bluuebunny/crossref_metadata_2025 huggingface dataset:
A review of the epidemiology of psoriasis vulgaris in the community
Authors: Plunkett Anne , Marks Robin
Published: June 2007

Standard diagnostic criteria for epidemiological studies of psoriasis are currently lacking. In their absence, clinical examination and diagnosis of psoriasis by dermatologists provides the gold standard to underpin epidemiological research in psoriasis. The methods of data collection used most frequently include cross‐sectional studies, case‐control studies, cohort studies, and surveys of hospital and private practice attendance. Estimates of psoriasis prevalence made in cross‐sectional studies employing clinical examinations as the survey instrument have ranged from 0.3 to 2.5%. Psoriasis incidence has been estimated at 60.4 per 100 000 person years in one cohort study. Several factors have been identified as being associated either with causation of psoriasis or with triggering exacerbations or remissions, including genetic determinants, racial and regional variation, injury and infection, cigarette smoking, alcohol, diet and other diseases.
Familial Kaposi's sarcoma and Paget's disease of bone
Authors: Hale Lloyd R , Kelly John VV
Published: June 2007

Familial Kaposi's sarcoma and familial Paget's disease of bone have not previously been reported to occur in the one patient or the one family. We report on an 82‐year‐old female of Lebanese descent who was recently diagnosed with Kaposi's sarcoma and Paget's disease. Of the patient's eight siblings, seven had Paget's disease and two of these also had Kaposi's sarcoma. Histocompatibility leucocyte antigen (HLA) class I and II typing of the patient showed: A2, A3; B35, Bx; Bw6; Cw4; DRβ1*1101 (an HLA‐DR5 subtype) DRβ3 and DQβ1*0301. Previous reports have described possible associations of familial Kaposi's sarcoma with HLA‐DR5 and Paget's disease with DR2, DRβ1*1104, DPβ1*04and DQw1. Genetic factors and possible viral aetiologies fur each condition are reviewed.
Pretibial myxoedema presenting as a scar infiltrate
Authors: Tong David W , Ho Kenneth K
Published: June 2007

A 41‐year‐old man developed pretibial myxoedema localized to soars following treatment for hyperthyroidism. Pre‐existing scars on both lower legs, present for more than 20 years, were infiltrated with firm and nonpitting nodules and plaques over his shins. The clinical presentation of this patient highlights pretibial myxoedema as a cause of scar infiltration. The pathogenesis or pretibial myxoedema is reviewed.
Auricular ossification
Authors: Yeatman Josephine M , Varigos George A
Published: June 2007

A patient with extensive bilateral auricular ossification presented with chondrodermatitis nodularis helicis on one side. The condition was otherwise asymptomatic. Ossification was delected on radiological and histological examination. Underlying medical conditions were nut Pound. We believe this developed as a eon‐sequence of cold injury. Auricular ossification is an unusual cause of the so‐called petrified external ear, in which the subcutaneous tissue is stony hard, it is more commonly caused by dystrophic calcification. Calcification and ossification are clinically identical and histological examination is required to definitively differentiate them.
Acquired self‐healing Blaschko dermatitis in an adult
Authors: Betti Roberto , Vergani Raffaella , Gualandri Lorenzo , Crosti Carlo
Published: June 2007

A 24‐year‐old woman with a 3 year history of Blasehkitis is presented. The dermatosis consisted of erythematous vesicular papules following Blasehko's lines on her left trunk. A moderate itching was described by the patient initially. Resolution occurred spontaneously after 3 months with hypopigmentation. Histological examination demonstrated a perivascular inflammatory infiltrate in the subpapillary dermis with lymphocytic exocytosis.
Desmoplastic trichoepithelioma
Authors: Zuccati Giuliano , Massi Daniela , Mastrolorenzo Antonio , Urbano Francesco G , Paoli Simone , Reali Umberto M
Published: June 2007

A 20‐year‐old male presented with a 4 year history of a solitary nodule, 8 mm in diameter on the left temple. It was covered by normal skin, with a central depression and elevated borders. Histopathology showed numerous born cysts amidst nests and strands of basaloid cells surrounded by a dense fibrous stroma. The clinical and histopathological features were characteristic of desmoplastic trichoepithelioma.
Skin and eye injury due to latex of Excoecaria agallocha*
Authors: Kumarasinghe SPW , Seneviratne R
Published: June 2007

A case report of severe skin and eye injury due to Excoecaria agallocha is presented to highlight the toxic, nature of the latex of this common mangrove plant.
Are non‐absorbable indicators of comparable value in the human stomach made abnormal by taurocholic acid?
Authors: Ivey K. J. , Parsons C.
Published: June 2007

1. The substances chromium‐51 (51CrCl3) and phenolsulphonphthalein (phenol red; PR) were compared as non‐absorbable indicators in the human stomach after alteration of ionic permeability by taurocholic acid.

2. Control and test solutions containing 10 mm taurocholic acid and indicators at pH 1 were instilled into the stomach and sampled immediately and after 15 min. The ratios of the initial and final concentrations of the indicators (Ci/Cf) were compared.

3. Correlation coefficients of the Ci/Cf ratios for the two indicators were 0·91 in control studies and 0·75 after taurocholic acid instillation; there was no significant difference between either indicator. During taurocholic acid instillation, Ci/Cf values tended to fall compared to controls.

4. In a smaller number of subjects in whom polyethylene glycol (PEG) was also measured as a non‐absorbable indicator, results were similar to those obtained with 51Cr and PR.

5. 51Cr, PR and PEG are comparable indicators in the normal human stomach and when it is made abnormal by a lipid‐soluble agent such as unionized taurocholic acid, though the correlation between indicators is reduced in the abnormal stomach.

6. No evidence of increased absorption of any indicator was found in spite of the increased ionic permeability produced by taurocholic acid.
Pressure‐flow relationships in the peripheral circulation of the dog with isoprenaline
Authors: Green Jerry Franklin
Published: June 2007

1. The effects of isoprenaline on the pressure‐flow relationships in the peripheral circulation were studied in five anaesthetized dogs during right heart bypass procedures.

2. Isoprenaline (1 μg/kg per min) produced a significant drop in arterial pressure and arterial resistance.

3. There was a significant decrease in the resistance to venous return which resulted in a significant increase in venous return.

4. The findings suggest that the increase in cardiac output produced by isoprenaline results in large part from dilatation of venous resistance vessels.
Structural requirements for angiotensin analogues to accumulate cyclic AMP and release vasopressin from the incubated rat neurohypophysis
Authors: Gagnon D. J. , Sirois P. , Park W. K.
Published: June 2007

1. Angiotensin I, a decapeptide, stimulated the accumulation of cyclic 3',5'‐AMP (cyclic AMP) and the release of vasopressin from incubated rat neurohypophyses.

2. Various octapeptides related to angiotensin II were capable of producing similar neurohypophyseal effects.

3. Longer incubation periods were needed with peptides having alterations or omission (e.g. heptapeptide 2–8) at position 1 of the parent molecule to evoke similar effects to those of angiotensin II.

4. Our results suggest strongly that physiological doses of angiotensin‐related molecules stimulate the secretion of vasopressin through cyclic AMP, and that the neurohypophyseal receptor responsible for these effects is similar to that involved in their peripheral actions.
Plasma and tissue iron changes in the rat after acute administration of ethionine
Authors: Loh T. T. , Archdeacon J. W.
Published: June 2007

1. Ethionine administered acutely to the adult female rat markedly elevates and then lowers plasma iron concentration over several days. Liver iron undergoes a reverse cycle.

2. Ethionine does not cause changes in the blood parameters, including total plasma iron‐binding capacity and plasma iron clearance. Erythrocytes of rats injected with ethionine show altered responses to hypertonicity.

3. Increased reticulo‐endothelial activity of the spleen, indicated by increased uptake of 59Fe‐labelled erythrocytes by liver and spleen, apparently contributes to plasma iron elevation. Also the liver releases iron which further raises plasma iron.
Pharmacokinetics of tritiated ouabain, digoxin and digitoxin in guinea‐pigs
Authors: Proppe D.
Published: June 2007

1. Elimination rates of tritiated ouabain, digoxin and digitoxin after single intravenous administrations were investigated in guinea‐pigs, the total radioactivity in whole blood being traced for a period of up to 2 weeks.

2. In the initial rapid phase of elimination between 2 and 30 min following intravenous glycoside administration, the concentration decline of radioactivity in the blood was found to be identical for the three glycosides investigated, this part of the elimination curve displaying a hyperbolic shape.

3. During this early elimination phase, rapid metabolic degradation and excretion of digoxin had already taken place. The maximum concentration of radioactivity in the bile was reached 4 min following intravenous administration of 3H‐digoxin. The positive inotropic response occurred in the cat heart‐lung preparation 1·5 min after intravenous injection of a therapeutic dose of digoxin, indicating a quick occupation of binding sites in the tissues.

4. The biological half‐lives of tritiated ouabain, digoxin and digitoxin averaged 11 h, 2·5 days and 4·1 days, respectively, as determined by the terminal exponential elimination phase, in guinea‐pigs. This terminal phase was attained 6–12, 7–24, and 24–48 h after administration of ouabain, digoxin and digitoxin, respectively.

5. The findings reveal that in the guinea‐pig, as has been demonstrated in man, the elimination rates of the three glycosides increase according to their hydrophobic properties.

6. The biological half‐lives of tritiated ouabain, digoxin and digitoxin obtained in the guinea‐pig closely resemble those found in healthy man.
Pentaerythritol trinitrate and glyceryl trinitrate on intramyocardial oxygenation and perfusion in the dog. Krogh analysis of transmural metabolism
Authors: Howe Burton B. , Weiss Harvey R. , Wilkes Sandra B. , Winbury Martin M.
Published: June 2007

1. The effect of intravenous pentaerythritol trinitrate and glyceryl trinitrate on left ventricular subepicardial (epi) and subendocardial (endo) Po2 and perfusion were compared in anaesthetized open‐chest mongrel dogs. Tissue Po2 was determined simultaneously at a depth of 3 mm (epicardial) and 9 mm (endocardial) with small platinum electrodes by polarography. In a separate series of dogs tissue perfusion of those regions was measured by hydrogen (H2) clearance using similar electrodes.

2. Both nitrates increased endocardial Po2 while epicardial Po2 was not altered. Perfusion was determined at the point of the maximal rise in endocardial Po2 (4–7 min after injection of either nitrate). At that period average coronary artery inflow and epicardial perfusion were decreased but endocardial perfusion was not significantly altered.

3. Using the data on Po2, hydrogen clearance and intercapillary distance, the effect of the nitrates on transmural metabolism (oxygen consumption) was estimated by Krogh analysis. Basal endocardial metabolism was 20–30% higher than epicardial metabolism. The nitrates reduced metabolism in each region. The absolute decrease in oxygen consumption was greater in the endocardium.

4. The results show that both pentaerythritol trinitrate and glyceryl trinitrate improve endocardial oxygenation by producing a more favourable balance between perfusion and oxygen requirements in that region.
PLASMALEMMAL CALCIUM IN CARDIAC EXCITATION‐CONTRACTION COUPLING
Authors: Lüllmann Heinz , Peters Thies
Published: June 2007

1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force.

2. In mammalian heart muscle there is a network of large transverse tubules throughout the cell. These structures are regularly arranged at the level of the sarcomeric Z‐ and I‐lines and increase the cell surface by a factor often.

3. Experimental evidence favours the assumption that the plasmalemma could be the site of a loosely bound superficial Ca fraction which becomes ionized upon depolarization and is again bound upon repolarization of the cardiac cell membrane.

4. A mechanism is discussed which bases the excitation‐contraction coupling process on a physicochemical interaction of calcium with membrane phospholipids. The degree of interaction is thought to be governed by the transmembrane electric field, the induced dipole moment of membrane constituents, and proton activity within the membrane.
PROSTAGLANDINS: ANTINOCICEPTIVE EFFECT OF PROSTAGLANDIN E1 IN THE RAT
Authors: Sanyal A. K. , Bhattacharya S. K. , Keshary P. R. , Srivastava D. N. , Debnath P. K.
Published: June 2007

1. The antinociceptive effect of prostaglandins E1, E2 and F2α was studied in albino rats. Though all three prostaglandins produced similar degrees of sedation, only prostaglandin E1 (PGE1) produced a dose‐related antinociceptive activity.

2. The antinociceptive activities of equi‐analgesic doses of morphine (7.5 mg/kg, i.p.) and PGE1 (2.0 mg/kg, i.p.) were inhibited to almost similar extents after pretreatment with drugs known to reduce central turnover of serotonin receptors, namely reserpine, fenclonine (p‐chlorophenylalanine), methysergide and 5,6‐dihydroxytryptamine.

3. Prostaglandin F2α (2.0 mg/kg, i.p.) significantly inhibited the antinociceptive effects of both morphine and PGE1.

4. The prostaglandin synthesis inhibitors, indomethacin and diclofenac, significantly inhibited morphine analgesia.

5. Probenecid markedly prolonged the duration of antinociceptive effect of morphine and the duration of PGE1‐induced potentiation of subanalgesic dose of morphine.

6. The results suggest that, in albino rats, PGE1‐induced antinociceptive activity is serotonin mediated and that morphine analgesia is not only mediated through serotonin but also through prostaglandins (PGE1?) and 5‐hydroxyindole acetic acid, the serotonin metabolite.
PLASMA LEVELS FOLLOWING SINGLE INTRAVENOUS, ORAL AND MULTIPLE ORAL DOSAGE IN NORMOTENSIVE AND HYPERTENSIVE SUBJECTS
Authors: Barnett A. J. , Bobik A. , Carson V. , Korman J. S. , McLean A. J.
Published: June 2007

1. The pharmacokinetics of methyldopa after oral and intravenous administration was studied in hypertensive and normotensive patients. After intravenous administration methyldopa plasma concentrations decayed according to a two‐compartment open model.

2. For intravenous administration the overall elimination constant Ke1 was 0.56 ± 0.03 h−1, the volume of distribution of the central compartment 0.29±0.08 1 kg−1 and the plasma clearance rate 11.2±0.6 1 h−1.

3. Plasma half‐times during the β‐phase of the methyldopa plasma decay curve following intravenous and oral administration were 2.8±1.3 and 2.1±0.7 h, respectively.

4. Maximal plasma levels in hypertensive out‐patients show great variation and range from 0 to 1.9 μg ml−1.

5. No relationships were found between maximal methyldopa plasma levels in patients under treatment and control of hypertension.
BETA‐ADRENOCEPTOR‐MEDIATED EFFECTS OF CLENBUTEROL (NAB 365) ON TRACHEA, HEART AND SKELETAL MUSCLE IN ANAESTHETIZED GUINEA‐PIGS
Authors: Bohmer Karin , O'Donnell Stella R.
Published: June 2007

1. Intravenous injection of clenbuterol (NAB 365) in anaesthetized guinea‐pigs produced decreases in tracheal segment pressure and in soleus muscle contractions and a slight increase in heart rate. These responses were reduced by propranolol.

2. Clenbuterol was less potent than isoprenaline on the trachea and soleus muscle and even less potent on the heart. The maximum response to clenbuterol was the same as that to isoprenaline on the trachea and the soleus muscle but it was not more than 30% of that to isoprenaline on the heart. There was no significant difference between the potencies of clenbuterol on the trachea and the soleus muscle.

3. The onset of the responses to clenbuterol were slower and the duration of action longer than those to isoprenaline.

4. High doses of clenbuterol blocked isoprenaline responses on heart rate.

5. Clenbuterol showed selectivity for the trachea and the soleus muscle (β2‐adrenoceptors) as compared with the heart (β1‐adrenoceptors). This could result, at least in part, from its partial agonist activity on the heart.
ANTIARRHYTHMIC DRUGS AND IN VIVO MYOCARDIAL EXCITABILITY IN THE DOG
Authors: Hasin Y. , Rogel S.
Published: June 2007

1. It has been demonstrated in an earlier study that the threshold for capturing the canine ventricle in situ varies at each time interval during the relative refractory period with a wide range of current levels. Thus, there is no single threshold curve, as is commonly accepted, but rather a range defined by upper limit of threshold (TU) and a lower limit (TL). TU is the minimal current level which always produced a generalized ventricular response. A wide range of lesser current levels produced a local response but with inconsistent propagation throughout the ventricle. TL is the maximal current level which was never able to elicit a generalized response.

2. Applying the method used for the determination of these limits, the present study was undertaken to characterize the effect of quinidine, lignocaine, procainamide and verapamil in therapeutic doses on TU and TL.

3. It was found that quinidine, lignocaine and procainamide elevated TU and TL during the relative refractory period, but only quinidine did so during diastole as well. Verapamil, however, did not have any significant influence on excitability. Procainamide had the least effect on the absolute refractoriness of the ventricular muscle as judged by the rightward displacement of the TU and TL curves, while quinidine and lignocaine exhibited a significant displacement regarding TU but much less so for TL.

4. The proposition is entertained that TL represents true local excitability of the ventricular muscle and TU represents the stimulus needed for propagation throughout the heart during the most unfavourable conditions for such spread.

5. Relative changes of TU/TL as a function of TU are considered to express the capability of the locally induced potential to evoke a generalized response: quinidine diminished, procainamide increased, and lignocaine had no effect on this parameter.
THE ACTIONS OF SOME α‐ADRENORECEPTOR AGONISTS AND ANTAGONISTS IN AN ANTINOCICEPTIVE TEST IN MICE
Authors: Bentley G.A. , Copeland I.W. , Starr Jennifer
Published: June 2007

1. It has been shown that a number of sympathomimetic drugs, administered subcutaneously, have potent antinociceptive activity in the mouse abdominal constriction test. These drugs were found to be equieffective antagonists of the nociceptive action of acetic acid and acetylcholine. Of the drugs tested, clonidine was the most potent, being almost 60 times more active than morphine, whilst noradrenaline and oxymetazoline were approximately three and five times less active respectively than clonidine. Phenylephrine was without effect after doses of 2 mg/kg.

2. The regression lines relating the magnitude of the antinociceptive effect of noradrenaline and oxymetazoline to log dose were moved to the right in an approximately parallel manner after subcutaneous administration of piperoxane, 8 and 16 mg/kg. The antinociceptive action of clonidine was also antagonised by piperoxane, but to a lesser extent. Phentolamine had no antagonistic effect on any of these three a‐agonists after subcutaneous doses of 16 mg/kg.

3. Oxymetazoline and clonidine, when given by intracisternal injection, were approximately eight‐three and fifty times more potent respectively than by subcutaneous administration, and their antinociceptive action was not antagonized by piperoxane, 16 mg/kg subcutaneously, or 50 μg/kg intracisternally.

4. It is postulated that the antinociceptive action of the a‐agonists is due to an effect on α‐adrenoreceptors located on sensory nerve endings in the peritoneum, and that the affinities of these receptors for the α‐agonists and antagonists is different from that shown by either pre‐ or postsynaptic α‐adrenoreceptors. It also appears likely that the antinociceptive action of clonidine and oxymetazoline when given by intracisternal injection involves different mechanisms from their peripheral effects.
COMPARATIVE STUDIES ON THE PHARMACOLOGICAL ACTIONS OF ANTIARRHYTHMIC DRUGS IN ISOLATED RAT PAPILLARY MUSCLE
Authors: Sugimoto J. , Nagata M. , Morita M.
Published: June 2007

1. The effects of ajmaline, cocaine, phenytoin, lignocaine, procainamide, propranolol, quinidine and trimetazidine on the contractility and the refractory period of isolated rat papillary muscles were compared.

2. At the higher concentrations used, all drugs suppressed the contractile tension of the rat papillary muscles.

3. The effects of these drugs on the refractory period were compared at concentrations at which the contractile tension was suppressed by 30% of the control. At this point, lignocaine, procainamide, ajmaline and quinidine prolonged the refractory period more than two‐fold while the effects of propranolol and phenytoin were slight, cocaine and trimetazidine had little or no effect.
COMPARATIVE STUDY OF CHRONOTROPIC AND INOTROPIC EFFECTS OF DOPAMINE AND SEVEN DERIVATIVES ON THE ISOLATED, BLOOD‐PERFUSED DOG ATRIUM
Authors: Chiba S.
Published: June 2007

1. The effects of seven dopamine amino acid conjugated derivatives were compared with those of dopamine on sinus rate and contractile force using the isolated, blood‐perfused dog atrium preparation.

2. Each of these dopamine derivatives induced dose‐related positive chronotropic and inotropic effects.

3. The positive chronotropic and inotropic effects were obtained with the same rank order of potency for each effect with six of the dopamine derivatives. Their rank order and relative potency (dopamine = 1000) were: N‐Ileu‐dopamine (3)> N‐Glu‐Pro‐dopamine (1) =N‐Ala‐Glu‐dopamine (l)>N‐Gly‐Gly‐dopamine (0.3) = N‐γ‐Glu‐dopamine (0.3)>N‐Gly‐Gly‐Leu‐dopamine (0.1)>N‐Gly‐Gly‐Pro‐dopa‐mine (0.01).

4. In doses producing equal positive inotropic effects, the positive chronotropic effect of N‐Gly‐Gly‐Leu‐dopamine was much less than with the other derivatives tested. Its potency compared to dopamine (= 1000) was 0.3 for the inotropic and 0.1 for the chronotropic effect.

5. The duration of action of doses of the derivatives producing approximately equal positive inotropic responses was in the order N‐Ileu‐dopamine =N‐γ‐Glu‐dopamine =N‐Gly‐Pro‐dopamine =N‐Ala‐Glu‐dopamine > N‐Gly‐Gly‐dopamine = N‐Gly‐Gly‐Leu‐dopamine =N‐Gly‐Gly‐Pro‐dopamine > dopamine.
PREVENTION OF ACUTE GASTRIC ULCERATION IN THE RAT BY CIMETIDINE, A HISTAMINE H2‐RECEPTOR ANTAGONIST
Authors: Lee S. P. , Tasman‐Jones C.
Published: June 2007

1. Intraperitoneal injections of cimetidine into rats markedly reduced gastric acid production. When given at a dose of 50 mg/kg body weight, rate of acid production fell from a mean of 2.73 μmol/min (s.d. = 0.32) to a lowest level of 0.81 (s.d. = 0.28): the difference was highly significant (P< 0.005). When given in a dose of 100 mg/kg, the rate of acid production further fell to 0.18 μmmol/min (s.d. = 0.12; P< 0.001).

2. Treatment with cimetidine in doses of 100 mg/kg 8‐hourly during a 24 h period of restraint prevented the development of acute gastric ulceration in the rat. Pretreatment with cimetidine also protected against the ulcerogenic effects of intragastrically administered bile or lysolecithin.

3. The marked sustained reduction of acid production most probably accounts for the protective effect of cimetidine against ulcer production in the rat stomach.
THE INFLUENCE OF SEROTONIN ON THE MITOTIC RATE IN THE COLONIC CRYPT EPITHELIUM AND IN COLONIC ADENOCARCINOMA IN RATS
Authors: Tutton P. J. M. , Barkla D. H.
Published: June 2007

1. The mitotic rate in the crypts of Lieberkiihn of the descending colon and in dimethylhydrazine‐induced adenocarcinomata of the descending colon of rat was measured using a stathmokinetic technique.

2. Intraperitoneal injection of a small dose (10 jug/kg) of serotonin resulted in an increase in the tumour cell mitotic rate.

3. Blockade of serotonin receptors by 2‐bromolysergic acid diethylamide and depletion of tissue serotonin levels following injection of DL‐6‐fluorotryptophan both result in a decrease in the tumour cell mitotic rate.

4. Treatment with serotonin, 2‐bromolysergic acid diethylamide and DL‐6‐fluorotryptophan were all without effect on the colonic crypt cell mitotic rate.
INCREASED BILIARY EXCRETION OF OUABAIN INDUCED BY BUCOLOME IN THE RAT
Authors: Kitani K. , Kanai S. , Miura R.
Published: June 2007

1. Following the intravenous injection of 3H‐ouabain (0.4 or 0.6 mg/100 g body weight) the plasma concentration and biliary excretion of ouabain were compared for control male Wistar rats and rats given bucolome (BC, l‐cyclohexyl‐5‐n‐butyl‐2,4,6,‐trioxoperhydroxypyrimidine, 20 mg/100 g) 40 min before the ouabain injection. In bucolome treated rats, the bile flow rate was 80–90% higher than in control rats and the biliary excretion rate of ouabain for the 40 min post‐injection period was significantly higher in bucolome treated rat groups. The increase was due to an approximately two‐fold increase in the excretion rate in the first 10 min period. On the other hand, plasma concentration of ouabain was significantly higher in bucolome treated rats compared with control rats at corresponding time intervals. Plasma volume as determined by 131I‐labelled albumin dilution was not decreased in bucolome treated rats.

2. The results indicated that the significant increase in biliary excretion of ouabain administration was due to the enhancement of the hepatic transport and/or biliary excretion process and not due to an increase in hepatic uptake.
SOME BIOCHEMICAL RESPONSES OF RAT SKELETAL MUSCLE TO A SINGLE SUBCUTANEOUS INJECTION OF A TOXIN (NOTEXIN) ISOLATED FROM THE VENOM OF THE AUSTRALIAN TIGER SNAKE NOTECHIS SCUTA TUS SCUTA TUS
Authors: Pluskal M. G. , Harris J. B. , Pennington R. J. , Eaker D.
Published: June 2007

1. Some biochemical responses of mammalian skeletal muscle to a single subcutaneous injection of a purified toxin from the venom of the Australian tiger snake, Notechis scutatus scutatus, have been investigated to determine the role of changes in peptide hydrolase enzymes in the muscle wasting caused by notexin administration.

2. Within 6 h of injection, serum creatine kinase activity was increased by five‐to ten‐fold, and remained elevated for at least 24 h.

3. There was an initial inflammatory response in the muscle adjacent to the site of injection; by 12 h after injection, muscle wet weight increased by 60%.

4. After the initial increase, wet weight fell to about 50% of normal at 7 days. Normal wet weight was achieved by 20 days after the injection. Over the period 1–20 days after the injection of the toxin, the changes in wet weight were mirrored by changes in non‐collagen protein content.

5. The activities of cathepsin B and acid proteinase were increased following the injection of the toxin. By 2 days after injection, there was a ten‐fold increase in the activity of cathepsin B, and a seven‐fold increase in the activity of acid proteinase. The activity of both enzymes became normal by 20 days.

6. Experiments utilizing a variety of cytotoxic drugs suggested that the acid proteinase and cathepsin B are primarily located within invading phagocytic cells.

7. The results are discussed with reference to the previously described pathology of toxin‐damaged skeletal muscle.
THE INFLUENCE OF SUBACUTE DYFLOS ADMINISTRATION ON THE SENSITIVITY TO AGONISTS OF LONGITUDINAL AND CIRCULAR MUSCLE PREPARATIONS OF THE GUINEA‐PIG ILEUM
Authors: Mitchelson F. , O'Shea R. A.
Published: June 2007

1. Changes in the EC50 values to various agonists in longitudinal and circular muscle preparations of guinea‐pig ileum were investigated following daily pretreat‐ment of the animals for 10 days with dyflos (1.2 mg/kg, s.c).

2. In the longitudinal muscle no significant change in sensitivity to acetylcholine and potassium chloride was noted following dyflos treatment. Marked subsensitivity to carbachol and histamine was observed.

3. In circular muscle a marked supersensitivity to acetylcholine occurred and there was no change in sensitivity to carbachol.

4. Dyflos treatment induced an increase in the slope of the log concentration‐response curve and the maximal contractile response obtained to agonists in both longitudinal and circular muscle preparations. An increase in tissue mass was also associated with dyflos pretreatment.

5. Subsensitivity development was not attributable to changes in affinity for agonists at the receptor site but rather to changes at the post‐receptor level leading to a nonspecific subsensitivity.
EFFECTS OF ADRENALINE AND ISOPRENALINE ON HEPATIC VENOUS HAEMODYNAMICS AND VENOUS RETURN IN THE DOG
Authors: Cyong J. C. , Horiguchi Y. , Tanaka K. , Itoh H.
Published: June 2007

1. The effects of adrenoceptor agonists on venous haemodynamics were examined, utilizing the lower half perfusion method in dogs.

2. Femoral arterial pressure, central venous pressure, thoracic vena caval flow, abdominal vena caval flow, renal venous flow and femoral venous flow were measured simultaneously using electronic transducers and electromagnetic flow‐meters. Hepatic volume change was monitored by the strain‐gauge arch.

3. Single injections of both adrenaline (1.0 μ/kg) and isoprenaline (1.0 μg/kg) intra‐aortically produced an increase in venous return, adrenaline transiently and isoprenaline continuously.

4. Epinephrine increased hepatic venous flow, while isoprenaline increased only abdominal vena caval flow.

5. These findings suggest that effects of α‐adrenoceptors are more pronounced on the hepatic vein, while on other peripheral veins, effects of β‐adrenoceptors are more pronounced.
THE DENSITY OF ADRENERGIC NERVES AT VARIOUS LEVELS IN THE GUINEA‐PIG LUNG
Authors: O'Donnell Stella R. , Saar Nili , Wood L. J.
Published: June 2007

1. Guinea‐pig tracheal and lung segments were systematically examined for adrenergic nerves using the fluorescence histochemical technique. Fluorescence in nerves was enhanced with α‐methylnoradrenaline or by pretreating the animals with nialamide.

2. There was a progressive decrease in density of fluorescent fibres in airway smooth muscle from the laryngeal end of the trachea, which was densely innervated, to the bronchioles, which contained only occasional fibres. This was despite obvious fluorescence in blood vessels in the lung.

3. It is suggested that, if adrenergic nerves are involved in reflex bronchodilatation in this species, they directly control larger airways and other factors, e.g. non‐adrenergic inhibitory nerves, may be important in the control of smaller airways.
DIFFERENTIAL BLOCKADE OF OCTOPAMINE AND DOPAMINE RECEPTORS BY ANALOGUES OF CLOZAPINE AND METOCLOPRAMIDE
Authors: Dougan D. F. H. , Wade D. N.
Published: June 2007

1. Sulpiride, but not procainamide, antagonizes the excitatory effects of (±)‐octopamine receptors in the Tapes ventricle. Neither compound attenuates dopamine excitation.

2. Clozapine will attenuate the effects of (±)‐octopamine and (‐)‐α‐methyl octopamine at the octopamine receptor but not the excitatory effects of dopamine at dopamine receptors.

3. Clozapine is more potent than its 2‐positional isomer HF 2046 in attenuating octopamine excitation. However, HF 2046, unlike clozapine, will attenuate the excitatory effects of dopamine.

4. These data indicate that replacement of the 8‐chloro substituent in the clozapine nucleus with a 2‐chloro substituent decreases the ability of the compound to blockade octopamine receptors. However, the 2‐chloro‐substituted compound (HF 2046) now has the added ability to blockade excitatory dopamine receptors.

5. The greater potency of clozapine than HF 2046 as an octopamine antagonist suggests that it is the 8‐chloro‐substituted aromatic ring of clozapine which overlaps the aromatic site usually occupied by the octopamine aromatic ring.
THE EFFECTS OF SYMPATHOLYTIC DRUGS ON THE CARDIOVASCULAR RESPONSE TO TILTING IN ANAESTHETIZED CATS
Authors: Nolan P. L. , Bentley G. A.
Published: June 2007

1. Using cats anaesthetized with chloralose and urethane, comparison was made of the abilities of several antihypertensive and sympatholytic drugs to lower systemic blood pressure, and to depress the compensatory cardiovascular responses to bilateral carotid occlusion and to 45° head‐up tilting. Similar comparisons were also made of the effects of these drugs on the perfusion pressure of the vascularly isolated autoperfused hindquarters, and the response of this to carotid occlusion and tilting. The effects of bilateral vagotomy and haemorrhage on these responses were also studied.

2. It was found that hypotensive doses of both bretylium and guanethidine (3.0mg/kg, i.v.) markedly depressed the ability of cats to restore their systemic blood pressure and to constrict their hindquarters vasculature during tilting. Both drugs depressed the carotid occlusion reflex in the systemic, but not in the hindquarters, circulation. Neither propranolol, 2.0mg/kg, i.v., nor bilaterial vagotomy had any effect on these parameters and haemorrhage sufficient to cause marked hypotension was without effect on the systemic responses to carotid occlusion or tilting.

3.Clonidine (1.0, 5.0 and 25/μg/kg, i.v.), xylazine (62.5, 125 and 250μg/kg, i.v.) and reserpine (0.5 and 2.0mg/kg, i.v.) all caused considerable hypotension but had no effect on the response to tilting of the systemic circulation, apart from somewhat prolonging recovering time. The highest dose of clonidine moderately depressed the hindquarters perfusion pressure, and the response of this to tilting.

4. Clonidine (5.0 and 25μg/kg, i.v.) and xylazine (125 and 250/μg/kg, i.v.) depressed the systemic pressor responses elicited by the ganglion stimulants DMPP and McN‐A‐343. This may indicate that the ability of clonidine to prolong the pressure recovery during tilt may be due to impaired peripheral sympathetic transmission.

5. It is concluded that drugs which significantly reduce the compensatory pressure responses to tilting in anaesthetized cats may also cause postural disturbances in man, whilst drugs which merely prolong the period required for pressure compensation seem much less likely to cause serious clinical impairment of orthostatic reflexes. It appears that the cardiovascular response to bilateral carotid occlusion may not provide a good index of the integrity of orthostatic reflexes.
THE EFFECT OF CORTICOTROPHIN (ACTH) ADMINISTRATION ON THE PRESSOR ACTION OF ANGIOTENSIN II, NORADRENALINE AND TYRAMINE IN SHEEP
Authors: McDougall J. G. , Barnes Alison M. , Coghlan J. P. , Denton D. A. , Fan J. S. K. , Scoggins B. A. , Whitworth Judith A.
Published: June 2007

1. Pressor responses to angiotensin II, noradrenaline and tyramine were examined in sheep prior to and during the development of corticotrophin‐induced hypertension.

2. Pressor responses to angiotensin II amide did not change with corticotrophin (ACTH) administration. Small significant increases in pressor responses to noradrenaline occurred at low doses only (0.27 and 1.06 /imol/h). Significant increases in response to tyramine occurred after 24 h of ACTH administration, but were not maintained after 6 days of ACTH. These changes are quantitatively small and do not suggest that changes in pressor sensitivity contribute significantly to the rise in blood pressure following ACTH administration.

3. Sodium depletion significantly reduced the pressor responses to angiotensin II amide at all doses and to tyramine in the middle range only, but did not affect the responses to noradrenaline.
EFFECTS OF 1‐SAR‐8‐ALA‐ANGIOTENSIN II ON SYSTEMIC AND PULMONARY HAEMODYNAMICS IN HYPERTENSIVE PATIENTS
Authors: Fagard R. , Amery A. , Lijnen P. , Reybrouck T. , Joossens J.‐V. , Billiet L. , Moerman E. , De Schaepdryver A.
Published: June 2007

1.The angiotensin II antagonist, 1‐Sar‐8‐Ala‐angiotensin II (saralasin), was infused intravenously at a rate of 10 μg/kg per min in thirty‐three hypertensive patients, on a normal sodium diet (130 mmol per day) and/or during sodium depletion by low sodium diet (20 mmol per day) and chlorthalidone.

2. In both series, saralasin induced a transient rise in intra‐arterial pressure (P < 0.01), accompanied by a slight decrease in heart rate (P < 0.01). The elevation of systolic arterial pressure reached its maximum after 4 min and was more pronounced in sodium‐replete patients. Plasma noradrenaline was significantly elevated by 29.7% (P<0.01), but the rise in pressure was not related to concomitant changes in plasma noradrenaline.

3. After the initial pressor effect, arterial pressure, heart rate, cardiac output and total peripheral resistance remained unchanged in the sodium‐replete patients, while in the sodium‐depleted conditions mean arterial pressure and peripheral resistance were reduced, by 17.8% and 18.6% (P< 0.001) respectively, within 60min. Reflex increases in heart rate (+3.8%) and cardiac output (+ 11.1%) occurred after 10 min (P<0.05), but were not sustained thereafter.

4. Pulmonary vascular resistance was not affected by saralasin. In sodium‐depleted patients, pulmonary capillary wedge pressure decreased by 1.2mmHg (P<0.01), with parallel changes of pulmonary artery pressure (P< 0.01).
LEFT ATRIAL RECEPTOR INHIBITION OF CARDIAC EFFERENT VAGAL ACTIVITY IN THE DOG
Authors: Chapman L. W. , Mittman U. , Prickett C. , Richmond W.
Published: June 2007

1. The tachycardia produced by atrial receptor stimulation has been reported to be ‘solely’ due to an increased sympathetic activity, but not inhibitable by propranolol. We examined the effect of left atrial balloon inflation in chloralose‐anaesthetized dogs on heart rate with and without propranolol (l. Omg/kg) and on the activity in single cardiac efferent fibres of the vagus nerve.

2. Propranolol reduced the cardiac response to balloon inflation by one‐third, but did not abolish the tachycardia. Efferent cardiac vagal activity was 3.8 ± 0.4 spikes/s and 2.3 ± 0.7 spikes/s prior to and during balloon inflation respectively.

3. It was concluded that the left atrial receptors produce a tachycardia by decreasing cardiac parasympathetic and increasing sympathetic efferent activities.
PRESSURE‐VOLUME RELATIONSHIPS IN THE LEFT ATRIA OF ANAESTHETIZED DOGS
Authors: Fahim M.
Published: June 2007

1. Pressure‐volume relationships of the left atria were studied in thoracotomized dogs anaesthetized with sodium pentobarbitone and ventilated artificially. Controlled volumes of saline were injected into the left atrium using a method by which the injections were triggered by the R wave of the normal ECG, during the period of the V wave of the left atrial pressure waveform.

2. The change in the amplitude of the V wave was found to be linearly related to the injected volume. Similar observations made while the pulmonary artery was occluded revealed that this linearity in the pressure‐volume relationship of the atrium extended down to small volumes.
BLOOD FLOW AND RELATIVE TISSUE OXYGENATION OF NORMAL AND PARTIALLY ISCHAEMIC MYOCARDIUM: EFFECT OF CO2
Authors: Lipp J. A. , Weiss H. R.
Published: June 2007

1. Ischaemia of a portion of the myocardium in the dog heart was produced by tying off a small branch of a coronary artery: flow in the occluded region was reduced from 5 to 82% of the initial value.

2. The effect of inhalation of 5% CO2 in air on relative tissue PO2 and perfusion in normal and partially ischaemic myocardium was determined.

3. After 10 min inhalation of 5% CO2, there was an increase in tissue perfusion as measured by hydrogen desaturation; the increase was inversely proportional to the degree of flow reduction.

4. Relative intramyocardial PO2 measured polarographicafly, decreased with occlusion and increased after CO2 inhalation; the changes were inversely proportional to the degree of reduction in Po2

5. The increase in flow after CO2 inhalation suggests that partially ischaemic myocardial tissue is capable of further vasodilation.
THE EFFECTS OF DIAZEPAM ON RAT ISOLATED HEART MUSCLE
Authors: Sugimoto J. , Nagata M. , Ikeda Y.
Published: June 2007

1. The effects of diazepam on spontaneously beating right atrium, left atrium and papillary muscle isolated from a rat heart were compared to those of chlorpro‐mazine and phenytoin.

2. Arrhythmic contractions induced by threshold electrical stimulation in the rhythmic spontaneous contractions of the right atrium were prevented by diazepam (10 μg/ml). These arrhythmic contractions were not prevented by chlorpromazine (0.01–10 μg/ml), or by phenytoin (0.1–10μg/ml).

3. The refractory periods of the heart muscle, estimated by use of Govier's method, was increased by diazepam (10 μg/ml) by 90.5% in the left atrium and 54.4% in the papillary muscles. Chlorpromazine (1.0 μg/ml) and phenytoin (10 μg/ ml) increased the refractory period of papillary muscle by 42.8 and 54.1%, respectively, but had little effect on the refractory period of the left atrium.

4. The maximum driving frequency of the left atrium was decreased by diazepam (10 μg/ml) by 25.1% and by chlorpromazine (1.0 μg/ml) by 33.3%, while that of papillary muscle was little influenced by the drugs at these concentrations. Phenytoin (0.1–10 μg/ml) had little effect on the maximum driving frequency of the left atrium or of papillary muscle.

5. The rate and force of spontaneous contractions of the right atrium were decreased by phenytoin (10 μg/ml) by 36.7% and 97.0%, respectively. Diazepam (0.1–10 μg/ml) had little effect on rate and produced a concentration‐dependent increase in force up to 151.5%. Chlorpromazine (0.01–1.0 μg/ml) had little effect on either the rate or force of spontaneous contraction of the right atrium.

6. The contractile force of the left atrium and of papillary muscle driven by electrical stimulation was depressed by diazepam (20 μg/ml), chlorpromazine (2.0 μg/ml) and phenytoin (20 μg/ml)‐ Diazepam (0.5–10 μg/ml) produced a concentration‐dependent increase in force of up to 204.7% in the left atrium and 163.1% in papillary muscle. Chlorpromazine (0.01–1.0 μ/ml) had little effect on the force of the driven left atrium, but produced a concentration‐dependent decrease in force of papillary muscle down to 40.1%. Phenytoin (10 μg/ml) reduced the force of contraction by 84.6 and 92.7%, respectively, in the left atrium and papillary muscle.
PROSTAGLANDINS IN THE CONTROL OF BLOOD FLOW IN CANINE SKELETAL MUSCLE
Authors: Einstein Rosemarie , Goodman A. H.
Published: June 2007

1. The effects of systemic hypoxia, arterial occlusion and muscle exercise on blood flow and oxygen uptake of the hind limb of anaesthetized areflexic dogs were assessed. The control responses were compared to those elicited after administration of meclofenamic acid (2 mg/kg, i.v.).

2. Meclofenamic acid reduced resting blood flow by approximately 20%.

3. The increase in blood flow during 6 min periods of hypoxia was inversely related to arterial oxygen saturation and this relationship was not altered significantly by meclofenamic acid.

4. The magnitude of the reactive hyperaemias following arterial occlusion for 5‐40 s was dependent on the occlusion time. The peak changes in vascular conductance relative to the resting values were similar before and after administration of meclofenamic acid.

5. Direct stimulation of the muscles of the hind limb with 0.5‐5 Hz produced frequency‐dependent increases in blood flow and oxygen uptake to the limb. Although these responses were depressed after meclofenamic acid, the relationship between blood flow and oxygen uptake was not changed. The responses to stimulation with 10 Hz were not affected by meclofenamic acid.

6. An isolated chick rectum, superfused with re‐oxygenated venous blood from the hind limb during muscle stimulation at 10 Hz showed an initial relaxation, followed by contraction. The contraction was abolished after administration of meclofenamic acid.

7. From these results it appears that the release of prostaglandins is not essential for hyperaemais associated with vessel occlusion, systemic hypoxia or muscle exercise.
COMPARISON OF THE VASCULAR EFFECTS OF ADENOSINE, AMP, ADP AND ATP ON ISOLATED BLOOD‐PERFUSED INTERNAL AND EXTERNAL CAROTID ARTERIES OF DOGS
Authors: Chiba S. , Ohhashi T. , Azuma T.
Published: June 2007

1. The effects of adenosine and adenine nucleotides were studied on arterial vasculature in blood‐perfused arterial preparations of dogs which were isolated from the internal and external carotid arteries. Each compound was administered directly into the cannulated artery over a period of 4 s.

2. In both arterial preparations, adenosine produced a dose‐related vasodilatation and was more potent than AMP. On the other hand, ATP produced a dose‐related vasoconstriction and was more potent than ADP.
DIFFERENTIAL CHRONOTROPIC AND INOTROPIC EFFECTS OF 2‐NICOTINAMIDOETHYL NITRATE (SG‐75) IN THE DOG ISOLATED ATRIUM
Authors: Chiba S. , Furukawa Y. , Kobayashi M.
Published: June 2007

1. The chronotropic and inotropic effects of the anti‐anginal agent SG‐75 (2‐nicotinamidoethyl nitrate) and 1‐verapamil were investigated in isolated blood‐perfused canine atrial preparations. The compounds were administered via the cannulated sinus node artery.

2. SG‐75 induced a selective negative inotropic as opposed to a chronotropic effect. Verapamil showed no selective negative chronotropic or inotropic activity.

3. Effects of SG‐75 and 1‐verapamil on the frequency‐force relationship were studied. SG‐75 produced a uniform depression of the developed tension at all frequencies tested which the depression with 1‐verapamil was greater at higher than at lower frequencies.
STUDIES ON INTERACTION OF TIMOLOL, HYDROCHLOROTHIAZIDE AND AMILORIDE IN THE RAT
Authors: Scriabine A. , Watson L. S. , Ludden C. T. , Russo H. F. , Bohidar N. R.
Published: June 2007

1. The acute effects of hydrochlorothiazide, amiloride, timolol and their combinations on diuresis and arterial pressure were studied in rats.

2. Timolol did not modify the diuretic and saluretic effects of hydrochlorothiazide and/or amiloride and had no diuretic or antidiuretic effects alone.

3. At a single dose of 1 25 mg/kg, p.o., timolol alone had no antihypertensive effect in spontaneously hypertensive rats.

4. The antihypertensive effect of hydrochlorothiazide + amiloride+timolol was significantly greater than with any of the drugs alone.
RESPONSIVENESS OF HYPERTENSIVE SUBJECTS TO PRAZOSIN
Authors: Stokes G. S. , Monaghan J. C. , MacCarthy E. P. , Oates H. F.
Published: June 2007

1. Plasma drug levels and blood pressure changes produced by a single 2 mg oral dose of prazosin were determined in nine hypertensive patients.

2. Regression analysis showed that there was a high degree of correlation between plasma prazosin concentration and change in mean blood pressure.

3.There were marked differences between patients in their responsiveness to prazosin.
INFLUENCE OF MANGANESE IONS ON THE CONTRACTION OF THE GUINEA‐PIG ISOLATED VAS DEFERENS
Authors: Sugimoto J. , Hanasaki K. , Takemoto H. , Shintani H.
Published: June 2007

1. The CaCl2‐induced contraction of guinea‐pig isolated vas deferens, pre‐treated with tetrasodium edetate and then transferred to edetate‐free sucrose medium, was increased in the presence of MnCl2 in extremely low concentrations (0005‐001 mmol/l) but was suppressed by the salt in concentrations higher than 1 0 mmol/1.

2. The KCl‐induced contraction of the preparation, kept in a sucrose medium without edetate‐pretreatment, was suppressed by MnCl2 (0 005‐0 5 mmol/l) in a concentration‐dependent manner.

3. The noradrenaline‐induced contraction of the preparation kept in Locke's solution, was not influenced by MnCl2 in concentrations lower than 0 1 mmol/l but was inhibited by higher concentrations (0 1‐1 0 mmol/l).