bluuebunny/crossref_metadata_2025_split huggingface dataset:
ROLE OF NITRIC OXIDE PRODUCED BY CONSTITUTIVE AND INDUCIBLE NITRIC OXIDE SYNTHASES IN THE MOUSE GASTRIC FUNDUS
Authors: Arab HA , Hassanpour H , Bozorgi A 
Published: May 2008

SUMMARY

In the present study, the role of nitric oxide (NO) produced by constitutive and inducible nitric oxide synthases (cNOS and iNOS, resepctively) on the contraction and relaxation of fundus in normal and lipopolysaccharide (LPS)‐treated mice was examined.
A whole fundic ring isolated from mice pretreated with reserpine was mounted in an organ bath containing Krebs’ solution with 0.001 mmol/L atropine. Rings were contracted initially by 5‐hydroxytryptamine (5‐HT; 0.03 mmol/L) before relaxation was induced using ATP (0.03 mmol/L), ADP (0.03 mmol/L), pentoxifylline (0.002 mmol/L), electrical field stimulation (EFS; 50 V, 1 msec, 50 Hz, 3 min) and l‐arginine (0.05 mmol/L). All drugs and EFS induced significant relaxation of isolated rings. The relaxations induced were significantly inhibited by NG‐nitro‐l‐arginine methyl ester (l‐NAME; 1.0 mmol/L). However, the iNOS inhibitors l‐N6‐(1‐iminoethyl) lysine hydrochloride (l‐NIL; 1.0 mmol/L) and amino guanidine (AMG; 1.0 mmol/L) had no significant effect on tissue relaxation.
Then, the relaxant effects of 0.03 mmol/L ATP were tested on precontracted isolated fundic rings taken from 10 mg/kg LPS‐treated animals. The non‐selective NOS inhibitor l‐NAME (10 mg/kg), the iNOS inhibitors l‐NIL (3 mg/kg) and AMG (20 mg/kg) and betamethasone (0.1 mg/kg) were used to examine the role of NO produced by iNOS in the relaxation responses. It was found that the level of contraction induced by 0.03 mmol/L 5‐HT in rings isolated from LPS‐treated animals was significantly (P < 0.5) less than that in rings from untreated mice. However, precontracted tissues from LPS‐treated mice were significantly relaxed by ATP and the relaxation response to ATP was significantly inhibited by l‐NIL, ANG and betamethasone, but not by l‐NAME.
We suggest that, in LPS‐treated mice, the production of NO from iNOS produces a reduction in the contractile response, as well as a decrease in NO formation by cNOS, resulting in changes to smooth muscle cell function.
ROLE OF BRAIN PROSTANOIDS IN GLUCAGON‐LIKE PEPTIDE‐1‐INDUCED CENTRAL ACTIVATION OF SYMPATHO‐ADRENOMEDULLARY OUTFLOW IN RATS
Authors: Arai Junichi , Okada Shoshiro , Yamaguchi‐shima Naoko , Shimizu Takahiro , Sasaki Tsuyoshi , Yorimitsu Mieko , Wakiguchi Hiroshi , Yokotani Kunihiko 
Published: May 2008

SUMMARY

The aim of the present study was to characterize the source of plasma catecholamines induced by centrally administered glucagon‐like peptide‐1 (GLP‐1), with regard to brain prostanoids, in urethane‐anaesthetized rats.
Glucagon‐like peptide‐1 and other compounds were administered intracerebroventricularly (i.c.v.) and blood samples were collected via a cannula inserted into the femoral artery. Catecholamines were extracted from plasma with activated alumina and were assayed electrochemically using high‐performance liquid chromatography.
At 0.3, 1.0 and 3.0 nmol/animal, GLP‐1 dose‐dependently elevated plasma levels of noradrenaline and adrenaline and the 1.0 nmol GLP‐1‐induced response was dose‐dependently reduced by 5 and 10 nmol/animal exendin (5–39), a selective GLP‐1 receptor antagonist. The GLP‐1‐induced elevation of concentrations of both catecholamines was abolished by 1.2 µmol/animal indomethacin, an inhibitor of cyclo‐oxygenase, whereas 1.2 µmol/animal baicalein, a lipoxygenase inhibitor, had no effect.
Both furegrelate (1.8 µmol/animal; an inhibitor of thromboxane A2 synthase) and (+)S‐145 (625 nmol/animal; a thromboxane A2 receptor antagonist) attenuated the GLP‐1‐induced increases in plasma adrenaline concentrations, but had no effect on the increases in plasma noradrenaline. The GLP‐1‐induced increase in plasma adrenaline concentrations was abolished by acute bilateral adrenalectomy, but the procedure had no effect on increases in plasma noradrenaline.
These results suggest that, in rats, centrally administered GLP‐1 induces the secretion of adrenaline from the adrenal medulla by brain thromboxane A2‐mediated mechanisms, whereas the peptide evokes the release of noradrenaline from sympathetic nerves by brain prostanoids via mechanisms other than those mediated by thromboxane A2.
EFFECT OF UROTENSIN II ON SKIN MICROVESSEL TONE IN DIABETIC PATIENTS WITHOUT HEART FAILURE OR ESSENTIAL HYPERTENSION
Authors: Zomer E , De Ridder I , Kompa A , Komesaroff P , Gilbert RE , Krum H 
Published: May 2008

SUMMARY

Urotensin II (UII) is a potent vasoconstrictor peptide. Increased plasma levels and kidney expression of UII and its receptor have been observed in diabetes mellitus (DM). The aim of the present study was to evaluate the direct effect of exogenous UII on microvascular tone in DM patients compared with healthy controls.
Vasoactive effect of UII (10−12, 10−9 and 10−7 mol/L) on skin microvascular tone was evaluated in 12 controls and 12 DM patients (Type 1 or Type 2) without concomitant heart failure or essential hypertension using the non‐invasive technique of iontophoresis and laser Doppler velocimetry. In addition, responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were evaluated.
Urotensin II dose‐dependently dilated skin microvasculature in control subjects (–51.8 ± 59.4, 138.6 ± 101.5, 204.2 ± 115.7 and 207.5 ± 81.6 arbitrary flux units (AFUs) for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively) and dose‐dependently vasoconstricted the microvasculature in DM patients (100.8 ± 81.2, 46.2 ± 85.1, 35.4 ± 81.4 and 26.6 ± 79.6 AFUs for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively). Blood flow in control subjects and DM patients was differed significantly, with pair‐wise comparisons indicating differences for 10−9 and 10−7 mol/L UII (P = 0.04 and P = 0.003). Results of blood flow in diet‐controlled DM patients (204.7 ± 193.6, 261.2 ± 212.8, 256.1 ± 202.9 and 233.7 ± 115.9 AFUs for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively) were similar to those in control subjects compared with results for DM patients receiving antidiabetic medication (48.8 + 80.0, –61.4 ± 49.1, –75.0 ± 40.0, –91.7 ± 80.0 AFUs for MilliQ and 10−12, 10−9 and 10−7 mol/L UII, respectively). Between‐group significance remained after adjustment for baseline blood pressure values.
Acetylcholine vasodilator responses were attenuated in DM patients compared with those in control subjects (1309.5 ± 488.6 vs 3498.0 ± 912.5 AFUs, respectively), whereas SNP responses were similar in the two groups (1467.9 ± 411.3 vs 1984.4 ± 410.7 AFUs, respectively).
In conclusion, UII causes net vasoconstriction in DM. The UII‐induced increases in peripheral vascular tone may contribute to DM‐related cardiovascular complications.
PERIPHERAL DOPAMINE D2‐LIKE RECEPTORS HAVE A REGULATORY EFFECT ON CARBACHOL‐, HISTAMINE‐ AND PENTAGASTRIN‐STIMULATED GASTRIC ACID SECRETION
Authors: Eliassi Afsaneh , Aleali Fereshteh , Ghasemi Taieb 
Published: May 2008

SUMMARY

It has been documented that dopamine, an important regulator of gastric function in the brain–gut axis, has an inhibitory effect on the gastric acid secretion. It has also been suggested that dopamine D1, D2 and D5 receptor proteins are present in the gastrointestinal tract from the stomach through to the distal colon. Therefore, we hypothesized that peripheral D2 receptors may be involved in the control of stimulated gastric acid secretion. To address this question, we examined the effect of quinpirole, a selective D2 receptor‐like agonist, and domperidone, a peripheral D2 receptor antagonist, on rat gastric acid secretion.
Quinpirole (0.0001–0.5 mg/kg, i.p.) was administered simultaneously with intravenous infusions of histamine, pentagastrin, and carbachol. In some experiments, domperidone (3 and 7 mg/kg) was administered 30 min before quinpirole injection.
We found that intraperitoneal injection of quinpirole (0.0001–0.5 mg/kg) suppressed stimulated gastric acid secretion induced by histamine (0.08 mg/100 g per h), pentagastrin (1 µg/100 g per h) and carbachol (4 µg/100 g per h) in a dose‐dependent manner. This inhibitory effect of quinpirole persisted until the end of the experiments (90–120 min) and was completely suppressed by domperidone (7 mg/kg).
In conclusion, the results of the present study suggest that peripheral D2‐like receptors have an inhibitory effect on histaminergic‐, pentagastrin‐ and cholinergic‐stimulated gastric acid secretion. This inhibitory effect may be mediated by enteric dopaminergic neurons and/or non‐neuronal membranes.
INHIBITION OF TOLL‐LIKE RECEPTOR‐4, NUCLEAR FACTOR‐κB AND MITOGEN‐ACTIVATED PROTEIN KINASE BY LIGNOCAINE MAY INVOLVE VOLTAGE‐SENSITIVE SODIUM CHANNELS
Authors: Lee Ping‐Ying , Tsai Pei‐Shan , Huang Ya‐Hsien , Huang Chun‐Jen 
Published: May 2008

SUMMARY

We have shown previously that lignocaine inhibits the upregulation of inducible nitric oxide synthase (iNOS), a crucial factor that initiates the systemic inflammatory response during sepsis, possibly through voltage‐sensitive sodium channels (VSSC). Toll‐like receptor‐4 (TLR‐4), nuclear factor (NF)‐κB and mitogen activated protein kinases (MAPKs) participate in the upstream regulation of iNOS expression induced by endotoxin. In the present study, we investigated the effects of lignocaine in the regulation of the expression of these enzymes. The role of VSSC in the effects of lignocaine was also investigated.
Confluent murine macrophages (RAW264.7 cells) were randomized to receive lipopolysaccharide (LPS; 100 ng/mL), LPS + lignocaine (50 µmol/L), LPS + tetrodotoxin (TTX; 1 µmol/L; a VSSC inhibitor), LPS + lignocaine + veratridine (Ver; 50 µmol/L; a VSSC activator) or LPS + TTX + Ver. After reacting with LPS for 0, 15, 30, 45 and 60 min, cell cultures were harvested and enzyme expression was evaluated.
We found that LPS significantly increased the concentrations of TLR‐4, NF‐κB and MAPKs, including extracellular regulated kinase (ERK), c‐jun N‐terminal kinase (JNK) and p38 MAPK, in activated macrophages. Lignocaine and TTX significantly attenuated the effects of LPS on TLR‐4, NF‐κB, ERK and p38 MAPK expression, but not on JNK. Veratridine mitigated the effects of lignocaine and TTX.
These data demonstrate that lignocaine has significant inhibitory effects on the activation of TLR‐4, NF‐κB and MAPKs in activated macrophages. Moreover, these effects involve VSSC.
EFFECT OF ANAESTHETIC AGENTS ON P‐WAVE DISPERSION ON THE ELECTROCARDIOGRAM: COMPARISON OF PROPOFOL AND DESFLURANE
Authors: Owczuk Radoslaw , Wujtewicz Magdalena A , Sawicka Wioletta , Polak‐Krzeminska Agnieszka , Suszynska‐Mosiewicz Aleksandra , Raczynska Krystyna , Wujtewicz Maria 
Published: May 2008

SUMMARYAnaesthetics influence cardiac electrical activity by various mechanisms; thus, they may have pro‐arrhythmic or anti‐arrhythmic actions. Increased P‐wave dispersion is associated with a risk of paroxysmal atrial fibrillation. The aim of the present study was to analyse the impact of propofol and desflurane on changes in P wave dispersion, which may reflect the anti‐arrhythmic effects of these drugs.Fifty patients undergoing scheduled surgery were included in the study. Patients were divided into two equal groups: a propofol group and a desflurane group. Patients in the propofol group were initially administered 2.5 mg/kg propofol, followed by infusion of 6 mg/kg per h propofol. Anaesthesia in the desflurane group was achieved using inhalation induction, with concentrations up to 8–12.5 vol%. When signs of adequate anaesthesia were observed, the concentration of desflurane was reduced to 6 vol%. An electrocardiogram (ECG) was obtained before induction and then again 1, 3 and 5 min after the initiation of propofol infusion or the induction of anaesthesia in the desflurane group; additional measurements were performed after tracheal intubation. P‐wave dispersion was assessed by differences in maximal and minimal P‐wave duration on a 12‐lead ECG.P‐wave dispersion did not change over time in the desflurane group. In the propofol group, there was a significant decrease in P‐wave dispersion after 3 and 5 min of anaesthesia. Significant differences were observed between study groups after 1, 3 and 5 min of anaesthesia, and disappeared after tracheal intubation. Mean and maximal P‐wave duration did not change in either group.In conlcusion, propofol decreases P‐wave dispersion and this seems to be connected with the anti‐arrhythmic properties of the drug.
POTASSIUM CHANNEL CURRENTS IN RAT MESENCHYMAL STEM CELLS AND THEIR POSSIBLE ROLES IN CELL PROLIFERATION
Authors: Wang Shao‐Ping , Wang Jian‐An , Luo Rong‐Hua , Cui Wen‐Yu , Wang Hai 
Published: May 2008

SUMMARYMesenchymal stem cells (MSC) have shown considerable promise for the regeneration and repair of damaged tissue. However, the electrophysiological properties of K+channels in MSC are not well established and little is known about the role of K+channels in the regulation of MSC proliferation.We detected three distinct outward currents in MSC: (i) a delayed rectifier current (IKDR); (ii) a Ca2+‐activated K+current (IKCa); and (iii) a transient outward K+current (Ito). All three were present either alone or in combination in almost all cells (90%) investigated. However, 10% of cells did not express a functional current within physiological potentials.Reverse transcription–polymerase chain reaction was used to identify mRNA associated with functional ionic currents. Kv1.2 and Kv2.1 were associated with IKDR; Slo and KCNN4 were associated with IKCa; and Kv1.4 and Kv4.3 were associated with Ito.The Kv channel blockers amiodarone, tetraethylammonium and verapamil, as well as increased extracellular K+levels, inhibited proliferation of cultured MSC.In MSC treated with Kv channel blockers or an increased extracellular concentration of K+, the proportion of cells in the S phase decreased significantly and the proportion of cells in the G0/G1phase tended to increase, indicating that the cells were prevented from entering the S phase of the cell cycle.Our findings suggest that rat MSC heterogeneously express distinct types of K+current, of which the voltage‐gated IKDR‐like K+current is most common. Kv channel activity modulates the progression of the cell cycle, affecting the proliferation of MSC.
PERIPHERAL PLASMA CORTICOTROPIN‐RELEASING FACTOR CONCENTRATION DOES NOT CORRELATE WITH AUGMENTED COLONIC MOTILITY IN RESPONSE TO RESTRAINT STRESS IN RATS
Authors: Nakade Yukiomi , Pappas Theodore N , Takahashi Toku 
Published: May 2008

SUMMARYCorticotropin‐releasing factor (CRF) alters colonic motor function in response to restraint stress. It remains unclear whether peripheral CRF released by restraint stress correlates with stress‐mediated colonic motility.One strain gauge transducer was sutured on the serosal surface of the mid colon and a silastic cannula was inserted into the jugular vein. Seven days after surgery, the wires from the transducers were connected to the recording system and colonic motility was recorded. Rats were subjected to restraint stress for 90 min and blood samples were obtained every 30 min.Immediately after the start of stress loading, phasic contractions were observed that lasted during restraint stress loading. Intracisternal injection of CRF elicited rapid augmentation of colonic motility, similar to that of restraint stress.The plasma CRF concentration (4 pg/mL) remained unaltered within the first 30 min after stress loading, but increased gradually to 23 pg/mL at 90 min after the beginning of restraint stress. There was no positive correlation observed between plasma CRF concentrations and restraint stress‐stimulated colonic motility.These findings indicate that central CRF has a predominant role in stress‐induced augmentation of colonic motility. It remains unclear whether a delayed response of plasma CRF concentrations in response to restraint stress is involved in mediating colonic motility.
EFFECTS OF DIFFERENT TREATMENTS FOR HYPERTHYROIDISM ON THE HYPOTHALAMIC–PITUITARY–ADRENAL AXIS
Authors: Lizcano Fernando , Salvador Javier 
Published: May 2008

SUMMARY

To investigate the effects of iopanoic acid (IA) and carbimazole on increased activity of the hypothalamic–pituitary–adrenal (HPA) axis in hyperthyroidism, we studied 14 women with hyperthyroidism caused by Graves’ disease (n + 11) or toxic multinodular goitre (n + 3) before and after carbimazole or IA treatment. Seven normal women comprised the control group.
Changes in thyroid‐stimulating hormone, total and free thyroid hormones, arginine vasopressin (AVP), urinary free cortisol, adrenocorticotrophin (ACTH) and cortisol in response to human corticotrophin‐releasing hormone (hCRH; 100 µg, i.v.) were estimated under basal conditions and after treatment with IA (3 g/day; n + 7) for 7 days or carbimazole (30 mg/day; n + 7) for 1 month.
A higher ACTH response, with normal cortisol secretion, was observed in hyperthyroid patients in response to hCRH compared with the control group. After 7 days treatment, IA induced a significant reduction in total tri‐iodothyronine (T3) and free T3 to normal levels and a stronger ACTH response to hCRH, whereas plasma and urinary cortisol levels remained unchanged. Patients treated with carbimazole showed normalization of thyroid hormone levels, a reduction in basal and stimulated ACTH secretion and higher urinary free cortisol levels compared with pretreatment levels. Neither IA nor carbimazole treatment had any effect on AVP levels in hyperthyroid patients.
In conclusion, hyperthyroid patients showed HPA axis hyperactivity of central origin with reduced cortisol responses, which were reversed by carbimazole treatment. The differential effects of IA and carbimazole on HPA function indicate that thyroid hormones have a role in modulation of the HPA axis.
APPLICATION OF AN ADENOVIRAL VECTOR ENCODING SOLUBLE TRANSFORMING GROWTH FACTOR‐β TYPE II RECEPTOR TO THE TREATMENT OF DIABETIC NEPHROPATHY IN MICE
Authors: Kondo Takehito , Takemura Genzou , Kosai Ken‐ichiro , Ohno Takamasa , Takahashi Tomoyuki , Esaki Masayasu , Goto Kazuko , Maruyama Rumi , Murata Ichijiro , Minatoguchi Shinya , Fujiwara Takako , Fujiwara Hisayoshi 
Published: May 2008

SUMMARY

In the present study, we examined the effects of inhibiting transforming growth factor (TGF)‐β in a mouse model of diabetic nephropathy.
An adenovirus harbouring the gene encoding soluble TGF‐β type II receptor (Ad.CAG‐sTβRII), a competitive inhibitor of TGF‐β, was injected into hindlimb muscles (systemic delivery) of mice 5 weeks after the induction of diabetes with streptozotocin. The control group was injected with an adenovirus encoding the LacZ gene (Ad‐LacZ).
Five weeks after administration, anti‐TGF‐β gene therapy was found to have had no effect on renal function, albuminuria or glucose metabolism in mice with diabetic nephropathy. Nonetheless, this gene therapy did significantly reduce fibrosis in both glomeruli and renal tubules. These effects were accompanied by attenuation of the increased expression of α‐smooth muscle actin normally seen in kidneys of diabetic mice and better preservation of glomerular cell numbers, although the thickness of the glomerular capillary basement membrane was unchanged. The plasma concentration of soluble TGF‐β type II receptor peaked on Day 7 after treatment, but was undetectable by Day 14. Moreover, a second treatment with Ad.CAG‐sTβRII failed to prolong the interval of gene product expression in the blood.
The present anti‐TGF‐β gene therapy showed a significant antifibrotic effect in a model of diabetic nephropathy, but failed to improve renal function. The inadequacy of the observed effect is likely due to the relatively short interval of gene product expression. This problem will have to be overcome if gene therapies for slowly progressing diseases, like diabetic nephropathy, are to be realised.
INVOLVEMENT OF BOTH ENDOPLASMIC RETICULUM‐ AND MITOCHONDRIA‐DEPENDENT PATHWAYS IN CARDIOTOXIN III‐INDUCED APOPTOSIS IN HL‐60 CELLS
Authors: Chien Ching‐Ming , Yang Sheng‐Huei , Chang Long‐Sen , Lin Shinne‐Ren 
Published: May 2008

SUMMARY

Cardiotoxin (CTX) III, a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. In the present study, we investigated the mechanisms underlying the anticancer activity of CTX III in human leukaemia (HL‐60 cells).
Cardiotoxin III activated the endoplasmic reticulum (ER) pathway of apoptosis in HL‐60 cells, as indicated by increased levels of calcium and glucose‐related protein 78 (Grp78), and triggered the subsequent activation of µ‐calpain and caspase 12.
In addition, CTX III initiated the mitochondrial apoptotic pathway in HL‐60 cells, as evidenced by an increased Bax/Bcl‐2 ratio, the release of cytochrome c and activation of caspase 9.
In the presence of 50 µmol/L Z‐ATAD‐FMK (a caspase 12 inhibitor) and 100 µmol/L Z‐LEHD‐FMK (a caspase 9 inhibitor), the CTX III‐mediated activation of caspase 9 and caspase 3 was significantly reduced. There was no significant effect of the caspase 12 inhibitor Z‐ATAD‐FMK on mitochondrial cytochrome c release.
Cardiotoxin III‐mediated activation of caspase 12 was not abrogated in the presence of the caspase 9 inhibitor Z‐LEHD‐FMK, indicating that caspase 12 activation was not downstream of caspase 9.
These results indicate that CTX III induces cell apoptosis via both ER stress and a mitochondrial death pathway.
COPPER AND ANGIOGENESIS: UNRAVELLING A RELATIONSHIP KEY TO CANCER PROGRESSION
Authors: Finney Lydia , Vogt Stefan , Fukai Tohru , Glesne David 
Published: May 2008

SUMMARY

Angiogenesis, the formation of new capillaries from existing vasculature, is a critical process in normal physiology as well as several physiopathologies. A desire to curb the supportive role angiogenesis plays in the development and metastasis of cancers has driven exploration into anti‐angiogenic strategies as cancer therapeutics. Key to this, angiogenesis additionally displays an exquisite sensitivity to bioavailable copper. Depletion of copper has been shown to inhibit angiogenesis in a wide variety of cancer cell and xenograft systems. Several clinical trials using copper chelation as either an adjuvant or primary therapy have been conducted. Yet, the biological basis for the sensitivity of angiogenesis remains unclear. Numerous molecules important to angiogenesis regulation have been shown to be either directly or indirectly influenced by copper, yet a clear probative answer to the connection remains elusive.
Measurements of copper in biological systems have historically relied on techniques that, although demonstrably powerful, provide little or no information as to the spatial distribution of metals in a cellular context. Therefore, several new approaches have been developed to image copper in a biological context. One such approach relies on synchrotron‐derived X‐rays from third‐generation synchrotrons and the technique of high resolution X‐ray fluorescence microprobe (XFM) analysis.
Recent applications of XFM approaches to the role of copper in regulating angiogenesis have provided unique insight into the connection between copper and cellular behaviour. Using XFM, copper has been shown to be highly spatially regulated, as it is translocated from perinuclear areas of the cell towards the tips of extending filopodia and across the cell membrane into the extracellular space during angiogenic processes. Such findings may explain the heightened sensitivity of this cellular process to this transition metal and set a new paradigm for the kinds of regulatory roles that the spatial dynamics of cellular transition metals may play.