bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of GH reserve before and after successful treatment of adult patients with Cushing's syndrome
Authors: Tzanela Marinella , Karavitaki Niki , Stylianidou Christiana , Tsagarakis Stylianos , Thalassinos Nikos C. 
Published: December 2004

Abstractobjective  Several studies have demonstrated impaired GH secretion in patients with active Cushing's syndrome (CS). It has been suggested that persistence of GH deficiency, despite treatment of cortisol excess, may delay the recovery of these patients and therefore temporary treatment with GH may have some benefit. However, the time course of restoration of GH secretion after successful treatment of CS has only been investigated in a limited number of mostly paediatric reports. The aim of the present study was the evaluation of GH reserve in adult patients with CS before and after correction of cortisol excess.design and patients  Sixteen patients (12 females, four males) with CS aged 44·7 ± 5·05 years were recruited. These included seven patients with Cushing's disease, four patients with ectopic ACTH secretion and five patients with adrenal adenoma. All patients were evaluated before any therapeutic intervention. Twelve patients were successfully treated following appropriate surgery and these were further studied. The combined pyridostigmine/GHRH test was used to assess GH reserve in these patients. In a proportion of cases an insulin tolerance test (ITT) was also used.results  Before any therapeutic intervention, an impaired GH response to PD/GHRH was noted in all patients. Restoration of GH response at 6 months was observed in six patients (50%); at 12 months in two; at 18 months in one patient. Two of the patients with no restoration of GH response at 12 months did not accept further investigation. Only one patient did not achieve an adequate GH response even when tested 30 months following cure of CS. Restoration of GH reserve was more commonly observed in those patients in whom there was recovery of the HPA axis. There was a good correlation between peak GH levels to PD + GHRH and ITT. No statistically significant difference was revealed in IGF‐I levels between pre‐ and post‐treatment evaluation.conclusions  Adult patients with active Cushing's syndrome demonstrate a profound suppression of stimulated GH secretion. In the majority of these patients the disruption of GH secretion is normalized within a year after successful treatment of endogenous cortisol excess.
A Proteasome Inhibitor Prevents Vascular Hypertrophy In Deoxycorticosterone Acetate‐Salt Hypertensive Rats
Authors: Takaoka Masanori , Ohkita Mamoru , Itoh Makoto , Kobayashi Yutaka , Okamoto Hisako , Matsumura Yasuo 
Published: December 2004

SUMMARY1. In the present study, we investigated the potential of the proteasome inhibitor N‐benzyloxycarbonyl‐Ile‐Glu(O‐t‐Bu)‐Ala‐leucinal (PSI) to prevent vascular hypertrophy induced by deoxycorticosterone acetate (DOCA) and salt in rats.2. Vehicle (35% ethanol, 35% polyethylene glycol and 30% saline solution)‐treated DOCA‐salt rats developed marked hypertension at 4 weeks. Morphological studies on the rats given vehicle showed aortic hypertrophy, with a significant increase in wall thickness, wall area and wall‐to‐lumen ratio. A significant decrease in vascular wall hypertrophy was observed in PSI (3 mg/kg)‐treated DOCA‐salt rats. In addition, a marked increase in aortic endothelin (ET)‐1 content was evident in vehicle‐treated DOCA‐salt rats compared with findings in sham‐operated rats. A significant attenuation of this increase occurred in PSI‐treated DOCA‐salt rats.3. These results indicate that PSI can prevent the vascular hypertrophy in DOCA‐salt hypertensive rats and the effect is accompanied by suppression of ET‐1 production in the aorta. We suggest that a proteasome‐dependent proteolytic system has an important role in the development of vascular hypertrophy in cases of DOCA‐salt‐induced hypertension, possibly through the enhancement of ET‐1 production in vascular tissues.
Reduced effect of caffeine on twitch contraction of oesophageal striated muscle from stroke‐prone spontaneously hypertensive rats
Authors: Sekiguchi Fumiko , Kawata Kyoko , Shimamura Keiichi , Sunano Satoru 
Published: December 2004

Summary1. There are known differences in the sensitivity to caffeine between skeletal muscle (soleus) of normotensive Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The present study was performed in order to examine differences in the effects of caffeine on twitch contraction between visceral striated muscle using the outer layer of the oesophagus from WKY rats and stroke‐prone SHR (SHRSP).2. Caffeine, at concentrations ranging from 0.3 to 10 mmol/L, exhibited potentiating effects on twitch contraction in preparations from both WKY rats and SHRSP. The potentiating effect of caffeine was markedly less prominent in preparations from SHRSP compared with preparations from WKY rats.3. The rate of contraction and relaxation, the time to peak tension and 80% relaxation time were not significantly altered by caffeine at concentrations lower than 3 mmol/L in preparations from either strain.4. With 10 mmol/L caffeine, the rate of relaxation was markedly reduced and the 80% relaxation time was prolonged, with no significant changes in the rate of contraction, in preparations from WKY rats. These changes were significantly smaller in preparations from SHRSP.5. The duration of the action potential was greater in preparations from SHRSP than in preparations from WKY rats, although the membrane potential and the amplitude of the action potential were not significantly different between preparations from WKY rats and SHRSP.6. Caffeine, at 10 mmol/L, prolonged the duration of the action potential in preparations from both strains. The effect of caffeine was not different between preparations from WKY rats and SHRSP.7. The results of the present study suggest that caffeine augments release of Ca2+ from the sarcoplasmic reticulum (SR) at low concentrations and attenuates Ca2+ re‐uptake at 10 mmol/L. Decreased reactivity of SR to caffeine may be a cause of the lesser potentiation of twitch contraction by caffeine in preparations from SHRSP.
Effects of hypochlorite and hydrogen peroxide on cardiac autonomic receptors and vascular endothelial function
Authors: Sand Carsten , Peters Stephan LM , Pfaffendorf Martin , Van Zwieten Pieter A 
Published: December 2004

Summary1. Reactive oxygen species (ROS) are known to be involved in the progression of various cardiovascular diseases. One source of ROS is activated neutrophils, which can release superoxide anion radicals and hydrogen peroxide by membrane‐bound NAD(P)H oxidases. These ROS not only destroy bacteria, but may also affect mammalian tissue. In addition, hydrogen peroxide serves as a substrate for myeloperoxidase, an enzyme that is released by activated neutrophils during inflammatory processes, as seen, for instance, in reperfusion injury and atherosclerosis. Myeloperoxidase catalyses the oxidation of chloride by hydrogen peroxide, yielding hypochlorite, an extremely potent oxidant.2. The purpose of the present study was to evaluate the effects of hypochlorite on a variety of receptor‐dependent processes in rat isolated left atria and rat thoracic aorta and to compare these results with the phenomena observed after incubation with hydrogen peroxide.3. In the presence of hypochlorite (300 µmol/L), the positive inotropic response of α1‐adrenoceptor stimulation by methoxamine (300 µmol/L) was converted into a negative inotropic response. In contrast, the positive inotropic effects of the β1/β2‐adrenoceptor agonist isoprenaline (3 µmol/L) and endothelin (ET)‐1 (100 nmol/L) remained largely unaffected.4. The inversion of α1‐adrenoceptor‐mediated inotropy was not obtained in the presence of hydrogen peroxide (500 µmol/L). Hydrogen peroxide did not affect the positive inotropic response of isoprenaline, but it completely abolished the inotropic effect of ET‐1.5. The effect of cardiac M2‐receptor stimulation was studied in the presence of hypochlorite and hydrogen peroxide. The negative inotropic response to acetylcholine (ACh) was significantly enhanced after hypochlorite incubation compared with control.6. In the rat thoracic aorta, endothelial function, evaluated by means of ACh‐induced vasodilation, was completely abolished in the presence of hypochlorite (100 µmol/L), but remained unaffected by treatment with the same concentration of hydrogen peroxide.7. From these data, we conclude that hypochlorite exerts more toxic properties than its precursor hydrogen peroxide, leading to substantial physiological alterations in cardiac and vascular tissue.
Deficient prepulse inhibition of acoustic startle in Hooded‐Wistar rats compared with Sprague‐Dawley rats
Authors: Van Den Buuse Maarten 
Published: December 2004

Summary1. Prepulse inhibition of acoustic startle has been suggested as a model of sensorimotor gating and central sensory information processing. Prepulse inhibition is impaired in patients with schizophrenia and responses can be restored by antipsychotic drug treatment. In the present study, startle and prepulse inhibition of startle were compared in different rat strains.2. Sprague‐Dawley rats showed robust inhibition of startle responses by increasing intensities of prepulse delivered just before the startle stimulus. In contrast, at both 4 and 10 weeks of age, rats of the Hooded‐Wistar line had markedly reduced prepulse inhibition, although startle responses were not different.3. Treatment with the dopamine receptor agonist apomorphine (0.1 mg/kg) or the N‐methyl‐d‐aspartate (NMDA) receptor antagonist MK‐801 (0.1 mg/kg) caused disruption of prepulse inhibition in Sprague‐Dawley rats. In Hooded‐Wistar rats, apomorphine further reduced the already low level of prepulse inhibition, but MK‐801 treatment had no significant effect. This suggests that the impaired prepulse inhibition in Hooded‐Wistar rats could be caused by changes in glutamatergic activity and/or NMDA receptors in these rats.4. In photocell cages, spontaneous exploratory activity and inner zone activity were significantly lower in Hooded‐Wistar rats than in Sprague‐Dawley rats. Similarly, on the elevated plus‐maze, Hooded‐Wistar rats showed a lower propensity to visit the open arms. In contrast, amphetamine (0.5 mg/kg)‐induced locomotor hyperactivity, an animal model of psychosis, was enhanced in Hooded‐Wistar rats.5. These data suggest that the Hooded‐Wistar line could be a useful genetic animal model to study the interaction of glutamatergic and dopaminergic mechanisms in anxiety and schizophrenia.
Depressor effect induced by dipeptide, Val‐Tyr, in hypertensive transgenic mice is due, in part, to the suppression of human circulating renin–angiotensin system
Authors: Matsui Toshiro , Hayashi Atsumi , Tamaya Kei , Matsumoto Kiyoshi , Kawasaki Terukazu , Murakami Kazuo , Kimoto Ko‐ichi 
Published: December 2004

Summary1. In the present study, the depressor action of the dipeptide Val‐Tyr, with an in vivo antihypertensive effect, was investigated in transgenic mice carrying the human renin gene cross‐mated with mice bearing the human angiotensinogen gene (Tsukuba Hypertensive Mouse; THM).2. Single oral administration of Val‐Tyr (0.1 mg/g) to 11‐week‐old THM resulted in a prolonged reduction of blood pressure for up to 9 h. The effect clearly demonstrated that the Val‐Tyr absorbed acted on the enhanced human renin–angiotensin system (RAS).3. After Val‐Tyr administration, an approximate eightfold higher increment of plasma Val‐Tyr was observed at 1 h (3406 ± 211 fmol/mL plasma) compared with the level observed at 0 h; plasma concentrations of Val‐Tyr returned to baseline levels at 6 h.4. Transient changes in plasma concentrations of angiotensin (Ang) I and AngII only at 1 h were consistent with plasma Val‐Tyr concentrations, suggesting that that the long‐lasting reduction in blood pressure was achieved by the latent hypotensive mechanism of Val‐Tyr and not by transient suppression of the circulatory RAS.5. Ageing of the THM greatly affected the depressor action of Val‐Tyr, with no significant reduction in blood pressure observed in 18‐ and 24‐week‐old THM.
The p42/44mitogen‐activated protein kinase inhibitor PD 98059, but not U 0126, increases a K+ current in cardiomyocytes
Authors: Aimond F , Fauconnier J , Donadille D , Vassort G 
Published: December 2004

Summary1. The effects of the mitogen‐activated protein kinase (MAPK) inhibitors PD 98059 and U 0126, useful tools to investigate MAPK involvement in intracellular signal transduction pathways, were assessed on cardiomyocytes.2. In rat freshly isolated ventricular myocytes, under current‐clamp conditions, PD 98059 (40 µmol/L) shortened the action potential. Under whole‐cell patch‐clamp, this compound slowly induced a fast activating sustained outward K+ current that was sensitive to 1 mmol/L Ba2+, 100 µmol/L Gd3+, 3 mmol/L 4‐aminopyridine and 100 µmol/L tetracain. The PD 98059‐induced current was prevented by 40 µmol/L AACOCF3, a cytosolic phospholipase A2 inhibitor.3. U 0126 (1 µmol/L), a recently developed highly potent p42/44 MAPK inhibitor, did not alter K+ currents.4. PD 98059, but not U 0126, increased arachidonic acid content, probably as a consequence of its reported cyclo‐oxygenase inhibitory effect.5. These observations indicate that PD 98059 activates a TREK‐1 like current. Thus, this MAPK inhibitor has to be used with caution because alterations in cell metabolism can be secondary to changes in electrophysiological behaviour.
Oxidized LOw‐density lipoprotein sensitizes human vascular smooth muscle cells to FAS (CD95)‐mediated apoptosis
Authors: Takarada Shigeho , Imanishi Toshio , Hano Takuzo , Nishio Ichiro 
Published: December 2004

Summary1. It was investigated in the present study whether oxidized low‐density lipoprotein (oxLDL) was implicated in the susceptibility of human vascular smooth muscle cells (VSMC) to Fas‐mediated death. Human fetal aorta smooth muscle cells were treated with agonistic anti‐Fas antibody (CH11) and oxLDL and cell death was then determined by viability and DNA fragmentation.2. The results of the present study show that cross‐linking of Fas receptor with anti‐Fas antibody in the presence of oxLDL induced death and DNA fragmentation in human VSMC, which were blocked by the caspase inhibitor z‐VAD.fmk, followed by the upregulation of cell surface Fas.3. The data indicate that oxLDL is implicated in death in VSMC and provide evidence that oxLDL is involved in Fas signal transduction. The present study proposes a novel mechanism(s) by which VSMC become susceptible to Fas ligand.4. One of the mechanisms proposed by which oxLDL upregulates cell surface Fas is by inhibiting the degradation of Fas through the ubiquitin–proteasome pathway.
Role of angiotensin II, sympathetic stimulation and salt in the development of structural vascular changes in rat kidney
Authors: Simon Geza , Jäckel Marta , Illyes Gyorgy 
Published: December 2004

Summary1. Functional and structural vasoconstriction of renal cortical arteries is the earliest change leading to hypertension. In the present study, the interaction of a subpressor dose of angiotensin (Ang) II, a 2% NaCl diet and sympathetic stimulation in the form of overnight cold exposure was investigated in the development of renal structural vascular changes in male Sprague‐Dawley rats.2. Morphometric measurements of renal cortical resistance arteries and volume density measurements of renal cortical components were performed in eight groups of rats after 12 weeks of treatment: AngII; 2% NaCl diet; cold exposure (5°C); AngII plus 2% NaCl diet; AngII plus cold exposure; cold exposure plus 2% NaCl diet; ANG II plus 2% NaCl diet plus cold exposure; and sham operation and treatment (control).3. The average weekly systolic blood pressure of AngII‐treated plus salt‐fed rats was increased, whereas that of cold‐stressed plus salt‐fed rats at room temperature decreased compared with controls. The blood pressure rise of the former group was accompanied by an increased wall‐to‐lumen ratio (WLR) of cortical resistance arteries and decreased glomerular volume, whereas the reduction in blood pressure in the latter group was accompanied by a decreased WLR of cortical resistance arteries and increased volume density of cortical renal tubules. There were no changes in either the blood pressure or renal structure of the other groups.4. There is a parallel relationship between changes in preglomerular structural vascular resistance and changes in blood pressure in rats. It remains to be determined whether renal cortical structural changes are the cause of, or are compensatory for, chronic changes in blood pressure.
Dietary mushroom (Pleurotus ostreatus) ameliorates atherogenic lipid in hypercholesterolaemic rats
Authors: Hossain Shahdat , Hashimoto Michio , Choudhury Emran Kabir , Alam Nuhu , Hussain Shahjalal , Hasan Moynul , Choudhury Shahabuddin Kabir , Mahmud Ishtiaq 
Published: December 2004

Summary1. The effects of edible oyster mushroom Pleurotus ostreatus on plasma and liver lipid profiles and on the plasma total anti‐oxidant status were estimated in hyper‐ and normocholesterolaemic Long Evans rats.2. The feeding of 5% powder of the fruiting bodies of P. ostreatus mushrooms to hypercholesterolaemic rats reduced their plasma total cholesterol by approximately 28%, low‐density lipoprotein–cholesterol by approximately 55%, triglyceride by approximately 34%, non‐esterified fatty acid by approximately 30% and total liver cholesterol levels by > 34%, with a concurrent increase in plasma high‐density lipoprotein–cholesterol concentration of > 21%. However, these effects were not observed in mushroom‐fed normocholesterolaemic rats.3. Mushroom feeding significantly increased plasma fatty acid unsaturation in both normo‐ and hypercholesterolaemic rats.4. Plasma total anti‐oxidant status, as estimated by the oxidation of 2,2′‐azino‐bis‐[3‐ethylbenz‐thiazoline‐6‐sulphonic‐acid], was significantly decreased in mushroom‐fed hypercholesterolaemic rats, concomitant with a decrease in plasma total cholesterol.5. The present study suggests that 5% P. ostreatus supplementation provides health benefits, at least partially, by acting on the atherogenic lipid profile in the hypercholesterolaemic condition.
Insulin resistance modifies plasma fatty acid distribution and decreases cardiac tolerance to in vivo ischaemia/reperfusion in rats
Authors: Morel S , Berthonneche C , Tanguy S , Toufektsian M‐C , Foulon T , De Lorgeril M , De Leiris J , Boucher F 
Published: December 2004

Summary1. The early stage of insulin resistance, also termed the ‘prediabetic state’, is characterized by the development of hyperinsulinaemia, which maintains normoglycaemia under fasting conditions. The metabolic disorders induced in myocardial cells during this stage of the disease may constitute a basis for an alteration of the tolerance of the heart to ischaemia and reperfusion.2. To test this hypothesis, male Wistar rats were fed a 66% fructose diet for 4 weeks, inducing a prediabetic state. Rats were then subjected to in vivo left coronary artery ligation followed by reperfusion. Blood samples were collected for plasma lipid profile determination.3. The prediabetic state significantly increased the severity of ischaemia‐induced arrhythmias (arrhythmia score 1.4 ± 0.2 vs 2.0 ± 0.0 in control and fructose‐fed rats, respectively; P < 0.05) and the size of infarction (infarct size 41.2 ± 3.0 vs 56.0 ± 2.0% in control and fructose‐fed rats, respectively; P < 0.01). This alteration of the tolerance to in vivo ischaemia/reperfusion may be the consequence of an increase in mono‐unsaturated fatty acids and a decrease in ω3 polyunsaturated fatty acids in fructose‐fed‐rats.4. In conclusion, because it is known that the prediabetic state increases the incidence of cardiovascular diseases by promoting coronaropathy, our study suggests that this metabolic disorder may also affect the prognosis of heart disease by decreasing the tolerance of cardiomyocytes to ischaemic insults.
Exaggerated response to restraint stress in rats congenic for the chromosome 1 blood pressure quantitative trait locus
Authors: Cui Zong Hu , Ikeda Katsumi , Kawakami Kohei , Gonda Tatsuo , Nabika Toru , Masuda Junichi 
Published: December 2004

Summary1. To understand the roles of a putative hypertension gene in the chromosome 1 quantitative trait locus (QTL) region, the response to restraint stress was studied in strains congenic for this QTL.2. To establish congenic strains, the QTL region was introgressed from stroke‐prone spontaneously hypertensive rats (SHRSP)/Izm to Wistar‐Kyoto/Izm (WKY/Izm) rats by repeated backcrossing. Two congenic strains (WKYpch1.0 and WKYpch1.1) were established to cover the whole QTL region between D1Wox29 and D1Arb21 (approximately 40 cM) and a smaller region between D1Smu11 and D1Arb21 (approximately 10 cM), respectively. After telemetry probes were implanted, rats were exposed to restraint stress to investigate the blood pressure response.3. Basal blood pressure measured by radiotelemetry differed significantly between WKY rats and WKYpch1.0 (103 ± 10 and 116 ± 4 mmHg, respectively; P = 0.002 by anova). When exposed to restraint stress, WKYpch1.0 showed a greater increase in blood pressre than did WKY rats. The exaggerated response in the WKYpch1.0 strain was abolished by chemical sympathectomy using guanethidine. The WKYpch1.1 rats did not differ significantly from WKY rats either in basal blood pressure or in the response to restraint stress.4. In conclusion, a QTL for high blood pressure was successfully introgressed in the established congenic strain, WKYpch1.0. A gene (or genes) in the chromosome 1 QTL region modulates the cardiovascular responses to restraint stress in these congenic rats, probably through the sympathetic nervous system.
Effect of denuded endothelial cells on arginine amidase activity released from rabbit arteries
Authors: Naito Tatsuya , Ishii‐Nozawa Reiko , Miyazaki Kyosuke , Shimokawa Ken‐ichi , Matsuda Yoshifumi , Takeuchi Koichi 
Published: December 2004

Summary1. We examined the secretion of arginine amidase activity from rabbit aorta and ear arteries.2. The amount of arginine amidase activity spontaneously secretion from the aorta was significantly less than that secreted from the ear artery. Dermatan sulphate significantly facilitated the secretion of arginine amidase activity from both the aorta and ear artery.3. The dermatan sulphate‐enhanced secretion of arginine amidase activity from the aorta and ear artery was reduced by denudation of the endothelium.4. These findings may indicate that spontaneous release of arginine amidase activity from vascular smooth muscle and the enhancement of secretion of arginine amidase activity produced by dermatan sulphate depends on the endothelium.