bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional Evidence For Anti‐Oxidant Action Of Fluvastatin On Low‐Density Lipoprotein Using Isolated Macrophages And Aorta
Authors: Kagota Satomi , Yamaguchi Yu , Nakamura Kazuki , Kunitomo Masaru 
Published: March 2003

SUMMARY1. Fluvastatin has been reported to have not only a hypocholesterolaemic effect, but also a protective effect on low‐ density lipoprotein (LDL) from oxidation. We functionally evaluated the anti‐oxidant effect of fluvastatin on oxidation of LDL by copper ions in vitro using mouse macrophages and rabbit aorta preparations.2. After native LDL (N‐LDL) from rabbit plasma had been pre‐incubated in the presence or absence of fluvastatin (10 μmol/L) for 4 h, the N‐LDL was mildly oxidized by incubation with 5 μmol/L CuCl2 for 5 h and two oxidized LDL, fluvastatin‐pretreated (Flu‐OxLDL) and ‐non‐treated (OxLDL), were prepared. The level of thiobarbituric acid‐reactive substances (TBARS) in Flu‐OxLDL and OxLDL markedly increased compared with N‐LDL. The degree of increment was significantly less in Flu‐OxLDL than OxLDL.3. When macrophages were incubated with Flu‐OxLDL or OxLDL, the amount of cholesteryl ester that accumulated in the macrophages markedly increased compared with N‐LDL. The degree of increment was significantly less in Flu‐OxLDL than OxLDL.4. Acetylcholine‐induced endothelium‐dependent relaxations in rabbit aortic rings were impaired in the presence of either Flu‐OxLDL or OxLDL. The degree of impairment was significantly less in Flu‐OxLDL.5. The increased TBARS level, facilitated cholesteryl ester accumulation in macrophages and impaired endothelium‐dependent relaxation elicited by OxLDL were not affected by simultaneous treatment with fluvastatin (10 μmol/L).6. These findings indicate that fluvastatin can protect plasma LDL from oxidative modification and, thereby, prevent cholesterol accumulation in macrophages and endothelial dysfunction in blood vessels. This additional anti‐oxidative effect of fluvastatin may be beneficial for preventing the progression of atherosclerosis.
Effects Of Experimental Obstructive Jaundice On Contractile Responses Of Dog Isolated Blood Vessels: Role Of Endothelium And Duration Of Bile Duct Ligation
Authors: Utkan Zafer N , Utkan Tijen , Sarioglu Yusuf , Gönüllü Nuri N 
Published: March 2003

SUMMARY1. We examined the effects of experimental obstructive jaundice caused by bile duct ligation (BDL) on vascular smooth muscle function, as well as the underlying mechanisms involved, by recording responses to noradrenaline (NA), 5‐hydroxytryptamine (5‐HT) and acetylcholine (ACh) in canine isolated renal arteries and to NA in isolated mesenteric arteries in vitro. All studies were performed 7 days after the onset of BDL in renal arteries and 3, 7 and 15 days after the onset of BDL in mesenteric arteries.2. The maximum contraction evoked by both NA and 5‐HT was significantly attenuated with no change in agonist potency (pD2 value) in renal arteries with endothelium obtained from 7 day BDL dogs when compared with those from sham‐operated controls (SO). However, the reduction almost disappeared when the endothelium was removed. In contrast, no change in the responsiveness of renal arteries to KCl could be detected at 7 day BDL. Endothelium‐dependent relaxations produced by ACh were significantly increased in renal artery rings from 7 day BDL dogs, but the endothelium‐independent relaxations produced by papaverine in BDL preparations were not changed when compared with SO controls.3. At 7 and 15 days after BDL, the Emax values of the mesenteric ring of BDL dogs to NA were significantly lower than that of SO controls, whereas 3 days after surgery there was no significant difference. The pD2 values in arteries obtained from 15 day BDL animals were significantly lower than those obtained from SO control animals. However, no significant changes in pD2 values were seen 3 and 7 days after the onset of BDL.4. In conclusion, it is suggested that enhanced production and/or release of nitric oxide, mainly of endothelial origin, is associated with reduced vascular responses to contractile agents in experimental obstructive jaundice and that this effect is related to the duration of obstructive jaundice. These results may explain, at least in part, a cause of hypotension that leads to renal failure in patients with obstructive jaundice.
Brain Versus Peripheral Angiotensin Ii Receptors In Hypovolaemia: Behavioural And Cardiovascular Implications
Authors: De Luca Laurival A , Sugawara Alexandre M , Menani José V 
Published: March 2003

SUMMARY1. Angiotensin (Ang)II is involved in responses to hypovolaemia, such as sodium appetite and increase in blood pressure. Target areas subserving these responses for AngII include the cardiovascular system in the periphery and the circumventricular organs in the brain.2. Conflicting data have been reported for the role of systemic versus brain AngII in the mediation of sodium appetite.3. The role for systemic AngII and systemic AngII receptors in the control of blood pressure in hypovolaemia is well established. In contrast with systemic injections, i.c.v injections of AngII non‐peptide AT1 and AT2 receptor antagonists, such as losartan and PD123319, do not reduce arterial pressure in sodium‐depleted (furosemide injection plus removal of ambient sodium for 24 h) rats. Thus, brain AngII receptors are likely not important for cardiovascular responses to hypovolaemia induced by sodium depletion.4. Intracerebroventricular injections of losartan or PD123319 increase arterial pressure when injected at relatively high doses. This hypertensive effect is unlikely to be an agonist effect on brain AngII receptors. Increases in arterial pressure produced by i.c.v. losartan are attenuated by lesions of the tissue surrounding the anterior third ventricle (AV3V). The hypertensive effect of i.c.v. AngII is abolished by lesions of the AV3V.5. Hypertension induced by AngII receptor antagonists is consistent with hypotension induced by AngII acting in the brain. However, the full physiological significance of this hypotensive effect mediated by brain AngII receptors remains to be determined.
Neuroexcitatory Effects Of Morphine And Hydromorphone: Evidence Implicating The 3‐Glucuronide Metabolites
Authors: Smith Mt 
Published: March 2003

SUMMARY1. Morphine is recommended by the World Health Organization as the drug of choice for the management of moderate to severe cancer pain.2. Education of health professionals in the past decade has resulted in a large increase in the prescribing of opioids, such as morphine, and in the magnitude of the doses administered, resulting in an improvement in the quality of pain relief available for many cancer patients.3. However, the reported incidence of neuroexcitatory side effects (allodynia, myoclonus, seizures) in patients administered large doses of systemic morphine or its structural analogue, hydromorphone (HMOR), has also increased.4. Clinically, increasing the magnitude of the morphine or HMOR dose administered to patients already exhibiting neuroexcitatory opioid related side effects, results in an exacerbation rather than an attenuation of the excitatory behaviours.5. In contrast, cessation of the opioid or rotation to a structurally dissimilar opioid (e.g. from morphine/HMOR to methadone or fentanyl), usually results in a restoration of analgesia and resolution of the neuroexcitatory opioid side effects over a period of hours to days.6. To explain the clinical success of ‘opioid rotation’, it is essential to understand the in vivo metabolic fate of morphine and HMOR.7. Following systemic administration, morphine and HMOR are metabolized primarily to the corresponding 3‐glucuronide metabolites, morphine‐3‐glucuronide (M3G) and hydromorphone‐3‐glucuronide (H3G), which are not only devoid of analgesic activity but evoke a range of dose‐dependent excitatory behaviours, including allodynia, myoclonus and seizures, following intracerebroventricular (i.c.v.) administration to rats.8. Several studies have shown that, following chronic oral or subcutaneous morphine administration to patients with cancer pain, the cerebrospinal fluid (CSF) concentrations of M3G exceed those of morphine and morphine‐6‐glucuronide (analgesically active morphine metabolite) by approximately two‐ and five‐fold, respectively.9. These findings suggest that when the M3G concentration (or H3G by analogy) in the CSF exceeds the neuroexcitatory threshold, excitatory behaviours will be evoked in patients.10. Thus, rotation of the opioid from morphine/HMOR to a structurally dissimilar opioid, such as methadone or fentanyl, will allow clearance of M3G/H3G from the patient central nervous system over hours to days, thereby producing a time‐dependent resolution of the neuroexcitatory behaviours while maintaining analgesia with methadone or fentanyl.
First Report Of Active Renin In Rat Amniotic Fluid
Authors: Caragounis Aphrodite , Koutsis Kathy , Wlodek Mary E , Wilkinson‐Berka Jennifer La , Nicolantonio Robert Di 
Published: March 2003

SUMMARY1. Epidemiological studies indicate that a reduced birthweight increases the likelihood of human cardiovascular disease later in life. The role of hormonal factors in this finding is not known. Given that angiotensin II is believed to be a fetal regulator of growth, we have examined in the hypertensive Ren‐2 transgenic rat whether it has active renin in its amniotic fluid and whether this is associated with fetal underdevelopment.2. We found that while the Sprague‐Dawley rat contained no active renin in its amniotic fluid near term (20 days), Ren‐2 amniotic fluid contains high levels of active renin and is associated with a reduced fetal weight.3. This is the first report of active renin in the rat and allows the possibility that renin overproduction plays a role in reduced fetal growth and the prenatal ‘programming’ of essential hypertension that has been proposed to occur in humans.
Reversal of Anticancer Drug Resistance by Macrolide Antibiotics in Vitro and in Vivo
Authors: Wang Li , Kitaichi Kiyoyuki , Hui Cai Shao , Takagi Kenji , Takagi Kenzo , Sakai Miyuki , Yokogawa Koichi , Miyamoto Ken‐ichi , Hasegawa Takaaki 
Published: March 2003

SUMMARY1. The combined effects of the macrolide antibiotics erythromycin, josamycin, clarithromycin and YM17K (3,4′‐dideoxy mycaminosyl tylonolide hydrochloride) on in vitro intracellular accumulation of vinblastine or cyclosporine (Cs)A and on the in vivo antitumour activity of vinblastine were investigated using mouse leukaemia P388 cells (P388/S) and anticancer drug‐resistant (P388/ADR) cells. These effects were compared with those of a calcium antagonist (verapamil) or immunosuppressants (FK506 and CsA).2. All tested macrolide antibiotics increased the accumulation of both vinblastine and CsA in P388/ADR cells in a dose‐ dependent manner, but their potency was lower than that of verapamil, CsA or FK506.3. When vinblastine (200 μg/kg) was administered intraperitoneally with each of the macrolide antibiotics (10 or 100 mg/kg) or with verapamil (25 mg/kg) once a day for 10 days in P388/ADR‐bearing mice, combined effects of vinblastine with the macrolide antibiotics (erythromycin, clarithromycin and YM17K) or verapamil were observed.4. The present study suggests that macrolide antibiotics may overcome anticancer drug resistance by inhibiting the binding of vinblastine or CsA to P‐glycoprotein in P388/ADR cells.5. We believe that these results are encouraging for combination chemotherapy to overcome P‐glycoprotein‐dependent anticancer drug‐resistant tumours in clinical practice.
Effects Of The New Hydroxy‐3‐Methylglutaryl Coenzyme A Reductase Inhibitor Fluvastatin On Anti‐Oxidant Enzyme Activities And Renal Function In Streptozotocin‐Induced Diabetic Rats
Authors: Kurusu Atsushi , Shou Ichiyu , Nakamura Shinji , Fukui Mitsumine , Shirato Isao , Tomino Yasuhiko 
Published: March 2003

SUMMARY1. The effects of 11 week treatments with the new hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor fluvastatin on renal intrinsic anti‐oxidant enzyme (AOE) activities and renal function were evaluated in streptozotocin (STZ)‐induced diabetic rats.2. Renal intrinsic AOE activities, creatinine clearance and urinary albumin excretion were examined in STZ‐induced diabetic rats. The levels of total cholesterol (TC), triglyceride (TG) and phospholipid (PL) were also examined.3. In general, renal AOE activities and function were lower in diabetic rats than in non‐diabetic Sprague‐Dawley rats.4. Decreases in TC, TG and PL levels and urinary albumin excretion by the HMG‐CoA reductase inhibitor fluvastatin improved renal function and produced a non‐uniform alteration in renal AOE; only glutathione peroxidase (GSH‐Px) activity increased significantly with fluvastatin treatment.5. It appears that the improvement in renal function and albuminuria may be related to increases in GSH‐Px activity, but there was no correlation between changes in renal function and changes in the activity of Mn‐superoxide dismutase or catalase.
Relevance Of Cytochrome P450 Levels In The Actions Of Enflurane And Isoflurane In Mice: Studies On The Haem Pathway
Authors: Buzaleh Ana Maria , Martinez Maria del Carmen , Batlle Alcira Maria del Carmen 
Published: March 2003

SUMMARY1. The effect of the fluorinated ether anaesthetics enflurane and isoflurane in mice on haem metabolism and regulation in different metabolic states, such as depression and induction of cytochrome P450 produced by allylisopropylacetamide (AIA) and imidazole, respectively, was investigated.2. Mice previously treated with AIA (350 mg/kg, i.p.) or imidazole (400 mg/kg, i.p.) received a single dose (1 mL/kg, i.p.) of enflurane or isoflurane and were killed 20 min after anaesthetic administration.3. Induction of δ‐aminolevulinic acid synthetase (ALA‐S) activity was found, as expected, in animals receiving AIA and also in animals treated with AIA plus anaesthesia, but no change in the activity of either porphobilinogenase (PBGase) or porphobilinogen deaminase (PBG‐D) activities was detected in these two groups of animals. An additional increase in haem destruction was observed in the AIA plus isoflurane‐treated group. When mice were injected with imidazol alone or in combination with the anaesthetics, ALA‐S activity was increased 50–90% in all groups, but again no change in PBGase or PBG‐D activity was observed. Haem oxygenase was diminished in mice receiving imidazole and anaesthesia.4. In conclusion, neither enflurane nor isoflurane caused additional disturbances in haem metabolism to those produced by AIA or imidazole alone.
Tachykinin NK1 and NK3 Receptors In The Prefrontal Cortex Of The Human Brain
Authors: Tooney Paul A , Au Gough G , Chahl Loris A 
Published: March 2003

SUMMARY1. The tachykinins are neuropeptides found in both the central and peripheral nervous systems that play a role in inflammation and pain mechanisms and some autonomic reflexes and behaviours.2. Although the distribution of the tachykinin receptors has been described in the brains of various animal species, little is known about the distribution of the NK1 and NK3 receptors in the human brain.3. The present paper examines the distribution of the NK1 and NK3 receptors in the prefrontal cortex of formalin‐fixed post‐mortem human brain tissue by immunohistochemical techniques.4. The majority of NK1 receptor immunoreactivity appeared as a thin band of punctate staining at the pial surface, with dark brown dots of NK1 receptor immunoreactivity predominantly scattered across the mid to upper cortical layers.5. The NK3 receptor immunoreactivity was found in the glia limitans at the pial surface, where astrocytes and beaded fibres were intensely stained. Dots of NK3 receptor immunoreactivity were scattered across all cortical layers. In the white matter, astrocytes and beaded fibres displayed NK3 receptor immunoreactivity, particularly in areas surrounding blood vessels.
Lymphatic Vasomotion
Authors: Helden Dirk F Van , Zhao Jun 
Published: March 2003

SUMMARY1. Experimental findings in the past decade have greatly advanced present understanding of electrical/mechanical rhythmicities in smooth muscle, including vasomotion. Lymphatic vessels show strong vasomotor activity and have provided a key experimental system to study these processes.2. Evidence from lymphatic vessels, blood vessels and other smooth muscles indicates that rhythmical contractions arise through a Ca2+ store‐controlled pacemaker mechanism, which can function to cause smooth muscle constriction.3. Such a model fits with observations that vasomotion can be near synchronous over large vessel lengths involving many cells.4. The alternative interpretation that smooth muscle rhythmicities are generated by a cardiac‐like electrical pacemaker mechanism has not been substantiated in any smooth muscle preparation under normal physiological conditions. However, elements of this latter mechanism are likely to be present at least in some smooth muscles, serving to modulate pacemaking.
Quantitative Analysis Of Vascular To Cardiac Selectivity Of L‐ And T‐Type Voltage‐Operated Calcium Channel Antagonists In Human Tissues
Authors: Angus Ja , Sarsero D , Fujiwara T , Molenaar P , Xi Q 
Published: March 2003

SUMMARY1. Classical L‐type voltage‐operated calcium channel (VOCC) antagonists dilate blood vessels, depress myocardial contractility and slow cardiac conduction.2. We compared four L‐type VOCC antagonists and a novel tetralol derivative, mibefradil, reportedly 10‐fold more selective for T‐ (transient) over L‐type VOCC in two in vitro assays of human tissue, namely isolated small arteries from the aortic vasa vasorum in a myograph and right atrial trabeculae muscle under isometric force conditions.3. In arteries contracted with K+ (62 mmol/L), the relaxation pIC50 values for the VOCC antagonists felodipine, nifedipine, amlodipine, verapamil and mibefradil were 8.30, 7.78, 6.64, 6.26 and 6.22, respectively. In atrial trabeculae, the pIC50 values to inhibit the inotropic response to a submaximal concentration of isoprenaline (6 nmol/L) for felodipine, nifedipine, verapamil, amlodipine and mibefradil were 7.21, 6.95, 6.91, 5.94 and 4.61, respectively.4. Taking the anti‐log (pIC50 vessel – pIC50 atrium) the vascular relaxation to cardiac depression potency ratios for mibefradil, felodipine, nifedipine, amlodipine and verapamil were 41, 12, 7, 5 and 0.22, respectively.5. We conclude that, in human tissue assays, perhaps T‐ over L‐type VOCC selectivity confers the most favourable vascular selectivity on mibefradil. Alternatively, splice variants of L‐type VOCC in the vasculature (CaV1.2b) may be more sensitive to mibefradil than the splice variants in the heart (CaV1.2a).
Proceedings of the Australian Neuroscience Society Symposium: Schizophrenia A PREDICTED CORTICAL SEROTONERGIC/CHOLINERGIC/GABAERGIC INTERFACE AS A SITE OF PATHOLOGY IN SCHIZOPHRENIA
Authors: Dean Brian 
Published: March 2003

SUMMARY1. The pathological process that precipitates schizophrenia has yet to be identified. However, many lines of evidence suggest that a change in the functioning of the frontal cortex is an important abnormality that underlies schizophrenia.2. Studies in Brodmann’s area 9, obtained post‐mortem, have shown changes in 5‐hydroxytryptamine 5‐HT2A, muscarinic M1 and GABAA receptors in tissue from subjects with schizophrenia.3. Animal studies suggest a site in the cortex where there would be an interaction between serotonergic and cholinergic innervation and that this interaction would involve the 5‐HT2A and the M1 receptor. This site, in turn, would be a potent modulator of GABA activity and, hence, levels of GABAA receptors.4. From combining these data, a theoretical site is proposed that, if proven to exist in human cortex, is likely to be central to the pathology of that illness.
Experimental Biology 2000 Symposium on Differential Control of Sympathetic Outflow DIFFERENTIAL REGULATION OF BROWN ADIPOSE AND SPLANCHNIC SYMPATHETIC OUTFLOWS IN RAT: ROLES OF RAPHE AND ROSTRAL VENTROLATERAL MEDULLA NEURONS
Authors: Morrison Shaun F 
Published: March 2003

SUMMARY1. The medullary premotor neurons determining the sympathetic outflow regulating cardiac function and vasoconstriction are located in the rostral ventrolateral medulla (RVLM). The present study sought evidence for an alternative location for the sympathetic premotor neurons determining the sympathetic nerve activity (SNA) controlling brown adipose tissue (BAT) metabolism and thermogenesis.2. The tonic discharge on sympathetic nerves is determined by the inputs to functionally specific sympathetic preganglionic neurons from supraspinal populations of premotor neurons. Under normothermic conditions, BAT SNA was nearly silent, while splanchnic (SPL) SNA, controlling mesenteric vasoconstriction, exhibited sustained large‐amplitude bursts.3. The rostral raphe pallidus (RPa) contains potential sympathetic premotor neurons that project to the region of sympathetic preganglionic neurons in the thoracic spinal cord. Disinhibition of neurons in RPa elicited a dramatic increase in BAT SNA, with only a small rise in SPL SNA.4. Splanchnic SNA was strongly influenced by the baroreceptor reflex, as indicated by a high coherence with the arterial pressure wave, a significant amplitude modulation over the time‐course of the cardiac cycle and a marked inhibition of SPL SNA during a sustained increase in arterial pressure. When activated, the bursts in BAT SNA exhibited no correlation with arterial pressure and were not affected by increases in arterial pressure.5. Because these characteristics and reflex responses in sympathetic outflow have been shown to arise from the on‐going or altered discharge of sympathetic premotor neurons, the marked differences between SPL and BAT SNA provide strong evidence supporting the hypothesis that vasoconstriction and thermogenesis (metabolism) are controlled by distinct populations of sympathetic premotor neurons, the former in the RVLM and the latter, potentially, in the RPa.
Central Nervous System Regeneration: Mission Impossible?
Authors: Fry Elizabeth J 
Published: March 2003

SUMMARY1. Attempts to induce clinical repair after central nervous system injury, such as spinal cord damage, are likely to involve several protocols because eliciting a regenerative response from an injured central neuron is a complex task. Future treatments, applied when a window of opportunity exists, address the requirements for regeneration.2. Application of trophic support to the lesion site for axotomized neurons aims to initiate and maintain a cell body response conducive to axonal regrowth.3. Surgical intervention may provide a bridge across the injury site that contains either Schwann cells or olfactory bulb ensheathing cells derived from the patient’s own tissue.4. The application of antibodies may block the inhibitory action of myelin‐associated molecules and other glial elements.5. Gene therapy may induce the correct cascade of guidance molecules to be released at appropriate times.6. Physical rehabilitation may ensure that muscle wastage is reduced and encourages functional reconnection.