bluuebunny/crossref_metadata_2025 huggingface dataset:
Biological Characterization and Complete Genome Sequence of a Possible Strain of Indian cassava mosaic virus from Jatropha curcas in India
Authors: Snehi Sunil Kumar , Srivastava Ashish , Raj Shri Krishana
Published: July 2012

The outbreak of a severe mosaic disease with a significant incidence was noticed on Jatropha curcas plants growing in Lucknow, Northern India. The causal virus was successfully transmitted by whiteflies (Bemisia tabaci) and grafting from naturally infected to healthy J. curcas plants. The association of Begomovirus with the mosaic disease of J. curcas was detected by PCR using primers specific to DNA‐A of Begomoviruses. Further, full‐length DNA‐A genome of ∼2.7 kb was amplified by RCA followed by digestion with Bam HI restriction enzyme. Cloning and sequencing of obtained amplicons resulted in 2740 nucleotides of complete DNA‐A consisting of six ORFs and IR region (GenBank Accession HM230683). The sequence analysis revealed highest 85% similarities with Jatropha curcas mosaic virus, 77–84% with Indian cassava mosaic virus and 73–76% with Sri Lankan cassava mosaic virus isolates. Phylogenetic analysis of the Begomovirus isolate also showed a clear‐cut distinct relationship with earlier reported Begomoviruses from Jatropha curcas and other Begomoviruses. On the basis of the guidelines of the International Committee on Taxonomy of Viruses (ICTV‐2008), our virus isolate was identified as a possible strain of Indian cassava mosaic virus, and its name Jatropha mosaic India virus (JMIV) is proposed.
Morphological, biochemical and phylogenetic assessments of water‐bloom‐forming tropical morphospecies of Microcystis (Chroococcales, Cyanobacteria)
Authors: Le Ai Nguyen Vinh , Tanabe Yuuhiko , Matsuura Hiroshi , Kaya Kunimitsu , Watanabe Makoto M.
Published: July 2012

Previous polyphasic analyses of five morphospecies of the water‐bloom‐forming cyanobacterial genus Microcystis, Microcystis aeruginosa (Kützing) Lemmermann (=Microcystis aeruginosa (Kützing) Kützing), Microcystis ichthyoblabe Kützing, Microcystis novacekii (Komárek) Compère, Microcystis viridis (A. Braun) Lemmermann, and Microcystis wesenbergii (Komárek) Komárek in Kondratieva, have shown them to be conspecific and they have been proposed to be included under the binomial Microcystis aeruginosa (Kützing) Lemmermann. However, several morphospecies from tropical regions, such as Microcystis bengalensis Banerji, Microcystis panniformis Komárek, Komárková‐Legnerová, Sant'anna, Azevedo & Senna, Microcystis protocystis Crow, Microcystis pseudofilamentosa Crow, Microcystis ramosa Bharadwaya, and Microcystis robusta (Clark) Nygaard, have never been analyzed biochemically or phylogenetically; consequently, their taxonomic status is uncertain. To resolve this issue, we collected 57 strains of Microcystis from Vietnam for taxonomic analysis using a polyphasic approach. Strains were assigned to the six tropical morphospecies listed above or to four morphospecies with cosmopolitan distributions (M. aeruginosa, M. ichthyoblabe, M. novacekii, and M. wesenbergii). Several strains produced colony variants in different culture media; some of these variants had forms that overlapped with those of other morphospecies. Cell diameters varied widely between strains (2.6–9.3 µm) and were unrelated to morphospecies discrimination criteria. Strains of the 10 morphospecies examined had similar fatty acid compositions and closely similar 16S rRNA gene sequences (>99.2% similar). Phylogenetic analyses using 16S rRNA gene and 16S–23S internal transcribed spacer sequences did not identify any clear separations corresponding to morphospecies concepts or microcystin‐producing abilities. Thus, the six tropical morphospecies (M. bengalensis, M. panniformis, M. protocystis, M. pseudofilamentosa, M. ramosa, and M. robusta) are not natural taxonomic units within the genus Microcystis and should be included under M. aeruginosa.
Iridal coloboma induces dyscoria during miosis in FLS mice
Authors: Matsuura Tetsuro , Tsuji Naho , Kodama Yasushi , Narama Isao , Ozaki Kiyokazu
Published: July 2012

Objective  Fatty liver Shionogi (FLS) mice exhibit characteristic retinochoroidal coloboma because of a failure in fusion of the embryonic optic fissure. However, the same pathogenesis should result in iridal coloboma that has not been reported in this strain. The purpose of this study was to describe the physiologic and morphometric changes in iridal tissue involved in ocular coloboma in FLS mice.

Procedures  The miotic response after light exposure was evaluated in three strains of live mice, and the shape and location of the pupil were judged macroscopically. Subsequently, macroscopic abnormalities in the anterior segment and fundus were observed postmortem in all mice. During miotic and mydriatic responses in the eyes of live male FLS mice with dyscoric and normal pupils, each iris was measured in four radial directions. The enucleated eyes were examined morphometrically and histologically in both sexes of FLS mice.

Results  Inferior corectopia upon light‐induced miosis was clearly detected in live FLS mice. The deviated pupils were not round but oval‐shaped. Clinical and postmortem examination revealed that all dyscoric eyes had hypoplastic and dysfunctional irides inferiorly in FLS mice. Histopathological examination confirmed that both the dilator and sphincter muscles and iris stroma were quantitatively diminished in the affected inferior iris. Meanwhile, the rate of fundus (retinochoroidal) coloboma in eyes exhibiting dyscoria was remarkably high, although some dyscoric eyes had no fundus coloboma.

Conclusions  Fatty liver Shionogi mice had iridal coloboma, resulting in inferior corectopia upon light‐induced miosis as an indicator of ocular coloboma.
Canine ocular tumors following ciliary body ablation with intravitreal gentamicin
Authors: Duke Felicia D. , Strong Travis D. , Bentley Ellison , Dubielzig Richard R.
Published: July 2012

Iridociliary tumors are the second most common primary ocular tumor in dogs and are usually benign. A review of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) database in 2009 suggested a potential correlation between malignant iridociliary epithelial tumors and ciliary body ablation by intravitreal gentamicin injection for the treatment of glaucoma. The purpose of this case series was to determine whether there is evidence of such a correlation in the COPLOW collection. Mining of the COPLOW database revealed that a significant number (39.5%) of canine globes with a history of ciliary body ablation were subsequently diagnosed with primary ocular tumors at enucleation, most commonly iridociliary epithelial tumors and melanocytic tumors. It is possible that neoplasia was present but unrecognized at the time of ciliary body ablation. These tumors had a higher than expected incidence of malignancy. These cases underscore the importance of reserving ciliary body ablation with gentamicin for disease‐free eyes.
Histological and histochemical study of the duodenum of the plains viscacha (Lagostomus maximus) at different stages of its ontogenetic development
Authors: Tano de la Hoz María Florencia , Flamini Mirta Alicia , Díaz Alcira Ofelia
Published: July 2012

The general objective of this study focused on the duodenal histological and histochemical analysis of fetuses and adults of plains viscacha (Lagostomus maximus) from the Buenos Aires province (Argentina). Histological techniques, histochemical procedures for localizing and characterizing glycoproteins (GPs) and lectin histochemical techniques for the identification of specific sugar residues were used. The duodenal structure of all age groups here considered was typical of mammals. We identified a proliferation phase and an epithelial morphogenesis in mid‐gestational fetuses, an intermediate period of cell differentiation in at‐term fetuses and a posterior stage of physiological maturation in adults. According to histochemistry, the diverse GPs elaborated and secreted into the duodenum show a high degree of histochemical complexity related to the multiple functions of mucus in the digestive tract. The GPs in the duodenum of L. maximus and their glycosylation patterns varied according to the animal's age and the developmental state of the organ.
Conservation planning under climate change: accounting for adaptive potential and migration capacity in species distribution models
Authors: Hamann Andreas , Aitken Sally N.
Published: July 2012

Aim

A number of assumptions underpinning the use of species distribution models to predict biological responses to climate change are violated for temperate and boreal tree species that are widespread, long‐lived and genetically adapted to local climate conditions. To address this situation, we propose a methodology to account for the potential effects of genetic structure, adaptive potential and limited migration capacity.

Location

British Columbia, Canada.

Methods

Similar to the widely used ‘no migration’ and ‘unlimited migration’ scenarios, we employ more refined biological response scenarios to evaluate the potential effects of genetic adaptation to local environments and the capacity of species to adapt and migrate. These scenarios are realized by two sets of geographic delineations that partition the species range into multiple populations and that subdivide the study area into smaller landscape units.

Results

In a case study for British Columbia, we demonstrate how the approach can be used to evaluate the adequacy of a reserve system of 906 protected areas to ensure long‐term maintenance of forest genetic resources for 48 tree species. We find that between 35% and 85% of locally adapted populations in protected areas are maintained under a median climate change scenario until the end of the century. A sensitivity analysis shows that assumptions about migration and adaptation capacity of species have a major effect on the projected conservation status.

Main conclusions

We propose that the results of species distribution models have practical value for conservation planning if the focus is on maintenance rather than loss of suitable habitat. Accounting for genetic structure, adaptive potential and migration capacity through best‐case and worst‐case scenarios provide important information to effectively allocate limited resources available for conservation action.
THE ACTIVITY OF DIFFERENT STEROIDS IN PRODUCING THYMIC INVOLUTION
Authors: SHEWELL JENNIFER
Published: July 2012

The assay method for corticotrophin, in which the involution of the thymus of the nestling rat is measured, can be applied successfully as a quick and simple screening test for biologically active corticosteroids. The sensitivity of the test is such that injection of a standard dose of cortisone acetate produces different results when made up in different media, or injected by different routes. A standard procedure for dispensing and injecting the steroids has therefore been adopted. Of the steroids investigated, it is noticeable that those possessing marked thymolytic activity are also steroids with therapeutic properties.
EFFECT OF CHAIN LENGTH OF ALIPHATIC AMINES ON HISTAMINE POTENTIATION AND RELEASE
Authors: MONGAR J. L.
Published: July 2012

Diamines in the series NHa.(CH2)n.NH2 specifically potentiate histamine contractions of the guinea‐pig ileum and inhibit the enzymatic destruction of histamine. These activities are greatest with short‐chain compounds (n⋍5). Diamines also release histamine from isolated tissues and depress the contractility of plain muscle and the motility of paramecia. These activities increase with chain‐length and are probably limited only by solubility. The parallelism between histamine‐releasing activity and toxicity also extends to the monoamines in the series CH3.(CH2)n‐1.NH2. Histamine‐releasing activity of both series increases with increase of pH and can mainly be attributed to the non‐ionized base.

From the results on the effect of chain‐length and ionization on activity, it is suggested that aliphatic amines release histamine by penetration of the cell membrane in the non‐ionized form, followed by exchange in the ionic form with intracellular histamine.
THE ACTION OF ERGOTAMINE ON THE INTRACRANIAL VENOUS PRESSURE AND ON THE CEREBRAL VENOUS OUTFLOW OF THE DOG
Authors: CARPI A. , VIRNO M.
Published: July 2012

The effect of ergotamine and dihydroergotamine on the cerebral circulation was studied in the dog, anaesthetized with chloralose, by recording the intracranial venous pressure and the venous outflow from the superior cerebral vein. Under optimal experimental conditions, ergotamine (5 to 10 μg./kg.) and dihydroergotamine (100 μg./kg.) gave a marked and long‐lasting cerebral vasoconstriction accompanied by a slight hypertension. The cerebral vasoconstriction provoked by ergotamine may be very small and was sometimes absent when the cerebral blood‐flow was low. This vasoconstrictor effect is more pronounced the higher the initial intracranial venous pressure and hence the cerebral blood‐flow. After the induction of a cerebral vasodilatation by 48/80 or strychnine, the vasoconstrictor action of ergotamine was more pronounced. The effect was not observed when CO2 was employed to modify the intracranial venous pressure. Simultaneous registration of the cerebral, nasal cavity, and kidney vascular responses demonstrated the relative specificity of the action of ergotamine on the cerebral vessels. The small doses of ergotamine used may weaken or abolish the vasoconstrictor action of adrenaline on cerebral vessels. The modification of the responses of the cerebral circulation which such factors as anaesthesia, respiratory acidosis, and operative trauma can produce have been confirmed and emphasized. The results support the view that the vasoconstrictor action of ergotamine on the cerebral vessels might account for the therapeutic value of this drug in migraine.
SOME ACTIONS OF SUBSTITUTED CHOLINE PHENYL ETHERS, PARTICULARLY OF CHOLINE 2:6‐XYLYL ETHER
Authors: EDGE N. D. , MASON D. F. J. , WYLLIE J. H.
Published: July 2012

Marked nicotine‐like stimulant properties are possessed by choline phenyl ether and choline o‐tolyl ether, and to a decreasing extent by choline 2:6‐xylyl ether and choline 2:4:6‐mesityl ether. The compounds all show neuromuscular blocking properties, which are of short duration and pass from mainly decamethonium‐like to mainly curare‐like as more methyl groups are added to the phenyl nucleus. This series of compounds also possesses muscarinic, weak anti‐adrenaline and vasodilator properties, as well as long‐lasting local anaesthetic effects in the two compounds tested by intradermal injection.
THE ACTION OF HYPOGLYCAEMIC SULPHONYLUREAS ON CARBOHYDRATE METABOLISM IN THE FASTED RAT
Authors: FRY I. KELSEY , WRIGHT P. H.
Published: July 2012

Tolbutamide and carbutamide given orally to fasted rats cause a rise in the liver glycogen content 1 1/2 to 3 1/2 hr. after administration of the drugs. Glycogen accumulates preferentially in the right lobe. Subcutaneously injected tolbutamide has the same effect. Both sulphonylureas cause inhibition of glucose‐6‐phosphatase activity of rat liver homogenates in vitro, but at drug concentrations comparable with those found in plasma of treated patients the degree of inhibition is less than 10%. Livers from treated rats show normal glucose‐6‐phosphatase activity. The glucose uptake of the isolated rat diaphragm is unaffected by the sulphonylureas added in vitro. Diaphragms from treated rats show normal glucose uptake in the presence or absence of insulin. The inferences to be drawn from these results are discussed in the light of previous work. It is concluded that the sulphonylureas exert their hypoglycaemic action by inhibiting glycogenolysis and it is suggested that they might do so by inhibiting release of glucagon from the pancreas.
THE ASSOCIATION OF BLOOD CHOLINESTERASE LEVELS WITH THE SUSCEPTIBILITY OF ANIMALS TO SARIN AND ETHYL PYROPHOSPHATE POISONING
Authors: CALLAWAY S. , DAVIES D. R.
Published: July 2012

An association between the blood cholinesterase (ChE) levels and the toxicity of sarin and ethyl pyrophosphate has been established. This has been demonstrated in two types of experiment. In the first, guinea‐pigs were given a non‐lethal dose of sarin (isopropyl methylphosphonofluoridate) which reduced the blood ChE to 20% of normal, and at intervals, as the ChE level of the blood gradually recovered, separate batches were given a second dose of the same size. A comparison was then made between the blood ChE levels immediately prior to the injection of the second dose and the mortality rate. In the second, a relatively small dose of sarin or ethyl pyrophosphate was given daily to rabbits until the enzyme value fell to a steady level. LD50 values were then determined on such groups and compared with those found in saline treated ones. In both guinea‐pigs and rabbits it has been shown that a depression of blood ChE to below 40% indicated an increased toxicity of sarin and ethyl pyrophosphate to these species. The approximate quantitative relation appears to be that susceptibility is increased in the ratio 1.5 when the blood ChE is reduced by half.
THE ADRENALINE AND NORADRENALINE CONTENT OF THE ADRENAL GLAND OF THE CAT FOLLOWING DEPLETION BY ACETYLCHOLINE
Authors: BUTTERWORTH K. R. , MANN MONICA
Published: July 2012

This paper describes the attempts that were made to obtain a replacement of adrenaline and noradrenaline in the adrenal gland of the atropinized cat, subsequent to the depletion of the gland by repeated intravenous doses of acetylcholine. In the anaesthetized animal, there was no replacement of adrenal amines within 15 hours of the depletion. The further loss of amine that occurred during this time was prevented by the denervation of the gland. If the animal was allowed to recover from the anaesthetic there was some replacement of amines within 2 to 3 days, provided that the condition of the animal was satisfactory. By 6 to 7 days the total amine content had returned to its initial level, but there was now an alteration in the relative proportions of the two amines. Although the adrenaline was still well below the resting level, the noradrenaline was several times its initial value. By one month, the noradrenaline had decreased and the adrenaline had increased to their initial amounts and proportions. Thus this work gives evidence for the formation of adrenaline from noradrenaline.
THE RELEASE OF ADRENALINE AND NORADRENALINE FROM THE ADRENAL GLAND OF THE CAT BY ACETYLCHOLINE
Authors: BUTTERWORTH K. R. , MANN MONICA
Published: July 2012

The adrenal glands of atropinized cats were depleted of their content of adrenaline and noradrenaline by repeated intravenous doses of acetylcholine. In each experiment there was a similar percentage loss of both amines. This was irrespective of the degree of depletion, which ranged from 7.1% to 86.5%. In some experiments, adrenal blood was collected and it was found that the percentage of noradrenaline in the adrenal venous effluent (mean 62.0%) was similar to that in the amine lost from the depleted gland (mean 63.7%). In some experiments, the adrenaline and noradrenaline lost from the gland could be recovered quantitatively in the adrenal blood. The results indicate that, under these experimental conditions, synthesis is not taking place concurrently with the liberation of amines or that it is taking place so slowly as not to be detected.
A COMPARISON OF THE LOCAL EFFECTS OF VARIOUS INTRAMUSCULAR INJECTIONS IN THE RAT
Authors: PAGET G. E. , SCOTT H. McG.
Published: July 2012

A method is described for the assessment of the local reaction produced by intramuscular injections. This method involves the histological examinations of the injection site after injection of material into the hamstring muscles of the rat. The results obtained with both aqueous and oily materials are described; the correlation of these results with clinical observations in man is discussed.
THE EFFECTS OF MECAMYLAMINE IN THE CAT AS MODIFIED BY THE ADMINISTRATION OF CARBON DIOXIDE
Authors: PAYNE J. P. , ROWE G. G.
Published: July 2012

A series of cats, anaesthetized with chloralose, was given intravenously a sufficient quantity of mecamylamine to produce hypotension and a 50% neuromuscular block. Inhalation of carbon dioxide then produced a further depression of blood pressure and an increase in the neuromuscular blocking effect. It was shown that, following the administration of carbon dioxide, the plasma mecamylamine levels increased coincident with the increased pharmacological effects.
THE EFFECT OF HUMAN PLASMA ON THE GLUCOSE UPTAKE OF THE RAT DIAPHRAGM BEFORE AND AFTER ADMINISTRATION OF CARBUTAMIDE
Authors: AIMAN RANITA , KULKARNI R. D.
Published: July 2012

The glucose uptake of the rat diaphragm has been determined in the presence of the plasma of young volunteers before and after administration of carbutamide without and with added insulin. The increase in the glucose uptake of the rat diaphragm due to the added plasma above that in the medium alone has been termed plasma effect. The increase in the glucose uptake of the rat diaphragm with plasma and added insulin above that with only insulin in the medium has been termed plasma + insulin effect. There was a significant increase in the plasma effect and the plasma + insulin effect after carbutamide administration. The increase in the plasma‐insulin effect was significantly greater than the increase in the plasma effect. From these observations it has been suggested that carbutamide potentiates the action of insulin peripherally. Observed facts about carbutamide do not contradict this mechanism of action.
THE ANTAGONISM OF THE VASCULAR EFFECTS OF 5‐HYDROXYTRYPTAMINE BY BOL 148 AND SODIUM SALICYLATE IN THE HUMAN SUBJECT
Authors: GLOVER W. E. , MARSHALL R. J. , WHELAN R. F.
Published: July 2012

2‐Bromo‐(+)‐lysergic acid diethylamide (BOL 148) is a specific antagonist of the constrictor response of the forearm and hand blood vessels to intra‐arterial infusions of 5‐hydroxytryptamine. This has been shown to be a direct action in the tissue concerned, since the antagonism was as effective when the drug was given by local arterial injection as when given intravenously. Sodium salicylate is also a specific antagonist of 5‐hydroxytryptamine, but its action is indirect, occurring only when the general serum level was raised above 10 or 20 mg.%; local limb concentrations of 30 to 40 mg.% had no antagonistic effect. The mechanism of the antagonistic effect of salicylate is not known. It is not related to the associated hyperventilation but is possibly due to the secondary release of, or synergism with, some other substance, probably a hormone.
THE EFFECTS OF ANTICHOLINESTERASES ON THE BRONCHIOLES AND PULMONARY BLOOD VESSELS IN ISOLATED PERFUSED LUNGS OF THE DOG
Authors: DALY M. de BURGH
Published: July 2012

The effects of two potent inhibitors of cholinesterase, isopropylmethylphosphonofluoridate (sarin) and ethyl pyrophosphate (TEPP), were investigated on the bronchioles and pulmonary blood vessels in isolated dog lung preparations perfused with heparinized blood and ventilated artificially. These anticholinesterases caused gradual bronchoconstriction as indicated by a diminution in tidal air volume, a reduction in compliance and an increase in expiratory resistance. These effects were antagonized by atropine. An increase in pulmonary vascular resistance occurred which was enhanced by the addition of small quantities of acetylcholine to the perfusing blood. The pulmonary vascular effects of acetylcholine, sarin and TEPP were prevented and abolished by atropine. Evidence is presented which suggests that the site of action of these anticholinesterases is, at least in part, peripheral to the autonomic ganglia.
DETECTION AND MEASUREMENT OF ANTAGONISM TO FOLIC ACID
Authors: COLLIER H. O. J. , GRIMSHAW J. J. , HUSKINSON PATRICIA L.
Published: July 2012

Methods of testing competitive antagonism in bacterial systems are considered and evaluated with particular reference to antifolic acids. Four antifolic acids—pteridine O/129, methotrexate, CB2295 and CB2335—were examined for competitiveness and potency in three test systems—Leuc. citrovorum and folinic acid, Str. faecalis and folinic acid, and Str. faecalis and pteroylglutamic acid. For comparison, phenol and formaldehyde were studied in the Leuc. citrovorum and folinic acid system. Interpretation of results was based on families of log. concentration/growth curves obtained in each system in the presence and absence of each antagonist. These curves were usually simple sigmoids. From these families of curves, pA values were derived and reciprocal growth/reciprocal concentration curves were drawn. Pteridine O/129 was fully competitive in all systems, while methotrexate was fully competitive in the Str. faecalis and folinic acid system, but did not give simple sigmoids in the other two systems. CB2295 showed some competitive features in all and CB2335 in the two systems in which it was active. It is concluded that the methods adopted, based on those used in vertebrate pharmacology, provide a stringent test of competitiveness in bacterial systems.
INTRAVENTRICULAR ADMINISTRATION OF RESERPINE AND ITS METABOLITES TO CONSCIOUS CATS
Authors: DASGUPTA S. R. , HALEY T. J.
Published: July 2012

Intraventricular injection of reserpine in conscious cats produced relaxation of the nictitating membrane, miosis with narrowing of the palpebral fissure to a slit, avoidance of light, diarrhoea, anorexia, and tranquillization. Equivalent doses of trimethoxybenzoic acid, reserpic acid or methylreserpate separately or in combination did not produce such effects, indicating that these reserpine metabolites were not involved in these reserpine actions. 5‐Hydroxytryptamine alone or in combination with subthreshold doses of reserpine also did not duplicate the effects observed after effective doses of reserpine. The possible central sites of reserpine action are discussed.
THE INHIBITORY ACTION OF SOME ANTIMALARIAL DRUGS AND RELATED COMPOUNDS ON THE HEXOKINASE OF YEAST AND OF PLASMODIUM BERGHEI
Authors: FRASER DOROTHY M. , KERMACK W. O.
Published: July 2012

Of various antimalarial compounds tested, only proguanil failed to inhibit yeast hexokinase. The metabolite of proguanil, 10,580, was an effective inhibitor. Some compounds tested which were without antimalarial activity were potent inhibitors of yeast hexokinase. The degree of inhibition increased as the time during which the enzyme had been in contact with the drug increased, and the inhibitory action of mepacrine was reduced when the concentration of ATP was raised. The inhibition of yeast hexokinase by 10,732 was independent of the concentration of ATP.

The hexokinase of haemolysates of the reticulocytes of mouse or rat blood was not appreciably higher than that of similar haemolysates of normal erythrocytes. Preparations of mouse or rat erythrocytes parasitized with P. berghei possessed a much higher hexokinase activity.

The inhibiting action of various compounds on the hexokinase of P. berghei closely resembled those with yeast hexokinase. Again all antimalarial compounds (apart from proguanil) inhibited the enzyme, but some of the most potent inhibitors were devoid of antimalarial action. Amongst the chemotherapeutically active compounds, there appeared to be an approximate parallelism between antimalarial activity and potency as inhibitors of plasmodial hexokinase. The action of mepacrine on plasmodial hexokinase was reduced by raising the concentration of ATP, but, as with yeast hexokinase, the inhibition by 10,732 was independent of the ATP concentration.

From a consideration of the results, it seems doubtful whether this type of inhibitory effect plays more than a minor part in the mechanism of antimalarial action in vivo.
THE EFFECT OF ESERINE AND NEOSTIGMINE ON THE BLOOD PRESSURE OF CONSCIOUS RATS
Authors: MEDAKOVIĆ M. , VARAGIĆ V.
Published: July 2012

Small amounts of eserine salicylate (10 to 20 μg.) regularly caused a rise of blood pressure in non‐anaesthetized rats. Neostigmine methylsulphate in doses from 1 to 10 μg./animal usually caused a fall of blood pressure, or no change was observed; only in a few experiments was a rise of blood pressure noted. The pressor effect of eserine was abolished by atropine and reduced or abolished by yohimbine and phentolamine. Adrenalectomy did not change the response to eserine. The present experiments do not contradict earlier statements that the pressor effect of eserine was due to the discharge of impulses from a centre or centres in the central nervous system.
HISTAMINE RELEASE INHIBITION IN VITRO AND ANTIANAPHYLACTIC EFFECTS IN VIVO OF SOME CHEMICAL COMPOUNDS
Authors: McINTIRE F. C. , RICHARDS R. K. , ROTH L. W.
Published: July 2012

Several different types of compounds inhibited the release of histamine from the “platelet fraction” of rabbit blood when antigen was added to the blood of a sensitized rabbit in vitro. These compounds were all very toxic in vivo and could be tested only at low levels for their ability to protect animals against anaphylaxis. None of the compounds gave significant protection to sensitized animals when antigen was given intravenously. Three compounds protected animals against antigen administered as an aerosol. None of these showed any promise of clinical usefulness.

Of a number of compounds which have been reported to alleviate allergic symptoms, or to protect against anaphylaxis, none prevented the release of histamine in vitro to any considerable extent.
PHARMACOLOGICAL ACTIONS OF PURE MUSCARINE CHLORIDE
Authors: FRASER P. J.
Published: July 2012

The action of chromatographically pure crystalline muscarine chloride, prepared from Amanita muscaria, has been compared with acetylcholine chloride (ACh) on a number of different organs from a variety of species. Muscarine caused spasm in vivo and in vitro of muscles of the gut, uterus, urinary bladder, and bronchus. It also caused contraction of the horse ureter and carotid artery chain in vitro and slowed the isolated auricles of the guinea‐pig and rabbit, and the frog heart.

Muscarine caused a drop in blood pressure, although in vitro it produced either constriction or dilatation of the blood vessels of the rabbit ear.

All these actions resembled those of acetylcholine, though muscarine was usually more potent. Muscarine effects were readily prevented by atropine sulphate. It had a slight action on the frog rectus abdominis muscle, causing a contracture at high concentrations. Muscarine was destroyed neither by pepsin nor by boiling at any pH. It was inactive by mouth in a monkey in a quantity many times that which would cause poisoning by ingestion of Amanita muscaria in the human being. Muscarine neither inhibited nor was hydrolysed by either true‐ or pseudo‐cholinesterase. Muscarine chloride did not cause paralysis of the neuromuscular junctions of the rat diaphragm or of the cat gastrocnemius.
THE RELEASE OF CATECHOL AMINES FROM ISOLATED CHROMAFFIN GRANULES
Authors: EADE N. R.
Published: July 2012

Release of catechol amines from the chromaffin granules of the bovine suprarenal medulla has been studied. Aliphatic monoamines and diamines released catechol amines from chromaffin granules under conditions similar to those under which they are known to promote the release of histamine from suspensions of granules. Carbachol and histamine did not release catechol amines from granules.
ANALGESIC ACTIVITY OF DIPIPANONE HYDROCHLORIDE IN STUDENT VOLUNTEERS
Authors: CAHAL D. A.
Published: July 2012

Dipipanone hydrochloride raised the threshold to ischaemic pain in healthy human volunteers. The lowest dose producing a significant rise in pain threshold was 10.0 mg. The peak effect for all doses was reached after about 2 hr. Side effects, the most common of which were drowsiness, nausea, and vertigo, are described and analysed. The drug was shown to be a histamine liberator and to cause pain and tenderness at injection sites.
THE EFFECT OF ETHER AND PENTOBARBITONE SODIUM ON GASTROINTESTINAL FUNCTION IN THE INTACT RAT
Authors: REYNELL P. C. , SPRAY G. H.
Published: July 2012

The effect of ether and pentobarbitone anaesthesia on gastrointestinal motility and absorption has been studied by measuring simultaneously gastric emptying, small intestinal transit and intestinal absorption of glucose and iodide in intact rats. Both gastric emptying and intestinal transit are very slow under ether anaesthesia, but with pentobarbitone there is no significant delay. The absorption of glucose by the small intestine is significantly impaired by ether but not by pentobarbitone, and a tracer dose of iodide is absorbed normally under both forms of anaesthesia.
THE ACTION OF MORPHINE AND RELATED SUBSTANCES ON CONTRACTION AND ON ACETYLCHOLINE OUTPUT OF COAXIALLY STIMULATED GUINEA‐PIG ILEUM
Authors: PATON W. D. M.
Published: July 2012

Morphine depresses the twitch and tetanus of stimulated guinea‐pig ileum by reducing acetylcholine released from cholinergic nerve endings. Acetylcholine output per shock falls to roughly the same residual amount at varying stimulation rates. Since normal output per shock declines with increasing stimulus frequency, the proportionate effect of morphine diminishes as stimulus frequency rises. Acute “tolerance” to morphine and a state of “morphine‐dependence” can be produced. Phenadoxone, dihydromorphinone, metopon, methadone, and heroin are more active, codeine and pethidine less active, than morphine. Nalorphine also depresses the twitch and can desensitize the gut both to itself and to morphine.
THE ACTION OF NITROPHENOLS ON THE METABOLIC RATE OF RATS
Authors: CAMERON MARGARET A. M.
Published: July 2012

The effect of the mono‐ and di‐nitrophenols and certain related compounds has been determined on the rate of oxygen consumption, the rate of carbon dioxide output and the rectal temperature of the Wistar albino rat.

Of the compounds examined, only 2:4‐dinitrophenol and its derivative, 3:5‐dinitro‐o‐cresol, stimulated metabolic rate. 2‐Nitrophenol and 2:3‐, 2:6‐, and 3:5‐dinitrophenol produced no change in metabolic rate; 3‐nitrophenol and 2:5‐dinitrophenol had no action on carbon dioxide production although they caused a decrease in oxygen consumption. 4‐Nitrophenol and 3:4‐dinitrophenol increased only the rate of carbon dioxide output; 2‐amino‐4‐nitrophenol increased the rate of carbon dioxide output and decreased the rate of oxygen consumption; 4‐amino‐2‐nitrophenol caused depression of metabolic rate.

It was confirmed that neither rectal temperature nor carbon dioxide output could replace rate of oxygen consumption as a reliable index of metabolic stimulant action. An apparatus is described which facilitates measurement of the oxygen consumption of small mammals.
THE ACTION OF DOPAMINE ON THE ARTERIAL BLOOD PRESSURE OF THE GUINEA‐PIG
Authors: HORNYKIEWICZ O.
Published: July 2012

The depressor action of dopamine (β‐3:4‐dihydroxyphenylethylamine) upon the arterial blood pressure of the guinea‐pig has been studied. This effect begins without a latent period. It is often enhanced after the intravenous injection of iproniazid (Marsilid). The depressor response is sufficiently sensitive to serve as a method of bioassay of dopamine in microgram quantities. Observations on the depressor action of l‐dopa have also been made. This effect is also enhanced by iproniazid; it begins after a latent period. Epinine (β‐3:4‐dihydroxyphenylethylmethylamine) caused a pressor response, followed by a fall of arterial blood pressure. No evidence was obtained in support of the suggestion that the two amines, which are oxidized at similar rates by amine oxidase, cause a fall of blood pressure after their conversion to an aldehyde by the action of amine oxidase.
A COMPARISON OF THE PITUITARY INHIBITORY EFFECTS OF PREDNISONE, PREDNISOLONE, AND HYDROCORTISONE
Authors: HODGES J. R. , VERNIKOS JOAN
Published: July 2012

Prednisone, prednisolone and hydrocortisone, administered in doses of 1 mg. daily for thirty days, depressed the growth rate of rats. Prednisolone and hydrocortisone caused atrophy of the adrenal glands and increased the relative weights of the thyroid glands and testes. The apparently similar effects produced by prednisone were not significant. The seminal vesicles were not affected significantly by prolonged administration of prednisone, prednisolone or hydrocortisone. Pretreatment of rats with these steroids prevented the adrenal ascorbic acid depletion normally caused by laparotomy under ether anaesthesia. Prednisolone was slightly more potent and prednisone was considerably less potent than hydrocortisone in producing these effects.
EFFECTS OF RATE OF STIMULATION AND OF FATIGUE ON THE RESPONSE TO NEUROMUSCULAR BLOCKING AGENTS
Authors: WISLICKI L.
Published: July 2012

The response to neuromuscular blocking agents, as exemplified by suxamethonium and tubo‐curarine, may differ between symmetrical muscles. Increased rates of stimulation and fatigue both increase sensitivity to blocking agents. During recovery from suxamethonium block muscles may show a transitory failure to react to each stimulus with a contraction. Fatigue caused by prolonged indirect stimulation is prevented equally well by suxamethonium and tubocurarine in doses producing a complete block. The mechanism and significance of these findings are discussed.
METABOLIC FACTORS AND VENTRICULAR FIBRILLATION
Authors: GOODFORD P. J.
Published: July 2012

Ventricular fibrillation has been studied in the isolated rabbit heart to determine the effect of factors modifying the metabolism. Sodium azide, sodium monoiodoacetate and sodium fluoride were found to cause fibrillation, the effect of sodium fluoride being neutralized by magnesium chloride. Fibrillation was also caused by lack of glucose and could be arrested by adding glucose; the effect of glucose in arresting fibrillation was facilitated by insulin. In other experiments mannose and pyruvate could arrest fibrillation due to lack of glucose, but l(‐)lactate could not. The effect of temperature changes, of adrenaline and of cyanide were also studied. When all oxygen was removed from the perfusing solution fibrillation was arrested.
COMPARISON OF THE EFFECTS OF ESERINE AND NEOSTIGMINE ON THE LEECH MUSCLE PREPARATION
Authors: BHATTACHARYA B. K. , FELDBERG W.
Published: July 2012

The relative potencies of eserine and neostigmine were determined on three preparations of Cholinesterase. Eserine was found to be twice as potent as neostigmine on the pseudocholin‐esterase of horse plasma, half as potent on the true Cholinesterase of cat central nervous system, but twelve times as potent on the true Cholinesterase prepared from the leech body wall. On the leech preparation, about ten times smaller concentrations of eserine than of neostigmine were required to potentiate the acetylcholine response, but after removal of the anticholinesterase from the bath fluid, the potentiation persisted much longer after neostigmine than after eserine. The greater sensitivity of the leech muscle to eserine is fully accounted for by the fact that its Cholinesterase is more sensitive to eserine than to neostigmine. The longer lasting potentiation after neostigmine on the other hand suggests that this anticholinesterase becomes more firmly attached to the Cholinesterase receptors in this muscle than does eserine.
PERFUSION OF CEREBRAL VENTRICLES: ASSAY OF PHARMACOLOGICALLY ACTIVE SUBSTANCES IN THE EFFLUENT FROM THE CISTERNA AND THE AQUEDUCT
Authors: BHATTACHARYA B. K. , FELDBERG W.
Published: July 2012

In cats under chloralose anaesthesia the cerebral ventricles were perfused from a cannula in the lateral ventricle. The effluent was collected either from the cisterna or from the aqueduct. When acetylcholine was added to the perfusion fluid and its destruction was prevented by the addition of an anticholinesterase, its recovery in the internal effluent was incomplete and irregular. This could be explained mainly by the devious route the perfusion fluid had to take in order to reach the cisterna and the unavoidable mixture with the cerebrospinal fluid of the subarachnoidal space. When collection was from the aqueduct 90% or more of the acetylcholine added to the perfusion fluid was recovered. In the presence of an anticholinesterase in the perfusion fluid, acetylcholine appeared in the effluent. Neostigmine was more effective than eserine or dyflos. The acetylcholine originated mainly from structures lining the lateral and third ventricle because the amounts in the effluent from the aqueduct were only a little less than those in the cisternal effluent. When injected intravenously, eserine was found to pass more readily into the perfusion fluid than neostigmine, probably because eserine passes the blood‐brain barrier more readily than neostigmine. The method provides a quantitative approach for the study of the blood‐brain barrier for pharmacologically active substances.
THE PRESSOR EFFECT OF PEPTONE IN THE RAT
Authors: BERALDO W. T.
Published: July 2012

Peptone normally causes a rise of blood pressure in rats. Since the pressor response was not abolished or even diminished by adrenalectomy, it could not have been caused by a release of pressor substances from the adrenal glands. The group of drugs (dibenamine, dihydroergotamine, ergotamine, tolazoline, nicotine and hexamethonium) which antagonize or block the peptone‐induced pressor action suggests that the pressor effect may be secondary to a release of sympathin by the stimulation of sympathetic ganglia. Since it was not possible to duplicate the pressor response to peptone by either 48/80 or histamine, the hypothesis that peptone acts by liberating histamine can be ruled out.
THE TOXICITY OF 2‐HYDROXYIMINOMETHYL‐NMETHYLPYRIDINIUM METHANESULPHONATE (P2S)
Authors: DAVIES D. R. , WILLEY G. L.
Published: July 2012

The toxicity of 2‐hydroxyiminomethyl‐N‐methylpyridinium methanesulphonate (P2S) has been determined in a number of species by various routes. It is approximately equally toxic in the rat, mouse, and guinea‐pig. It is much more toxic in the dog. Atropine influences the toxicity of P2S differently in different species. From the results obtained attempts have been made to assess the maximum safe dose which can be given intramuscularly to man.
QUANTITATIVE ASSAYS OF OXYTOCIC DRUGS ON THE HUMAN POSTPARTUM UTERUS
Authors: MYERSCOUGH P. R. , SCHILD H. O.
Published: July 2012

Quantitative assays of oxytocic drugs were performed on the postpartum human uterus by means of external tocography. Since, owing to the rapid involution of the uterus, only two doses could be given to each patient, the assays were designed as incomplete randomized blocks of 2. A dose/response curve for ergometrine was established, and a comparative assay of ergometrine and methyl ergometrine carried out, the design and analysis of which is described in detail.
PHARMACOLOGICAL ACTIVITY OF 5‐PHENYL‐1: 3: 4‐THIADIAZOLE (L 1538), 2‐AMINO‐5‐PHENYL‐1: 3: 4‐THIADIAZOLE (L 1460) AND 2‐AMINO‐5‐(2‐THIENYL)‐1: 3: 4‐THIADIAZOLE (L 1458)
Authors: MAFFII G. , SONCIN E.
Published: July 2012

The pharmacological actions of 5‐phenyl‐1: 3: 4‐thiadiazole (L 1538), 2‐amino‐5‐phenyl‐1: 3: 4‐thiadiazole (L 1460) and 2‐amino‐5‐(2′‐thienyl)‐1: 3: 4‐thiadiazole (L 1458) have been studied and compared with those of other muscular relaxant drugs. The three compounds have paralysing effects in mice, rats, cats, and dogs. They block the tonic component of maximal electroshock seizures and protect against strychnine, though not against leptazol‐induced convulsions in mice. Like other centrally acting paralysing drugs, they depress spinal polysynaptic transmission in doses which leave monosynaptic transmission relatively unaffected. The rigidity of the decerebrate cat is reduced but not always abolished. The compounds do not induce synchronization in epidural electroencephalogram recordings. In doses not greatly affecting muscular tone and spontaneous activity, they prolong the hypnotic effects of pentobarbitone and other barbiturates in mice. Autonomic functions are only slightly affected. The similar actions of substituted thiadiazoles and 2‐amino‐benzothiazoles confirm a previous hypothesis that pharmacological equivalence may result either from condensing heterocyclic nuclei with aromatic nuclei or from introducing aryl substituents into them.
ANTIVIRAL ACTION OF DERIVATIVES OF ω‐AMINOACETOPHENONE
Authors: BRUG J. , DE BOCK C. A. , MOED H. D. , KLEIN A. J.
Published: July 2012

Numerous structural analogues of 3‐amino‐4‐hydroxy‐ω‐methylaminoacetophenone were tested for their effect on the multiplication of influenza virus (FM1 strain) in embryonated eggs, infected via the allantoic cavity. Antiviral activity was found in ω‐aminoacetophenones containing an amino and hydroxyl group in the aromatic nucleus in the ortho or para positions to each other. The most powerful antiviral activity was found in the series of ω‐alkylamino‐5‐amino‐2: 4‐dihydroxyacetophenones. Derivatives of acetophenone with other substituents in the aromatic nucleus or in the aliphatic chain were without activity. In vitro, several analogues inactive in the egg test, as well as those which were active, exerted a virucidal and to a lesser extent a haemagglutinin‐destroying action. Antiviral action in the allantoic test could not be prevented or inhibited by simultaneous administration of reducing substances, or of some amino‐acids or vitamins. No inhibition of virus multiplication occurred in embryonated eggs infected via the yolk sac, or in mice infected intranasally with FM1 virus. The activity in the allantoic test could be explained by the virucidal action of the compounds on the virus present in the allantoic fluid. No satisfactory interpretation of the empirical relationship between chemical structure and antiviral activity could be found.
THE UPTAKE OF ADRENALINE AND NORADRENALINE BY BLOOD PLATELETS OF THE PIG
Authors: BORN G. V. R. , HORNYKIEWICZ O. , STAFFORD ANNE
Published: July 2012

Pig platelets contained 0.2 to 2.6 ng. adrenaline/108 platelets (4 experiments). Noradrenaline was not detected in them. When platelet‐rich plasma was incubated at 37° with 1 or 10 μg. of added catechol amine/ml., the platelets continued to accumulate adrenaline for at least 120 min.; only about one‐third as much noradrenaline as adrenaline was taken up. The concentrations of adrenaline taken up by different platelet samples at the end of incubation for 90 min. were proportional to the concentration of adenosine triphosphate in the platelets.
A DEPRESSANT EFFECT OF ACETYLCHOLINE ON THE IDIO‐VENTRICULAR PACEMAKER OF THE ISOLATED PERFUSED RABBIT HEART
Authors: BENFORADO J. M.
Published: July 2012

In Langendorff preparations of the isolated rabbit heart, excision of the atria and severance of the atrio‐ventricular bundle resulted in the onset of idio‐ventricular rhythm at a rate much below the original sino‐atrial rate. The mean decrease in rate in twelve experiments was 61%. Acetylcholine perfusion decreased the idio‐ventricular rate still further. Physostigmine augmented this effect while atropine prevented or abolished it. Similar results were obtained with a rat heart. The results indicate that a cholinergic receptor mechanism is present at pacemaker sites in mammalian ventricles. However, when rabbit ventricles, beating under atrio‐ventricular nodal rhythm or idio‐ventricular rhythm, were cooled to the point of cardiac arrest, acetylcholine failed to cause reappearance of the cardiac beat.
THE ACTION OF SYMPATHOMIMETIC AMINES ON HEART RATE IN RELATION TO THE EFFECT OF RESERPINE
Authors: BEJRABLAYA D. , BURN J. H. , WALKER J. M.
Published: July 2012

When the heart‐lung preparation is made from a dog treated with reserpine, catechol amines such as noradrenaline and isoprenaline have a greater effect on the rate of the heart than they have in a preparation from a normal dog. Other sympathomimetic amines such as tyramine and ephedrine, on the other hand, are found to have lost their action. Since treatment with reserpine has been shown to cause the store of noradrenaline in the heart to disappear, and the infusion of noradrenaline into the preparation made from a reserpine‐treated animal restores the action of tyramine. it is concluded that substances like tyramine and ephedrine normally act by liberating noradrenaline from the store, and do not act directly. Cocaine, like reserpine, increases the effect of noradrenaline and decreases the effect of tyramine on the heart rate; it appears to block the release of noradrenaline from the store in the heart.