bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies of muscarinic receptor reserve linked to phosphoinositide hydrolysis in parotid gland and cerebral cortex
Authors: EK B. , ANTONSSON B.‐M. 
Published: December 2008

Hydrolysis of inositol phospholipids caused by muscarinic agonists was studied in the guinea‐pig parotid gland (PG) and cerebral cortex (CX). The present study describes the effect of two muscarinic agonists, carbachol and oxotremorine, on stimulation of phosphoinositide hydrolysis and on binding of [3H]NMS in the presence of the irreversible muscarinic antagonist benzilyl choline mustard (BCM).Carbachol and oxotremorine stimulated the formation of inositol phosphates in PG, pD2(Carb) = 5.3 ± 0.1, pD2(Oxo) = 5.9 ± 0.1 and in CX, pD2(Carb) = 4.3 ± 0.2, pD2(Oxo) = 5.8 ± 0.2. In the present study slices from both tissues have been exposed to 0.1 μM BCM for 2, 5 and 10 min. Treatment for 10 min caused a 75–85%, reduction in specific [3H]N‐methyl scopolamine ([3H]NMS) binding sites in both PG and CX. Following 2 min BCM treatment of PG a marked decrease in pD2value of the carbachol‐stimulated inositol phosphate formation was found. This effect was not found in CX. The results showed that a 30–40% reduction in binding sites shifted the carbachol concentration response curve to the right by one order of magnitude and reduced the oxotremorine‐induced release of inositol phosphates by approximately 20%. In PG, the BCM‐induced reduction of the carbachol‐stimulated inositol phosphate formation was paralleled by the reduction in receptor binding sites. Similar treatment, but in CX, showed a lower reduction of the carbachol‐stimulated inositol phosphate formation as compared to the reduction in receptor‐binding sites.The results from the present study indicate that stimulation of phosphoinositide hydrolysis in PG involves a receptor reserve, mainly via stimulation of M2‐muscarinic receptors.
The ability of ruthenium red to reduce the autonomic reflexes and peptide release evoked by capsaicin administration in the pig in vivo
Authors: ALVING K. , FRANCO‐CERECEDA A. 
Published: December 2008

In the present study we have investigated the cardiovascular effects and peptide‐releasing actions of different capsaicin doses in the absence and presence of the inhibitor of Ca2+ fluxes, ruthenium red, in the pig in vivo. Bolus injections of capsaicin (10, 100 and 1000μg kg‐1 i.v.) evoked a concentration‐dependent increase in mean arterial pressure and heart rate (HR), while in the bronchial and nasal circulations, a fall in vascular resistance was observed. At the highest capsaicin dose used, there was, in addition, a marked increase in arterial levels of calcitonin gene‐related peptide (CGRP)‐and neuropeptide Y (NPY)‐like immunoreactivity (LI). Ruthenium red (RR) significantly reduced the CGRP‐LI release, but not the outflow of NPY‐LI, at the highest dose of capsaicin as well as the functional effects evoked by low dose capsaicin administration. The inhibitory effects of RR were reversible, i.e. 30 min after ruthenium red administration, bolus injections of capsaicin (10 and 100 μg kg‐1) induced responses similar to those seen in controls.It is concluded that capsaicin given intravenously to the pig produces profound haemodynamic effects and release of CGRP‐ and NPY‐LI through direct activation of a population of C‐fibre endings and increased autonomic discharge. RR inhibits not only the local peptide‐releasing properties of capsaicin, but also the centrally directed discharge activity leading to reflex responses, with the latter being less sensitive to RR.
On the usefulness of Fura‐2 measurements of intrasynaptosomal calcium levels in rat cortical synaptosomes to study mechanisms of presynaptic function
Authors: HU P.‐S. 
Published: December 2008

Levels of [Ca2+]iin rat cortex synaptosomes were measured using the Ca2+indicator Fura‐2. Ca2+influx was induced by veratridine in a concentration‐dependent manner (1–10μm). The resulting increase in [Ca2+]iwas inhibited by tetrodotoxin (TTX). K+(18 mm) increased the [Ca2+]iwhich was not influenced by TTX. K+‐channel blockers such as 4‐aminopyridine,α‐andδ‐dendrotoxinper sewere ineffective. The veratridineinduced Ca2+influx in synaptosomes was reduced by L‐type Ca2+‐channel blockers, such as felodipine, nifedipine and PN‐200‐110, verapamil and diltiazem.ω‐Conotoxin, an N‐type Ca2+‐channel blocker, did not inhibit the veratridine‐stimulated [Ca2+]iincrease. Bay K 8644, an L‐channel agonist, stimulated an increase of [Ca2+]iin synaptosomes which was not sensitive to TTX.R‐N6‐Phenyl‐isopropyl‐adenosine (R‐PIA) and clonidine, agonists at adenosine A1‐receptors and α2‐adrenoceptors, respectively, did not influence the veratridinestimulated [Ca2+]iincrease. R‐PIA did not interact with Bay K 8644‐stimulated [Ca2+]iincrease in synaptosomes.The results for all the substances used show major differences between the effects on Ca2+influx in synaptosomes and on the electrically evoked neurotransmitter release in slice preparations. Thus, the synaptosome preparation is not a generally applicable experimental model for the study of Ca2+mechanisms of presynaptic neuromodulation.
Rhythmic contractions of isolated small arteries from rat: influence of the endothelium
Authors: GUSTAFSSON H. , MULVANY M. J. , NILSSON H. 
Published: December 2008

Small arteries of the mesenteric arcade from Wistar rats display rhythmic oscillations superimposed on the tonic contractile response when exposed to submaximal doses of noradrenaline. We have previously shown that mechanical removal of the endothelium abolishes these oscillations. In the present study different methods to eliminate or modify the influence of the endothelium were used in order to further characterize the mechanisms behind rhythmic contractions in these vessels.Endothelium was removed either mechanically or chemically by perfusing the vessels with 0.3% CHAPS. The absence of functional endothelium enhanced noradrenaline sensitivity and simultaneously abolished oscillations in tension and membrane potential, but did not affect resting membrane potential. The rhythmic activity was also reduced or abolished by exposure to haemoglobin, methylene blue, LY83583 orl‐NNA. Indomethacin and propranolol were without effect. Sodium nitroprusside or the permeant analogue of cyclic GMP, 8‐bromo cyclic GMP, restored rhythmic activity in precontracted endothelium‐denuded vessels. The data suggest that release of nitric oxide from the endothelium, and subsequent generation of cyclic GMP in the smooth muscle, activates oscillations in membrane potential and tension; the oscillator itself appears to be located within the smooth muscle cells.
Vascular effects of endothelin‐1 in the cat; modification by indomethacin andl‐NAME
Authors: GRANSTAM E. , WANG L. , BILL A. 
Published: December 2008

Intravenous infusion of endothelin‐1 (ET‐1) in the cat, 60 pmol × kg body wt‐1x min‐1for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 ± 4.8 mmHg (n= 6;P< 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70–80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18–23%. Pre‐treatment with indomethacin or a combination of indomethacin andl‐NAME caused vasoconstriction in many tissues and modified the responses to ET‐1 in a variable way, suggesting that normally, ET‐1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues.Intracerebroventricular infusion (i.c.v.) of ET‐1, 10 pmol × kg body wt‐1x min‐1, caused an increase in MAP of 79 ± 11 mmHg (n= 6;P< 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60–80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response.Our results indicate that in many tissues the vasoconstrictive effect of ET‐1 is influenced by indomethacin‐ andl‐NAME‐sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.
Commissioning and implementation of a stereotactic conformal radiotherapy technique using a general‐purpose planning system
Authors: Mosleh‐Shirazi M. Amin , Hansen Vibeke N. , Childs Peter J. , Warrington Alan P. , Saran Frank H. 
Published: December 2008

The purpose of this paper is to report on commissioning and clinical implementation of a customized system for pediatric stereotactic conformal radiotherapy (SCRT). The system is based on the Pinnacle treatment‐planning system and its interfaces with other equipment: (1) Beam models were optimized for our compact blocking system and a new LINAC. (2) Three CT‐to‐density conversion tables were evaluated, one using tabulated data for a commercial phantom, the second including additional points from the manufacturer's data for the inserts in an in‐house phantom, and the third using measured densities for the in‐house phantom materials combined with tabulated data for the commercial phantom. (3) Blocks were transferred to a computerized block cutter using in‐house software that extracted the block shape from the export file and custom‐fitted the additional necessary shapes. (4) In the absence of a DICOM RT Image link, a method based on screen data capture was used to export digitally reconstructed radiographs (DRRs) to two portal imaging systems for treatment verification. Lens shielding by multileaf collimation in the anterior‐posterior isocenter verification field was investigated. (1) Computed dose distributions using the beam models agreed with measurements well within published acceptability criteria. A difference of up to 1.0 mm was measured between the beam's eye views of aperture blocks and computed 50% isodose contours for a dose calculation grid. (2) The third table, which included measured densities, improved the accuracy of the calculated isocenter dose by up to 0.5% in typical patient SCRT treatments and up to 1.0% in a phantom with 5‐cm diameter inhomogeneity inserts. (3) The block export and customization process was shown to introduce no additional uncertainty. A 1‐mm block production uncertainty was measured using film dosimetry on six blocks. (4) The DRR transfer method did not introduce uncertainty into the process. Verification field shielding reduced lens dose by 12 to 15 times. In conclusion, this customized system for planning and verification of pediatric SCRT provides a high level of precision as well as reasonable practical efficiency.PACS numbers: 87.53.Kn, 87.53.Ly, 87.53.Oq, 87.53.Tf, 87.53.Uv
Clinical validation of the normalized mutual information method for registration of CT and MR images in radiotherapy of brain tumors
Authors: Veninga Theo , Huisman Henkjan , van der Maazen Richard W. M. , Huizenga Henk 
Published: December 2008

Image registration integrates information from different imaging modalities and has the potential to improve determination of target volume in radiotherapy planning. This paper describes the implementation and validation of a 3D fully automated registration procedure in the process of radiotherapy treatment planning of brain tumors. Fifteen patients with various brain tumors received computed tomography (CT) and magnetic resonance (MR) brain imaging before the start of radiotherapy. First, the normalized mutual information (NMI) method was used for image registration. Registration accuracy was estimated by performing statistical analysis of coordinate differences between CT and MR anatomical landmarks along the x‐, y‐ and z‐axes. Second, a visual validation protocol was developed to validate the quality of individual registration solutions, and this protocol was tested in a series of 36 CT‐MR registration procedures with intentionally applied registration errors. The mean coordinate differences between CT and MR landmarks along the x‐ and y‐axes were in general within 0.5 mm. The mean coordinate differences along the z‐axis were within 1.0 mm, which is of the same magnitude as the applied slice thickness in scanning. In addition, the detection of intentionally applied registration errors by employment of a standardized visual validation protocol resulted in low false‐negative and low false‐positive rates. Application of the NMI method for the brain results in excellent automatic registration accuracy, and the method has been incorporated into the daily routine at our institution. A standardized validation protocol ensures the quality of individual registrations by detecting registration errors with high sensitivity and specificity. This protocol is proposed for the validation of other linear registration methods.PACS numbers: 87.53.Xd, 87.57.Gg
Compensators: An alternative IMRT delivery technique
Authors: Chang Sha X. , Cullip Timothy J. , Deschesne Katharin M. , Miller Elizabeth P. , Rosenman Julian G. 
Published: December 2008

Seven years of experience in compensator intensity‐modulated radiotherapy (IMRT) clinical implementation are presented. An inverse planning dose optimization algorithm was used to generate intensity modulation maps, which were delivered via either the compensator or segmental multileaf collimator (MLC) IMRT techniques. The in‐house developed compensator‐IMRT technique is presented with the focus on several design issues. The dosimetry of the delivery techniques was analyzed for several clinical cases. The treatment time for both delivery techniques on Siemens accelerators was retrospectively analyzed based on the electronic treatment record in LANTIS for 95 patients. We found that the compensator technique consistently took noticeably less time for treatment of equal numbers of fields compared to the segmental technique. The typical time needed to fabricate a compensator was 13 min, 3 min of which was manual processing. More than 80% of the approximately 700 compensators evaluated had a maximum deviation of less than 5% from the calculation in intensity profile. Seventy‐two percent of the patient treatment dosimetry measurements for 340 patients have an error of no more than 5%. The pros and cons of different IMRT compensator materials are also discussed. Our experience shows that the compensator‐IMRT technique offers robustness, excellent intensity modulation resolution, high treatment delivery efficiency, simple fabrication and quality assurance (QA) procedures, and the flexibility to be used in any teletherapy unit.PACS numbers: 87.53Mr, 87.53Tf
LINAC‐based stereotactic radiosurgery for treatment of trigeminal neuralgia
Authors: Gerbi Bruce J. , Higgins Patrick D. , Cho Kwan H. , Hall Walter A. 
Published: December 2008

Trigeminal neuralgia (TN) is a disabling pain condition that has classically been treated using either surgical or medical techniques. Several researchers have shown that stereotactically delivered radiation can be an effective tool in the amelioration of this condition. For these studies, the Gamma Knife was used to deliver the radiation treatment. The target location was designated as the proximal nerve at the root entry zone, and doses greater than 70 Gy to the maximum point in a single fraction were found to be effective in controlling pain in 80% of the patients treated. LINAC‐based stereotactic radiosurgery has been notably absent from the treatment of TN, even though it has many similarities to Gamma Knife‐based stereotactic radiosurgery.The aim of this paper is to describe our LINAC‐based stereotactic technique for treatment of TN. We also compare treatment of TN using our technique to that using the Gamma Knife. We found that a LINAC‐based treatment of TN can be accomplished with accuracy comparable to treatments delivered using the Gamma Knife. The dose distributions are essentially equivalent for the two treatment approaches. The LINAC‐based system is easy to plan and offers the ability to reduce the involvement of sensitive structures from the treatment fields as well as the Gamma Knife system does. A disadvantage of the LINAC‐based system is the time involved for treatment.PACS number: 87.53.Tf 87.56.Da
Quality assurance: Fundamental reproducibility tests for 3D treatment‐planning systems
Authors: Able Charles M. , Thomas Michael D. 
Published: December 2008

The use of image‐based 3D treatment planning has significantly increased the complexity of commercially available treatment‐planning systems (TPSs). Medical physicists have traditionally focused their efforts on understanding the calculation algorithm; this is no longer possible. A quality assurance (QA) program for our 3D treatment‐planning system (ADAC Pinnacle3) is presented. The program is consistent with the American Association of Physicists in Medicine Task Group 53 guidelines and balances the cost‐versus‐benefit equation confronted by the clinical physicist in a community cancer center environment. Fundamental reproducibility tests are presented as required for a community cancer center environment using conventional and 3D treatment planning. A series of nondosimetric tests, including digitizer accuracy, image acquisition and display, and hardcopy output, is presented. Dosimetric tests include verification of monitor units (MUs), standard isodoses, and clinical cases. The tests are outlined for the Pinnacle3 TPS but can be generalized to any TPS currently in use. The program tested accuracy and constancy through several hardware and software upgrades to our TPS. This paper gives valuable guidance and insight to other physicists attempting to approach TPS QA at fundamental and practical levels.PACS numbers: 87.53.Tf, 87.53.Xd
Effects of field parameters on IMRT plan quality for gynecological cancer: A case study
Authors: Fung Albert Y.C. , Enke Charles A. , Ayyangar Komanduri M. , Thompson Robert B. , Zhen Weining , Raman Natarajan V. , Djajaputra David , Li Sicong , Nehru Ramasamy M. , Pillai Sushakumari , Sourivong Paul , Headley Mary , Yager Ann L. 
Published: December 2008

Traditional external beam radiotherapy of gynecological cancer consists of a 3D, four‐field‐box technique. The radiation treatment area is a large region of normal tissue, with greater inhomogeneity over the treatment volume, which could benefit more with intensity‐modulated radiation therapy (IMRT). This is a case report of IMRT planning for a patient with endometrial cancer. The planning target volume (PTV) spanned the intrapelvic and periaortic lymph nodes to a 33‐cm length. Planning and treatment were accomplished using double isocenters. The IMRT plan was compared with a 3D plan, and the effects of field parameters were studied. Delineated anatomical contours included the intrapelvic nodes (PTV), bone marrow, small bowel, bladder, rectum, sigmoid colon, periaortic nodes (PTV), spinal cord, left kidney, right kidney, large bowel, liver, and tissue (excluding the PTVs). Comparisons were made between IMRT and 3D plans, 23‐MV and 6‐MV energies, zero and rotated collimator angles, different numbers of segments, and opposite gantry angle configurations. The plans were evaluated based on dose‐volume histograms (DVHs). Compared with the 3D plan, the IMRT plan had superior dose conformity and spared the bladder and sigmoid colon embedded in the intrapelvic nodes. The higher energy (23 MV) reduced the dose to most critical organs and delivered less integral dose. Zero collimator angles resulted in a better plan than “optimized” collimator angles, with lower dose to most of the normal structures. The number of segments did not have much effect on isodose distribution, but a reasonable number of segments was necessary to keep treatment time from being prohibitively long. Gantry angles, when evenly spaced, had no noticeable effect on the plan. The patient tolerated the treatment well, and the initial complete blood count was favorable. Our results indicated that large‐volume tumor sites may also benefit from precise conformal delivery of IMRT.PACS numbers: 87.53.Kn, 87.53.Tf
Density scaling artifacts in dosimetry calculations
Authors: Dickof Peter 
Published: December 2008

Quality assurance dosimetry often requires the comparison of measured doses with those calculated by a treatment‐planning system for phantoms of density other than 1.000 g/cm3. The presence of an artifact in the Pinnacle3 treatment‐planning system can lead to systematic errors in such cases.a These errors are also present, although reduced in magnitude, in heterogeneous media.PACS: 87.53.Bn, 87.53.Xd
Treatment‐planning considerations for prostate implants with the new linear RadioCoil™ brachytherapy source
Authors: Meigooni Ali S. , Awan Shahid B. , Rachabatthula Venkata , Koona Rafiq A. 
Published: December 2008

Recently, various linear source models, for example, RadioCoil™, have been introduced to overcome the shortcomings of traditional “seed” type interstitial prostate brachytherapy implants, such as migration and clumping of the seeds. However, the existing prostate treatment‐planning systems have not been updated to perform dose calculation for implants with linear sources greater than 1.0 cm in length. In these investigations, two new models are developed for 3D dose calculation for a prostate implant with linear brachytherapy sources using the commercially available treatment‐planning systems. The proposed models are referred to as the linear‐segmented source (LSS) model and the point‐segmented source (PSS) model. The calculated dose distributions obtained by these models for a single linear source have been validated by their comparison with the Monte Carlo–simulated data. Moreover, these models were used to calculate the dose distributions for a multilinear source prostate implant, and the results were compared to “seed” type implants. The results of these investigations show that the LSS model better approximates the linear sources than the PSS model. Moreover, these models have shown a better approximation of the dose distribution from a linear source for 0.5 cm source segments as compared to 1.0 cm source segments. However, for the points close to the longitudinal axis of the source located outside the region bounded by the active length, both models show differences of approximately . These deficiencies are attributed to the limitations of the TG43 formalism for elongated sources.PACS number: 87.53.‐j
Evaluation of dose delivery accuracy of Gamma Knife by polymer gel dosimetry
Authors: Watanabe Yoichi , Akimitsu Tomohide , Hirokawa Yutaka , Mooij Rob B. , Perera G. Mark 
Published: December 2008

The BANG™ polymer gel dosimeter was used to evaluate 3D absorbed dose distributions in tissue delivered with Gamma Knife stereotactic radiosurgery systems. We compared dose distributions calculated with Leksell GammaPlan (LGP) treatment‐planning software with dose distributions measured with the polymer gel dosimeter for single‐shot irradiations. Head‐sized spherical glass vessels filled with the polymer gel were irradiated with Gamma Knife. The phantoms were scanned with a 1.0T MRI scanner. The Hahn spin‐echo sequence with two echoes was used for the MRI scans. Calibration relations between the spin‐spin relaxation rate and the absorbed dose were obtained by using small cylindrical vials, which were filled with the polymer gel from the same batch as for the spherical phantom. We made voxel‐by‐voxel comparisons of measured and calculated dose distributions for dose matrix elements. With the 3D dose data we calculated the tumor control probability (TCP) and normal tissue complication probability (NTCP) for a simple model. For the maximum dose of 100 Gy, the mean and one standard deviation of differences between the measured and the calculated doses were the following: Gy, and for 8‐mm, 14‐mm, and 18‐mm collimators, respectively. Tumor control probability values for measurements were smaller than the calculations by 0% to 7%, whereas NTCP values were larger by 7% to 24% for four of six experiments.PACS numbers: 87.53.‐j, 87.53.Dq, 87.53.Ly