bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of hepatitis C on survival in dialysis patients: a link with cardiovascular mortality?
Authors: Fabrizi F. , Dixit V. , Messa P.
Published: July 2012

Summary.  Recent evidence has been accumulated showing that anti‐HCV‐positive serologic status is significantly associated with lower survival in dialysis populations, but the mechanisms underlying this negative relationship are still unclear. The aim of this study was to conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus (HCV) infection on all‐cause and disease‐specific mortality of patients on regular dialysis. The relative risk of all‐cause, cardiovascular and liver disease‐related mortality was regarded as the most reliable outcome end‐point. Study‐specific relative risks were weighted by the inverse of their variance to obtain fixed‐ and random effect pooled estimates for mortality with HCV across the published studies. We identified fourteen observational studies involving 145 608 unique patients on long‐term dialysis. Pooling of study results demonstrated that anti‐HCV antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for adjusted relative risk (all‐cause mortality) was 1.35 with a 95% confidence interval (CI) of 1.25–1.47. Stratified analysis showed that the adjusted RR for liver disease‐related death was 3.82 (95% CI, 1.92; 7.61); heterogeneity statistics, Ri = 0.58 (P‐value by Q‐test = 0.087). The adjusted RR for cardiovascular mortality was 1.26 (95% CI, 1.10; 1.45); no heterogeneity was found (NS). This meta‐analysis of observational studies indicates that anti‐HCV‐positive patients on dialysis have an increased risk of either liver or cardiovascular disease‐related mortality compared with anti‐HCV‐negative patients. Further studies are in progress to understand better the link between HCV and cardiovascular risk among patients on maintenance dialysis.
Loss of floral polymorphism in heterostylous Luculia pinceana (Rubiaceae): a molecular phylogeographic perspective
Authors: ZHOU WEI , BARRETT SPENCER C. H. , WANG HONG , LI DE‐ZHU
Published: July 2012

Both deterministic and stochastic forces determine the representation and frequency of floral morphs in heterostylous plant populations. Phylogeographic analysis of molecular variation can provide information on the role of historical factors, including founder events, in affecting population morph structure. Here, we investigate geographical patterns of floral morph variation in a distylous shrub Luculia pinceana (Rubiaceae) by examining the relations between floral polymorphism and molecular (cpDNA and microsatellite) variation in 25 populations sampled throughout the distribution of the species in southwest China and adjacent countries. In 19 of the 25 populations, the frequency of floral morphs was not significantly different from the expected 1:1 ratio. The remaining populations were either L‐morph biased (2) or monomorphic (4) for this form and were morphologically differentiated from the remaining populations in several floral traits, that is, corolla tube length, sex organ position and stigma‐anther separation. Phylogeographic analysis supports the hypothesis that L. pinceana was initially split into west‐central and eastern lineages in the Early Pleistocene (∼1.982 Mya). A centrally located lineage composed of morph‐biased and monomorphic populations appears to have been subsequently derived from the west‐central lineage, perhaps by a founder event after the last glacial maximum. Hypotheses to explain why these populations have not returned to equilibrium morph frequencies are considered.
The efficiency of C4 photosynthesis under low light conditions in Zea mays, Miscanthus x giganteus and Flaveria bidentis
Authors: UBIERNA NEREA , SUN WEI , KRAMER DAVID M. , COUSINS ASAPH B.
Published: July 2012

The efficiency of C4 photosynthesis in Zea mays, Miscanthus x giganteus and Flaveria bidentis in response to light was determined using measurements of gas exchange, 13CO2 photosynthetic discrimination, metabolite pools and spectroscopic assays, with models of C4 photosynthesis and leaf 13CO2 discrimination. Spectroscopic and metabolite assays suggested constant energy partitioning between the C4 and C3 cycles across photosynthetically active radiation (PAR). Leakiness (φ), modelled using C4 light‐limited photosynthesis equations (φmod), matched values from the isotope method without simplifications (φis) and increased slightly from high to low PAR in all species. However, simplifications of bundle‐sheath [CO2] and respiratory fractionation lead to large overestimations of φ at low PAR with the isotope method. These species used different strategies to maintain similar φ. For example, Z. mays had large rates of the C4 cycle and low bundle‐sheath cells CO2 conductance (gbs). While F. bidentis had larger gbs but lower respiration rates and M. giganteus had less C4 cycle capacity but low gbs, which resulted in similar φ. This demonstrates that low gbs is important for efficient C4 photosynthesis but it is not the only factor determining φ. Additionally, these C4 species are able to optimize photosynthesis and minimize φ over a range of PARs, including low light.
Protective Effect of HLA‐DRB1*11 and Predisposition of HLA‐C*04 in the Development of Severe Liver Damage in Brazilian Patients with Chronic Hepatitis C Virus Infection
Authors: Marangon A. V. , Silva G. F. , de Moraes C. F. V. , Grotto R. M. T. , Pardini M. I. M. C. , de Pauli D. S. , Visentainer J. E. L. , Sell A. M. , Moliterno R. A.
Published: July 2012

The objective of this study was to investigate human leucocyte antigen (HLA) genes in patients chronically infected with hepatitis C virus (HCV) and to analyse the possible role of these genes in the progression of chronic hepatitis C. One hundred and forty‐five (145) Brazilian patients infected only with HCV genotype 1 were evaluated. HLA class I (A*, B*, C*) and class II (DRB1*, DQA1*, DQB1*) typing were carried out by PCR‐SSO, through Luminex technology. Associations were found with protection against development of liver damage by both DRB1*11 (5.0% versus 18.2%, P = 0.0016, OR = 0.23, CI 95% = 0.09–0.58; Pc=0.0208) and DRB1*11‐DQA1*05‐DQB1*03 haplotype (4.2% versus 15.3%, P = 0.0032; OR = 0.24, CI 95% = 0.08‐0.64). Liver damage was associated with HLA‐C*04 in patients with <20 years of infection (38.4% versus 9.1%, P = 0.002, OR = 6.25, CI 95% = 1.97–19.7; Pc=0.0238). It is concluded that HLA alleles can influence the development of liver damage in HCV type‐1 chronically infected Brazilian patients.
Overweight and impaired insulin sensitivity present in growing cats
Authors: Häring T. , Haase B. , Zini E. , Hartnack S. , Uebelhart D. , Gaudenz D. , Wichert B. A.
Published: July 2012

Obesity is a growing problem in pets as well as in humans. Overweight and obesity are linked to insulin sensitivity and subsequently in older cats, to an increased risk of developing diabetes mellitus. In the experimental cat population of the Institute of Animal Nutrition of the Vetsuisse Faculty, University of Zurich, an overweight phenotype in intact cats younger than 1 year became evident. The aims of the present study were to determine whether an association between insulin sensitivity and body condition score (BCS) or feline body mass index (FBMI) is already present during young adulthood in these cats and to test the hypothesis that the phenotype lean/overweight is significantly associated with monthly body weight during the growing period. Therefore, 41 kittens from the mentioned cat breeding colony were studied. They were weighed weekly and checked monthly (third to eighth month after birth) for BCS and FBMI. At the age of 8 months, they were classified into an overweight and lean phenotype based on BCS on a scale of 9 (median; maximum and minimum: overweight male (6.4; 6.8; 6.0); overweight female (6.1; 6.2; 6.0); lean male (5.4; 5.7; 5.0); lean female (5.2; 5.6; 5.0). A significant association between the phenotype and body weight was obvious during the growing period from the third to the 8 months (p = 0.0001). At month 8, body fat content was measured by dual energy X‐ray absorptiometry and a glucose tolerance test to determine the insulin sensitivity index was performed. Insulin sensitivity was significantly associated with BCS (p = 0.0007) and body fat content (p < 0.0001) but not with sex (p = 0.61). Our data provide evidence that already in young intact cats; insulin insensitivity is significantly associated with BCS or a presumed phenotype lean/overweight.
A survey of long‐term terrestrial ecology studies in Australia
Authors: YOUNGENTOB K. N. , LIKENS G. E. , WILLIAMS J. E. , LINDENMAYER D. B.
Published: July 2012

Long‐term ecological studies (LTES) are critical for understanding and managing landscapes. To identify important research gaps, facilitate collaborations and communicate results, several countries have established long‐term ecological research networks. A few initiatives to create such a network in Australia have been undertaken, but relatively few published data exist on the current state of LTES in Australia. In this paper, we present the results of an online survey of terrestrial LTES projects sent to academic, government and non‐governmental organization‐based researchers across Australia. We asked questions pertaining to the focus, scope, support and outcomes of LTES spanning 7 years or longer. Based on the information reported from 85 Australian LTES, we: (i) identify the biomes, processes and species that are under‐represented in the current body of research; (ii) discuss important contributing factors to the successful development and survival of these projects; and (iii) make recommendations to help increase the productivity and influence of LTES across research, management and policy sectors.
Alpha2‐adrenergic receptor activation regulates cortical interneuron migration
Authors: Riccio Orbicia , Hurni Nicolas , Murthy Sahana , Vutskits Laszlo , Hein Lutz , Dayer Alexandre
Published: July 2012

Monoamines such as serotonin and dopamine have been shown to regulate cortical interneuron migration but very little is known regarding noradrenaline. Similarly to other monoamines, noradrenaline is detected during embryonic cortical development and adrenergic receptors are expressed in transient embryonic zones of the pallium that contain migrating neurons. Evidence of a functional role for the adrenergic system in interneuron migration is lacking. In this study we first investigated the expression pattern of adrenergic receptors in mouse cortical interneuron subtypes preferentially derived from the caudal ganglionic eminences, and found that they expressed different subtypes of adrenergic receptors. To directly monitor the effects of adrenergic receptor stimulation on interneuron migration we used time‐lapse recordings in cortical slices and observed that alpha2 adrenergic receptors (adra2) receptor activation inhibits the migration of cortical interneurons in a concentration‐dependent and reversible manner. Furthermore, we observed that following adra2 activation the directionality of migrating interneurons was significantly modified, suggesting that adra2 stimulation could modulate their responsiveness to guidance cues. Finally the distribution of cortical interneurons was altered in vivo in adra2a/2c‐knockout mice. These results support the general hypothesis that adrenergic dysregulation occurring during embryonic development alters cellular processes involved in the formation of cortical circuits.
Protective role of neuropeptide Y Y2 receptors in cell death and microglial response following methamphetamine injury
Authors: Gonçalves Joana , Ribeiro Carlos F. , Malva João O. , Silva Ana P.
Published: July 2012

It has been reported that the hippocampus is very susceptible to methamphetamine (METH) and that neuropeptide Y (NPY) is an important neuroprotective agent against hippocampal excitotoxicity. However, there is very little information regarding the role of the NPYergic system in this brain region under conditions of METH toxicity. To clarify this issue, we investigated the role of NPY and its receptors against METH‐induced neuronal cell death in hippocampal organotypic slice cultures. Our data show that NPY (1 μm) is neuroprotective in DG, CA3 and CA1 subregions via Y2 receptors. Moreover, the selective activation of Y1 receptors (1 μm [Leu31,Pro34]NPY) partially prevented the toxicity induced by METH in DG and CA3 subfields, but completely blocked its toxicity in the CA1 pyramidal cell layer. Regarding Y2 receptors, its activation (300 nm NPY13–36) completely prevented METH‐induced toxicity in all subregions analysed, which involved changes in levels of pro‐ and anti‐apoptotic proteins Bcl‐2 and Bax, respectively. Besides neuronal cell death, we also showed that METH triggers a microglial response in the mouse hippocampus which was attenuated by Y2 receptor activation. To better clarify the effect of METH and the NPY system on microglial cells, we further used the N9 microglial cell line. We found that both NPY and the Y2 receptor agonist were able to protect microglia against METH‐induced cell death. Overall, our data demonstrate that METH is toxic to both neurons and microglial cells, and that NPY, mainly via Y2 receptors, has an important protective role against METH‐induced cell death and microgliosis.
Cardiovascular effects of GLP‐1 and GLP‐1‐based therapies: implications for the cardiovascular continuum in diabetes?
Authors: Burgmaier M. , Heinrich C. , Marx N.
Published: July 2012

Diabet. Med. 30, 289–299 (2013)

Aims  Glucagon‐like peptide‐1 receptor agonists and inhibitors of dipeptidyl peptidase‐4 that increase glucagon‐like peptide‐1 plasma concentrations are current treatment options for patients with diabetes mellitus. As patients with diabetes are a high‐risk population for the development of a severe and diffuse atherosclerosis, we aim to review the potential action of these drugs on cardiovascular disease and to summarize the potential role of present glucagon‐like peptide‐1‐based therapies from a cardiologist’s point of view.

Methods  Using a PubMed/MEDLINE search without language restriction, studies were identified and evaluated in order to review the effects of glucagon‐like peptide‐1‐based therapy on different stages of the cardiovascular continuum.

Results  Recent experimental as well as clinical data suggest that dipeptidyl peptidase‐4 inhibitors and glucagon‐like peptide‐1 receptor agonists—in addition to their metabolic effects—may have beneficial effects on the cardiovascular continuum at multiple stages, including: (1) cardiovascular risk factors; (2) molecular mechanisms involved in atherogenesis; (3) ischaemic heart disease; and (4) heart failure. Furthermore, retrospective analysis suggested decreased cardiovascular events in patients with glucagon‐like peptide‐1‐based therapies.

Conclusion  There are ample data to suggest beneficial effects of glucagon‐like peptide‐1‐based therapies on the cardiovascular continuum and large‐scale clinical trials are warranted to determine whether these effects translate into improved cardiovascular endpoints in humans.
The paradox of energy equivalence
Authors: Isaac Nick J. B. , Storch David , Carbone Chris
Published: July 2012

Energy equivalence, the notion that population energy flux is independent of body mass, has become a key concept in ecology. We argue that energy equivalence is not an ecological ‘rule’, as claimed, but a flawed concept beset by circular reasoning. In fact, the independence of mass and energy flux is a null hypothesis. We show that our mechanistic understanding of size–density relationships (SDRs) follows directly from this null model and the assumption that energy limits abundance. Paradoxically, without this assumption energy equivalence has no meaning and we lack a mechanistic understanding forSDRs. We derive an expression for the strength (r2) ofSDRsunder the null model, which provides a framework within which to compare publishedSDRs. This confirms that tight correlations between mass and abundance are a trivial consequence of the span of body masses considered. Our model implies that energy flux varies by five to six orders of magnitude among similarly sized mammals and to a far greater extent in birds. We conclude that the energetic paradigm can be strengthened by considering alternative, non‐energetic, hypotheses.
Face to (Face)Book: The Two Faces of Social Behavior?
Authors: Ivcevic Zorana , Ambady Nalini
Published: July 2012

Social networking sites such as Facebook represent a unique and dynamic social environment.

Objective

This study addresses three theoretical issues in personality psychology in the context of online social networking sites: (a) the temporal consistency of Facebook activity, (b) people's awareness of their online behavior, and (c) comparison of social behavior on Facebook with self‐ and informant‐reported behavior in real life.

Method

Facebook Wall pages of 99 college students (mean age = 19.72) were downloaded six times during 3 weeks and coded for quantity and quality of activity. Everyday social interactions were assessed by self‐ and friend report.

Results

Facebook activity showed significant consistency across time, and people demonstrated awareness of their online behavior. There was significant similarity between everyday traits and interactions and Facebook behavior (e.g., more posts by friends are related to Agreeableness). Some differences between online and everyday interactions warrant further research (e.g., individuals with more positive offline relationships are less likely to engage in back‐and‐forth conversations on Facebook).

Conclusions

The results indicate substantial similarity between online and offline social behavior and identify avenues for future research on the possible use of Facebook to compensate for difficulty in everyday interactions.
Macroeconomic Determinants of Carry Trade Activity
Authors: Anzuini Alessio , Fornari Fabio
Published: July 2012

Carry trades—popular strategies in the foreign exchange market—are long positions in high interest rate currencies financed through funds borrowed from low interest rate currencies. It has been shown for a number of bilateral exchange rates vis‐à‐vis the US dollar that shocks to interest rate differentials foster carry trade activity and lead to significant changes in the foreign exchange level. This paper considers which (or which combination of) structural shocks can be consistent with the implications of such an interest rate differential shock that has been identified in previous studies. It is especially demand and confidence shocks, rather than supply or monetary policy shocks, which are found to generate effects similar to those produced by an unexpected widening of the interest rate differential and overall lead to longer‐term gains from carry trade activity. Also provided is a measure of the potential gain/losses experienced by the actual positioning of market participants in the foreign exchange futures and conditional on the knowledge of the macroeconomic shock that occurred at the time of positioning.
Productivity, Networks, and Export Performance: Evidence from a Cross‐country Firm Dataset
Authors: Ricci Luca Antonio , Trionfetti Federico
Published: July 2012

This paper uses a newly assembled multi‐country multi‐industry firm‐level dataset to test the effect of productivity and networking on the export probability of firms. Results are in line with the new‐new trade theory and with the literature on the information value of networks. Firms are more likely to export if they are more productive, larger, and if they benefit from foreign networks (ownership and financial linkages), domestic networks (chamber of commerce, links to regulation), and communication networks (E‐mail, internet). Firms bear a lower probability of exporting if they are affected by state ownership or unionization networks. Overall, firms with better network connections by one standard deviation enjoy a 15% higher probability of exporting.
Gated barriadas: Responses to urban insecurity in marginal settlements in Lima, Peru
Authors: Plöger Jörg
Published: July 2012

The explosive growth of so‐called marginal settlements in Latin America's cities has received considerable academic attention in past decades. The inability of the state to adequately provide affordable housing for a rapidly growing urban population has meant that these neighbourhoods relied on community mobilization to achieve common objectives of basic infrastructure and legal recognition. With increasing consolidation and less need for coordinated action, many local organizations lost their rationale. Fear of crime and violence, a major concern in Latin American metropolises, is inscribed on the urban landscape by a growing number of gated and fortified residential enclaves for the better‐off. Marginal neighbourhoods, however, experience a ‘security gap’ as they receive insufficient police protection and lack the financial resources to employ private guards. In many cases, the real or perceived insecurities of inner‐city life have prompted organized bottom‐up, mostly informal and sometimes vigilante, responses. Drawing on research on the rise of informal security‐related interventions in the neighbourhoods of Lima Metropolitana, Peru, this paper explores the rationales underlying the different approaches and adoptions, including the involvement of the main actors, community associations and other local interest groups.
Does Aid for Trade Enhance Export Performance? Investigating the Infrastructure Channel
Authors: Vijil Mariana , Wagner Laurent
Published: July 2012

There are few empirical studies assessing the effectiveness of aid for trade as regards trade performance. Furthermore, existing work does not test which are the channels through which aid for trade has an impact on trade performance. We address this question using a two‐step empirical analysis. Relying on an export performance model, we first test whether institutions and infrastructure, our two potential channels of transmission, are significant determinants of export performance. Second, we test the impact of aid for trade sectoral flows on the previously detected determinants of export performance. We show, as part of the first step, that the infrastructure channel is a highly significant determinant of export performance, whereas the institutional channel turns out to have a limited positive impact on developing countries’ export performance. Furthermore, we show, from the second step, that aid for infrastructure, once instrumented, has a strong and positive impact on the infrastructure level. As a result, we find that a ten per cent increase in aid for infrastructure commitments per capita in developing countries leads to an average 2.34 per cent increase in the exports over GDP ratio. It is also equivalent to a 2.71 per cent reduction in tariff and nontariff barriers. These results highlight the high potential impact of aid for trade on developing countries’ export performance throughout the infrastructure channel.
Trust and Insurance Markets1
Authors: Guiso Luigi
Published: July 2012

Trust is a key determinants of any financial transaction. Exchanges in insurance markets are a particular type of financial transaction where a current payment – the premium – is exchanged for a promise of a future, contingent payment – the indemnity due when the casualty occurs. We argue that trust is key in fostering these type of exchanges. Trust enters two ways: it affects the willingness of the company to supply insurance when the insured can cheat by claiming indemnities that are not due; it discourages people from purchasing insurance if they do not trust the company promise of readily paying the indemnity when due. We prove theoretically and empirically the relevance of trust in insurance exchanges and discuss policies to foster it.
Exploring the effects of non‐medical versus medical approaches to the management of skin aging in women over sixty
Authors: Tamburic S. , Grant‐Ross P. , Labedzka M. , Daniels G.
Published: July 2012

Synopsis

This study was a pilot project, set up to assess ageing skin using a multi‐disciplinary approach. The main aim of this study was to evaluate whether the use of more radical (‘medical’) treatments in the management of skin ageing would bring superior results and ultimately make people look younger, than the use of cosmetics (‘non‐medical’ treatments). A simple post‐hoc study design was used, whereby medical treatments varied within the group, all of them completed at least 2 weeks before the start of the study. In addition, it was of interest to assess the suitability of the proposed combination of methods. A total of 21 female participants were recruited for this study: 11 for the non‐medical and 10 for the medical group. The multi‐disciplinary approach consisted of instrumental measurements, self‐assessment, expert assessment by Merz scales and a public perception survey. The majority of nearly 70 sets of instrumental skin data obtained in this study did not differ significantly between the non‐medical and the medical group. However, the medical group gave higher self‐assessment scores for their faces. The scores for hands were lower than scores for faces by both groups. This was partly supported by instrumental data (lower skin hydration on hands than on the face). The findings of the public perception survey of nine matched pairs of subjects scored the non‐medical group as younger looking. Data analysis has shown that the judgement of youthfulness did not depend on either the gender or the age of observers.
Body mass dynamics during incubation and duration of parental care in Pacific Dunlins Calidris alpina pacifica: a test of the differential parental capacity hypothesis
Authors: Jamieson Sarah E.
Published: July 2012

Breeding is energetically expensive and individuals face a trade‐off between current and future breeding investment. Due to their production of large eggs, female birds are thought to have substantially higher initial energetic investments than males, which decrease the female's offspring rearing capacity. The differential parental capacity hypothesis argues that this large initial investment limits the ability of female shorebirds to provide extended parental care, which can ultimately lead to offspring desertion. This hypothesis predicts that (1) during early incubation females will be in poorer condition than males, (2) both sexes will lose condition during incubation, but the decline in females will be slower than the decline in males and (3) there will be a positive relationship between female condition and the duration of maternal brood care. These predictions were tested using data on body mass adjusted for body size (as a proxy for condition) and parental care from Pacific Dunlins Calidris alpina pacifica nesting on the Yukon Kuskokwim Delta, Alaska. None of the predictions received support: females were heavier than males in early incubation, the overall pattern during incubation was that males gained mass while female mass remained relatively constant, and there was no relationship between female mass and maternal brood care duration. These results suggest that the factors influencing parental care decisions are more complex than a parent simply caring until it is physiologically unable to do so.
SOME PHARMACOLOGICAL ACTIONS OF FOUR SYNTHETIC ANALOGUES OF OXYTOCIN
Authors: BERDE B. , DOEPFNER W. , KONZETT H.
Published: July 2012

Four structural analogues of oxytocin were investigated with regard to their oxytocic, milk‐ejecting, pressor and diuretic/antidiuretic effects. In three of them the isoleucyl group of oxytocin was replaced by a phenylalanyl, leucyl, or valyl residue; in the fourth the asparaginyl group was replaced by a glutaminyl residue. Synthetic oxytocin and the international standard pituitary (posterior lobe) powder were used for comparison. Although the analogues showed marked differences in their oxytocic effects, there was a fairly good agreement between the results obtained on the isolated rat uterus and the blood pressure of the chicken for each polypeptide. The milk‐ejection pressure test gave much higher values throughout. The pressor and antidiuretic activities of the four analogues showed no obvious correlation with the values obtained in the other tests. The valyl and the leucyl analogues also had a diuretic effect. The phenylalanyl analogue was remarkable for the close correspondence between its oxytocic and antidiuretic effects: practically identical values were obtained for the potency, whether measured on the rat uterus in vitro, the blood pressure in the chicken, the cat uterus in situ or water diuresis in the rat. The leucyl analogue showed an oxytocic activity on the cat uterus in situ or the rabbit mammary gland roughly 7 to 9 times as high as that measured by means of the conventional bioassay methods, such as the blood pressure of the chicken or the rat uterus in vitro. The glutaminyl analogue, the weakest of the whole series, had only a modest effect on the mammary gland. The valyl analogue was the most interesting of the new polypeptides. Its oxytocic action on the cat uterus in situ and its milk‐ejecting effect were greater than that of synthetic oxytocin, whereas its antidiuretic and pressor effects were less. In cats and rats, the uterine effect was stronger in situ than in vitro. There were also distinct species differences between cats, rabbits, and rats in their sensitivity to valyl‐oxytocin.
THE RELATION BETWEEN SEDATION AND BODY TEMPERATURE IN THE MOUSE
Authors: LESSIN A. W. , PARKES M. W.
Published: July 2012

Chlorpromazine and reserpine reduce locomotor activity and prolong pentobarbitone hypnosis in mice. Both these effects are shown to be proportional to the fall in body temperature produced by these drugs. Other agents are shown to reduce body temperature and potentiate pentobarbitone. At ambient temperatures of 32° C. neither chlorpromazine nor reserpine is hypothermic or sedative. It is concluded that sedative effects in the mouse at ordinary room temperatures are related to the hypothermic properties of these drugs. At 36° C., while reserpine fails to potentiate pentobarbitone, chlorpromazine still does so.
PROLONGATION OF CHLORAL HYDRATE SLEEPING TIME BY 5‐HYDROXYTRYPTAMINE AND BY CERTAIN OTHER DRUGS
Authors: FASTIER F. N. , SPEDEN R. N. , WAAL HENDRIEKA
Published: July 2012

Various drugs have been tested for a capacity to prolong the hypnotic effect of chloral hydrate in mice. Amongst the compounds which, when injected subcutaneously in substantial amount shortly before the chloral hydrate (250 mg./kg. intraperitoneally), increased sleeping time significantly were adrenaline, noradrenaline, phenylephrine, methoxamine, 5‐hydroxytryptamine (serotonin), histamine, ergotamine, yohimbine, and atropine. The ability of these drugs to prolong chloral hydrate sleeping time could not be related to any common circulatory property, but most of the active drugs are known to lower body temperature under comparable conditions. It was found that mice which have been pre‐treated with 5‐hydroxytryptamine or adrenaline suffer a much greater fall of body temperature when chloral hydrate is given subsequently than do mice which have been given chloral hydrate alone. It is suggested that some, at least, of the drugs which prolong the effects of hypnotics do so by virtue of a hypothermic action.
OXIMES AND ATROPINE IN SARIN POISONING
Authors: ASKEW BERYL M.
Published: July 2012

Three oximes, monoisonitrosoacetone (MINA), pyridine‐2‐aldoxime methiodide (PAM) and diacetylmonoxime (DAM), have been examined in combination with atropine as antidotes in sarin poisoning. When treatment was administered 15 min. before sarin, atropine enhanced the protective effect of MINA and DAM 2 to 3 times and of PAM 9 to 10 times in mice and rats. In mice, rats, and guinea‐pigs, atropine increased by no more than 2 times the protective effect of all three oximes when given 30 sec. after sarin. Atropine given to monkeys 1 min. after sarin raised the LD50 approximately 3 times. When given in conjunction with MINA or DAM, the LD50 of sarin was raised 7 to 14 times.
LIPID BIOSYNTHESIS AND CHEMICALLY INDUCED PARALYSIS IN THE CHICKEN
Authors: AUSTIN L.
Published: July 2012

Dyflos (diisopropylphosphorofluoridate, DFP) retards the synthesis of lipid in the sciatic nerve of the chicken in vivo. A similar inhibition occurs in vitro, but only at relatively high concentrations (10−3m) of the drug. The major portion of the 14C supplied as acetate, and incorporated into lipid, is found with the fatty acids. Attempts to separate the lipids involved by paper chromatography were unsuccessful.
DIGOXIN, OUABAIN AND POTASSIUM MOVEMENTS IN RABBIT AURICLES
Authors: RAYNER BARBARA , WEATHERALL M.
Published: July 2012

Movements of potassium have been observed in isolated right and left auricles of rabbits by means of radioactive tracer. The tissues have been immersed in a modified Krebs saline at 37°, and in these conditions showed only small changes in ionic content over periods up to 6 hr. The extracellular volume, determined with inulin and with 24Na, was large (44.1 ml./100 g. tissue), and accounted for about 3.8% of the tissue potassium. Left auricles exchanged without gross inhomogeneity: the rate of exchange was about 1.5% of the total tissue potassium/min., though it was probably higher in the first half‐hour or hour after preparation. In right auricles the exchange was less homogeneous and included a faster component than that observed in left auricles. Digoxin and ouabain reduced the influx and had no appreciable effect on the efflux of potassium, so that the auricles lost potassium. The threshold concentrations which produced effects within 20 min. were of the order of 10−6 for ouabain and somewhat higher for digoxin. Irregularities or failure of contraction occurred when the tissue potassium was reduced by about 15%. Loss of potassium was accompanied by gain of sodium, but the tissue appeared unsuitable for making estimations of the rate of sodium movement.
THE EFFECT OF LYSERGIC ACID DIETHYLAMIDE, 5‐HYDROXYTRYPTAMINE, AND RELATED COMPOUNDS ON THE LIVER FLUKE, FASCIOLA HEPATICA
Authors: MANSOUR T. E.
Published: July 2012

The rhythmical activity of the liver fluke, Fasciola hepatica, was stimulated by 5‐hydroxytryptamine and by lysergic acid diethylamide at very low concentrations. The effect was peripheral and was not mediated through the central ganglion. Other amines also stimulated rhythmical activity, the most potent being the indolamines.

Bromolysergic acid diethylamide, and other analogues such as yohimbine, harmine, and dopamine, depressed rhythmical movement and antagonized the stimulant action of 5‐hydroxytryptamine and lysergic acid diethylamide. Evidence which suggests the presence of tryptamine receptors in the trematode is discussed.
THE ACTION OF 5‐HYDROXYTRYPTAMINE AND SOME OF ITS ANTAGONISTS ON THE UMBILICAL VESSELS OF THE HUMAN PLACENTA
Authors: ÅSTRÖM A. , SAMELIUS U.
Published: July 2012

The vasoconstrictor action of 5‐hydroxytryptamine (5‐HT) in the human placental preparation is about 10 times stronger than that of adrenaline and is antagonized by anti‐adrenaline compounds like phentolamine. Both 5‐HT and adrenaline are antagonized by yohimbine and chlorpromazine. Specific and strong anti‐5‐HT action is demonstrated for lysergic acid diethylamide (LSD) and tryptamine. Both LSD and tryptamine in larger doses have a vasoconstrictor action. Mescaline has no certain modifying effect on the action of 5‐HT, but itself causes vasoconstriction in large doses. The antihistamine drug phenbenzamine in histamine blocking doses abolishes the action of 5‐HT in half the preparations tested. The ganglionic blocking agent trimetaphan in large doses antagonizes the action of 5‐HT added subsequently, and also, to a lesser degree, the effect of adrenaline. Hexamethonium and tetraethylammonium bromides are ineffective in this preparation. No certain modifying action of reserpine on subsequently added 5‐HT could be demonstrated, and the same was true for heparin even in very high concentrations.
PROTECTION AGAINST THE LETHAL EFFECTS OF ORGANO‐PHOSPHATES BY PYRIDINE‐2‐ALDOXIME METHIODIDE
Authors: HOBBIGER F.
Published: July 2012

The mechanism responsible for the protection against lethal organophosphate poisoning by pyridine‐2‐aldoxime methiodide (P‐2‐AM) was studied in the mouse. Two types of organophosphates were used: ethyl pyrophosphate (TEPP), E 600, Ro 3–0340, and Ro 3–0422 which form with true cholinesterase a diethylphosphoryl enzyme (1) and DFP, D 600 and Ro 3–0351 which form with true cholinesterase a diisopropylphosphoryl enzyme (2).

In vitro and under the experimental conditions used more than 50% reactivation of (1) was obtained within 1 hr. by concentrations of P‐2‐AM ranging from 0.5 to 1 × 10−6 m; 30 times higher concentrations of the oxime were required to achieve the same effect with (2). In vivo reactivation of phosphorylated true cholinesterases in blood amounted to 10 to 24% within the first 30 min. if 25 mg./kg. P‐2‐AM was injected (i.p.) 5 min. before a sublethal dose of TEPP, E 600, Ro 3–0340, or Ro 3–0422 and reactivation reached a maximum within 1 to 2 hr. after the injection of the oxime. P‐2‐AM was more effective when given 30 min. after the organophosphate. The effect of 25 mg./kg. P‐2‐AM on the phosphorylated true cholinesterase in brain (experiments with TEPP and E 600) was negligible. A dose of 25 mg./kg. P‐2‐AM had no consistent effect on the phosphorylated true cholinesterases in blood and brain of mice injected with sublethal doses of DFP, D 600, or Ro 3–0351.

The protection by 25 mg./kg. P‐2‐AM against lethal doses of TEPP, E 600, Ro 3–0422, and Ro 3–0340 was greater than that obtained with 50 mg./kg. atropine sulphate, but the degree of protection was determined by the organophosphate itself and not its dialkylphosphoryl group. Protection by 25 mg./kg. P‐2‐AM against lethal doses of DFP, D 600, and Ro 3–0351 was negligible. The antidotal effect of P‐2‐AM was potentiated by atropine. Mice which were injected with atropine and P‐2‐AM were protected to a greater extent against DFP than against Ro 3–0422, and protection against DFP was only slightly less than protection against TEPP. This is difficult to reconcile with a specific action of P‐2‐AM on phosphorylated cholinesterases.
COMPARATIVE EFFECTS OF CHLORTETRACYCLINE AND CORTISONE ON A LOCAL MONILIAL LESION IN THE MOUSE
Authors: O'GRADY F. , THOMPSON R. E. M.
Published: July 2012

The course of a local, closed monilial lesion in the thigh of the mouse is described. Treatment of animals suffering from this lesion with subcutaneous chlortetracycline in near‐toxic doses leads to a persistent suppression of the lesion indistinguishable from a curative effect. Treatment with subcutaneous cortisone produces suppression of the lesion during treatment with subsequent “rebound.”

Super‐injection of the lesions with chlortetracycline produces a very large and persistent swelling. Treatment of these lesions with subcutaneous chlortetracycline in near‐toxic doses produces suppression and “rebound” resembling that seen in lesions super‐injected and treated with cortisone. Aspirin, chosen for its insolubility and acidity, and turpentine, chosen for its irritant effect, did not reproduce the effects of chlortetracycline or cortisone.

While it is possible that the suppressive effect of chlortetracycline and cortisone is in certain circumstances related, the local irritant effect of chlortetracycline plays an important part in the enhancement of these lesions.
CHEMOTHERAPEUTIC SCREENING OF COMPOUNDS AGAINST THEILERIA ANNULATA IN TISSUE CULTURE
Authors: HAWKING F.
Published: July 2012

Theileria annulata has been grown in tissue culture and these cultures have been used for screening compounds for chemotherapeutic activity against this parasite. The method described is simple and convenient for testing many compounds in a short time. Forty compounds, including anti‐malarials, trypanocides, and antibiotics, have been examined, but none has been found to be active.
THE CHROMATOGRAPHIC BEHAVIOUR OF WASP VENOM KININ, KALLIDIN AND BRADYKININ
Authors: MATHIAS A. P. , SCHACHTER M.
Published: July 2012

Wasp venom kinin which has hitherto appeared to be homogeneous can be resolved by ion‐exchange chromatography into a single major and two minor components. These are indistinguishable by their action on smooth muscle and by their rapid inactivation by chymotrypsin. All three components of wasp kinin are chromatographically different from kallidin or bradykinin. The close similarity of the latter compounds is confirmed by their identical behaviour on an ion‐exchange resin.
THE ACTION OF TUBOCURARINE ON CILIARY MOVEMENT
Authors: MILTON A. S.
Published: July 2012

Further investigation of the effect of tubocurarine on the transport of particles by cilia of the frog oesophagus has confirmed that, when Ringer solution buffered with bicarbonate was used, tubocurarine inhibited the movement in a concentration of 10−6 g./ml. If, however, Ringer solution with a phosphate buffer was used tubocurarine was without effect. The difference in action is probably due to changes in calcium ion concentration caused by the phosphate in the Ringer solution.
THE RELATIVE ACTIVITIES OF SOME TRYPTAMINE ANALOGUES ON THE ISOLATED RAT STOMACH STRIP PREPARATION
Authors: VANE J. R.
Published: July 2012

The relative potencies of analogues of tryptamine and 5‐hydroxytryptamine have been determined on the rat fundus preparation. This tissue had an amine oxidase activity, which, in the homogenate, was able to inactivate both tryptamine and 5‐hydroxytryptamine to about the same degree. Amine oxidase inhibitors potentiated the action of tryptamine and many analogues on the isolated rat fundus preparation, but not the action of 5‐hydroxytryptamine or of other hydroxytryptamines. This suggested that, in the isolated organ, the amine oxidase was unable to inactivate 5‐hydroxytryptamine, but could inactivate tryptamine, 5‐methoxytryptamine and many others. These results may be explained if it is supposed that tryptamine entered the cell, but because of the polar hydroxy 1 group 5‐hydroxytryptamine did not. This hypothesis is supported by the oil/water partition coefficients. The structure/activity of the various tryptamine derivatives is discussed in the light of this assumption.
THE DURATION OF ACTION OF SOME CARDIAC GLYCOSIDES AND AGLYCONES IN THE GUINEA‐PIG
Authors: RAND M. , STAFFORD ANNE
Published: July 2012

A method is described for determining the duration of action of cardiac glycosides and aglycones in the guinea‐pig. It is based on their property of potentiating the cardiac response to adenosine. The method is particularly suitable for those drugs with a short duration of action, whereas previous methods are more suitable for those drugs with longer durations of action. The duration of action of one‐fifth of the lethal dose has been found for: digoxigenin, lanatoside C, ouabain, digitoxigenin‐3‐one, digitoxin, 3‐acetyldigitoxigenin, digoxin, digitoxigenin, lanatoside A; these drugs are arranged in order of increasing duration of action. The possible relationship between the elimination of these drugs and their duration of action can provide an estimate of their rates of elimination.
THE ACCUMULATION OF ISONIAZID IN TISSUES, AND THE COURSE OF EXPERIMENTAL TUBERCULOSIS
Authors: VENULET J. , JAKIMOWSKA KRYSTYNA , JANOWIEC M. , URBANSKA ALICJA
Published: July 2012

In an attempt to find agents enhancing the infiltration of isoniazid into tissues, the authors have investigated the effect of the drug on oedema due to injection of egg white into the rat paw, when it was given alone and in conjunction with histamine, antazoline, carbachol, chlorpromazine, and a pyrogen. Isoniazid increased the oedema. All the substances, except antazoline, increased the rate at which isoniazid disappeared from the blood, and they all favoured accumulation of the drug in tissues. Treatment of experimental tuberculosis with subthreshold doses of isoniazid, in conjunction with the above compounds, gave better results than when isoniazid was used alone.
THE EFFECT OF SUBSTANCE P ON THE SUPERIOR CERVICAL GANGLION OF THE CAT
Authors: BELESLIN D. , RADMANOVIĆ B. , VARAGIĆ V.
Published: July 2012

Intra‐arterial injections of substance P in doses from 10 to 30 units potentiated the response of the nictitating membrane to submaximal stimulation of the preganglionic sympathetic nerve, while higher doses (30 to 100 units) usually depressed the response. The stimulating action of acetylcholine on the superior cervical ganglion (as judged by the response of the nictitating membrane) was also potentiated by substance P. The responses of the nictitating membrane to adrenaline, noradrenaline and tyramine were potentiated by substance P as well. It is concluded that the potentiating effect of substance P on the response of the nictitating membrane to sub‐maximal stimulation of the preganglionic sympathetic nerve is probably due to sensitization of acetylcholine receptors in the postsynaptic neurone. The present experiments do not explain how substance P potentiated the response to sympathomimetic amines.
THE MODE OF NEUROMUSCULAR BLOCKING ACTION OF CHLORPROMAZINE
Authors: SU C. , LEE C. Y.
Published: July 2012

The inhibitory action of chlorpromazine on skeletal muscle has been studied with isolated preparations. In the nerve‐muscle preparations of the frog sartorius and the rat diaphragm, the twitch responses to indirect stimulation are much more strongly depressed by chlorpromazine than those to direct stimulation. The conductivity of the nerve trunk is unaffected. The contractures of the frog rectus abdominis muscle caused by acetylcholine are depressed by chlorpromazine, but the contractures due to KCl are not influenced. Larger doses of chlorpromazine cause contracture by themselves, and this cannot be prevented by tubocurarine. In the sartorius muscle of the toad, the depolarization due to acetylcholine is reduced by chlorpromazine. The paralysing action of chlorpromazine adds to that of tubocurarine, and is antagonized to some extent by eserine or neostigmine. Muscles treated with chlorpromazine do not completely recover on washing. High concentrations of chlorpromazine depress the release of acetylcholine by motor‐nerve stimulation, although they do not affect the enzymic synthesis of acetylcholine by acetone‐dried powder of guinea‐pig brain. The differences between the neuromuscular block produced by chlorpromazine and that by tubocurarine are discussed.
THE EFFECTS OF AMBUCETAMIDE ON HUMAN MYOMETRIAL AND OTHER PREPARATIONS, AND ITS ANTAGONISM TO THE MENSTRUAL STIMULANT
Authors: PICKLES V. R. , CLITHEROE H. J.
Published: July 2012

A plain‐muscle stimulant, provisionally named the “menstrual stimulant,” may be involved in the causation of dysmenorrhoea. Since ambucetamide [α‐dibutylamino‐α‐(p‐methoxyphenyl)‐acetamide] has been claimed to alleviate this condition, its effects on the responses of human myometrial preparations to the menstrual stimulant have been studied. Ambucetamide regularly inhibited these responses, as well as those to vasopressin, and sometimes diminished the spontaneous rhythmical activity of the human myometrium. The rat and guinea‐pig uterus, the guinea‐pig and cat intestine preparations, showed more complex responses and may therefore be less suitable for testing antispasmodic drugs intended for treatment of dysmenorrhoea.
GANGLION‐BLOCKING PROPERTIES OF ATROPINE‐LIKE DRUGS
Authors: BAINBRIDGE J. G. , BROWN D. M.
Published: July 2012

The ganglion‐blocking properties of atropine, atropine methyl nitrate, oxyphenonium, poldine, methantheline and propantheline have been examined and compared with those of hexamethonium, mecamylamine, pentolinium and tetraethylammonium. The ganglion‐blocking activity was assessed by stimulating the preganglionic nerve to the superior cervical ganglion and recording directly the percentage depression in the postganglionic action potentials. In this way any ambiguity due to the peripheral actions of the drugs was removed. As a group the atropine‐like compounds are not markedly less potent than the ganglion‐blocking agents, but their action is relatively transient. This work suggests that the ganglion‐blocking action of atropine‐like substances plays no part in their therapeutic effects.