bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomic effects of some scorpion venoms and toxins
Authors: Gwee Matthew CE , Nirthanan Selvanayagam , Khoo Hoon‐Eng , Gopalakrishnakone Ponnampalam , Kini R Manjunatha , Cheah Li‐Sam 
Published: March 2003

Summary1. The autonomic effects of venoms and toxins from several species of scorpions, including the Indian red scorpion Mesobuthus tamulus, the Chinese scorpion Buthus martensi Karsch and the Israeli scorpion Leiurus quinquestriatus quinquestriatus, all belonging to Buthidae, and the Asian black scorpions Heterometrus longimanus and Heterometrus spinifer, belonging to Scorpionidae, are reviewed.2. The effects of the venoms of M. tamulus and L. q. quinquestriatus on noradrenergic and nitrergic transmission in the rat isolated anococcygeus muscle revealed that both venoms mediated their pharmacological effects via a prejunctional mechanism involving the activation of voltage‐sensitive sodium channels with consequent release of neurotransmitters that mediate target organ responses, similar to the effects mediated by other α‐scorpion toxins.3. Two new toxins, Makatoxin I and Bukatoxin, were purified to homogeneity from the venom of B. martensi Karsch. Determination of their complete amino acid sequences confirmed that both toxins belonged to the class of α‐scorpion toxins. The effects of both toxins on noradrenergic and nitrergic transmission in the rat anococcygeus muscle provided firm evidence that their pharmacological actions also closely resembled those mediated by other α‐scorpion toxins on neuronal voltage‐sensitive sodium channels.4. The venoms of H. longimanus and H. spinifer were found to have high concentrations of noradrenaline (1.8 ± 0.3 mmol/L) and relatively high concentrations of acetylcholine (79.8 ± 1.7 µmol/L) together with noradrenaline (146.7 ± 19.8 µmol/L), respectively, which can account for their potent direct cholinergic and noradrenergic agonist actions in the rat anococcygeus muscle.5. Our studies confirmed that the rat anococcygeus muscle is an excellent nerve–smooth muscle preparation for investigating the effects of bioactive agents on noradrenergic and nitrergic transmission, as well as the direct agonist actions of these agents on post‐synaptic α‐adrenoceptors and M3 muscarinic cholinoceptors. Although many studies, including our own, have documented that scorpion venoms and toxins mediate their primary effects via a prejunctional mechanism that leads to the marked release of various autonomic neurotransmitters, our studies have shown that there are exceptions to this generally accepted phenomenon. In particular, we have provided firm evidence to show that the venoms from H. longimanus and H. spinifer do not have such a prejunctional site of action but, instead, the venoms mediate their autonomic effects through direct agonist actions on post‐junctional muscarinic M3 cholinoceptors and α‐adrenoceptors.
Association of the SULT1A1 R213H polymorphism with colorectal cancer
Authors: Wong Chung Fai , Liyou Nancy , Leggett Barbara , Young Joanne , Johnson Anthony , McManus Michael E 
Published: March 2003

Summary1. Sulphotransferases are a superfamily of enzymes involved in both detoxification and bioactivation of endogenous and exogenous compounds. The arylsulphotransferase SULT1A1 has been implicated in a decreased activity and thermostability when the wild‐type arginine at position 213 of the coding sequence is substituted by a histidine. SULT1A1 is the isoform primarily associated with the conversion of dietary N‐OH arylamines to DNA binding adducts and is therefore of interest to determine whether this polymorphism is linked to colorectal cancer.2. Genotyping, using polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) analysis, was performed using DNA samples of healthy control subjects (n = 402) and patients with histologically proven colorectal cancer (n = 383). Both control and test populations possessed similar frequencies for the mutant allele (32.1 and 31%, respectively; P = 0.935). Results were not altered when age and gender were considered as potential confounders in a logistic regression analysis.3. Examination of the sulphonating ability of the two allozymes with respect to the substrates p‐nitrophenol and paracetamol showed that the affinity and rate of sulphonation was unaffected by substitution of arginine to histidine at position 213 of the amino acid sequence.4. From this study, we conclude that the SULT1A1 R213H polymorphism is not linked with colorectal cancer in this elderly Australian population.
A diet supplemented with thiolic anti‐oxidants improves leucocyte function in two strains of prematurely ageing mice
Authors: Guayerbas N , Puerto M , Ferrández MD , De la Fuente M 
Published: March 2003

Summary1. According to previous studies, Swiss mice of the same age showed striking interindividual differences in behaviour when exposed to a T‐maze test, with a slow performance being linked to an impaired immune function, hyperemotional response to stress and a shorter life span compared with mice that quickly explore the maze.These facts led us to propose the slow mice as a model of prematurely ageing mice (PAM).2. In the present study, we investigated whether this prematurely ageing model could be found in other strains of mice, such as BALB/c mice, by analysing several lymphocytes functions, such as adherence, chemotaxis, proliferative response to the mitogen concanavalin A (Con A), interleukin (IL)‐2 release and natural killer (NK) activity. In addition, we tested the probable beneficial effects on these functions of dietary supplementation with thioproline (TP) plus N‐acetylcysteine (NAC; 0.1% w/w of each anti‐oxidant) in female Swiss and BALB/c mice.3. Our model of premature ageing, previously reported in Swiss mice, has also been reproduced in the inbred BALB/c mouse strain, in which PAM showing an immunosenescence in several lymphocyte functions, such as lower chemotaxis, proliferative response to Con A, IL‐2 release and NK activity, as well as higher adherence, were observed. A short‐term (5 week) ingestion of TP + NAC by female Swiss and BALB/c mice improved leucocyte function, increasing chemotaxis, the proliferative response to Con A, IL‐2 release and NK activity and decreasing the adherence of lymphocytes.These effects are greatest in cells from PAM of both strains.4. In conclusion, our model of premature ageing has been reproduced in an inbred strain. In addition, the ingestion of a diet supplemented with two thiolic anti‐oxidants, such as NAC and TP, has been shown to be beneficial to the immune response in PAM.
Effect of creatine manipulation on fast‐twitch skeletal muscle of the mouse
Authors: Robinson Dean M , Loiselle Denis S 
Published: March 2003

Summary1. The effect of short‐term, reversible alteration of muscle total creatine content (Crtot) on force development was sought in fast‐twitch extensor digitorum longus (EDL) muscles of female mice.2. Three in vivo interventions were investigated: 1% creatine‐supplementation, treatment with the creatine‐uptake inhibitor β‐guanidino propionic acid (β‐GPA; 1%) or β‐GPA treatment followed by creatine supplementation for 5 days.3. The Crtot of isolated muscles, determined using reverse‐phase high‐performance liquid chromatography, was 133 ± 38 mmol/kgdry in 11 EDL control muscles and was not significantly affected by dietary creatine‐supplementation (152 ± 25 mmol/kgdry; n = 8). Significant creatine depletion was observed in the β‐GPA‐fed group (65 ± 6 mmol/kgdry; n = 9) and this was reversed by 5 days of creatine supplementation (133 ± 21 mmol/kgdry; n = 10).4. Creatine depletion did not affect maximum tetanic stress. However, when muscle creatine was restored by creatine supplementation, a substantial increase in tetanic stress was observed. Significant correlations were observed between Crtot and maximum tetanic stress (r = 0.56) and relaxation rate (r = 0.43). The enhancement of force was not due to effects of creatine on muscle fibre type because neither mechanical tests of fibre characteristics nor the fibre types of the muscles were affected.5. We conclude that, in muscles that contain large numbers of fast‐twitch fibres, maximum tetanic stress is determined, in part, by muscle creatine stores.
Endurance training adaptations modulate the redox–force relationship of rat isolated slow‐twitch skeletal muscles
Authors: Plant David R , Gregorevic Paul , Warmington Stuart A , Williams David A , Lynch Gordon S 
Published: March 2003

Summary1. Studies have shown that, in isolated skeletal muscles, maximum isometric force production (Po) is dependent on muscle redox state. Endurance training increases the anti‐oxidant capacity of skeletal muscles, a factor that could impact on the force‐producing capacity following exogenous exposure to an oxidant. We tested the hypothesis that 12 weeks treadmill training would increase anti‐oxidant capacity in rat skeletal muscles and alter their response to exogenous oxidant exposure.2. At the conclusion of the 12 week endurance‐training programme, soleus (slow‐twitch) muscles from trained rats had greater citrate synthase (CS) and catalase (CAT) activity compared with soleus muscles from untrained rats (P < 0.05). In contrast, CAT activity of extensor digitorum longus (EDL; fast‐twitch) muscles from trained rats was not different to EDL muscles of untrained rats. The CS activity was lower in EDL muscles from trained compared with untrained rats (P < 0.05).3. Equilibration with exogenous hydrogen peroxide (H2O2, 5 mmol/L) increased the Po of soleus muscles from untrained rats for the duration of treatment (30 min), whereas the Po of EDL muscles was affected biphasically, with a small increase initially (after 5 min), followed by a more marked decrease in Po (after 30 min). The H2O2‐induced increase in Po of soleus muscles from trained rats was less than that in untrained rats (P < 0.05), but no differences were observed in the Po of EDL muscles following training.4. The results indicate that 12 weeks endurance running training conferred adaptations in soleus but not EDL muscles. These adaptations were associated with an attenuation of the oxidant‐induced increase in Po of soleus muscles from trained compared with untrained rats. We conclude that endurance training‐adapted soleus muscles have a slightly altered redox–force relationship.
Peripheral injection of risperidone, an atypical antipsychotic, alters the bodyweight gain of rats
Authors: Ota Miyuki , Mori Keiji , Nakashima Akira , Kaneko Yoko S , Fujiwara Kentaro , Itoh Mitsuyasu , Nagasaka Akio , Ota Akira 
Published: March 2003

Summary1. Risperidone is an atypical antipsychotic drug that possesses 5‐hydroxytryptamine 5‐HT2 receptor antagonism combined with milder dopamine D2 receptor antagonism.2. Excessive bodyweight gain is one of the side‐effects of antipsychotics. Risperidone treatment causes a greater increase in the body mass of patients than treatment with conventional antipsychotics, such as haloperidol. Therefore, the present study was undertaken in order to address the aetiology of the risperidone‐induced bodyweight change in rats by examining the expression of leptin, an appetite‐regulating hormone produced in white adipose tissue (WAT), and uncoupling protein (UCP)‐1, a substance promoting energy expenditure in the brown adipose tissues (BAT).3. Eight‐week‐old male rats were injected subcutaneously with risperidone (0.005, 0.05 or 0.5 mg/kg) twice daily for 21 days. Both bodyweight and food intake were monitored daily. On day 21, rats were decapitated and their serum leptin and prolactin concentrations were measured. Expression levels of leptin, Ucp1 and β3‐adrenoceptor (β3‐AR) genes in WAT and BAT were quantified using real‐time polymerase chain reaction amplification.4. Injection of 0.005 mg/kg risperidone into rats increased food intake and the rate of bodyweight gain, as well as the augmentation of leptin gene expression in WAT. Injection of 0.05 mg/kg risperidone increased food intake and leptin gene expression in WAT, but the rate of bodyweight gain was not affected. Injection of 0.5 mg/kg risperidone caused a reduction in bodyweight gain, as well as enhanced Ucp1 gene expression in BAT and serum prolactin concentrations. The serum leptin concentration and β3‐AR gene expression in WAT and BAT were not affected by injection of 0.5 mg/kg risperidone.5. Although the changes in food intake observed in risperidone‐injected rats were rationalized neither by serum leptin nor prolactin concentrations, the reduction in the rate of bodyweight gain following injection of 0.5 mg/kg can be explained, in part, by increased energy expenditure, as revealed by the remarkable increase in the UCP‐1 mRNA expression level in BAT. The role of leptin in risperidone‐induced alterations in bodyweight gain remain to be clarified.
Effects of second‐generation histamine H1 receptor antagonists on the active avoidance response in rats
Authors: Nishiga Miyuki , Fujii Yoko , Konishi Masako , Hossen Maria Alejandra ,   Chiaki Kamei
Published: March 2003

Summary1. The aim of the present study was to establish a new schedule of active avoidance response in rats to estimate the central effects of second‐generation histamine H1 receptor antagonists.2. With the new schedule, a rat was placed into a dark room. A sliding door was opened after a delay of 5 s and, unless the animal moved into the lit room, an electric shock was delivered for 3 s. With the conventional schedule, the sliding door was opened immediately after the rat was placed into the dark room.3. Ketotifen, at a dose of 50 mg/kg, showed no significant effect on the retrieval of active avoidance response with the conventional schedule. However, with the new schedule, the drug caused significant inhibition of retrieval of the response, even at a dose of 10 mg/kg.4. Epinastine showed no significant effect on retrieval of the active avoidance response, even at a dose of 50 mg/kg with the new schedule.5. Cetirizine, at a dose of 50 mg/kg, caused a significant effect, indicating that cetirizine, at this dose, markedly inhibits memory retrieval.6. Both olopatadine and loratadine had potent effects; at doses of 20 and 50 mg/kg, respectively, these agents showed significant inhibitory effects on retrieval of the response.7. In conclusion, we have developed a new schedule of active avoidance response that can be used to estimate the central effects of second‐generation histamine H1 receptor antagonists.
Cardiovascular reflex responses after intrathecal ω‐conotoxins or dexmedetomidine in the rabbit
Authors: Blake Duncan W , Wright Christine E , Scott David A , Angus James A 
Published: March 2003

Summary1. The effects of thoracic intrathecal doses (1 µg/kg) of the α2‐adrenoceptor agonist dexmedetomidine and ω‐conotoxins MVIIA and CVID on vasoconstrictor and heart rate responses to acute central hypovolaemia were studied in seven chronically instrumented rabbits.2. Gradual inflation of an inferior vena cava cuff to reduce cardiac index (CI) by 8% per minute induced progressive vasoconstriction and an increase in heart rate (phase I). At approximately 40% of resting CI, there was sudden decompensation with failure of vasoconstriction and decrease in mean arterial pressure (MAP; phase II).3. Both intrathecal MVIIA and CVID decreased resting CI (by 20% at 3 h), but only MVIIA significantly reduced resting MAP (P = 0.003). Dexmedetomidine resulted in transient bradycardia, but no other significant change in the resting circulation. With simulated haemorrhage, the relationship between CI and vascular conductance was shifted after MVIIA (1–3 h after injection) so that there was less vasoconstriction and a reduced increase in heart rate by the end of phase I compared with other treatments (P = 0.002 and P = 0.009, respectively). One hour after injection, dexmedetomidine reduced the slope of the phase I vasoconstrictor response (P = 0.03), but did not significantly alter the end‐point of the response. With failure of vasoconstriction and the onset of phase II, vascular conductance was higher after MVIIA compared with controls. Both conotoxins caused progressive failure of vasoconstriction rather than recovery during phase II (P < 0.001).4. Intrathecal injections of these drugs to control chronic pain may compromise cardiovascular responses to changes in central blood volume. At the single doses studied, there were significant differences between the responses to simulated haemorrhage after MVIIA or dexmedetomidine compared with CVID, with the prolonged effect after MVIIA most likely to be of clinical significance.
Relationship between anti‐oxidant activities and doxorubicin‐induced lipid peroxidation in P388 tumour cells and heart and liver in mice
Authors: Liu Qi‐Yuan , Tan Benny KH 
Published: March 2003

Summary1. The present study found that, compared with mouse heart and liver, P388 ascitic tumour had significantly lower superoxide dismutase (SOD) activity and that compared with the mouse liver, the heart had significantly lower SOD and catalase activities, as well as a lower glutathione content.2. At 7.5 mg/kg, doxorubicin (DOX), a superoxide radical inducer, induced significant lipid peroxidation only in the tumour, whereas 15.0 mg/kg DOX induced lipid peroxidation in both the tumour and heart, but not in the liver.3. Overall, the results of the present study suggest that the differential anti‐oxidant activities in P388 ascitic tumour, heart and liver in mice may explain their differential responses and, hence, susceptibility to DOX‐induced lipid peroxidation.
The renal medullary interstitium: focus on osmotic hypertonicity
Authors: Sadowski Janusz , Dobrowolski Leszek 
Published: March 2003

Summary1. There has been continued interest in the functional role of the renal medullary interstitium and intense research in this area has furnished new information regarding the extent, dynamics and mechanisms determining fluctuations in medullary osmotic hypertonicity.2. Any change in the tonicity (interstitial solute concentration) indicates an imbalance of the rate of solute delivery to the interstitium (by tubular transport) and solute removal therefrom (by the microcirculation). It is often difficult to establish whether alteration of the delivery or removal triggered the change in medullary tissue tonicity.3. Newer in vivo studies have confirmed earlier predictions and indirect evidence indicating that the rate of NaCl transport in the ascending limb of the loop of Henle is the major determinant of medullary ionic hypertonicity.4. The hypothesis of a ‘washout’ of medullary solutes during increased medullary blood flow (MBF) has been re‐evaluated. A novel experimental approach has provided direct evidence of a modest dissipation of medullary solutes with increasing MBF and a modest accumulation of solutes with decreasing MBF.5. Increasing evidence is reviewed indicating that medullary tonicity is not only a regulated variable, but also that it may itself modulate the activity of multiple local endocrine and paracrine control systems and thereby affect local microcirculation and the function of medullary interstitial and tubular cells.
Pyruvate‐dependent preconditioning and cardioprotection in murine myocardium
Authors: Flood Amanda , Hack Benjamin D , Headrick John P 
Published: March 2003

Summary1. Whether pyruvate inhibits or can actually initiate myocardial preconditioning is unclear and whether pyruvate provides protection via its action as a ‘cosubstrate’ with glucose or via alternative mechanisms also remains controversial. We examined effects of a high concentration of pyruvate (10 mmol/L) alone or with 15 mmol/L glucose in mouse hearts subjected to 20 min ischaemia and 30 min reperfusion.2. Provision of 10 mmol/L pyruvate alone or as a cosubstrate markedly reduced ischaemic contracture and enhanced postischaemic recovery. Time to contracture was increased from approximately 3 min to over 8 min, peak contracture was reduced from 90 mmHg to less than 60 mmHg and postischaemic pressure development was also improved. Effects on contracture were independent of the presence of pyruvate during ischaemia and improved postischaemic recovery was evident with pre‐ischaemic pyruvate perfusion.3. Cardioprotection did not require the presence of pyruvate during ischaemia or reperfusion and effects of pyruvate pretreatment could be mimicked by pretreatment with 1 mmol/L dichloroacetate (DCA), an activator of pyruvate dehydrogenase.4. Myocardial adenosine efflux and Ca2+ content were elevated (by 215 and 65%, respectively) following pretreatment with pyruvate, potentially triggering a preconditioned state. A role for adenosine A1 receptors is supported by lack of added protection with pyruvate in hearts transgenically overexpressing adenosine A1 receptors.5. Collectively, these observations demonstrate that pre‐ischaemic treatment with pyruvate or DCA provides a beneficial preconditioning‐like effect in ischaemic and postischaemic myocardium. The response appears unrelated to glycolytic inhibition, but may be mediated via transient changes in adenosine levels and/or cellular Ca2+.
Comparison of the in vitro neuromuscular activity of venom from three australian snakes (Hoplocephalus stephensi, Austrelaps superbus and Notechis scutatus): Efficacy of tiger snake antivenom
Authors: Hodgson Wayne C , Eriksson Christer O , Alewood Paul F , Fry Bryan G 
Published: March 2003

Summary1. Tiger snake antivenom, raised against Notechis scutatus venom, is indicated not only for the treatment of envenomation by this snake, but also that of the copperhead (Austrelaps superbus) and Stephen's banded snake (Hoplocephalus stephensi). The present study compared the neuromuscular pharmacology of venom from these snakes and the in vitro efficacy of tiger snake antivenom.2. In chick biventer cervicis muscle and mouse phrenic nerve diaphragm preparations, all venoms (3–10 µg/mL) produced inhibition of indirect twitches. In the biventer muscle, venoms (10 µg/mL) inhibited responses to acetylcholine (1 mmol/L) and carbachol (20 µmol/L), but not KCl (40 mmol/L). The prior (10 min) administration of 1 unit/mL antivenom markedly attenuated the neurotoxic effects of A. superbus and N. scutatus venoms (10 µg/mL), but was less effective against H. stephensi venom (10 µg/mL); 5 units/mL antivenom attenuated the neurotoxic activity of all venoms.3. Administration of 5 units/mL antivenom at t90 partially reversed, over a period of 3 h, the inhibition of twitches produced by N. scutatus (10 µg/mL; 41% recovery), A. superbus (10 µg/mL; 25% recovery) and H. stephensi (10 µg/mL; 50% recovery) venoms. All venoms (10–100 µg/mL) also displayed signs of in vitro myotoxicity.4. The results of the present study indicate that all three venoms contain neurotoxic activity that is effectively attenuated by tiger snake antivenom.
Development and evaluation of a simple calorimeter for the measurement of resting metabolism
Authors: Tamura Toshiyo , Ichinoseki Noriko , Yoshimura Takumi , Torii Yoshihiko 
Published: March 2003

Summary1. A simple calorimeter based on the measurement of oxygen uptake has been developed.2. A respiratory simulator was used to evaluate oxygen uptake at different flow rates. A known concentration of mixed gases flows into the calorimeter via the respiratory simulator. Oxygen concentration and flow rate were measured and stored to memory for further analysis.3. Results indicate that large errors occur at low flow rates, but that the error is less than 5% under normal conditions.4. This device can be used to measure oxygen uptake under resting conditions.