bluuebunny/crossref_metadata_2025_split huggingface dataset:
Suppressive Effects Of Oxcarbazepine On Tooth Pulp‐Evoked Potentials Recorded At The Trigeminal Spinal Tract Nucleus In Cats
Authors: Kiguchi Sumiyoshi , Ichikawa Kiyoshi , Kojima Masami 
Published: March 2003

SUMMARY1. The purpose of the present study was to evaluate the antinociceptive effect of oxcarbazepine, a keto derivertive of carbamazepine (an anticonvulsant), in an animal model. To evoke a nociceptive response, we electrically stimulated the maxillary canine tooth pulp (MCTP) in anaesthetized (allobarbital–urethane), spontaneously breathing cats.2. The evoked potentials were recorded from the superficial layers of the caudal part of the trigeminal spinal tract nucleus (5ST). We examined a slow component with a large amplitude (the P3 component) in evoked compound potentials; its mean conduction velocity was 1.7 m/s, suggesting a response mediated by C‐fibres.3. To confirm that the P3 component was related to pain sensation, we used morphine, a most efficacious antinociceptive agent, in the present study. The P3 component was significantly suppressed by intravenous administration of morphine (3 mg/kg) and was also suppressed by microinjection of morphine (2 μg) into the recording site of the 5ST. These results suggest that the P3 component is involved in the transmission of nociceptive information.4. We compared the effect of oxcarbazepine with mexiletine; both are known to block neuronal Na+ channels. Intravenous administration of mexiletine suppressed the P3 component at a dose of 5 mg/kg. Microinjection of mexiletine (10 μg) into the recording site of the 5ST tended to suppress the P3 component, but this effect was not significant.5. Intravenous administration of oxcarbazepine (1–10 mg/kg) caused a dose‐dependent inhibition of the P3 component, which was significantly suppressed at 10 mg/kg oxcarbazepine. Intravenous administration of 10,11‐dihydro‐10‐hydroxy‐ 5H‐dibenz[b,f]azepine‐5‐carboxamide (MHD), a metabolite of oxcarbazepine, at doses of 3–30 mg/kg caused a dose‐dependent inhibition of the P3 component. Oxcarbazepine was not available for the microinjection study because it is not water soluble. We used MHD for the microinjection study instead of oxcarbazepine, because MHD can be dissolved in water up to 3 mg/mL. Microinjections of MHD (6 μg) into the recording site of the 5ST suppressed the P3 component. These results indicate that oxcarbazepine has an antinociceptive action.
An Electrophysiological Study Of The Effects Of Propofol On Native Neuronal Ligand‐Gated Ion Channels
Authors: Patten Debra , Foxon Graham R , Martin Keith F , Halliwell Robert F 
Published: March 2003

SUMMARY1. Pharmacological evidence suggests that some of the clinical actions of propofol may be mediated, at least in part, by positive modulation of the GABAA receptor chloride channel. The effect of propofol at other native neuronal ligand‐gated ion channels is unclear.2. To gain some insight into the effects of propofol at a range of native neuronal receptors, the present study has used an extracellular recording technique and determined its effects at GABAA, 5‐HT3, P2X and nicotinic acetylcholine (nACh) receptors of the rat isolated vagus nerve and the GABAA and strychnine‐sensitive glycine receptor of the rat isolated optic nerve. In addition, we have used patch‐clamp recording techniques to further investigate the effects of propofol at the GABAA and strychnine‐sensitive glycine receptors in rat cultured hippocampal neurons.3. Propofol (0.3–100 μmol/L) concentration‐dependently potentiated submaximal GABA‐evoked responses in the vagus nerve and shifted the GABA concentration–response curve to the left. In contrast, propofol at concentrations ranging from 1 to 10 μmol/L had little or no effect on 5‐HT3, P2X or nACh receptor‐mediated responses in the vagus nerve but, at 100 μmol/L, propofol inhibited these responses to approximately 50% of control. In the optic nerve, EC20 GABA‐evoked responses were also potentiated by propofol (10 μmol/L), while EC20 glycine‐evoked responses were minimally enhanced.4. Further investigations using cultured hippocampal neurons showed that submaximal (10 μmol/L) GABA‐evoked currents were potentiated by propofol (1–10 μmol/L), in a non‐voltage‐dependent manner, whereas submaximal (100 μmol/L) glycine‐evoked currents were unaffected.5. These data suggest that propofol, at therapeutic concentrations, exerts its principle pharmacological actions at GABAA receptors with relatively little effect at other neuronal ligand‐gated ion channels.
Proceedings of the Australian Physiological and Pharmacological Society Symposium: New Frontiers in Muscle Research Gene transfer: manipulating and monitoring function in cells and tissues
Authors: Panchal Rekha G , Williams David A , Kitchener Peter D , Reilly Angela M , Khan Jameel , Bowser David N , Petrou Steven 
Published: March 2003

SUMMARY1. The ectopic expression of genes has proven to be an extremely valuable tool for biologists. The most widely used systems involve electrically or chemically mediated transfer of genes to immortalized cell lines and, at the other end of the spectrum, transgenic animal models. As would be expected, there are compromises to be made when using either of these broad approaches. Immortalized cell lines have limited ‘physiological relevance’ and transgenic approaches are costly and out of the reach of many laboratories. There is also significant time required for the de novo generation of a transgenic animal.2. As a viable alternative to these approaches, we describe the use of recombinant adenovirus and Sindbis virus to deliver genes to cells and tissues.3. We exemplify this approach with studies from our laboratories: (i) an investigation of Ca2+ handling deficits in cardiac myocytes of hypertrophied hearts using infection with recombinant adenovirus encoding either green fluorescent protein (GFP) or the sarcoplasmic/endoplasmic reticulum calcium‐ATPase (Serca2a); (ii) a study of the mechanism of macrophage/microglial migration by infection of embryonic phagocytes with a GFP‐encoding virus and coculture with brain slices to then track the movement of labelled cells; and (iii) we are also exploiting the natural tropism of the Sindbis virus to label neurons in hippocampal brain slices in culture to resolve high‐resolution structure and to map neuronal connectivity.4. Further development of these approaches should open new avenues of investigation for the study of physiology in a range of cells and tissues.
Troglitazone Enhances Glucose Uptake Induced By α‐Adrenoceptor Stimulation Via Phosphatidylinositol 3‐Kinase In Rat Heart
Authors: Yoshioka Jun , Kusuoka Hideo , Imahashi Kenichi , Hashimoto Katsuji , Hori Masatsugu , Terakawa Taichiro , Nishimura Tsunehiko 
Published: March 2003

SUMMARY1. Thiazolidinedione‐derived agents have been reported to act as insulin sensitizers by augmenting insulin‐dependent stimulation of phosphatidylinositol 3‐kinase (PI3K) activity in a specific manner. It has been suggested that α‐adrenoceptor stimulation mediates glucose uptake through PI3K in the heart.2. To elucidate whether the thiazolidinedione‐derived agent troglitazone (TRO) affects glucose uptake induced by α‐adrenoceptor stimulation through PI3K, the rate of glucose uptake was quantified from the rate of accumulation of sugar phosphate (d[SP]/dt) using [31P] nuclear magnetic resonance spectroscopy after substitution of glucose with 2‐deoxyglucose in rat perfused heart. Hearts were stimulated with 100 μmol/L phenylephrine plus 10 μmol/L propranolol (α‐adrenoceptor stimulation), or 1 μmol/L isoproterenol plus 10 μmol/L phentolamine (β‐adrenoceptor stimulation).3. The d[SP]/dt in the α‐ and β‐adrenoceptor‐stimulated groups (0.45 ± 0.06 and 0.42 ± 0.04 μmol/min per g, respectively) was higher than that of the control group (0.27 ± 0.02 μmol/min per g; P < 0.01). The addition of 2 μg/mL troglitazone to α‐adrenoceptor stimulation augmented d[SP]/dt (0.72 ± 0.08 μmol/min per g; P < 0.05 vs the α‐adrenoceptor‐stimulated group), which was effectively blocked by 3 μmol/L wortmannin (0.35 ± 0.06 μmol/min per g; P < 0.01 vs troglitazone + α‐adrenoceptor stimulation group). However, addition of troglitazone to β‐adrenoceptor stimulation did not alter d[SP]/dt (0.33 ± 0.02 μmol/min per g; P = NS vs the β‐adrenoceptor‐stimulated group).4. These results indicate that troglitazone acutely enhances α‐adrenoceptor stimulation on glucose uptake through a PI3K‐dependent pathway, thus possibly improving glucose utilization in a catecholamine‐released state.
Time Of Day And Access To Food Alter Water Intake In Rats After Water Deprivation
Authors: Ang Kooi K , McKitrick Douglas J , Phillips Paddy A , Arnolda Leonard F 
Published: March 2003

SUMMARY1. Drinking behaviour after water deprivation is one of the standard tests used to study thirst in humans and animals. Diurnal cycle and food availability are known to influence water intake, but have not been considered in previous studies of thirst after water deprivation. In the present study, we examined the effects of diurnal variation and food availability on water intake after 24 h water deprivation in rats.2. All rats cycled through four treatments in varying order. These treatments were: (i) 24 h water deprivation with free access to food from 1900 h one day to 1900 h the next day, followed by free access to both food and water (Night‐with‐Food); (ii) 24 h water deprivation with free access to food from from 1900 h one day to 1900 h the next day, followed by free access to water but not food (Night‐without‐Food); (iii) 24 h water deprivation with free access to food from 0700 h one day to 0700 h the next day, followed by free access to both food and water (Day‐with‐Food); or (iv) 24 h water deprivation with free access to food from 0700 h one day to 0700 h the next day, followed by free access to water but not food (Day‐ without‐Food). The amount of water consumed during the first 6 h, post‐24 h water deprivation, was examined under each condition.3. There was a significant diurnal effect (P < 0.001) and a significant food availability effect (P = 0.007) on the water consumed in the 6 h period after water deprivation. Most water was consumed by the Night‐with‐Food group and the least amount of water was consumed by the Day‐without‐Food group. These effects persisted after correction for water intake during 6 h periods from 0700 and 1900 h with and without food but without previous water deprivation. The diurnal and food availability effects on water consumption were independent (P = 0.5).4. The coefficient of variability for each group suggests that the most sensitive measurements of water intake are obtained during the day in the absence of food.5. We conclude that both the time of day and access to food independently alter water intake in rats subjected to a previous 24 h water deprivation. Our study also supports the validity of performing water intake measurements in thirst studies in rats during the day.
Monocyte Integrin Expression And Monocyte–Platelet Complex Formation In Humans With Coronary Restenosis
Authors: Arefieva Tatiana I , Provatorov Sergey I , Samko Anatoly N , Krasnikova Tatiana L , Resink Therese J , Erne Paul , Tkachuk Vsevolod A , Chazov Eugeniy I 
Published: March 2003

SUMMARY1. In the present study, we sought to determine whether patients with restenosis after coronary stenting possess increased monocyte reactivity, as manifested by a higher level of adhesion molecule expression and an enhanced propensity to form monocyte–platelet aggregates after activation in vitro.2. Anti‐coagulated peripheral venous blood from 24 patients, 10 with and 14 without angiographically verified restenosis, was obtained. Leucocyte antigen expression and the number of leucocyte–platelet complexes were measured by flow cytometry after activation in whole blood.3. Surface integrin Mac‐1 (CD11b/CD18) and VLA‐4 (CD49d/ CD29) expression on monocytes and the relative number of monocyte–platelet complexes after in vitro activation were significantly elevated in patients with restenosis compared with patients without restenosis (fluorescence intensities of 1425 ± 76 vs 1195 ± 71, 87 ± 7 vs 65 ± 6 and 47 ± 4 vs 29 ± 3% for for Mac‐1, VLA‐4 and monocyte–platelet complexes, respectively; P < 0.05 for each parameter).4. The results suggest that restenosis is associated with increased monocyte VLA‐4 and Mac‐1 integrin expression and monocyte–platelet complex formation, which can be revealed after activation in vitro.
Investigation Of AM‐36: A Novel Neuroprotective Agent
Authors: Callaway Jk 
Published: March 2003

SUMMARY1. The neurochemical sequelae following cerebral ischaemia are complex, involving excess release of excitatory amino acids, particularly glutamate, disruption of ionic homeostasis due to Na+ and Ca2+ influx and generation of toxic free radicals, ultimately leading to cell death by both necrosis and apoptosis.2. Drugs that block components of this biochemical cascade, such as glutamate receptor antagonists, sodium channel blockers and free radical scavengers, have been investigated as putative neuroprotective agents. The knowledge that multiple mechanisms contribute to neuronal injury in ischaemia have led to the general recognition that a single drug treatment is unlikely to be beneficial in the treatment of cerebral ischaemia.3. AM‐36 [1‐(2‐(4‐chlorophenyl)‐2‐hydroxy)ethyl‐4‐(3,5‐bis(1,1‐dimethyl)‐4‐hydroxyphenyl)methylpiperazine] is one of a series of hybrid molecules designed to incorporate multiple neuroprotective mechanisms within the one structure. Primary screening tests demonstrated that AM‐36 inhibited binding to the polyamine site of glutamate receptors, blocked neuronal sodium channels and had potent anti‐oxidant activity. In neuronal cell cultures, AM‐36 inhibited toxicity induced by N‐methyl‐D‐aspartate (NMDA) and the sodium channel opener veratridine and, in addition, inhibited veratridine‐induced apoptosis.4. In a middle cerebral artery occlusion model of stroke in conscious rats, systemic administration of AM‐36 markedly reduced both cortical and striatal infarct volume and significantly improved functional outcome in motor performance, neurological deficit and sensorimotor neglect tests. AM‐36 was neuroprotective even when administration was delayed until 3 h systemically, or 5 h intravenously, after induction of stroke.5. These studies indicate that AM‐36 is a unique neuroprotective agent with multiple modes of action, making it an attractive candidate for the treatment of acute stroke in humans.
Recent Developments Concerning Diet And Hypertension
Authors: Beilin Lawrie J , Burke Valerie , Puddey Ian B , Mori Trevor A , Hodgson Jonathan M 
Published: March 2003

SUMMARY1. Recent data from randomized controlled dietary trials have shown blood pressure‐lowering effects of foodstuffs and dietary patterns to be of practical importance for both individual and population blood pressure control.2. The salient studies include Dietary Approaches to Stop Hypertension (DASH) trials, on complex dietary patterns and of additive effects of salt restriction, Trial of Nonpharmacologic Interventions in the Elderly (TONE), on weight control and sodium restriction as substitutes for drug therapy, and two Australian trials showing additive effects of dietary fish and weight control and of dietary protein and fibre in treated hypertensives.3. Regular coffee drinking raised blood pressure in older hypertensives, whereas potential antihypertensive effects of dietary anti‐oxidants require further scrutiny.
Different Aortic Reflection Wave Responses Following Long‐Term Angiotensin‐Converting Enzyme Inhibition And Beta‐Blocker In Essential Hypertension
Authors: Pannier Bruno M , Guerin Alain P , Marchais Sylvain J , London Gérard M 
Published: March 2003

SUMMARY1. In arterial hypertension, aortic wave reflections contribute to determining central systolic and pulse pressures. The present study assessed the central pressure alterations at the level of the common carotid artery following 1 month treatment with perindopril or atenolol and investigated during the 8 h following drug intake.2. Twenty patients suffering from permanent hypertension were included after a 4 week run‐in placebo period in a double‐blind, randomized cross‐over study comparing the angiotensin‐converting enzyme (ACE) inhibitor perindopril with the beta‐blocker atenolol during a 4 week treatment period.3. Before and during the 8 h after drug intake, serial measurements included brachial artery systolic and diastolic blood pressures (SBP and DBP, respectively; mercury sphygmomanometer), carotid artery SBP and pulse pressure (PP; applanation tonometry), aortic pulse wave velocity (Complior; Colson, Les Lilas, France) and arterial wave reflections from the aorta (applanation tonometry; Sphygmocor; PWV Medical, Sydney, NSW, Australia).4. Both treatments decreased brachial and carotid artery SBP, DBP and PP. Heart rate and pulse wave velocity decreased following atenolol (P < 0.001). Pulse wave velocity was reduced slightly following perindopril (NS). Arterial wave reflections were significantly (P < 0.001) decreased with perindopril in comparison with atenolol, but this effect on wave reflections was not associated with a larger decrease in carotid artery PP.5. Thus, during chronic treatment, ACE inhibition and selective β1‐adrenoceptor blockade resulted in a similar decrease in brachial and carotid artery PP, but only atenolol reduced heart rate. Aortic pulse wave velocity was reduced with both drugs, but atenolol appeared more effective in improving aortic stiffness. Arterial wave reflections were decreased only following perindopril.6. Central pulse pressure was improved following 1 month treatment with an ACE inhibitor or β‐adrenoceptor blockade following a decrease in arterial wave reflections with perindopril and a higher decrease in regional aortic stiffness with atenolol.
Vasculoprotective Effects Of Oestrogens
Authors: Arnal Jean‐François , Bayard Francis 
Published: March 2003

SUMMARY1. The rationale for preclinical research on the atheroprotective effect of oestrogens is based on the epidemiological evidence that women are protected against the clinical complications of atherosclerosis until menopause. However, this protection, probably due to sex hormones, is progressively lost within the years following menopause.2. In addition, numerous studies have clearly demonstrated the atheroprotective effect of oestrogens in all animal models.3. In the present paper, we first summarize our understanding of the pathophysiology of atherosclerosis. We then focus on the recognized target of oestradiol (E2) in the vessel wall: the classical target, namely the endothelium, and a recently characterized target, namely cells of the inflammatory–immune system. Finally, we discuss how unknown mechanisms in atherosclerosis could be responsible for the absence of effect of hormone‐replacement therapy in the Heart and Estrogen/ progestin Replacement Study (HERS).
Effects Of Endomorphin‐1 And ‐2 On μ‐Opioid Receptors In Myenteric Neurons And In The Peristaltic Reflex In Rat Small Intestine
Authors: Storr Martin , Hahn Andreas , Gaffal Evelyn , Saur Dieter , Allescher Hans D 
Published: March 2003

SUMMARY1. The aim of the present investigations was to characterize the effect of endomorphins on the function of rat small intestine smooth muscle and on the electrically induced ascending and descending reflex pathway of rat small intestine in vitro.2. Endomorphin‐1 and ‐2 left the basal tonus and the pharmacologically stimulated smooth muscle unchanged. In contrast, electrically induced twitch contractions were significantly reduced by endomorphin‐1 and ‐2 and this reduction was reversed by the μ‐opioid receptor antagonist Cys‐Tyr‐Orn‐Pen‐amide (CTOP), suggesting a specific μ‐opioid receptor‐mediated effect on neural tissue.3. In the reflex model, endomorphin‐1 caused a significant inhibition (IC50 2.3 × 10–8 mol/L) of the ascending contraction (10–8 mol/L: –28.3 ± 5.8%; 10–7 mol/L: –94.7 ± 0.2.8%; both P < 0.05; n = 7). Descending relaxation increased at a concentration of 10–8 mol/L endomorphin‐1 (+61.6 ± 24.5%; 10–7 mol/L: +237.0 ± 65.4%; both P < 0.05; n = 6).4. Endomorphin‐1 caused a further significant increase in the latency of the ascending contraction (10–8 mol/L: +44.7 ± 20.5%; 10–7mol/L: +93.5 ± 16.1%; both P < 0.05; n = 7), whereas the latency of the descending relaxation was unaltered (n = 7). Similar results were observed for endomorphin‐2.5. All effects could be reversed by a wash‐out afterwards and were blocked by pre‐incubation with CTOP (10–6 mol/L).6. Reverse transcription–polymerase chain reaction demonstrated mRNA expression of μ‐opioid receptors in the rat ileum longitudinal muscle/myenteric plexus preparation, as well as in the oesophagus and stomach.7. Endomorphin‐1 and ‐2 reduce the cholinergic‐induced contractile response of the rat ileal smooth muscle preparation via a presynaptic mechanism.8. By a specific and reversible interaction with μ‐opioid receptors, the ascending excitatory and descending inhibitory reflex responses were attenuated or facilitated, respectively.9. In conclusion, the endomorphins may be the physiological endogenous μ‐opioid receptor agonists in the rat small intestine.
Chronic Ethanol Consumption Alters Vascular Smooth Muscle Responses In Rats
Authors: Ladipo CO , Adigun SA , Nwaigwe CI , Adegunloye BJ 
Published: March 2003

SUMMARY1. The effect of chronic ethanol (10%) consumption for 5 months on vascular smooth muscle (VSM) using aortic rings of both sexes of Sprague‐Dawley rats was studied.2. Chronic ethanol consumption increased the sensitivity of VSM to noradrenaline (NA) in both male and female ethanol‐treated rats.3. There was no significant difference in the contractile response of male and female ethanol‐treated rats to NA. Hence, the enhancement of vascular contractility to the agonist due to chronic ethanol consumption is independent of gender.4. Vascular relaxation induced by acetylcholine showed similar responses in all experimental groups. Thus, chronic ethanol consumption seems to have no significant effect on the production of endothelium‐dependent relaxing factor.5. However, the VSM sensitivity to potassium chloride was increased in female ethanol‐treated rats, whereas male ethanol‐treated rats had similar responses as controls.6. The results suggest that the effect of chronic ethanol consumption on VSM varies with gender. Impairment of VSM in male ethanol‐treated rats is due partly to changes in the receptor‐operated channel, whereas in females it is due to changes in both receptor‐ and potential‐operated channels.