bluuebunny/crossref_metadata_2025 huggingface dataset:
An Old Debate Revisited: Applicability of Environmental Treaties in Times of International Armed Conflict Pursuant to the International Law Commission's ‘Draft Articles on the Effects of Armed Conflict on Treaties’*
Authors: Loets Adrian
Published: July 2012

The law of war relating to the protection of the environment is ineffective and fragmented. This article argues that the application of international environmental law during such times could significantly reduce the environmental toll of armed conflict. The applicability of peacetime agreements between belligerent States has remained controversial for decades. In November 2011, the United Nations General Assembly's Legal Committee adopted the International Law Commission's ‘Draft Articles on the effects of armed conflict on treaties’. These contain a presumption of continuation for a number of subject matters, including environmental law. The contribution analyzes the systematic structure of the ILC Draft Articles in relation to the prevailing case law, State practice and doctrine and provides an interpretation. In a second step, subject matters containing an environmental notion are presented and discussed. It is concluded that although the Draft Articles represent an important milestone, further regulation of wartime environmental damage is needed.
Lessons from Forestry for International Environmental Law
Authors: MacKenzie Catherine P.
Published: July 2012

This article reflects on the progress of international forest law since 1992 and makes suggestions for related areas of international environmental law, based on insights gained from the international forest regime. To do this, it explores principles of forest law that have emerged since 1992 and analyzes the relationship between national and international law in the context of the forest sector. It then discusses compliance with international forest agreements, concludes that agreements that include incentives for all parties to comply are more likely to be successful than those that do not, and draws from this lessons for lawmakers engaged in the development of related areas of international environmental law, such as international law on biodiversity and habitat protection. In particular, it emphasizes the importance of strengthening the rule of law, improving the implementation of existing agreements and including in new agreements incentives designed to ensure compliance by all parties.
Disentangling Climate Change Governance: A Legal Perspective
Authors: Quirico Ottavio
Published: July 2012

Climate change is by definition a global problem that is subject to a variety of regulatory initiatives. Besides the comprehensive framework established under the United Nations Framework Convention on Climate Change and the Kyoto Protocol, as strengthened by the recent Durban negotiations, a wide array of regulatory measures have been set up by public and private actors, either alone or via partnerships. This article aims to provide a brief overview and legal assessment of transnational regulatory networks for climate change, including both established regulators and rules. Indeed, the ‘regulatory proliferation’ in the field pushes to disentangle not only the reciprocal relationship between rules directly targeting climate change, but also the relationship between them and ‘external’ rules only indirectly relating to climate change. Mapping the existing climate change regulatory framework is essential for spotting potential loopholes and inconsistencies, correctly interpreting existing norms and eventually undertaking further regulatory action. Overall, the article concludes that within the context of a generally ‘complex’ regulatory regime, a gap currently exists between primary rules which gather an array of intertwined public–private regulatory initiatives and enforced secondary rules which encompass mainly obligations established by public actors only indirectly targeting climate change.
Trade Openness and International Fragmentation of Production in the European Union: The New Divide?
Authors: Guerrieri Paolo , Vergara Caffarelli Filippo
Published: July 2012

The relationship between international fragmentation of production, trade openness, and global export performance in the European Union (EU) from 2000 to 2009 is analyzed. As most trade models featuring international production sharing show, higher levels of fragmentation and of related international openness improve the export performance of a country. The empirical analysis confirms this hypothesis. This paper estimates an error correction model on the panel of the EU Member States and finds that inter‐European fragmentation and openness significantly improve their long‐run export performance. Policy implications could be that restrictive policies preventing firms from internationalizing production would weaken a country's position in global production networks, with long‐term negative effects on domestic jobs and growth.
Is Globalization Driving Efficiency? A Threshold Stochastic Frontier Panel Data Modeling Approach
Authors: Mastromarco Camilla , Serlenga Laura , Shin Yongcheol
Published: July 2012

In an earlier paper the authors proposed a two‐step approach to examine dynamic transmission mechanism under which globalization factors foster technology efficiency. In this paper the MSS model is extended by combining a panel threshold regression technique. This threshold stochastic frontier panel data model enables the analysis of regime‐specific stochastic frontiers and complex time‐varying patterns of technical efficiencies in a robust manner. Using a dataset of 44 countries over 1970–2007, income elasticities of labor and capital and time‐varying common efficiencies are found to be substantially different under superior and inferior frontiers. Capital and labor inputs are more productive under superior frontier. More importantly, common efficiencies have steadily increased under superior frontier, but technical efficiency has monotonically decreased for low income countries, supporting the so‐called club convergence hypothesis. Furthermore, the VAR‐based impulse response analyses suggest that openness factors through FDI and trade help the countries to improve production technology and efficiency position relative to the frontier only after the country has reached a certain level of development.
Where rights begin and end in Puerto Rico's gated communities
Authors: Dinzey‐Flores Zaire Z.
Published: July 2012

In 1992, Puerto Rico's governor and police superintendent incorporated the National Guard with local police in a militarized battle against crime. Mano dura contra el crimen (strong arm/iron fist against crime) policies led to the gating of 82 public housing communities in the island. Simultaneously, privileged private communities organized and petitioned municipalities to retrofit their neighbourhoods with gates in the name of safety. These enclosures followed the privatized management of all public housing communities in the island only a few years before. Based on ethnographic research, I examine the sociospatial outcomes of these policies, how they reframe community participation and deploy a discourse of self‐responsibility that distributes power unequally across private and public housing communities. While in the privileged communities these policies have cultivated community leaders and invigorated social life as residents take control over public space, the gates in the communities of the poor reflect a skeletal structure of democracy. Private management companies impose increasingly restrictive regulations in attempts to organize the community and the only recourse to participation is to engage in small acts of everyday resistance, from apathy to subversion. As part of larger neoliberal tendencies to retrench the ‘public’ in favour of the ‘private’, the mano dura policies curtail democracy as the voices of the poor are silenced and the scope of efficacy of the rich expands.
Havana: From local experiment to national reform
Authors: Hearn Adrian H. , Alfonso Félix J.
Published: July 2012

In April 2011 the Cuban government announced a suite of national reforms with deeper socioeconomic ramifications than the limited liberalizations it permitted in the 1990s. Although unprecedented in revolutionary Cuba, the proposed changes draw on previous efforts to manage decentralization, employment and the informal sector. The paper examines two case studies of prior experimentation with liberalization since 2000 in the municipality of Old Havana and the neighbouring district, Barrio Chino (Chinatown). We argue that the 2011 reforms are informed by specific lessons and insights from these two experiences and also by general development principles advocated by China.
Weak Dative Case In Norwegian Dialect Syntax
Authors: Åfarli Tor A. , Fjøsne Eldfrid Haaker
Published: July 2012

Abstract.  A remarkable fact about dative case in Norwegian dative dialects is that it bears all the marks of being a non‐structural (lexical, inherent) case as to the nature of its in situ generation, but still it is not preserved under A‐movement, which makes it a structural case according to the favoured diagnostic tests in generative grammar. We discuss the relevant data and argue that dative case in Norwegian should be classified as what we call a weak non‐structural case. Furthermore, we hypothesize that accusative and dative are more alike than previously thought, both being non‐structural cases, and in a development of Woolford (2006) we propose that all cases that are licensed inside vP should be counted as lexical or inherent non‐structural cases.
Measure Words as Nouns: A Perspective From Silent Years
Authors: Watanabe Akira
Published: July 2012

Abstract. This paper presents a novel type of evidence that measure words are nouns, not classifiers, in languages with numeral classifiers. The argument is based on striking similarities exhibited by expressions in English and in Japanese having to do with human age, especially when the head noun corresponding to ‘year’ is apparently missing. The most straightforward way of capturing these similarities is to treat measure words as nouns and posit a silent noun meaning ‘year’ in both languages.
Antecedent Containment: A Dependency Grammar Solution in Terms of Catenae
Authors: Osborne Timothy , Groß Thomas
Published: July 2012

Abstract. The paper presents a new solution to an old problem, the problem of antecedent containment and the infinite regress that it gives rise to. The solution is couched in a dependency grammar (DG) framework and is possible by acknowledging DGcatenae. The catena is a novel unit of syntactic analysis. Pronouns that appear to be contained within their antecedents actually take non‐constituent catenae as their antecedents. These catenae quite naturally exclude the pronouns, so that antecedent containment never occurs. This account acknowledges surface configurations only. No appeals are made to derivational mechanisms or abstract representations.
Two Types of External Argument Licensing – The Case of Causers*
Authors: Schäfer Florian
Published: July 2012

Abstract. This article argues that the thematic licensing of causer arguments is not a strictly lexical property but depends on the event configuration within the verbal phrase. The central observation leading to this conclusion is that three morphosyntactically different types of causer‐DPs are subject to the same licensing condition: they are licit only in the context of a bi‐eventive, resultative event structure. This licensing constellation is not only provided by lexically bi‐eventive verbs, but also by overt syntactic composition of a mono‐eventive verb with a secondary result predicate where the mono‐eventive verb does not license causers on its own. The latter constellation argues against coding causer‐roles in a verb’s lexical entry. Instead, it argues for an account that assumes event decomposition of lexically resultative verbs and some version of a configurational θ‐theory. Concentrating on existing syntactic versions of such an account, it is shown that they need to be updated to cover the set of data presented in this paper. A central claim put forward is the need to dissociate the verbal layers introducing causative‐resultative event structure (which acts asthematic licenserof causers) from those layers introducing external arguments syntactically (formal licensers). Concerning the latter, it is shown that causers, although thematically external arguments, are not necessarily introduced by a Voice projection on top of the verbal predicate.
China’s Growing Influence in Southeast Asia – Monetary Policy and Equity Markets
Authors: Johansson Anders C.
Published: July 2012

This study analyses the potential transmission of China’s monetary policy shocks to equity markets in Southeast Asia. Impulse response functions indicate that the impact of a monetary expansion in China is significant and positive for four of the five Southeast Asian equity markets. One explanation for this result is that monetary policy shocks in China lead to an increase in demand for goods and services in both China and abroad, which then shows up in the foreign equity market. The results in this paper provide evidence of China’s influence in Southeast Asia and its financial markets. The transmission effect is small and very short lived, but can be expected to increase if the current trends of a deepening economic integration between China and Southeast Asia and a maturing Chinese central bank continue.
Inequality Perceptions, Distributional Norms, and Redistributive Preferences in East and West Germany
Authors: Kuhn Andreas
Published: July 2012

This paper analyzes differences in inequality perceptions, distributional norms, and redistributive preferences between East and West Germany. As expected, there are substantial differences with respect to all three of these measures. Surprisingly, however, differences in distributional norms are much smaller than differences with respect to inequality perceptions or redistributive preferences. Moreover, individuals from East Germany tend to be more supportive of state redistribution and progressive taxation and they are less likely to have a conservative political orientation. I finally show that a substantial part of these differences in political preferences can be explained by underlying differences in redistributive preferences.
Unexpected outcomes of invasive predator control
Authors: Garnett S. T.
Published: July 2012

Read the Feature Paper: Unexpected outcomes of invasive predator control: the importance of evaluating conservation management actions

Other Commentaries on this paper: Evidence, models, conservation programs and limits to management

Response from the authors: Integrating research, monitoring and management into an adaptive management framework to achieve effective conservation outcomes
Improved survival in cerebral palsy in recent decades?
Authors: Strauss David , Rosenbloom Lewis , Shavelle Robert , Brooks Jordan
Published: July 2012

This letter is commented on by Reid et al. on page 867‐868 of this issue
Vagus nerve stimulation in children with intractable epilepsy
Authors: PRESSLER RONIT M
Published: July 2012

This commentary is on the original article by Klinkenberg et al. on pages 855‐861 of this issue.
Combined effects of climate and management on plant diversity and pollination type in alpine grasslands
Authors: Hoiss Bernhard , Gaviria Julian , Leingärtner Annette , Krauss Jochen , Steffan‐Dewenter Ingolf
Published: July 2012

Aim

Climate and habitat management are two key drivers for patterns of biodiversity, but little is known about relative importance, interactions and nonlinear effects of climate and management on species richness and trait variation of plants.

Location

Alps (Germany).

Methods

We studied patterns of species richness and pollination types in 34 alpine grasslands along an altitudinal climatic gradient comparing grazed, mown and non‐managed grasslands. Two vegetation assessments were conducted in 2009 on ten 4‐m² plots per study site and per survey.

Results

In total, 484 vascular plant species were recorded. Species richness peaked at intermediate temperatures and was highest in grazed grasslands compared with mown and non‐managed grasslands. No significant interaction between management effects and climate was found. Species richness of insect‐pollinated plants peaked at lower temperatures (higher altitudes) than species richness of wind‐pollinated plant species. The proportion of wind‐pollinated plants decreased with decreasing temperature, but the vegetation cover of wind‐pollinated plants increased with decreasing temperature.

Main conclusions

Our results indicate that managing alpine grasslands by extensive grazing maintains high plant diversity over the full subalpine gradient. Rising temperatures with climate change and an upward shift of the diversity peak of plants might result not only in reduced overall diversity because of reduced grassland area at higher altitudes but also in changed species composition and adaptive potential of pollination types.
The geopolitics of Buddhist reincarnation: contested futures of Tibetan leadership
Authors: McConnell Fiona
Published: July 2012

In attending to a religion and a region often overlooked in critical geopolitics, this paper examines the intersections between issues of legitimacy, agency and authority, and the case of Tibetan Buddhism. Buddhist values and political policies are deeply intertwined in the Tibetan case, to the extent that the political philosophy of Tibet – both prior to 1959 and in exile – is chos srid gnyis ldan, or ‘religion and politics combined’. Central to this conflation has been the figure of the Dalai Lama who, since 1642, has been the spiritual and political leader of Tibet. However, in March 2011, the current and 14th Dalai Lama declared his retirement from political life and devolution of political power to the directly elected exile Prime Minister (Kalon Tripa). Six months later, His Holiness issued a statement on the future of his own successor, declaring that he has the ‘sole legitimate authority’ over the reincarnation of the next Dalai Lama. Within days the Chinese Government responded by declaring that ‘the title of Dalai Lama is conferred by the central government and is illegal otherwise’. In historically contextualising and critically analysing these recent events, this paper challenges conventional transpositional mappings of secular modernity and religious traditionalism onto the Chinese and Tibetan leadership respectively. It concludes by making the case for a more sustained critical geopolitical engagement with Buddhist communities, leaders and politics.
Evaluation of lidocaine treatment on frequency of cardiac arrhythmias, acute kidney injury, and hospitalization time in dogs with gastric dilatation volvulus
Authors: Bruchim Yaron , Itay Srugo , Shira Ben‐Halevy , Kelmer Efrat , Sigal Yudelecitch , Itamar Aroch , Gilad Segev
Published: July 2012

Objective

To assess the efficacy of IV lidocaine in decreasing complication rate and improving the outcome in dogs with gastric dilatation volvulus (GDV).

Design

Prospective non‐controlled study of 83 lidocaine‐treated dogs with GDV compared to 47 untreated historical controls with GDV.

Setting

University veterinary teaching hospital.

Animals

One hundred and thirty client‐owned dogs with naturally occurring GDV.

Interventions

Study group dogs were treated at presentation with lidocaine (2 mg/kg, IV bolus) followed by constant rate infusion (CRI) of 0.05 mg/kg/min for 24 h. Historical control dogs did not receive any lidocaine.

Measurements and Main Results

There were no group differences in age, body weight, time lag from onset of clinical signs to presentation, rectal temperature and pulse rate at presentation, and proportion of gastric wall necrosis. The proportions of cardiac arrhythmias and acute kidney injury (AKI) were significantly (P< 0.001 andP= 0.045,respectively) lower in the lidocaine group (10/83 [12%] versus 18/47 [38.3%] and 3/83 [3.6] versus 0/47). Median hospitalization time period was shorter (P= 0.05) in the lidocaine group compared to the controls (median 48 h; range 24–360 h versus median 72 h; range 24–144 h, respectively).

Conclusion and Clinical Relevance

Early treatment with IV lidocaine bolus, followed by CRI of lidocaine for 24 h post presentation decreased the occurrence of cardiac arrhythmias, AKI and hospitalization time period significantly in lidocaine‐treated dogs with GDV compared to untreated historical controls. Due to the nonblinded, placebo‐uncontrolled, nonrandomized nature of the current study, further evaluation of the efficacy of lidocaine in dogs with GDV is warranted.
The effects of intracerebroventricularly administered noradnamine and other sympathomimetic amines upon leptazol convulsions in mice
Authors: JONES B. J. , ROBERTS D. J.
Published: July 2012

The influence of some intracerebroventricularly administered sympathomimetic amines on leptazol‐induced convulsions has been investigated.

Noradnamine and high doses of dopamine proved to be anticonvulsant and also antagonized the facilitative effects of reserpine.

Noradrenaline and octopamine also antagonized reserpine‐induced facilitation but were without effect on leptazol alone; by contrast tyramine and small doses of dopamine lowered the threshold for leptazol convulsions.

A possible interpretation of these results is presented.
Antagonism by fenamates and like‐acting drugs of bronchoconstriction induced by bradykinin or antigen in the guinea‐pig
Authors: COLLIER H. O. J. , JAMES G. W. L. , PIPER PRISCILLA J.
Published: July 2012

Nine non‐steroidal anti‐inflammatory drugs were tested for antagonism of bradykinin‐induced bronchoconstriction in guinea‐pig lungs in vivo. Only one, benzydamine, was inactive.

The descending order of potency of the active anti‐inflammatory drugs was meclofenamate = Scha 306>Scha 87/2>indoxole>Mi85>indomethacin>glafenine>ibufenac.

Of eight other drugs tested, chlorpromazine, phenoxybenzamine and four others were inactive, whereas phenelzine and mebanazine possessed activity.

In tests at two dose‐levels of meclofenamate, the dose‐ratio of bradykinin increased proportionately with the dose of meclofenamate.

The anti‐bradykinin effect of meclofenamate was still observed after destruction of the brain and spinal cord, after bilateral adrenalectomy or after blockade of β‐receptors for adrenaline.

Meclofenamate did not release catecholamines from the adrenal medulla or prevent such a release by bradykinin given intra‐arterially.

The fenamates and like‐acting drugs reduced the intensity of anaphylactic bronchoconstriction in guinea‐pigs treated with mepyramine or propranolol. The descending order of potency was meclofenamate>flufenamate>mefenamate.

Dose/response curves for the antagonism of anaphylactic bronchoconstriction by the fenamates, in the presence of propranolol, turned downwards at high doses.

These findings suggest that the fenamates may find a useful place in the treatment of bronchial asthma or other conditions involving allergic ventilatory impairment.
The action of acetylcholine and other drugs on the efflux of potassium and rubidium from smooth muscle of the guinea‐pig intestine
Authors: BURGEN A. S. V. , SPERO L.
Published: July 2012

A method is described for measuring continuously the efflux of potassium or rubidium from smooth muscle of the guinea‐pig.

Muscarinic drugs cause at maximum a 100‐fold increase in the efflux rate, due to a direct increase in permeability and only to a minor extent secondary to depolarization. With acetylcholine the dose response curve for producing efflux is displaced to 1,000 times higher concentrations than that for contraction.

The shift varies with different agonists. The efflux and contractile responses to agonists are antagonized to an equivalent extent by atropine and several other reversible antagonists but benzhexol has a relatively greater effect on efflux. An estimate of spare receptors was obtained with benzilylcholine mustard and was similar for both responses. Dibenamine and local anaesthetics led to a parallel shift of the contraction dose response curve but a depression without shift in the efflux response.

The most satisfactory explanation of these results is that there are two types of the muscarinic receptor in the smooth muscle of the guinea‐pig intestine.
Comparison of the effects of I.C.I. 50172 and propranolol on the cardiovascular responses to adrenaline, isoprenaline and exercise
Authors: BRICK I. , HUTCHISON K. J. , McDEVITT D. G. , RODDIE I. C. , SHANKS R. G.
Published: July 2012

The intravenous infusion of I.C.I. 50172 in doses up to 20 mg reduced, although not significantly, the increase in heart rate produced by the infusion of isoprenaline in healthy volunteers; the response to adrenaline was significantly reduced. The infusion of 1 mg propranolol abolished these responses

After the pre‐treatment of subjects with atropine or hexamethonium, I.C.T. 50172 produced a significant reduction in an isoprenaline tachycardia. This reduction was not competitive and did not exceed 50%.

The intravenous injection of 4 mg I.C.I. 50172 reduced an exercise tachycardia; its effect was less than that of 4 mg propranolol. This difference became greater as the doses of the two drugs were increased. The dextro isomer of propranolol had no effect on the exercise tachycardia; I.C.I. 45763 reduced it to the same extent as propranolol.

The intravenous injection of I.C.I. 50172 reduced the increase in heart rate produced by tilting a normal subject from the supine to 80° head‐up position. After the administration of atropine, I.C.I. 50172 almost abolished the response. In the presence of atropine, I.C.I. 50172 was as active as propranolol in reducing the increase in heart rate on tilting.

The reason for the differences in the effects of I.C.I. 50172 on the increases in heart rate brought about by the three procedures is not clear.

The increase in forearm blood flow produced by the infusion of isoprenaline into the brachial artery was not reduced by the intra‐arterial administration of I.C.I. 50172.
The assay of anti‐pyretic drugs in mice, using intracerebral injection of pyretogenins
Authors: CASHIN C. H. , HEADING CHRISTINE E.
Published: July 2012

A simple, cheap, and reliable method is described for the screening of new compounds for anti‐pyretic activity. It involves the intracerebral injection of a suitable pyretogenin in conscious mice.

The pyretic response is related to the logarithm of the dose in a substantially linear manner when “E” Pyrogen is used.

A selection of established anti‐pyretic drugs were effective in oral doses approaching those used clinically, which shows that the method is unusually sensitive.

The response to intracerebral pyretogenin is not unduly influenced by drugs known to cause hypothermia.

It is suggested that “E” Pyrogen injected intracerebrally has a direct effect on the central nervous system, rather than an indirect action through release of endogenous pyrogen.
Taloximine, a new respiratory stimulant with bronchodilator properties
Authors: DALY M. J. , LIGHTOWLER J. E. , PICKERING R. W.
Published: July 2012

A novel phthalazine analogue taloximine (1‐hydroxyimino‐4(2‐dimethylaminoethoxy)‐1, 2‐dihydrophthalazine monohydrochloride monohydrate) stimulated respiration in conscious rabbits at doses of 7 mg/kg and above.

Taloximine antagonized the depressant action of morphine on respiration in rabbits at doses of 10 mg/kg. At high doses it resuscitated rabbits after they had been given lethal doses of sodium pentobarbitone.

In in vitro preparations of the trachea or bronchus taloximine was about equiactive with aminophylline. In the Konzett‐Rössler preparation the intravenous ED50 for taloximine was about 18% of that of aminophylline, whereas after oral administration the two drugs were equiactive.

Taloximine, unlike aminophylline, did not protect guinea‐pigs against anaphylactic microshock to egg albumen.

Taloximine shortened the duration of the loss of righting reflex in mice due to hexobarbitone more effectively than bemegride, nikethamide or vanillic acid diethylamide.

In the dose required to stimulate respiration taloximine had only slight cardiovascular effects. Up to four times this dose produced no evidence of general excitation of the central nervous system.
Relationship between the uptake, binding and pharmacological action of procaine in the isolated heart
Authors: BOULLIN D. J. , SULLIVAN T. J.
Published: July 2012

The uptake, efflux and pharmacological actions of procaine hydrochloride were studied on isolated hearts of female guinea‐pigs. The hearts were perfused with Krebs solution containing 14C‐procaine (0.1–500 μg/ml.) by the Langendorff technique at 37° C, using a constant flow pump. Hearts and cardiac effluent were assayed for procaine by liquid scintillation spectrometry.

Accumulation of procaine did not appear to involve active transport mechanisms for the following reasons. The rate of procaine uptake was most rapid at the highest perfusion concentration (500 μg/ml.), when it was three times faster than at the lowest concentration (0.1 μg/ml.); it was not affected by lowering the temperature to 3° C. The ratio of the concentration of procaine in the heart to the concentration in the perfusing fluid decreased with increasing concentration in the perfusion fluid.

When the efflux of 14C‐procaine from hearts previously perfused with procaine‐containing Krebs solution for 10 min was compared with the efflux of 14C‐inulin, the patterns of efflux of both compounds were similar, and showed at least two exponential components. At the highest concentration of procaine (500 μg/ml.) the efflux of procaine was more rapid than that of inulin.

A relationship was found between the pharmacological action of procaine, the rate of uptake and the level of procaine in the heart. When the procaine‐containing perfusion fluid was changed to a procaine‐free solution, the heart rate increased rapidly, and there was a rapid decline in the levels of procaine in the hearts.

It is concluded that guinea‐pig hearts accumulate procaine by a passive diffusion process, and that the pattern and rate of efflux indicate that the drug is loosely bound. If it is permissible to extrapolate from these findings to the antiarrhythmic effect in man, the short duration of its action may be due to loose binding rather than to rapid metabolic inactivation.
Metabolism and excretion of 3‐hydroxyphenyltrimethylammonium and neostigmine
Authors: HUSAIN M. A. , ROBERTS J. B. , THOMAS B. H. , WILSON A.
Published: July 2012

Carbon‐14 labelled 3‐hydroxyphenyltrimethylammonium (3‐OH PTMA), an active metabolite of neostigmine, has been given to rats by intramuscular injection and its excretion, distribution and metabolism have been studied.

A method is described for the separation and estimation of free and conjugated 3‐OH PTMA in urine and liver.

In the first hour, about 20% of a dose is excreted in the urine as free 3‐OH PTMA and thereafter the rate of excretion of glucuronide conjugate exceeds that of free 3‐OH PTMA. In 24 hr 76.8% of the dose is excreted in urine mainly as the conjugate.

The peak concentration of radioactivity in blood occurs within 30 min and in liver within 1 hr after administration. More than 90% of the radioactivity in liver occurs as the glucuronide conjugate. Relatively high concentrations of radioactivity were found in liver and heart.

In the hen 3‐OH PTMA is rapidly excreted by renal tubular secretion.

Experiments with carbon‐14 labelled neostigmine show that up to 1 hr mainly unchanged neostigmine is excreted in urine; thereafter increasing amounts of free 3‐OH PTMA and its glucuronide conjugate are excreted.

It is concluded that the duration of action of neostigmine is determined by its rapid renal excretion and by its metabolism to the glucuronide conjugate of 3‐OH PTMA.
Interactions of ouabain and noradrenaline in isolated rabbit's atria
Authors: TODA N.
Published: July 2012

The present study was made using sympathetic nerve‐atria preparations, conventional atrial preparations and left atria isolated from rabbits in order that interactions of ouabain and noradrenaline on the transmembrane potential of S‐A nodal pacemaker fibres, the pacemaker rate and the contractile force of the left atrium could be investigated.

In pacemaker action potentials, the maximal diastolic potential was decreased, the early repolarization was accelerated and the late repolarization was slowed by toxic concentrations of ouabain. Oscillating potentials of the diastolic pacemaker membrane were produced.

Stimulation of the postganglionic sympathetic nerve caused an increase in the slope of diastolic depolarization, resulting in an acceleration of the pacemaker rate. In the presence of ouabain, the pacemaker action potential configuration was significantly altered by nerve stimulation in preparations which showed ouabain‐induced bradycardia, but the potential configuration was not changed by nerve stimulation in preparations which showed ouabain‐induced tachycardia. Cardiac noradrenaline altered the ion permeability of the cardiac pacemaker membrane during diastole, but it had no effect during systole. Sympathetic nerve stimulation transiently corrected the overshoot and the repolarization of atrial action potentials altered by toxic concentrations of ouabain.

The positive chronotropic effect of sympathetic nerve stimulation was not affected by either therapeutic or toxic concentrations of ouabain. Ouabain shifted the concentration‐chronotropic response curve for exogenous noradrenaline to the left, but did not shift the curve for tyramine.

Relationship between the developed tension and the rate of contraction was altered differently by ouabain and by noradrenaline. The positive inotropic effect of noradrenaline was not significantly altered by therapeutic concentrations of ouabain but it was inhibited by toxic concentrations.
The effects of saxitoxin and tetrodotoxin on nerve conduction in the presence of lithium ions and of magnesium ions
Authors: EVANS M. H.
Published: July 2012

It has been shown that nerve fibres from rat cauda equina will conduct action potentials after immersion in saline in which lithium chloride is substituted for sodium chloride.

Both saxitoxin and tetrodotoxin inhibit lithium‐generated action potentials. The concentration of toxin needed to inhibit the lithium‐generated action potentials is similar to that needed to inhibit sodium‐generated action potentials.

If magnesium chloride is added to the saline to give a concentration of 10–15 mm there is usually a slight fall in amplitude of the compound action potential. Saxitoxin and tetrodotoxin now inhibit the action potential to a greater degree than in the absence of magnesium ions.
Glycol metabolites of noradrenaline in brain tissue
Authors: SHARMAN D. F.
Published: July 2012

A gas chromatographic method using electron capture detection is described for the estimation of those catecholamines and their metabolites which possess one or two free alcoholic hydroxyl groups. It is based on acetylation of phenolic hydroxyl and primary and secondary amino groups in aqueous solution, extraction into a water immiscible solvent and esterification of alcoholic hydroxyl groups with heptafluorobutyric anhydride.

The method has been successfully applied to the detection and estimation of free 4‐hydroxy‐3‐methoxyphenylethylene glycol (MOPEG) and free 3,4‐dihydroxyphenylethylene glycol (DOPEG) in hypothalamic brain tissue.

Although it was possible to measure noradrenaline and normetanephrine by the same method in pure solution, crude tissue extracts could not be used, despite their suitability for estimating the glycol metabolites.
Actions of adrenaline on the potassium balance of the isolated heart
Authors: STAFFORD ANNE
Published: July 2012

The action of adrenaline on the K+ balance of the isolated heart was found to depend on the ionic composition and the temperature of the perfusion fluids used.

When the perfusion fluid contained 145 mm Na+, 1·7 mm Ca++ and 3–9 mm K+, adrenaline caused the hearts to gain K+; when the K+ concentration was reduced to 1·2 mm, adrenaline caused a loss of K+. Both were actions on β receptors.

When the Ca++ or the Na+ concentration in the perfusion fluid was reduced, together with a reduction in K+, adrenaline no longer produced K+ loss from the hearts, but produced a gain of K+.

When the temperature of the perfusion fluid was reduced to 25° C, adrenaline still produced a gain of K+ by hearts perfused with fluid containing 3·2 mm K+, but did not produce a loss of K+ from hearts perfused with fluid containing 1·2 mm K+.
Liberation of a bradykinin‐like substance in the circulating blood of dogs by trypsin, chymotrypsin and nagarse
Authors: FERREIRA S. H. , SILVA M. ROCHA E
Published: July 2012

Using the blood‐bathed organ technique with cat jejunum as the test organ, it was shown that kinin was regularly released by infusions of trypsin, chymotrypsin and nagarse into the blood supervising the tissue or into the jugular vein of dogs.

Intravenous injections of the three enzymes, in doses which did not change plasma bradykininogen (BKG) level, induced generation of kinin in the circulating blood.

Nagarse in kinin‐liberating concentrations did not liberate angiotensin in the circulating blood.

The responses of the cat jejunum strip, and the systemic hypotension induced by the three enzymes, were enhanced by treatment of the dog with a bradykinin potentiator.

Injection of the enzymes in the blood perfused hind leg of the dog caused a fall in the vascular resistance. In this preparation, bradykinin potentiating factor (BPF) potentiated trypsin, but not the effects of chymotrypsin and nagarse injections.

It is suggested that the blood pressure lowering effect of low doses of trypsin is due mainly to kinin release. Chymotrypsin and nagarse, in addition to having a direct action on the vascular smooth muscles, also have indirect hypotensive effects due to the liberation of kinin.
The action of certain haloalkylamines on some biological activities of bradykinin
Authors: AL‐KATIB H. A. , BABA W. I.
Published: July 2012

Bradykinin and histamine reduced the blood pressure in normotensive anaesthetized rabbits. They produced a pressor or biphasic response when the initial arterial pressure was lowered by acute haemorrhagic shock or mecamylamine blockade. When blood pressure was lowered by pretreatment with reserpine, bradykinin remained depressor and histamine produced a biphasic response.

Phenoxybenzamine abolished the pressor responses to bradykinin and histamine, but potentiated and prolonged the depressor response to bradykinin.

Phenoxybenzamine‐OH and SY28‐OH modified neither the pressor nor depressor responses to histamine, nor the pressor response to bradykinin. However, they greatly potentiated and prolonged the hypotensive effect of bradykinin.

In the isolated rabbit ear preparation, the initial vascular tone influenced the responses to bradykinin and histamine. In preparations having low vascular tone they were vasoconstrictors, but when the tone was raised by angiotensin or noradrenaline, they were vasodilatators.

Phenoxybenzamine blocked the vasconstrictor effect of bradykinin in a rabbit ear preparation having low vascular tone and phenoxybenzamine or its related ethanolamine potentiated the vasodilator response to bradykinin in preparations in which the tone was high.

The significance of these findings is discussed.
3H‐Nicotine in cat superior cervical and nodose ganglia after close‐arterial injection in vivo
Authors: BROWN D. A. , HOFFMANN P. C. , ROTH L. J.
Published: July 2012

Concentrations of 3H‐nicotine in the superior cervical and nodose ganglia of anaesthetized cats were measured after close‐arterial injection.

Shortly after injection there was a higher concentration of 3H‐nicotine in the superior cervical ganglion than in the nodose ganglion. Mean concentration ratios, superior cervical ganglion/nodose ganglion (S/N ratios) were: 2 min after injection, 1.60 ± 0.19; 4 min, 1.21 ± 0.19; 8 min, 0.92 ± 0.05. These ratios were independent of the dose of nicotine over the range 4 to 200 μg in 0.2 ml.

There was no comparable difference in the concentrations of injected 14C‐inulin or 3H2O in the two ganglia, or in total water content.

Procedures which reduced the pharmacological action of nicotine (pre‐treatment with hexamethonium, admixture of 14C‐inulin) tended to reduce the S/N ratio for nicotine.

Autoradiographs showed that nicotine entered the neurones of both superior cervical and nodose ganglia.

It was concluded that the higher concentration of nicotine in the superior cervical ganglion was probably related to its selective pharmacological action at this site, and may have been due to a greater intracellular retention of nicotine.
An uptake of radioactivity from (±)‐3H‐isoprenaline and its inhibition by drugs which potentiate the responses to (—)‐isoprenaline in the guinea‐pig isolated trachea
Authors: FOSTER R. W.
Published: July 2012

The uptake of radioactivity derived from (±)‐3H‐isoprenaline by the guinea‐pig isolated trachea has been measured, and the assumption is made that all the radioactivity is due to isoprenaline.

40% of the total (±)‐3H‐isoprenaline taken up was loosely bound to the tissue while 25% was firmly bound.

The firmly bound component of the uptake was more susceptible to inhibition by drugs than the loosely bound component.

Desipramine and cocaine did not reduce the accumulation of firmly bound isoprenaline.

Cooling to 23° C, guanethidine and phentolamine caused a moderate reduction in the accumulation of firmly bound isoprenaline.

Phenoxybenzamine and (±)‐metanephrine caused a highly significant reduction in the accumulation of firmly bound isoprenaline.

These findings are discussed in relation to previous studies of the uptake of isoprenaline and of other processes which may be related.

The inhibition of uptake by the agents examined correlated with their potentiation of the action of (—)‐isoprenaline found previously.

It is suggested that a tissue uptake can significantly modify the pharmacological response to isoprenaline in vitro.
Intra‐hepatic vascular response to sodium nitrite
Authors: GEUMEI AIDA , ISSA I. , MAHFOUZ M.
Published: July 2012

In the perfused liver of the dog, sodium nitrite produced vasoconstriction in the hepatic arterial bed and, particularly, in the portal venous vascular bed.

These effects on the hepatic vasculature may account in part for the reduction of venous return and diminution in cardiac output recorded by other workers, and may therefore be a factor in the clinical efficacy of the nitrites in angina pectoris.
Possible protective action of antialdosterone compounds in myocardial necrosis in rats
Authors: MOUDGIL LALTA RANI
Published: July 2012

Experimental myocardial necrosis was produced in rats by injection of large doses of isoprenaline.

The effectiveness of four aldosterone antagonists in preventing this myocardial necrosis was studied.

The relative effectiveness of these compounds in preventing isoprenaline‐induced necrosis was found to be Sc 5233>Sc 9420 (spironolactone)>Sc 11927 and Sc 8109.

The reported relative effectiveness of these compounds as aldosterone antagonists is Sc 11927>Sc 9420, Sc 8109>Sc 5233.

The significance of these findings is discussed.
Histochemical fluorescence studies on noradrenaline accumulation by Uptake2in the isolated rat heart
Authors: CLARKE D. E. , JONES C. J. , LINLEY P. A.
Published: July 2012

. The distribution of noradrenaline accumulated by Uptake2(Iversen, 1965) in the isolated perfused rat heart has been observed using histochemical fluorescence microscopy.

. On the basis of the technique used, noradrenaline seems to be predominantly associated with the cardiac muscle cells, but sympathetic nerves and other cardiac structures also serve as retention sites.

. Phenoxybenzamine, normetanephrine and perfusion with noradrenaline at 20° C all decreased noradrenaline accumulation.

. Lowered temperature significantly increased the perfusion pressure and significantly decreased the [14C]‐sorbitol space in perfused hearts.

. The implications of these results are discussed.
Actions of phenylephrine on β‐adrenoceptors in guinea‐pig trachea
Authors: CHAHL LORIS A. , O'DONNELL STELLA R.
Published: July 2012

. Phenylephrine produced relaxation of the isolated guinea‐pig tracheal chain preparation, its potency being 1/5 that of noradrenaline on normal tissues.

. The potentiation of phenylephrine by cocaine (10−5M) was only slight. Thus on cocaine‐treated tissues phenylephrine was 1/45 as potent as noradrenaline.

. The dose‐response lines to phenylephrine were shifted in a parallel manner by propranolol 10−8M and 10−7M, suggesting that the relaxations were mediated through β‐adrenoceptors.

. Phenylephrine had a lower intrinsic activity than the catecholamines and produced multiphasic dose‐response lines at the higher doses used in the presence of propranolol (10−6M). These observations have been explained by the evidence obtained that phenylephrine is a partial agonist with β‐adrenoceptor blocking activity.

. From experiments using α‐adrenoceptor blocking drugs, it has been concluded that stimulation of α‐adrenoceptors has little influence on the β‐adrenoceptor relaxation to phenylephrine on the guinea‐pig tracheal chain preparation.
Studies on the peripheral pharmacology of fenazoxine, a potential antidepressant drug
Authors: BASSETT J. R. , CAIRNCROSS K. D. , HACKET N. B. , STORY MARGOT
Published: July 2012

. The action of fenazoxine, a cyclized analogue of orphenadrine, has been studied on peripheral tissues innervated by adrenergic and cholinergic nerves. The hypothesis that cyclization of the alkyl amino chain of orphenadrine results in a molecule which retains the noradrenaline sensitizing action of orphenadrine but lacks the antimuscarinic activity has been investigated.

. The antimuscarinic activity of fenazoxine, on guinea pig ileum, was approximately 1/30 that of orphenadrine.

. Fenazoxine, desmethylimipramine and cocaine potentiated the response to noradrenaline and sympathetic nerve stimulation on the cat nictitating membrane, isolated rabbit ear artery and isolated driven atrial strip preparations.

. On the driven atrial strip preparation, fenazoxine at concentrations of 5 × 10−7M and 1 × 10−6M produced a small potentiation of the inotropic response to isoprenaline. At 5 × 10−6M and 5 × 10−5M fenazoxine antagonized the inotropic response to tyramine.

. Chronic denervation of the cat nictitating membrane abolished the potentiating action of fenazoxine.

. The results presented suggest that fenazoxine inhibits the uptake of catecholamines in a manner similar to that reported for desmethylimipramine and cocaine.

. Evidence is also presented which suggests that fenazoxine, like desmethylimipramine, possesses anti‐noradrenaline activity at higher concentrations.
Effects of ganglion blocking agents on nicotine extensor convulsions and lethality in mice
Authors: ACETO M. D. , BENTLEY H. C. , DEMBINSKI J. R.
Published: July 2012

. The ganglion blocking agents, chlorisondamine, pentamethonium, mecamylamine, decamethonium and hexamethonium all block nicotine extensor convulsions when administered intraventricularly in mice. Tetraethylammonium was inactive.

. For the intraventricular route, there is a relationship between ganglionic blocking potency and blocking of nicotine extensor convulsions. Indirect evidence suggests that the site(s) of action of nicotine extensor convulsions and lethality is central in origin and associated with brain areas near the ventricles.

. When ganglion blocking agents are given orally, subcutaneously or intravenously varying degrees of protection can be observed probably depending on factors such as whether or not the drugs cross the blood‐brain barrier, absorption, etc., and the effectiveness in protecting mice from nicotine is not related to ganglionic blocking potency.

. Atropine and morphine given intraventricularly or subcutaneously did not protect mice from the LD95 of nicotine. Chlorpromazine gave very erratic results and phenobarbitone was effective subcutaneously and to a lesser extent intraventricularly.