, tyramine and McN‐A‐343 by reserpine was partly reversed by tranylcypromine. Noradrenaline and (±)‐dopa infusions were ineffective by themselves, but increased the effects of tranylcypromine in restoring the responses to angiotensin, tyramine and McN‐A‐343 after reserpine.

Infusion of α‐methyldopa markedly increased the responses to angiotensin, tyramine and McN‐A‐343 after these had been reduced by reserpine.

The results suggest that the pressor response to angiotensin in the conscious cat is partly mediated by release of noradrenaline from peripheral neuronal stores.
Antibacterial activity of dihydro‐1,3‐oxazine derivatives condensed with aromatic rings in positions 5, 6
Authors: CHYLIŃSKA J. B. , JANOWIEC M. , URBAŃSKI T.
Published: July 2012

The antibacterial activity in vitro of dihydro‐1,3‐oxazine derivatives with aromatic rings condensed in positions 5, 6 was examined.

Of more than thirty compounds examined, two (T 615 and T 638) showed marked activity against various strains of Mycobacterium tuberculosis at concentrations below 2 μg/ml.

These two compounds also showed marked activity against Escherichia coli, Clostridium pneumoniae and Salmonella typhi.

Both showed marked activity in vivo against tuberculosis produced in mice and guinea‐pigs by various strains of Mycobacterium such as human strain ‘Sz’, bovine ‘An 5’ and H37Rv non‐resistant and resistant to isonicotinic acid hydrazide (INH), streptomycin (SM) and p‐aminosalicylic acid (PAS).
Inhibitory and excitatory effects of sympathomimetic amines on muscle strips from the stomach of the guinea‐pig
Authors: BAILEY DIANA M.
Published: July 2012

Responses of muscle strips from the stomach of the guinea‐pig have been recorded. Sympathomimetic amines cause inhibitory, motor or biphasic responses.

The motor components of the responses of the preparations were greatly enhanced by the removal of the mucosal layers.

The inhibitory responses to isoprenaline, noradrenaline and phenylephrine were antagonized by propranolol or by sotalol. The inhibitory responses to noradrenaline and phenylephrine but not isoprenaline were antagonized by phentolamine. Therefore, both α‐ and β‐adrenoceptors may subserve inhibition.

The motor responses to noradrenaline and phenylephrine were often potentiated by propranolol or sotalol and were antagonized by phentolamine. Therefore, motor responses to sympathomimetic amines appear to involve α‐adrenoceptors.

The responses to sympathomimetic amines and their antagonists were not modified by hyoscine or by tetrodotoxin. It is concluded that the adrenoceptors mediating the responses recorded from these preparations are located on the smooth muscle cells rather than on a nervous pathway.
Response to acetylcholine and nicotine of the perfused vessels of the rabbit ear
Authors: GRAHAM J. D. P. , SUHAILA A. , TAI A.
Published: July 2012

The vessels of the isolated rabbit ear were perfused at 23 mbar with Krebs solution with (tonic) and without (atonic) noradrenaline (5.9 × 10−7M) at selected temperatures of 20°–38° C. Peripheral resistance units (PRU) were calculated from the observed peak flow rates and alterations caused by drugs expressed as Δ% PRU.

ACh is constrictor in the atonic vessel.

ACh is a vasodilator of the tonic vessel perfused with NA. This effect is potentiated by anticholinesterase and by denervation, unaffected by botulinum toxin and antagonized by atropine. ACh also dilates the vessel perfused with vasopressin.

Increasing the temperature reduces the responses to ACh but increases the effect of anticholinesterase.

Nicotine causes a dose dependent dilatation of the tonic vessels, reduced but not abolished by C6, by atropine, by botulinum toxin and by denervation.

Nicotine causes a dose dependent constriction of the atonic vessels, abolished by C6 and by phentolamine, reduced by denervation, but unaffected by botulinum toxin.
Metabolism of small multiple doses of (14C) nicotine in the cat
Authors: TURNER D. M.
Published: July 2012

The distribution and metabolism of (2′‐14C) nicotine given as a series of small intravenous injections (4 μg/kg every 60 s for 20 min) have been studied in the cat.

Blood concentrations of (14C) nicotine reached a maximum of 100 ng/ml at 20 min whereas blood concentrations of cotinine were maximal shortly afterwards.

The maximum concentration of nicotine in the blood was greater than that obtained by giving the same total dose as a continuous infusion ((4 μg/kg)/min for 20 min).

Urinary excretion accounted for 90% of the total multiple dose in 72 hours. After 24 h, however, only 2.5% of the radioactivity as (14C) nicotine and 0.05% as (14C) cotinine was excreted.

Gastric juice after 2 h contained significant amounts of activity which was almost entirely composed of (14C) nicotine and (14C) cotinine.

There were significant regional differences in the concentration of (14C) nicotine in the brain; amounts were greatest in cerebral hemispheres and smallest in the spinal cord. The hypothalamus and thalamus contained significantly higher concentrations of (14C) nicotine than the whole mid brain. (14C) Cotinine concentrations were highest in the cerebellum.
An implanted reservoir of morphine solution for rapid induction of physical dependence in rats
Authors: GOODE P. G.
Published: July 2012

Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs. Morphine was withdrawn by washing out the reservoir with drug vehicle. The daily dose of morphine, or substitute drug received by each rat was determined by difference by estimating the drug remaining in reservoir washings.

Withdrawal symptoms were more pronounced after 9 days than after 4 days of dosing with morphine.

Body weight loss, maximal at 24 h, and increased defaecation during the first 7 h were the chief physiological signs of morphine withdrawal. The body weight loss was the result of hypodipsia and anorexia exacerbated by increased defaecation.

When substituted for morphine in the reservoir, methadone and codeine completely prevented body weight loss and increased defaecation. while pethidine was effective against increased defaecation, but not against 24 h body weight loss. The opiate‐antagonist analgesics pentazocine, nalorphine and cyclazocine either had no effect on withdrawal symptoms or increased their severity.

In morphine dependent rats under continued morphine administration subcutaneous doses of the opiate‐antagonists nalorphine, cyclazocine and naloxone all precipitated the withdrawal symptoms of body weight loss and increased defaecation. The weak antagonist pentazocine caused a significantly increased defaecation, but no significant change in body weight, while the opiates pethidine. codeine and methadone had no significant effect on body weight or defaecation.

The advantages of inducing dependence by this method of dosing are discussed.