bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle‐stimulating hormone starting dose in in vitro fertilisation cycles
Authors: La Marca A , Papaleo E , Grisendi V , Argento C , Giulini S , Volpe A
Published: July 2012

Please cite this paper as: La Marca A, Papaleo E, Grisendi V, Argento C, Giulini S, Volpe A. Development of a nomogram based on markers of ovarian reserve for the individualisation of the follicle‐stimulating hormone starting dose in in vitro fertilisation cycles. BJOG 2012;119:1171–1179.

Objective  To elaborate a nomogram based on markers of ovarian reserve for the calculation of the appropriate starting dose of follicle‐stimulating hormone (FSH).

Design  Cohort study of infertile women.

Setting  In vitro fertilisation (IVF) unit, University Hospital of Modena, Italy.

Population  Women aged 18–40 years (n = 346) and undergoing their first IVF cycle.

Methods  Serum FSH and anti‐Müllerian hormone (AMH) measurement.

Main outcome measures  Development of a model for the prediction of ovarian response to FSH.

Results  A model based on age, AMH and FSH was able to accurately predict the ovarian sensitivity and accounted for 30% of the variability of ovarian response to FSH. An FSH dosage nomogram was constructed and overall it predicts a starting FSH dose <225 IU in 55.1 and 25.9% of women younger and older than 35 years, respectively.

Conclusions  In the present study we clearly demonstrated that the daily FSH dose may be calculated on the basis of a woman’s age and two markers of ovarian reserve, namely AMH and FSH, with the first two vari;s (age and AMH) being the most significant predictors. The nomogram we developed seems easily applicable for clinicians during their daily clinical practice.
Cytomegalovirus antibody status at 17–18 weeks of gestation and pre‐eclampsia: a case–control study of pregnant women in Norway
Authors: Strand KM , Odland ML , Iversen A‐C , Nordbø SA , Vik T , Austgulen R
Published: July 2012

Please cite this paper as: Strand K, Odland M, Iversen A, Nordbø S, Vik T, Austgulen R. Cytomegalovirus antibody status at 17–18 weeks of gestation and pre‐eclampsia: a case–control study of pregnant women in Norway. BJOG 2012;119:1316–1323.

Objective  To assess the association between maternal cytomegalovirus (CMV) antibodies in mid‐pregnancy and pre‐eclampsia.

Design  Nested case–control study.

Setting  Pregnancies registered in the Norwegian Mother and Child Cohort Study (MoBa): a large population‐based pregnancy cohort (1999–2006).

Sample  A cohort of 1500 women with pre‐eclampsia and 1000 healthy pregnant women.

Methods  Plasma samples and pregnancy‐related information were provided by the MoBa. Antibody status (CMV IgG and CMV IgM) and levels (CMV IgG) at 17–18 weeks of gestation were determined by enzyme‐linked immunosorbent assay (ELISA).

Main outcome measure  A diagnosis of pre‐eclampsia, as defined in the Medical Birth Registry of Norway.

Results  There was no evidence of an effect of CMV IgG seropositivity on the likelihood of developing pre‐eclampsia, and CMV IgG antibody levels among women who were seropositive did not differ between groups. Adjusted for maternal age, parity and smoking, the odds ratio for pre‐eclampsia in women seropositive for CMV IgG was 0.89 (95% CI 0.74–1.05; P = 0.17). The proportions of women who were seropositive for IgM did not differ between women with pre‐eclampsia and women who were healthy (P = 0.98). Among nulliparous women, the proportion of women who were seropositive for CMV IgG was slightly lower among women with pre‐eclampsia (53.5%) than among healthy women (59.8%) (P = 0.03). Subgroup analyses were performed for women with early or late onset pre‐eclampsia, with preterm delivery and/or with neonates that were small for gestational age, but antibody status did not differ between pre‐eclampsia subtypes and controls.

Conclusions  The presence of maternal antibodies to CMV was not associated with pre‐eclampsia in our study. The results suggest that CMV infection is unlikely to be a major cause of pre‐eclampsia.
Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy? A randomised controlled trial
Authors: Stafne SN , Salvesen KÅ , Romundstad PR , Torjusen IH , Mørkved S
Published: July 2012

Please cite this paper as: Stafne S, Salvesen K, Romundstad P, Torjusen I, Mørkved S. Does regular exercise including pelvic floor muscle training prevent urinary and anal incontinence during pregnancy? A randomised controlled trial. BJOG 2012;119:1270–1280.

Objective  To assess whether pregnant women following a general exercise course, including pelvic floor muscle training (PFMT), were less likely to report urinary and anal incontinence in late pregnancy than a group of women receiving standard care.

Design  A two‐armed, two‐centred randomised controlled trial.

Setting  Trondheim University Hospital (St. Olavs Hospital) and Stavanger University Hospital, in Norway.

Population  A total of 855 women were included in this trial.

Methods  The intervention was a 12‐week exercise programme, including PFMT, conducted between 20 and 36 weeks of gestation. One weekly group session was led by physiotherapists, and home exercises were encouraged at least twice a week. Controls received regular antenatal care.

Main outcome measures  Self‐reported urinary and anal incontinence after the intervention period (at 32–36 weeks of gestation).

Results  Fewer women in the intervention group reported any weekly urinary incontinence (11 versus 19%, P = 0.004). Fewer women in the intervention group reported faecal incontinence (3 versus 5%), but this difference was not statistically significant (P = 0.18).

Conclusions  The present trial indicates that pregnant women should exercise, and in particular do PFMT, to prevent and treat urinary incontinence in late pregnancy. Thorough instruction is important, and specific pelvic floor muscle exercises should be included in exercise classes for pregnant women. The preventive effect of PFMT on anal incontinence should be explored in future trials.
Modelling seasonal changes in the distribution of Common Quail Coturnix coturnix in farmland landscapes using remote sensing
Authors: Sardà‐Palomera Francesc , Puigcerver Manel , Brotons Lluís , Rodríguez‐Teijeiro José Domingo
Published: July 2012

Species’ distribution models are widely used in landscape ecology but usually lack explicit information about species’ responses to ecosystem dynamics, leading to uncertainty when applied to the prediction of seasonal change in distributions. In this study, we aimed to build a species’ distribution model for the Common Quail Coturnix coturnix, a farmland species that shows changes in its distribution in response to seasonal changes in habitat suitability. During the course of three breeding seasons we collected temporal replicates of presence–absence data in 13 sampling locations in four countries (Morocco, Portugal, Spain and France). We used generalized linear mixed models to relate the species’ presence or absence to environmental variables and to the normalized difference vegetation index at each sampling location through the seasons, the latter variable being an indicator of within‐ and between‐season habitat changes. The preferred model showed that occurrence was highly dependent on habitat changes associated with crop seasonality, as measured by the normalized difference vegetation index. Common Quail selected areas with dense vegetation and warm climate and tracked spatial changes in these two parameters. The model allows accurate mapping of within‐ and between‐season distribution changes. Such changes are related to habitat variations caused mainly by drought and agricultural practices. Our results demonstrate that seasonal changes in farmland ecosystems can be incorporated into a simple distribution model, and our approach could be applied to other species to predict the effects of agricultural changes on the distribution of birds inhabiting farmland landscapes.
dFatp regulates nutrient distribution and long‐term physiology in Drosophila
Authors: Sujkowski Alyson , Saunders Samantha , Tinkerhess Martin , Piazza Nicole , Jennens Joanna , Healy Lindsey , Zheng Li , Wessells Robert
Published: July 2012

Nutrient allocation and usage plays an important part in regulating the onset and progression of age‐related functional declines. Here, we describe a heterozygous mutation in Drosophila (dFatp) that alters nutrient distribution and multiple aspects of physiology. dFatp mutants have increased lifespan and stress resistance, altered feeding behavior and fat storage, and increased mobility. Concurrently, mutants experience impairment of cardiac function. We show that endurance exercise reverses increased lipid storage in the myocardium and the deleterious cardiac function conferred by dFatp mutation. These findings establish a novel conserved genetic target for regulating lifespan and physiology in aging animals. These findings also highlight the importance of varying exercise conditions in assessing aging functions of model organisms.
Using ballistocardiography to measure cardiac performance: a brief review of its history and future significance
Authors: Vogt Emelie , MacQuarrie David , Neary John Patrick
Published: July 2012

Ballistocardiography (BCG) is a non‐invasive technology that has been used to record ultra‐low‐frequency vibrations of the heart allowing for the measurement of cardiac cycle events including timing and amplitudes of contraction. Recent developments in BCG have made this technology simple to use, as well as time‐ and cost‐efficient in comparison with other more complicated and invasive techniques used to evaluate cardiac performance. Recent technological advances are considerably greater since the advent of microprocessors and laptop computers. Along with the history of BCG, this paper reviews the present and future potential benefits of using BCG to measure cardiac cycle events and its application to clinical and applied research.
Accommodative and tonic convergence and anatomical contracture in partially accommodative and non‐accommodative esotropia
Authors: Lee Tae‐Eun , Kim Seung‐Hyun
Published: July 2012

Citation information: Lee TE & Kim SH. Accommodative and tonic convergence and anatomical contracture in partially accommodative and non‐accommodative esotropia. Ophthalmic Physiol Opt 2012, 32, 535–538. doi: 10.1111/j.1475‐1313.2012.00924.x

Purpose:  To compare accommodative convergence, tonic convergence, and anatomical contracture quantitatively in partially accommodative esotropia vs non‐accommodative esotropia.

Methods:  Patients with an esotropia who had undergone surgery under general anaesthesia were evaluated. They were divided into two groups: 17 patients had partially accommodative esotropia and 15 patients had non‐accommodative esotropia (basic esotropia). We supposed that the total esodeviation (Eso) was composed of three components: accommodative convergence (AC), tonic convergence (TC), and anatomical contracture (AnC). We measured the preoperative angle of esodeviation with (AC) or without glasses (Eso) in awakening state at 1/3 m and the preoperative esodeviation under general anaesthesia (AnC). TC was calculated by the formula TC = EsoD−AC−AnC.

Results:  The average ratios of TC/Eso, AC/Eso and AnC/Eso were 46%, 32%, and 22%, respectively in the partially accommodative esotrope group, and 28%, 1%, and 71%, respectively in the non‐accommodative esotropes. These differences were significant for AC/Eso and AnC/Eso (p < 0.0001) but not for TC/Eso (p = 0.15).

Conclusions:  Among the three components, tonic convergence was responsible for a larger portion of esodeviation than anatomical contracture in partially accommodative esotropia, whereas anatomical contracture played a greater role in the non‐accommodative esotropia group.
Changes during winter in water‐stable aggregation due to crop residue quality
Authors: Le Guillou C. , Angers D. A. , Leterme P. , Menasseri‐Aubry S.
Published: July 2012

There is a need to develop practices that contribute to increased water‐stable aggregation (WSA) during winter in a humid temperate climate when soil is particularly prone to water erosion. Our objectives were to determine the effects of crop residue quality on WSA during winter and to relate these effects to biochemical indicators of fungal and bacterial biomass. Three graminae crop residues were selected for their different C/N ratios and biochemical characteristics (green oat residues, C/N = 18.8; wheat straw, C/N = 125.6; and mature miscanthus residues, C/N = 311.3). In October 2009, crop residues were added with an equivalent amount of C in the 0–10 cm layer to a Luvisol in north‐west France. WSA, expressed as mean weight diameter (MWD), amino sugar, soil mineral N and water contents were measured at regular intervals during 5 months. Aggregate MWD of the control soil decreased rapidly and remained low until the last sampling date in March which illustrates the structural vulnerability of bare soils in winter in this pedo‐climatic area. The incorporation of all three crop residues had significant positive impacts on aggregate MWD. Despite widely different C/N ratios, the maximum MWD under each treatment was similar (three times greater than the control soil). Maximum MWD occurred at times that clearly depended on residue quality. Maximum values occurred early for green oat (29 day), but were delayed to 50 day for wheat straw and to 154 day for miscanthus. Results from correlation analysis suggest that variations in WSA were partly mediated by microbial agents with a dominant effect of bacteria for green oat and a combined role of fungal and bacterial biomass for wheat straw. We suggest that the maximum MWD associated with the miscanthus late in the experiment is related to changes in the composition of the fungal community. Overall, our study shows that autumn application of crop residues increases WSA during winter with its effect being microbially mediated and determined by residue quality.
Researching mobility and emplacement: examining transience and transnationality in international student lives
Authors: Collins Francis Leo
Published: July 2012

The mobility of international students represents an important emerging focus for human geographers interested in the dynamic intersections between education, migration and globalisation. Researching the lives of international students also poses certain methodological challenges, particularly for researchers focused on the local emplacement of students who in many cases are relatively temporary residents of the cities and towns they study in. This paper addresses these challenges through reflection on one methodological approach to examining the intersections between the transnational mobilities of South Korean international students and their situated encounters in the urban spaces of Auckland, New Zealand. The project employed a mixed qualitative approach focused on linking the mobility of student lives to their everyday involvement in Auckland through diary‐writing, map‐drawing and research on personal homepages alongside interviews, observation and a survey. The discussion pays particular attention to the integration of findings from these distinct research techniques. It also points to the importance of methodological flexibility and experimentation for researchers seeking to capture the different transnational and urban dimensions of the lives of mobile individuals like international students, and the need to tailor research approaches to the needs of specific populations – fitting research into lives.
Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide
Authors: ANDÉN N.‐E. , CORRODI H. , FUXE K. , HÖKFELT T.
Published: July 2012

Lysergic acid diethylamide (LSD) and the 5‐hydroxytryptamine (5‐HT) precursor, 5‐hydroxytryptophan produced similar functional effects in rat spinal cord and brain to the 5‐hydroxytryptamine precursor 5‐hydroxytryptophan, which indicates that LSD stimulates central 5‐HT receptors.

By means of combined histochemical and biochemical techniques it was found that LSD reduced the turnover rate of brain and spinal cord 5‐HT, studied after inhibition of the tryptophan hydroxylase by α‐propyldopacet‐amide. The turnover of brain noradrenaline but not dopamine was somewhat accelerated.

The functional and chemical effects by LSD were related to dose and to time. They were not observed after the LSD analogues 2‐bromo‐LSD and methysergide.

The retardation of the 5‐HT turnover by LSD may be due to negative feed‐back mechanisms evoked by direct stimulation of the central 5‐HT receptors.
The action of tyramine on the rabbit ear artery
Authors: de la LANDE I. S. , WATERSON J. G.
Published: July 2012

The vasoconstrictor potency of extraluminal tyramine on the isolated perfused rabbit ear artery is considerably greater than that of intraluminal tyramine.

Chronic denervation, which caused the noradrenergic storage structures in the medial‐adventitial border of the artery to disappear, reduces the potency of extraluminal tyramine more than that of intraluminal tyramine so that the difference in potency for the two routes of administration tends to disappear. Cocaine exerts a greater inhibitory effect on responses to extraluminal tyramine than on those to intraluminal tyramine.

It is concluded that the indirect component plays a more prominent part in the responses to extraluminal tyramine than in those to intraluminal tyramine. This conclusion is supported by analysis of the diphasic response of the artery to intraluminal injection of tyramine under perfusion conditions which permit intraluminal fluid to mix with the extraluminal fluid. Evidence is presented that the first phase of the response is mediated by intraluminal tyramine, and the second phase by extraluminal tyramine.
The neuromuscular blocking action of a series of bicyclic bis‐onium esters
Authors: MARSHALL I. G.
Published: July 2012

Thirteen bicyclic dicholine esters have been tested on mammalian and avian skeletal muscle preparations.

One of the compounds exhibited depolarizing activity in all the preparations.

Three of the compounds exhibited depolarizing or dual‐blocking activity in avian and denervated mammalian preparations, but exhibited non‐depolarizing blocking activity in innervated mammalian preparations.

The remaining compounds exhibited non‐depolarizing blocking activity with evidence of an additional facilitatory action.

The activity exhibited was dependent upon the onium substituents and the structure of the bicyclic ring.

All the compounds exhibited a choline‐reversible block in the rapidly stimulated rat diaphragm preparation and six of them exhibited a secondary choline‐reversible block of the rapidly stimulated cat tibialis anterior muscle.
The effect of chlorpromazine on cerebral glucose, ATP, ADP, AMP and ATPase in the mouse
Authors: CHOWDHURY A. K. , SKINNER ANNETTE , SPECTOR R. G. , YAP S.‐L.
Published: July 2012

Administration of chlorpromazine 10 mg/kg intraperitoneally to mice produced no alteration in cerebral adenosine triphosphate (ATP), adenosine diphosphate (ADP) or adenosine monophosphate (AMP). In these animals there was an increase in the glucose content of the supernatants of homogenates of liver and brain following acid hydrolysis.

Chlorpromazine 40 mg/kg intraperitoneally did not affect Mg++ activated adenosine triphosphatase (ATPase) activity in the brain.
A comparison of some cardiovascular properties of propranolol, MJ 1999 and quinidine in relation to their effects in hypertensive animals
Authors: FARMER J. B. , LEVY G. P.
Published: July 2012

A comparison of some cardiovascular effects of propranolol, MJ 1999 and quinidine has been made in rats and dogs.

After intravenous, subcutaneous or oral administration to rats and dogs, propranolol was found to be 2–4 times more potent than MJ 1999 in blocking the chronotropic and vasodepressor responses to intravenously administered isoprenaline.

Propranolol and quinidine affected the e.c.g. of rats and dogs in a similar manner.

At dose‐levels causing effective blockade of β‐receptors propranolol and MJ 1999 had no hypotensive effect after short‐ or long‐term administration to conscious hypertensive rats and dogs.

At very high dose‐levels propranolol and quinidine, but not MJ 1999, lowered blood pressure in the hypertensive rat. This effect of propranolol is probably related to one or more of the properties that propranolol and quinidine have in common rather than to a blockade of β‐receptors.

The possible relevance of these results to the use of propranolol as a hypotensive agent in man is discussed.
The reversal of the central effects of noradrenaline by antidepressant drugs in mice
Authors: COWELL PAULINE , DAVEY M. J.
Published: July 2012

Noradrenaline given directly into the lateral cerebral ventricles induced hypothermia in mice. This hypothermia was antagonized and eventually reversed to a hyperthermia by imipramine‐like antidepressant drugs.

The mechanism of action involved in this effect of antidepressant drugs has been studied using nortriptyline as a typical representative of antidepressant drugs.

Nortriptyline pretreatment did not modify either the uptake, subcellular distribution, or the metabolism of 3H‐noradrenaline injected into the lateral cerebral ventricles.

Nortriptyline had the same order of activity in reversing the hypothermia produced by the intraventricular injection of noradrenaline irrespective of whether it was given directly into the lateral cerebral ventricles or subcutaneously.

Noradrenaline given subcutaneously caused hyperthermia in mice which antagonized and reversed the hypothermia induced by noradrenaline given directly into the lateral ventricles.

The antagonism by both noradrenaline given subcutaneously and nortriptyline was reduced to the same degree by α‐ and β‐adrenoceptive receptor blocking agents.

Nortriptyline, at dose levels required to antagonize and reverse the hypothermia induced by intraventricular injections of noradrenaline, potentiated the hyperthermia caused by noradrenaline given subcutaneously in conscious mice and the pressor responses to noradrenaline given either intravenously or into the lateral ventricles in anaesthetized mice.

It is suggested that imipramine‐like antidepressant drugs antagonize the hypothermia produced by intraventricular injections of noradrenaline by potentiating the hyperthermic effects of that part of the centrally administered noradrenaline that passes to the periphery rather than a direct central antagonism of the effects of noradrenaline.
Kinins and anti‐inflammatory steroids
Authors: EISEN V. , GREENBAUM L. , LEWIS G. P.
Published: July 2012

This investigation was designed to re‐examine the possibility that antiinflammatory steroids interfere with the kinin‐forming system.

We conclude that the anti‐inflammatory action of corticosteroids cannot be explained by the inhibition of kinin formation. This view is based on the following findings.

Neither hydrocortisone nor prednisolone nor dexamethasone inhibited the activation or activity of intrinsic plasma kinin forming enzymes resulting from dilution, incubation with kininase inhibitors, or exposure to glass, monosodium urate microcrystals or to precipitated complexes of rheumatoid factor and aggregated human γ‐globulin.

Hydrocortisone did not inhibit the action of the active kinin‐forming enzymes, human salivary or urinary kallikrein, or plasmin on purified kininogen.

Hydrocortisone, prednisolone and dexamethasone did not inhibit the hydrolysis of benzoyl‐arginine‐ethyl ester by human plasmin, plasma kallikrein or hog pancreatic kallikrein.

Kinin formation occurred normally in plasma taken from two patients receiving betamethasone and one receiving prednisone.
Sustained complete autonomic blockade
Authors: HALMAGYI D. F. J. , NEERING I. R. , VARGA D. , PULLIN JOY
Published: July 2012

A 3‐hr period of complete autonomic blockade was induced in anaesthetized sheep and dogs using a continuous intravenous infusion of trimetaphan camphorsulphonate and atropine. Circulatory, respiratory and metabolic parameters were studied over 24 hr or until the animal died, whichever came first.

After termination of the blockade all animals remained hypotensive and within a few hours all died in irreversible shock which was not accompanied by any of the otherwise characteristic respiratory or metabolic consequences of circulatory failure.

Administration of trimetaphan alone for a similar period was innocuous.

When during complete autonomic blockade a continuous infusion of dopamine or hypertensin was additionally administered mortality rate was halved but all survivors remained hypotensive.
An in vitro study of the intestinal absorption of pyridinium aldoximes
Authors: CRONE H. D. , KEEN T. E. B.
Published: July 2012

The transfer rates of three pyridinium aldoximes, a non‐quaternary pyridine aldoxime and choline across the wall of sacs from the jejunum of rats were measured in vitro.

The transfer rates observed for any one of the quaternary compounds could be inversely correlated with the transmural potential of the particular sac studied, but there was no correlation with the rates of water or glucose transfer.

2‐hydroxyiminomethyl‐N‐methylpyridinium iodide (PAM) had a transfer rate seven times less than that of its non‐quaternary analogue, 2‐hydroxyimino‐methyl pyridine.

Neither neostigmine nor EDTA affected the transfer rate of PAM in the conditions used.

It was concluded that the transfer of the quaternary compounds could be explained by diffusion through aqueous pores.
Effects of progesterone therapy on the stilboestrol‐induced sensitivity of isolated rat uterus preparations
Authors: KHAN I. , AHMED N.
Published: July 2012

Progesterone treatment (50 mg/kg) in ovariectomized rats antagonizes the effects of stilboestrol 100 μg/kg on the vaginal mucosa and uterine weight; but the sensitivity to acetylcholine, oxytocin and 5‐hydroxytryptamine is increased by factors 4, 11 and 3, respectively.

In intact animals a similar progesterone treatment (50 mg/kg) antagonizes the effects of stilboestrol 100 μg/kg on vaginal smears, uterine weight and uterine sensitivity. The uterine sensitivity to acetylcholine, oxytocin and 5‐hydroxytryptamine is, however, decreased by a factor of 2, 1.4 and 17.7, respectively.

These experiments show that the ovary is essential for the desensitizing effects of progesterone. The suggestion is put forward that another substance is released from the ovary by progesterone.
The influence of salicylate on platelets and whole blood adenine nucleotides
Authors: DAVIES D. T. P. , HUGHES A. , TONKS R. S.
Published: July 2012

The addition of sodium salicylate to freshly withdrawn human blood or native platelet‐rich plasma significantly delays platelet aggregation in vitro.

The administration of acetylsalicylic acid to human subjects also significantly delays platelet aggregation in their whole blood and there is a short delay in the formation of fibrin but this is not statistically significant.

Salicylate, whether added to human blood in vitro as sodium salicylate or given by mouth as acetylsalicylic acid, significantly reduces the platelet clumping activity of adenosine diphosphate (ADP) added to whole blood in vitro.

The administration of aspirin in high doses for several days produces a marked increase in the total adenine nucleotide content of whole blood. The percentage of adenosine triphosphate (ATP) was increased, that of ADP decreased while there is an obvious increase in the ATP: ADP ratio.

There is little correlation between the plasma salicylate level and the delay aspirin produces in platelet aggregation in vitro or the changes that occur in the levels of ADP or ATP in whole blood during administration of aspirin.

Significant correlations do occur, however, between the delay in platelet aggregation in vitro and (i) the percentage increase in the ATP concentration, (ii) the percentage decrease in ADP concentration, (iii) the percentage change in the ATP: ADP ratio observed during aspirin administration.
The effects of phenobarbitone, leptazol, dexamphetamine, iproniazid, imipramine, LSD, chlorpromazine, reserpine and hydroxyzine on the in vivo levels of adenine nucleotides and phosphocreatine in the rat brain
Authors: WILSON W. S.
Published: July 2012

Enzymic and ion‐exchange chromatographic analyses were used to measure adenosine triphosphate (ATP), diphosphate (ADP) and monophosphate (AMP) in brain extracts from rats treated with a wide range of centrally acting drugs. Phosphocreatine (PC) was assayed by the acid molybdate method.

An anaesthetic dose of phenobarbitone caused an increase in brain levels of ATP and PC, and a reduction in ADP and AMP. A convulsant dose of leptazol gave rise to precisely opposite effects. Subanaesthetic (hypnotic) and subconvulsive doses of the two drugs, respectively, produced no alterations in brain nucleotide levels.

Among the psychotropic drugs, dexamphetamine, LSD and hydroxyzine, at the doses used, caused no changes in brain levels of the adenine nucleotides. Iproniazid and imipramine caused slight increases in the ATP level and ATP/ADP ratio, respectively. Chlorpromazine failed to give rise to any effect in the nucleotides 3 hr after administration, but produced a rise in brain ATP after 6 hr. Reserpine, on the other hand, caused a fall in the ATP/ADP ratio 6 hr after injection.

These results indicate that some psychotropic drugs can cause small changes in the rat brain ATP/ADP ratio but do not support claims by certain workers that such changes correlate closely with the behavioural effects of these drugs.
The interaction between monoamine oxidase inhibitors and narcotic analgesics in mice
Authors: ROGERS K. J. , THORNTON J. A.
Published: July 2012

The administration of either iproniazid or tranylcypromine to mice potentiates the acute toxicity of pethidine, morphine, pentazocine and phenazocine.

Blood levels of pentazocine in mice pretreated with tranylcypromine do not differ from the levels in animals not receiving the monoamine oxidase (MAO) inhibitor.

There is no correlation between changes in brain and liver MAO activity and the increased pethidine toxicity.

A comparison is made between the change in pethidine toxicity and the changes in the concentration of cerebral noradrenaline, dopamine and 5‐hydroxytryptamine following the injection of tranylcypromine.

It is concluded that the increased toxicity of potent analgesics in combination with MAO inhibitors is not due to a decelerated metabolism of the analgesic drug, but is related to an increased concentration of cerebral 5‐hydroxytryptamine. A critical level of this monoamine, in the brain, may be necessary before the drug interaction will take place.
Ionic interactions in acetylcholine contraction of the denervated rat diaphragm
Authors: FREEMAN SHIRLEY E. , TURNER R. J.
Published: July 2012

The nature of the drug‐receptor interaction in the acetylcholine‐induced contraction of the denervated rat diaphragm was studied both by altering the external ionic environment and by determining its drug sensitivity.

The response to acetylcholine was insensitive to tetrodotoxin or saxitoxin, but was abolished by procaine.

It was unaffected by levels of MnCl2 sufficient to block the response of the innervated diaphragm to electrical stimulation, although higher levels reduced the response. The effect of Mn++ on the innervated diaphragm was overcome by raising the external Ca++ level; this was ineffective in the denervated preparation.

In spite of its insensitivity to tetrodotoxin the acetylcholine contraction was reduced and prolonged by low external Na+ levels. This prolongation was not found when Li+ substituted for Na+.

Increasing the external level of Ca++ or Mg++ 3 to 5‐fold reduced the acetylcholine contraction; high Ca++ also prolonged it. Reduction in the divalent cation level was without effect.

Procaine inhibition of the acetylcholine response was largely competitive, as was inhibition due to (+)‐tubocurarine. This was shown by probit analysis and the dose‐ratio test.

Thiocyanate (12 mm) augmented and prolonged the contraction; this action was modified by altering the Ca++ or Mg++ level of the solution.

The acetylcholine receptor resembles that of the innervated postsynaptic membrane.
Reversal by pronethalol of dibenamine blockade: a study on the seminal vesicle of the guinea‐pig
Authors: GUIMARÃES S.
Published: July 2012

The guinea‐pig seminal vesicle has been shown to be a very suitable test object for the study of mechanisms involving α‐adrenoceptive receptors, because no β‐receptors were found in this preparation.

Adrenaline, noradrenaline and phenylephrine were directly acting agonists, their ED50 values being 7·1 × 10−6M, 1·5 × 10−5M and 2·7 × 10−5M, respectively.

Pretreatment with reserpine had no influence on the contractions caused by adrenaline, noradrenaline and phenylephrine but abolished or greatly reduced the contractions caused by dopamine. Cocaine enhanced the effects of adrenaline, noradrenaline and phenylephrine and reduced those of dopamine.

Pronethalol (6·8 × 10−5M) reversed the α‐receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine; it did not affect the blockade by dibenamine of responses to histamine.

Reversal of the blockade by dibenamine was observed only when its concentration was such that it caused a parallel shift of the dose‐effect curves of the agonists to the right; higher concentrations, which caused an unsurmountable depression of the maximal contraction, were not antagonized by pronethalol.

It is assumed that the reversal is dependent on a direct action on α‐receptors, “spare receptors” being probably involved.
PMN‐kinin and kinin metabolizing enzymes in normal and malignant leucocytes
Authors: GREENBAUM L. M. , FREER R. , CHANG J. , SEMENTE G. , YAMAFUJI K.
Published: July 2012

Studies have been carried out on the kinin‐forming and kinin destroying activity of rabbit macrophages obtained from the lung before and after BCG injection and from the peritoneal cavity following mineral oil injection. A similar study was carried out with L‐1210 leukaemic cells obtained from the peritoneal cavity of mice.

The macrophages and leukaemic cells contain enzymes that form kinins from purified kininogen substrates at acid pH. The kinin‐forming activity is not limited to the lysosomal fraction of the cell since it is found in extra‐lysosomal compartments. Delta‐guanidovaleryl benzyl ester partially inhibits the kinin‐forming activity. Trasylol does not inhibit the kinin‐forming activity of these cells, but does inhibit the kininases of these cells. The lack of effectiveness of this agent as a general anti‐inflammatory agent is thus explained.

The kininases of the normal and malignant cells are also inhibited by chloromethyl ketones such as tosyl‐lysine chloromethyl ketone (TLCK) and tosyl‐phenylalanine‐chloromethyl ketone (TPCK) as well as by copper salts. Hydroxyquinoline has no inhibitory action on these cells, indicating that they differ from the plasma kininases.

Investigation of the kinins produced by enzymes in rabbit and human polymorphonuclear (PMN) cells has demonstrated the formation of a kinin that differs from bradykinin and other known mammalian kinins in its pharmacological properties, molecular weight, and amino‐terminal end group. This peptide has been named PMN‐kinin.

Overall, the investigation has demonstrated the importance of white cells in contributing to the formation and destruction of “extra‐plasma” sources of kinins by enzymes which differ from plasma enzymes. Anti‐inflammatory agents may have different actions on these cell enzymes from those on plasma enzymes.
Excitatory action of sympathomimetic amines on 5‐hydroxytryptamine receptors of gut
Authors: INNES I. R. , KOHLI J. D.
Published: July 2012

Twenty‐two sympathomimetic amines were tested for excitatory activity on isolated guinea‐pig ileum, rabbit jejunum, and rat stomach.

Eight amines contracted all or almost all guinea‐pig ileum preparations; five amines contracted half the preparations and relaxed the others. Nine amines were consistently relaxant. Structural requirements for excitatory activity were not clear.

Six amines contracted rat stomach and only four contracted rabbit jejunum. Only β‐phenylethylamine and (—)‐amphetamine contracted all three preparations.

The excitatory effects of the sympathomimetic amines on guinea‐pig ileum seem to be due to an action on 5‐hydroxytryptamine receptors. This conclusion is based on evidence that their excitatory action is antagonized by 2‐bromo‐Iysergic acid diethylamide, by morphine and by desensitization with 5‐hydroxytryptamine, and that there is cross‐protection between 5‐hydroxytryptamine and the excitatory sympathomimetic amines against block by phenoxybenzamine.
The pharmacology of fenclozic acid (2‐(4‐chlorophenyl)‐thiazol‐4‐ylacetic acid; I.C.I. 54, 450; ‘Myalex’); a new compound with anti‐inflammatory, analgesic and antipyretic activity
Authors: NEWBOULD B. B.
Published: July 2012

Fenclozic acid (2‐(4‐chlorophenyl)thiazol‐4‐ylacetic acid; I.C.I. 54, 450; “Myalex”) is one representative of a new class of compounds with antiinflammatory, analgesic and antipyretic properties as evidenced by its activity in a variety of tests in rats, mice and guinea‐pigs.

In tests of short duration the potency of fenclozic acid is similar to that of phenylbutazone.

In tests of longer duration fenclozic acid is more potent than phenylbutazone.

The activity of fenclozic acid is not mediated by stimulation of the adrenals and the compound is devoid of corticosteroid‐like activity.
Mechanism of the antagonism between guanethidine and dexamphetamine
Authors: GERKENS J. F. , McCULLOCH M. W. , WILSON J.
Published: July 2012

The effects of dexamphetamine were studied on the responses of rabbit ileum, rabbit ear artery and sheep spleen to sympathetic nerve stimulation after exposure to guanethidine and in the absence of guanethidine.

In the absence of guanethidine, dexamphetamine enhanced the responses to sympathetic stimulation and, in the spleen, this was shown to be due to an increase in noradrenaline output. However, the increase in these responses was much less than the increase obtained in preparations treated with guanethidine.

Cocaine, in a concentration which produced the same effect on noradrenaline uptake as the concentration of dexamphetamine used, was also effective in reversing the adrenergic neurone blocking actions of guanethidine.

It is suggested that the antagonism between dexamphetamine and guanethidine is due to a reduction in the uptake of guanethidine by the nerve endings rather than to interaction of the two drugs at the receptor site for the adrenergic neurone blocking action of guanethidine.
Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones
Authors: BHAGAT B.
Published: July 2012

. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H‐noradrenaline 1 hr after its intravenous administration.

. Twenty‐four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction.

. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α‐methyl‐tyrosine showed that cardiac synthesis of noradrenaline increased about four‐fold after demedullation and about three‐fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines.

. There was no change in catechol‐o‐methyl‐transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats.

. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones.
The metabolism of orally administered l‐DOPA in Parkinsonism
Authors: CALNE D. B. , KAROUM F. , RUTHVEN C. R. J. , SANDLER M.
Published: July 2012

. Gas‐liquid chromatographic methods were used to measure urinary acidic and alcoholic metabolites of l‐DOPA, which had been administered in high oral dosage to patients with postencephalitic and idiopathic Parkinsonism.

. The output of these compounds was normal before treatment. During drug therapy, large quantities of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were excreted but traces only of 4‐hydroxy‐3‐methoxyphenylethanol. Noradrenaline metabolites showed little change in output other than a small increase in 4‐hydroxy‐3‐methoxymandelic acid.

. Information was obtained about a number of minor routes of degradation which might be implicated in the therapeutic action of l‐DOPA. A raised output of m‐hydroxyphenylacetic acid pointed to p‐dehydroxylation of dihydroxyphenylacetic acid by gut flora. Evidence of transamination as a minor metabolic pathway was obtained by finding appreciable urinary levels of 4‐hydroxy‐3‐methoxyphenyllactic acid. A keto‐acid precursor of this compound may act as competitive inhibitor of an enzyme active in the normal degradation route of tyrosine, p‐hydroxyphenylpyruvic acid oxidase, for increased amounts of p‐hydroxyphenyllactic acid, the major metabolic derivative of p‐hydroxyphenylpyruvic acid, accumulated in the urine during DOPA treatment.
Effect of monoamineoxidase inhibitors on 5‐hydroxytryptamine output from perfused cerebral ventricles of anaesthetized cats
Authors: GOODRICH CECILIE A.
Published: July 2012

. In cats anaesthetized with pentobarbitone sodium, intraperitoneal injections of four inhibitors of monoamine oxidase (MAO) were shown to increase the 5‐hydroxytryptamine (5‐HT) in the effluent from the perfused cerebral ventricles.

. Weight for weight, tranylcypromine was found to be about twice as potent as pheniprazine, eight times as potent as nialamide and sixty times as potent as pargyline.

. The effect of tranylcypromine was also examined after reserpine had been injected into the cerebral ventricles or after p‐chlorophenylalanine, given intraperitoneally. In both conditions tranylcypromine retained its ability to increase the 5‐HT output from the perfused cerebral ventricle, but the effect was attenuated, more after p‐chlorophenylalanine than after reserpine.

. Evidence is put forward that in both conditions the brain is not completely depleted of its 5‐HT, but that the 5‐HT is only reduced, more after p‐chlorophenylalanine than after reserpine.
A sequential screening test based on the running component of audiogenic seizures in mice, including reference compound PD50 values
Authors: COLLINS A. J. , HORLINGTON M.
Published: July 2012

. The running component of audiogenic seizures in mice has been used as the basis of a sequential screening test for the detection of a variety of centrally acting drugs.

. For acceptance by the test, an active compound must completely suppress the running component in a total of sixteen mice at a dose of 1/5 LD50 intraperitoneally.

. Considerable economies in the numbers of animals required for screening have been achieved, the mean number of mice required to reject an inactive compound being 2ṁ0.

. The running component is highly sensitive to anticonvulsants and general central depressants, and insensitive to phenothiazine tranquillizers and morphine. Reserpine caused an increase in the severity of the running component.

. The statistical model used in this test is of general application to screening test situations which use quantal data.
The pharmacology of the cholinoceptor in muscle preparations of Ascaris lumbricoides var. suum
Authors: NATOFF I. L.
Published: July 2012

. The preparation of a muscle strip of Ascaris lumbricoides for the study of the effect of drugs in vitro is described.

. Stimulant drugs which are classified as nicotine‐like in mammalian pharmacology increased the isometric tension of this preparation. These drugs were, in descending order of potency: dimethylphenylpiperazinium, nicotine, acetylcholine, carbachol, decamethonium and pyridine‐2‐aldoxime methiodide.

. Muscarine‐like drugs (oxotremorine, methacholine, pilocarpine) had no activity.

. Potassium and barium ions stimulated the tissue, while the anti‐cholin‐esterases, dichlorvos and eserine, increased the resting tension of the preparation and potentiated the responses to acetylcholine.

. Adrenaline neither stimulated the tissue nor affected the responses to nicotine‐like drugs.

. The relative potency of several blocking agents which antagonize the responses to nicotine‐like drugs was assayed. These blocking agents were, in descending order of potency: mecamylamine, (+)‐tubocurarine, hexamethonium, atropine and piperazine. Acetylcholine, dimethylphenylpiperazinium and pyridine‐2‐aldoxime methiodide apparently act on a common receptor, for each blocking agent had a similar molar inhibitory concentration against these stimulants.

. It is concluded that the cholinoceptor in muscle preparations of Ascaris lumbricoides is pharmacologically similar to that of the mammalian autonomic ganglion.
The effect of a large dose of atropine upon the performance of routine tasks
Authors: MOYLAN‐JONES R. J.
Published: July 2012

. A field trial was conducted in order to assess the effect upon tasks, including hard labour, skilled work, the use of instruments and tools and shooting, of giving 6 mg of atropine sulphate by injection to twenty‐three adult male volunteers.

. Impairment of performance was seen in these tasks under the influence of the drug, but this was statistically significant only in some of them.

. Drowsiness occurred in twenty‐one men and perceptual disorders were common, but two men were almost completely resistant to the effects of the drug.

. The implications of the therapeutic use of comparable doses of atropine are discussed.
Interaction between (±)‐amphetamine and atropine on the rat cardiovascular system
Authors: ALLAN DOROTHY , BAIRD J. R. C. , ELLIS KATHLEEN E. J.
Published: July 2012

. The effects of atropine on the pithed rat blood pressure after (±)‐amphetamine depend on the pattern of the cardiovascular responses to the latter.

. If the pressor response to amphetamine is followed by oscillations of blood pressure and a reduction in pulse pressure or by a fall in blood pressure terminating in circulatory failure, atropine increases blood pressure, but if it is not followed by these patterns, atropine decreases blood pressure.

. The fall in blood pressure produced by atropine after amphetamine might be due to weak alpha‐adrenoceptor blockade.
A comparison of the anti‐arrhythmic actions of I.C.I. 50172 and (—)‐propranolol and their effects on intracellular cardiac action potentials and other features of cardiac function
Authors: PAPP J. GY. , WILLIAMS E. M. VAUGHAN
Published: July 2012

. I.C.I. 50172 had marked quinidine‐like effects on intracellular cardiac action potentials at concentrations above 20 mg/l. (6·61 × 10−5m). The rate of rise and overshoot of the action potential, conduction velocity and contractions were decreased. (–)‐Propranolol had similar effects at less than 1/30 this concentration.

. I.C.I. 50172 had 1/100 the activity of (–)‐propranolol as a local anaesthetic. Since this is also the ratio of their in vitro β‐receptor blocking activities, I.C.I. 50172 provides no net increase in specificity of β‐receptor blockade.

. In contrast, the in vivo activity of I.C.I. 50172 in protecting anaesthetized guinea‐pigs against ouabain‐induced ventricular fibrillation was 40% that of (–)‐propranolol.

. Structure‐activity relations of β‐receptor blocking drugs are discussed.