bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of nitric oxide and tachykinins in the effects induced by protease‐activated receptors in rat colon longitudinal muscle
Authors: Mulè Flavia , Baffi Maria Carmela , Capparelli Anna , Pizzuti Roberta 
Published: June 2003

The aim of the present study was to verify a possible involvement of nitric oxide (NO) and of tachykinins in the contractile and relaxant effects caused by the activation of protease‐activated receptor (PAR)‐1 and PAR‐2 in the longitudinal muscle of rat colon.
Mechanical responses to the PAR‐1 activating peptides, SFLLRN‐NH2 (10 nM–10 μM) and TFLLR‐NH2 (10 nM–10 μM), and to the PAR‐2‐activating peptide, SLIGRL‐NH2 (10 nM–10 μM), were examined in vitro in the absence and in the presence of different antagonists.
The relaxation induced by SFLLRN‐NH2, TFLLR‐NH2 and SLIGRL‐NH2 was antagonised by the inhibitor of NO synthase L‐Nω‐nitroarginine methyl ester (300 μM), or by the inhibitor of the guanylyl cyclase, 1‐H‐oxodiazol‐[1,2,4]‐[4,3‐a]quinoxaline‐1‐one (10 μM).
The contractile responses to PAR‐1 and PAR‐2 activation were concentration‐dependently attenuated by SR140333 (0.1–1 μM), NK1 receptor antagonist, or by SR48968 (0.1–1 μM), NK2 receptor antagonist. The combined pretreatment with SR140333 (1 μM) and SR48968 (1 μM) produced additive suppressive effects on the contractile responses to PAR activation. Pretreatment of the preparation with capsaicin (10 μM) markedly reduced the contractions evoked by SFLLRN‐NH2, TFLLR‐NH2 and SLIGRL‐NH2, while ω‐conotoxin GVIA (0.2 μM) had no effect.
The present results suggest that in rat colonic longitudinal muscle, PAR‐1 and PAR‐2 activation can evoke (i) relaxation through the production of NO or (ii) contraction through the release of tachykinins, likely, from sensory nerves. These actions may contribute to motility disturbances during intestinal trauma and inflammation.

British Journal of Pharmacology (2003) 139, 598–604. doi:10.1038/sj.bjp.0705273
Bisphenol A diglycidyl ether‐induced apoptosis involves Bax/Bid‐dependent mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome c and Smac/DIABLO
Authors: Fehlberg Sebastian , Gregel Cornelia M , Göke Alexandra , Göke Rüdiger 
Published: June 2003

Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) antagonist, which is able to induce apoptosis in tumor cells independently of PPAR‐γ in caspase‐dependent and ‐independent manners. Additionally, BADGE promotes TRAIL‐induced apoptosis.
We report that BADGE activates via Bax and caspases‐2 and ‐8 both the intrinsic and extrinsic apoptotic pathways using Bid as a shunt.
BADGE stimulates the mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome c and second mitochondria‐derived activator of caspase/direct IAP‐binding protein with low pl (Smac/DIABLO). The release of cytochrome c could not be blocked by inhibitors of caspases‐3, ‐8 and ‐9 indicating that BADGE acts upstream of caspases‐3 and ‐9 and does not involve caspase‐8 to release cytochrome c.
While the caspase‐independent apoptotic effect might be mediated by AIF, the sensitizing effect of BADGE against other apoptotic substances is most likely mediated by the X‐linked inhibitor of apoptosis inhibitor Smac/DIABLO.
Our data suggest that BADGE or BADGE derivatives could represent promising substances for the treatment of neoplasms improving the antitumoral activity of TRAIL.

British Journal of Pharmacology (2003) 139, 495–500. doi:10.1038/sj.bjp.0705275
Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult sensory neurones in culture: a novel role of prostaglandins
Authors: von Banchet Gisela Segond , Scholze Anita , Schaible Hans‐Georg 
Published: June 2003

Peripheral inflammation causes an increase in the proportion of primary afferent neurones that express neurokinin1 (NK1) receptors for substance P (SP). This upregulation may contribute to the neuronal mechanisms of inflammatory pain. The aim of this study was to identify endogenous mediators that stimulate upregulation of NK1 receptors in dorsal root ganglion (DRG) neurones. Cultured DRG neurones from the adult normal rat were exposed for 2 days to media that contained specific mediators, namely potassium in high concentration, prostaglandin E2 (PGE2), somatostatin (SRIF), and compounds influencing second messenger cascades. After fixation neurones were labelled with an NK1 receptor antibody.
Repetitive addition of the inflammatory mediator PGE2 or dibutyryl‐cyclic adenosine 3′,5′ monophophate (db‐cAMP) to the culture medium enhanced the proportion of neurones with NK1 receptor‐like immunoreactivity from about 12% up to 40%. PGE2‐induced upregulation was prevented by coadministration of PGE2 and a protein kinase A inhibitor or SRIF to the medium. High potassium concentration, protein kinase C inhibitors and omission of nerve growth factor from the medium had no effect.
In calcium‐imaging experiments, bath application of SP evoked increases of the intracellular calcium concentration in about 20% of the neurones. This proportion increased to about 40% after PGE2‐pretreatment, but the increase was prevented when PGE2 and SRIF were coadministered to the medium.
These data show that the expression of NK1 receptor‐like immunoreactivity in DRG neurones is regulated by the inflammatory mediator PGE2. This upregulation depends on the intracellular adenylyl cyclase–protein kinase A pathway.

British Journal of Pharmacology (2003) 139, 672–680. doi:10.1038/sj.bjp.0705278
Endothelium‐independent relaxation to cannabinoids in rat‐isolated mesenteric artery and role of Ca2+ influx
Authors: Vanessa Ho W ‐S , Robin Hiley C 
Published: June 2003

Three cannabinoid receptor agonists, anandamide (CB1 receptor‐selective) and the aminoalkyl‐indoles, JWH 015(2‐methyl‐1‐propyl‐1H‐indol‐3‐yl)‐1‐napthalenylmethanone; (CB2 receptor‐selective), R‐(+)‐WIN 55,212‐2 (R‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl)pyrrolol[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐napthalenylmethanone; slightly CB2 receptor‐selective), as well as the enantiomer S‐(−)‐WIN 55,212‐3(S‐(−)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl)pyrrolol[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐napthalenylmethanone; inactive at cannabinoid receptors), induced endothelium‐independent relaxation of methoxamine‐precontracted isolated small mesenteric artery of rat. KCL (60 mM) precontraction did not affect relaxation to the aminoalkylindoles, but reduced that to anandamide.
SR14176A (N‐(piperidin‐1‐yl)‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide; 3 μM; CB1 receptor antagonist) inhibited relaxation only to JWH 015 and anandamide. Neither AM 251 (N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide; CB1 antagonist) nor SR 144528 (N‐[(1S)‐endo‐1,3,3‐trimethyl bicyclo[2.2.1] heptan‐2‐yl]‐5‐(4‐chloro‐3‐methylphenyl)‐1‐(4‐methylbenzyl)‐pyrazole‐3‐carboxamide; CB2 antagonist; both at 3 μM) affected any of the relaxations.
Vanilloid receptor desensitisation with capsaicin reduced anandamide relaxation; addition of SR 141716A (3 μM) then caused further inhibition. SR 141716A did not affect capsaicin‐induced relaxation.
The aminoalkylindoles inhibited CaCl2‐induced contractions in methoxamine‐stimulated vessels previously depleted of intracellular Ca2+. These inhibitory effects were greatly reduced or abolished in ionomycin‐(a calcium ionophore) contracted vessels. Anandamide also caused vanilloid receptor‐independent, SR 141716A‐ (3 μM) insensitive, inhibition of CaCl2 contractions.
In conclusion, the aminoalkylindoles JWH 015, R‐(+)‐WIN 55,212‐2 and S‐(−)‐WIN 55,212‐3 relax rat small mesenteric artery mainly by inhibiting Ca2+ influx into vascular smooth muscle. Anandamide causes vasorelaxation by activating vanilloid receptors, but may also inhibit Ca2+ entry. Relaxation to JWH 015 and anandamide was sensitive to SR 141716A, but there is no other evidence for the involvement of CB1 or CB2 receptors in responses to these compounds.

British Journal of Pharmacology (2003) 139, 585–597. doi:10.1038/sj.bjp.0705280
Growth hormone secretagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin‐specific receptor
Authors: Pierno Sabata , Luca Annamaria De , Desaphy Jean‐François , Fraysse Bodvael , Liantonio Antonella , Didonna Maria Paola , Lograno Marcello , Cocchi Daniela , Smith Roy G , Camerino Diana Conte 
Published: June 2003

Growth hormone secretagogues (GHS) exhibit potent growth hormone (GH)‐releasing activity through the activation of a pituitary receptor. Here, we consider the possibility that GHS can target a specific receptor in rat skeletal muscle and have a role in the control of muscle function.
By means of the intracellular microelectrode technique, we found that in vitro application of hexarelin and L‐163,255 dose dependently reduced resting chloride (gCl) and potassium (gK) conductances in rat skeletal muscle. These effects were prevented by the GHS‐receptor antagonist [D‐Lys‐3]‐GHRP‐6, and by either phospholipase C or protein kinase C (PKC) inhibitors. Ghrelin, a natural ligand of GHS receptors, also induced a reduction of muscle gCl and gK, which was antagonised by [D‐Lys‐3]‐GHRP‐6.
Both GHS shifted the mechanical threshold for the contraction of muscle fibres towards more negative voltages. Accordingly, by means of FURA‐2 fluorescent measurements, we demonstrated that L‐163,255 induced a resting [Ca2+]i increase, which was reversible and not blocked by nifedipine or removal of external Ca2+.
Ageing is a condition characterised by a deficit of GH secretion, which in turn modifies the electrical and contractile properties of skeletal muscle. In contrast to GH, chronic treatment of aged rats with hexarelin or L‐163,255 failed to restore the electrical and contractile muscle properties. Moreover, the two GHS applied in vitro were able to antagonise the beneficial effect on gCl and gK obtained through chronic treatment of aged animals with GH.
Thus, skeletal muscle expresses a specific GHS receptor able to decrease gCl and gK through a PKC‐mediated intracellular pathway. This peripheral action may account for the lack of restoration of skeletal muscle function in long‐term GHS‐treated aged animals.

British Journal of Pharmacology (2003) 139, 575–584. doi:10.1038/sj.bjp.0705284
Effects of G‐protein‐specific antibodies and Gβγ subunits on the muscarinic receptor‐operated cation current in guinea‐pig ileal smooth muscle cells
Authors: Yan H ‐D , Okamoto H , Unno T , Tsytsyura Ya D , Prestwich S A , Komori S , Zholos A V , Bolton T B 
Published: June 2003

The effects on the whole‐cell carbachol‐induced muscarinic cationic current (mIcat) of antibodies against the α‐subunits of various G proteins, as well as the effect of a Gβγ subunit, were studied in single guinea‐pig ileal smooth muscle cells voltage‐clamped at −50 mV. Ionized intracellular calcium concentration, [Ca2+]i, was clamped at 100 nM using a 1,2‐bis(2‐aminophenoxyl‐ethane‐N,N,N′,N′‐tetraacetic acid)/Ca2+ mixture.
Application of ascending concentrations of carbachol (1–300 μM) activated mIcat (mean amplitude 0.83 nA at 300 μM carbachol; EC50 8 μM; Hill slope 1.0). A 20 min or longer intracellular application via the pipette solution of Gi3/Go or Go antibodies resulted in about a 70% depression of the maximum response without change in the EC50 value. In contrast, antibodies against α‐subunits of Gi1, Gi1/Gi2, Gi3, Gq/G11 or Gs protein over a similar or longer period did not significantly reduce mIcat. Antibodies to common Gβ or infusion of the Gβγ subunit itself had no effect on mIcat.
If cells were exposed briefly to carbachol (50 or 100 μM) at early times (<3 min) after infusion of antibodies to Gαi3/Gαo or to Gαo had begun, carbachol responses remained unchanged even after 20–60 min; that is, the depression of mIcat by these antibodies was prevented.
These data show that Gαo protein couples the muscarinic receptor to the cationic channel in guinea‐pig ileal longitudinal smooth muscle and that Gβγ is not involved. They also show that prior activation of the muscarinic receptor presumably causes a long‐lasting postactivation change of the G protein, which is not reflected in mIcat, but acts to hinder antibody binding.

British Journal of Pharmacology (2003) 139, 605–615. doi:10.1038/sj.bjp.0705289
Foetal cystic abdominal masses
Authors: McEwing Rachael , Hayward Christina , Furness Margaret 
Published: June 2003

SummaryFoetal abdominal cysts are frequently found on routine antenatal ultrasound. Various sonographic features might help in their differential diagnosis. However, a definitive diagnosis is often not made until postnatal life, and detection of an intra‐abdominal cyst antenatally rarely alters obstetric management. A review of possible causes of a foetal abdominal cyst is presented.
Radiological manifestations of malignant pleural mesothelioma
Authors: Au Virginia WK , Thomas Meredith 
Published: June 2003

SummaryMalignant pleural mesothelioma has had a rising incidence in Australia over the past 40 years. This pictorial essay gives a brief account of the condition, summarizes the various radiological manifestations and aims at increasing the awareness of a disease that is expected to reach its peak incidence in the early decades of the twenty‐first century.
Transjugular liver biopsy effecting changes in clinical management
Authors: Lee David , Chitturi Shivakumar , Kench James , George Jacob , Fuller Steven , Bradstock Ken , Lin Rita , Wong Kai Ping , Young Noel 
Published: June 2003

SummaryAlthough transjugular liver biopsies are frequently performed in patients with impaired blood coagulation, their impact on effecting changes in clinical management has not been assessed. We reviewed our experience with 43 consecutive transjugular liver biopsies performed over 3 years (1998−2000) at Westmead Hospital, Sydney, Australia. The technical success, procedural complication rates and subsequent management of these patients were ascertained from the medical case records. Forty‐two (28 men) patients were studied. The indications for liver biopsy were as follows: assessment of hepatitis/cirrhosis status (n = 21), evaluation of liver dysfunction following bone marrow transplantation (n = 19) and miscellaneous (n = 2). All liver biopsies were performed with a Cook 20‐G transjugular cutting needle device. Adequate histological samples were obtained in 42 (98%) of the 43 biopsies performed. The pre‐biopsy diagnoses were confirmed by histology in 28 cases (65%). A change in clinical diagnosis was observed in 12 (28%) patients, and there were changes to subsequent management in all 12 patients. Four patients developed procedural complications, including small neck haematomas in two patients and a self‐limiting biliary fistula in one. The only major complication was an extracapsular bleed from a hepatic laceration. This patient required emergency surgery but recovered. Transjugular liver biopsies can be effectively and safely performed in high‐risk patients with impaired coagulation. They aid accurate histological appraisal of liver dysfunction in these patients and influence clinical decision‐making.
Breast compression in mammography: How much is enough?
Authors: Poulos Ann , McLean Donald , Rickard Mary , Heard Robert 
Published: June 2003

SummaryThe amount of breast compression that is applied during mammography potentially influences image quality and the discomfort experienced. The aim of this study was to determine the relationship between applied compression force, breast thickness, reported discomfort and image quality. Participants were women attending routine breast screening by mammography at BreastScreen New South Wales Central and Eastern Sydney. During the mammographic procedure, an ‘extra’ craniocaudal (CC) film was taken at a reduced level of compression ranging from 10 to 30 Newtons. Breast thickness measurements were recorded for both the normal and the extra CC film. Details of discomfort experienced, cup size, menstrual status, existing breast pain and breast problems were also recorded. Radiologists were asked to compare the image quality of the normal and manipulated film. The results indicated that 24% of women did not experience a difference in thickness when the compression was reduced. This is an important new finding because the aim of breast compression is to reduce breast thickness. If breast thickness is not reduced when compression force is applied then discomfort is increased with no benefit in image quality. This has implications for mammographic practice when determining how much breast compression is sufficient. Radiologists found a decrease in contrast resolution within the fatty area of the breast between the normal and the extra CC film, confirming a decrease in image quality due to insufficient applied compression force.
Primary angiitis of the central nervous system: MRI features and clinical presentation
Authors: Singh Surendra , John Susan , Joseph Thykkoothathil Pappy , Soloman Thilak 
Published: June 2003

SummaryWe report the MRI features in a series of four patients with primary angiitis of the central nervous system (PACNS). Based on MRI features, clinical presentation, paraclinical investigations and laboratory tests, including cerebrospinal fluid (CSF) analysis, various differentials were considered. In two patients with MRI findings of cortical, subcortical and deep white matter lesions, lack of mass effect, focal areas of bleed and heterogeneous parenchymal, leptomeningeal or pial enhancement and a normal magnetic resonance angiography, a differential diagnosis of primary angiitis of the CNS was also considered. In all patients, an open brain biopsy was advised to establish a definitive diagnosis of PACNS. Here, we briefly discuss the MRI features, correlation with clinical presentation and paraclinical parameters for the diagnosis of this entity. We also briefly review the literature.
Survey of effective dose levels from typical paediatric CT protocols
Authors: McLean Donald , Malitz Nathan , Lewis Sarah 
Published: June 2003

SUMMARYConcern over reported large radiation doses leading to a high cancer risk for paediatric CT patients has prompted considerable investigation in paediatric CT. The recent release of software from Germany has allowed effective doses to be calculated from CT protocol information and radiation measurement for standard paediatric patient sizes for both sexes. An initial study has been undertaken in nine radiology departments, four of which were dedicated paediatric departments, for routine chest and abdominal CT procedures. The dose calculation software is based on Monte Carlo simulation of X‐ray conditions during a CT procedure and utilized a ‘tomographic’ phantom model of a 7‐year‐old child and an 8‐week‐old baby to allow calculation of organ dose and hence effective dose. Results of the survey indicate that effective doses were higher for females than males, and higher for abdominal procedures. Slightly higher effective doses were calculated for the child compared to the baby. All centres but one recorded lower effective doses with their current protocols than if they had used recommended CT protocols found in the literature. Analysis of the survey data indicates that scan parameters are the main cause of dose variations, although the type of scanner can affect dose by a factor of 2 (when comparing different units) as well as variation in anatomy scanned in protocols. Dose reduction appears to be most closely linked with reduced mAs and increased pitch as expected. The calculation of effective dose appears to be a key factor in assessing CT protocols, particularly for paediatric patients.
Australian and New Zealand radiation oncology work practices in 2000
Authors: Veness Michael , Rikard‐Bell Glenys , Ward Jeanette 
Published: June 2003

SummaryIn 1996, a Faculty of Radiation Oncology (FRO) survey was sent to all practising radiation oncologists in Australia and New Zealand (ANZ) ascertaining work practices and attitudes (n = 138). In December 2000, we sent all practising ANZ radiation oncologists (n = 183) a survey in which we reproduced questions about work practice (response rate 75%). The majority of ANZ radiation oncologists were male (n = 102, 73.9%), in full time employment (n = 125, 90.6%) and subspecialized (n = 103, 74.6%). The median number of new patients seen per year was 300 (range, 10−700). However, 15% of radiation oncologists saw 350 new patients per year and 19% saw greater than 400 new patients per year. The median time allocated to work was 50 h each week. Nearly all respondents (90%) desired some amount of protected time with a median desirable of eight hours each week (range, 2−30 h, mode 8 h). The majority (n = 95, 68.8%) of respondents were members of TROG. A minority (n = 25, 18.1%) had obtained a postgraduate qualification. Many also had a clinical academic appointment (n = 60, 43.5%). Over 70 percent of respondents (n = 100, 72.5%) indicated enrolment of their patients in clinical trials. The increase in radiation oncologists with postgraduate qualifications and  commitment to clinical research, through TROG membership and patients recruited to clinical trials, is very encouraging. However, our findings demonstrate little, if any, improvement in the total weekly clinical workload of a radiation oncologist. The recent move to subspecialization has not resulted in a decrease in clinical workload. In some aspects of work practice, such as time for self‐education and research, the situation appears to be worsening.
Treatment of localized prostate cancer using a combination of high dose rate Iridium‐192 brachytherapy and external beam irradiation: Initial Australian experience
Authors: Stevens MJ , Stricker PD , Saalfeld J , Brenner PC , Kooner R , O'Neill GFA , Duval PJ , Jagavkar RS , Cross P , Martland J 
Published: June 2003

SummaryCombination high dose rate brachytherapy (HDRB) and external beam radiation therapy is technically and clinically feasible as definitive treatment for localized prostate cancer. We report the first large Australian experience using this technique of radiation dose escalation in 82 patients with intermediate‐ and high‐risk disease. With a median follow up of 3 years (156 weeks), complications were low and overall prostate‐specific antigen progression‐free survival was 91% using the American Society for Therapeutic Radiology and Oncology consensus definition. The delivery of hypofractionated radiation through the HDRB component shortens overall treatment time and is both biologically and logistically advantageous. As a radiation boost strategy, HDRB is easy to learn and could be introduced into most facilities with brachytherapy capability.