APPLICATION OF QUERCETIN FOR CORRECTION OF THE IMPAIRMENT OF THE FUNCTIONAL STATE OF THE ENDOTHELIUS OF VESSELS (CLINICAL AND EXPERIMENTAL STUDY). / ZASTOSUVANNIa KVERTsETYNU DLIa KOREKTsIÏ PORUShEN' FUNKTsIONAL'NOGO STANU ENDOTELIIu SUDYN (KLINIKO-EKSPERYMENTAL'NE DOSLIDZhENNIa).

OBJECTIVE: in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS). MATERIAL AND METHODS: Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo. RESULTS: Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function. CONCLUSIONS: Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT.

Calcification of the thoracic aorta on low-dose chest CT predicts severe COVID-19.

BACKGROUND: Cardiovascular comorbidity anticipates poor prognosis of SARS-CoV-2 disease (COVID-19) and correlates with the systemic atherosclerotic transformation of the arterial vessels. The amount of aortic wall calcification (AWC) can be estimated on low-dose chest CT. We suggest quantification of AWC on the low-dose chest CT, which is initially performed for the diagnosis of COVID-19, to screen for patients at risk of severe COVID-19. METHODS: Seventy consecutive patients (46 in center 1, 24 in center 2) with parallel low-dose chest CT and positive RT-PCR for SARS-CoV-2 were included in our multi-center, multi-vendor study. The outcome was rated moderate (no hospitalization, hospitalization) and severe (ICU, tracheal intubation, death), the latter implying a requirement for intensive care treatment. The amount of AWC was quantified with the CT vendor's software. RESULTS: Of 70 included patients, 38 developed a moderate, and 32 a severe COVID-19. The average volume of AWC was significantly higher throughout the subgroup with severe COVID-19, when compared to moderate cases (771.7 mm3 (Q1 = 49.8 mm3, Q3 = 3065.5 mm3) vs. 0 mm3 (Q1 = 0 mm3, Q3 = 57.3 mm3)). Within multivariate regression analysis, including AWC, patient age and sex, as well as a cardiovascular comorbidity score, the volume of AWC was the only significant regressor for severe COVID-19 (p = 0.004). For AWC > 3000 mm3, the logistic regression predicts risk for a severe progression of 0.78. If there are no visually detectable AWC risk for severe progression is 0.13, only. CONCLUSION: AWC seems to be an independent biomarker for the prediction of severe progression and intensive care treatment of COVID-19 already at the time of patient admission to the hospital; verification in a larger multi-center, multi-vendor study is desired.

Microwave Assisted Synthesis of 4-Phenylquinazolin-2(1H)-one Derivatives that Inhibit Vasopressor Tonus in Rat Thoracic Aorta.

Quinazolinones have pharmacological effects on vascular reactivity through different mechanisms. We synthesized 4-phenylquinazolin-2(1H)-one derivatives under microwave irradiation and tested them on the rat thoracic aorta. The prepared compounds 2a-2f were obtained in about 1 h with suitable yields (31-92%). All derivatives produced vasorelaxant effects with IC50 values ranging from 3.41 ± 0.65 µM to 39.72 ± 6.77 µM. Compounds 2c, 2e and 2f demonstrated the highest potency in endothelium-intact aorta rings (IC50 4.31 ± 0.90 µM, 4.94 ± 1.21 µM and 3.41 ± 0.65 µM respectively), and they achieved around 90% relaxation (30 µM). In aorta rings without an endothelium, the effect of compound 2f was abolished. Using the MTT assay to test for cell viability, only compound 2b induced cytotoxicity at the maximum concentration employed (30 µM). The results show that vasorelaxation by 4-phenylquinazolin-2(1H)-one derivatives might depend on the activation of a signalling pathway triggered by endothelium-derived factors.

Optimization of Whole-Body CT Examinations of Polytrauma Patients in Comparison with the Current Diagnostic Reference Levels. / Optimierung von Ganzkörper-CT-Untersuchungen an Polytraumatisierten anhand des Vergleichs mit den aktuellen diagnostischen Referenzwerten.

PURPOSE: Evaluation of the dose values of a polytrauma whole-body CT examination used in clinical practice with regard to the 2016 updated diagnostic reference levels and reduction of the mean exposure levels using simple optimization steps. MATERIALS AND METHODS: In each case, 100 exposure values before and after dose optimization were compared with the old and new diagnostic reference levels. The grayscale values and the signal-to-noise ratio (SNR) were determined for the lung, the aortic arch and the liver. A visual assessment of the image quality was performed by two radiologists on the basis of a Likert scale (0 - non-diagnostic, 1 - poor visualization, 2 - moderate visualization, 3 - good visualization, 4 - excellent visualization) for CT examinations both before and after optimization. RESULTS: The acquired exposure values after dose optimization were below the old and new diagnostic reference levels (1319.98 ±â€Š463.16 mGy ·â€Šcm) while the mean value of the exposure values before optimization (1774.96 ±â€Š608.78 mGy ·â€Šcm) exceeded the current diagnostic reference levels. The measured grayscale values (HU) were (before versus after optimization): lung - 833 HU vs. - 827 HU (p = 0.43), aortic arch 341 HU vs. 343 HU (p = 0.70) and liver 68 HU vs. 67 HU (p = 0.35). After dose optimization the SNR in the lung was minimally higher, while it was minimally lower in the two other regions than before the optimization. Visual assessment of the image quality showed almost identical values with 3.85 evaluation points before and 3.82 evaluation points after dose optimization (p = 0.57). CONCLUSION: Due to the updating of the diagnostic reference levels, an analysis of the own exposure values is necessary in order to be able to detect high values promptly and to initiate appropriate measures for dose reduction. Appropriate adaptation of the examination parameters with consideration of the necessary image quality allows a significant reduction of the radiation exposure in most cases, also on CT devices of older generations. KEY POINTS: · In many cases a dose reduction below the DRLs is already possible by optimizing the examination technique.. · In order to ensure a diagnostic image quality, the control of the image quality is unavoidable in a dose reduction.. · Through suitable parameter adjustments a compliance with the DRLs is also possible, using CT devices of older generation without iterative image reconstruction.. CITATION FORMAT: · Schäfer SB, Rudolph C, Kolodziej M et al. Optimization of Whole-Body CT Examinations of Polytrauma Patients in Comparison with the Current Diagnostic Reference Levels. Fortschr Röntgenstr 2019; 191: 1015 - 1025.

MWDS-2016: THE SLOW DISSOLUTION RATE FOR PLUTONIUM NITRATE INTAKES AT THE MAYAK FACILITY.

The slow dissolution rate of material deposited in the lung plays a key role in determining the eventual radiation dose received by the lung. It is therefore of great importance to establish a reliable value for this parameter, to incorporate into the latest Mayak Worker Dosimetry System (MWDS-2016). Disparate values have been obtained for the slow dissolution rate of plutonium nitrate. A volunteer study performed by Public Health England (PHE) and an analysis of United States Transuranium and Uranium Registries (USTUR) case 0269 have yielded slow dissolution rates in the region of 10-40 × 10-4 d-1. However, autopsies performed on 20 Mayak workers, exposed predominantly to nitrates, have resulted in estimates of slow dissolution rates of around 2.4 × 10-4 d-1. Three hypotheses have been proposed to explain this discrepancy: (1) a slower dissolution rate in the interstitium, (2) a third exponential component in the dissolution function and (3) a small component of oxide in the aerosol to which Mayak 'nitrate' workers were exposed. This paper describes tests of these competing hypotheses. Bayesian methods have been applied to the following datasets: PHE volunteer data; Beagle dog data; USTUR cases and Mayak worker data. It is concluded that a mixture of oxide and nitrate material, with the oxide forming ~14% of the intake, best describes the Mayak dissolution rate, without introducing values for other parameters which conflict with other studies.

Tin-filtered low-dose chest CT to quantify macroscopic calcification burden of the thoracic aorta.

OBJECTIVES: To compare a low-dose, tin-filtered, nonenhanced, high-pitch Sn100 kVp CT protocol (Sn100) with a standard protocol (STP) for the detection of calcifications in the ascending aorta in patients scheduled for cardiac surgery. METHODS: Institutional Review Board approval for this retrospective study was waived and the study was HIPAA-compliant. The study included 192 patients (128 men; age 68.8 ± 9.9 years), of whom 87 received the STP and 105 the Sn100 protocol. Size-specific dose estimates (SSDE) and radiation doses were obtained using dose monitoring software. Two blinded readers evaluated image quality on a scale from 1 (low) to 5 (high) and the extent of calcifications of the ascending aorta on a scale from 0 (none) to 10 (high), subdivided into 12 anatomic segments. RESULTS: The Sn100 protocol achieved a mean SSDE of only 0.5 ± 0.1 mGy and 0.20 ± 0.04 mSv compared with the mean SSDE of 5.4 ± 2.2 mGy achieved with the STP protocol (p < 0.0001). Calcification burden was associated with age (p < 0.0001), but was independent of protocol with mean calcification scores of 0.48 ± 1.23 (STP) and 0.55 ± 1.25 (Sn100, p = 0.18). Reader agreement was very good (STP κ = 0.87 ± 0.02, Sn100 κ = 0.88 ± 0.01). The STP protocol provided a higher subjective image quality than the Sn100 protocol: STP median 4, interquartile range 4-5, vs. SN100 3, 3-4; p < 0.0001) and a slightly better depiction of calcification (STP 5, 4-5, vs. Sn100 4, 4-5; p < 0.0001). CONCLUSIONS: The optimized Sn100 protocol achieved a mean SSDE of only 0.5 ± 0.1 mGy while the depiction of calcifications remained good, and there was no systematic difference in calcification burden between the two protocols. KEY POINTS: • Tin-filtered, low-dose CT can be used to assess aortic calcifications before cardiac surgery • An optimized Sn100 protocol achieved a mean SSDE of only 0.5 ± 0.1 mGy • The depiction of atherosclerosis of the thoracic aorta was similar with both protocols • The depiction of relevant thoracic pathologies before cardiac surgery was similar with both protocols.

Hypotensive acute effect of photobiomodulation therapy on hypertensive rats.

The purpose of this study was to evaluate the acute effect of photobiomodulation therapy (PBM) on arterial pressure in hypertensive and normotensive rats with application in an abdominal region. Normotensive (2K) and hypertensive (2K-1C) wistar rats were treated with PBM. Systolic arterial pressure (SAP), diastolic arterial pressure (DAP), mean arterial pressure (MAP) and heart rate (HR) were measured before, during and after PBM application. The nitric oxide (NO) serum concentration was measured before and after PBM application. Vascular reactivity study was performed in isolated thoracic aortas. Aluminum gallium arsenide (GaAlAs) diode laser was used, at 660nm wavelength and 100mW optical output. The PBM application induced a decrease of SAP in 2K-1C rats. In 2K rats, the PBM application had no effect on SAP, DAP and MAP. Moreover, the magnitude of hypotensive effect was higher in 2K-1C than in 2K rats. The PBM application induced a decrease of HR in 2K-1C and 2K, with higher effect in 2K-1C rats. In 2K-1C, the hypotensive effect induced by PBM was longer than that obtained in 2K rats. PBM application induced an elevation of NO concentration in serum from 2K-1C and 2K rats, with higher effect in 2K-1C. In isolated aortic rings PBM effect is dependent of NO release, and is not dependent of nitric oxide synthase (NOS) activation. Our results indicate that the abdominal acute application of PBM at 660nm is able to induce a long lasting hypotensive effect in hypertensive rats and vasodilation by a NO dependent mechanism.

The evolution of radiation dose over time: Measurement of a patient cohort undergoing whole-body examinations on three computer tomography generations.

OBJECTIVES: To evaluate and compare the radiation dose and image quality of whole-body-CT (WBCT) performed on the 3rd-generation dual-source-CT (DSCT) with 2nd-generation DSCT and 64-slices-Single-Source-CT (SSCT) in a large patient cohort. MATERIAL AND METHODS: Using a monitoring and tracking software 1451, 747 and 1861 patients scanned with a one-spiral-thorax-abdomen-pelvis-CT-examination on a 3rd-, 2nd-generation DSCT and SSCT, respectively, were extracted from the PACS server. For the intra-individual analysis, 203 patients on the 3rd-generation DSCT were identified. Out of those 203 patients, 155 had the same examination on the 2nd-generation DSCT, 91 patients had the same examination on the SSCT and 43 patients had an examination on all three CT-generations. Automatic tube current modulation was active on all three CT-generations, whereas automatic tube voltage selection was only available on both DSCT-generations. Dose was recorded by the size-specific-dose-estimate-method (SSDE); signal-to-noise-ratio (SNR) and contrast-to-noise-ratio (CNR) were calculated placing a ROI on the ascending aorta/liver and the subcutaneous adipose tissue at comparable level. Image quality of axillary and mediastinal lymph nodes and adrenal glands was assessed by two experienced radiologists. RESULTS: Subjective image quality was excellent throughout all three CT-generations (p=0.38-0.98). Quantitative image quality in both DSCT generations was superior to SSCT (p<0.001). SNR and CNR in the liver parenchyma were superior in the 3rd-generation DSCT compared to the 2nd generation DSCT (p<0.001), whereas there was no difference in the aorta. In the inter-individual analysis, CTDIvol was lower by 26.9% and 44.3% in the 3rd-generation DSCT, when compared to the 2nd-generation DSCT and SSCT, respectively; SSDE was lower by 31.5% and 51% in the 3rd-generation DSCT, when compared to the 2nd-generation DSCT and SSCT, respectively. In the intra-individual comparison CTDIVol in the 3rd-generation DSCT was lower by 33% and 45%, when compared to the 2nd-gneration DSCT and the SSCT, respectively. Consequently, SSDE in the 3rd-generation DSCT was lower by 29% and by 43% when compared to the 2nd-generation DSCT and SSCT, respectively. CONCLUSION: State-of-the-art CT-equipment substantially reduce radiation dose without affecting image quality.

Lethal Aorto-Right Ventricular Defect After Transcatheter Aortic Valve Implantation in a Patient With Radiation-Induced Porcelain Aorta: Notes of Caution.

A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery because of porcelain aorta. We successfully implanted an Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA), but the patient was readmitted 3 weeks later for heart failure with a continuous murmur on auscultation. Echocardiography showed a small defect between the aorta and the infundibulum of the right ventricle, which was also confirmed with aortography and computed tomography. Medical therapy was optimized; however, he died unexpectedly a few weeks later. We concluded that irradiated tissues are particularly fragile and require specific attention during transcatheter aortic valve implantation. Furthermore, this case suggests that a more aggressive closure should have been applied.

Concomitant Imaging Dose and Cancer Risk in Image Guided Thoracic Radiation Therapy.

PURPOSE: Kilovoltage cone beam computed tomography (CT) (kVCBCT) imaging guidance improves the accuracy of radiation therapy but imposes an extra radiation dose to cancer patients. This study aimed to investigate concomitant imaging dose and associated cancer risk in image guided thoracic radiation therapy. METHODS AND MATERIALS: The planning CT images and structure sets of 72 patients were converted to CT phantoms whose chest circumferences (Cchest) were calculated retrospectively. A low-dose thorax protocol on a Varian kVCBCT scanner was simulated by a validated Monte Carlo code. Computed doses to organs and cardiac substructures (for 5 selected patients of various dimensions) were regressed as empirical functions of Cchest, and associated cancer risk was calculated using the published models. The exposures to nonthoracic organs in children were also investigated. RESULTS: The structural mean doses decreased monotonically with increasing Cchest. For all 72 patients, the median doses to the heart, spinal cord, breasts, lungs, and involved chest were 1.68, 1.33, 1.64, 1.62, and 1.58 cGy/scan, respectively. Nonthoracic organs in children received 0.6 to 2.8 cGy/scan if they were directly irradiated. The mean doses to the descending aorta (1.43 ± 0.68 cGy), left atrium (1.55 ± 0.75 cGy), left ventricle (1.68 ± 0.81 cGy), and right ventricle (1.85 ± 0.84 cGy) were significantly different (P<.05) from the heart mean dose (1.73 ± 0.82 cGy). The blade shielding alleviated the exposure to nonthoracic organs in children by an order of magnitude. CONCLUSIONS: As functions of patient size, a series of models for personalized estimation of kVCBCT doses to thoracic organs and cardiac substructures have been proposed. Pediatric patients received much higher doses than did the adults, and some nonthoracic organs could be irradiated unexpectedly by the default scanning protocol. Increased cancer risks and disease adverse events in the thorax were strongly related to higher imaging doses and smaller chest dimensions.

Acceleration of atherogenesis in ApoE-/- mice exposed to acute or low-dose-rate ionizing radiation.

There is epidemiological evidence for increased non-cancer mortality, primarily due to circulatory diseases after radiation exposure above 0.5 Sv. We evaluated the effects of chronic low-dose rate versus acute exposures in a murine model of spontaneous atherogenesis. Female ApoE-/- mice (60 days) were chronically irradiated for 300 days with gamma rays at two different dose rates (1 mGy/day; 20 mGy/day), with total accumulated doses of 0.3 or 6 Gy. For comparison, age-matched ApoE-/- females were acutely exposed to the same doses and sacrificed 300 days post-irradiation. Mice acutely exposed to 0.3 or 6 Gy showed increased atherogenesis compared to age-matched controls, and this effect was persistent. When the same doses were delivered at low dose rate over 300 days, we again observed a significant impact on global development of atherosclerosis, although at 0.3 Gy effects were limited to the descending thoracic aorta. Our data suggest that a moderate dose of 0.3 Gy can have persistent detrimental effects on the cardiovascular system, and that a high dose of 6 Gy poses high risks at both high and low dose rates. Our results were clearly nonlinear with dose, suggesting that lower doses may be more damaging than predicted by a linear dose response.

Irradiation of existing atherosclerotic lesions increased inflammation by favoring pro-inflammatory macrophages.

BACKGROUND AND PURPOSE: Recent studies have shown an increased incidence of localized atherosclerosis and subsequent cardiovascular events in cancer patients treated with thoracic radiotherapy. We previously demonstrated that irradiation accelerated the development of atherosclerosis and predisposed to an inflammatory plaque phenotype in young hypercholesterolemic ApoE(-/-) mice. However, as older cancer patients already have early or advanced stages of atherosclerosis at the time of radiotherapy, we investigated the effects of irradiation on the progression of existing atherosclerotic lesions in vivo. MATERIAL AND METHODS: ApoE(-/-) mice (28 weeks old) received local irradiation with 14 or 0 Gy (sham-treated) at the aortic arch and were examined after 4 and 12 weeks for atherosclerotic lesions, plaque size and phenotype. Moreover, we investigated the impact of irradiation on macrophage phenotype (pro- or anti-inflammatory) and function (efferocytotic capacity, i.e. clearance of apoptotic cells) in vitro. RESULTS: Irradiation of existing lesions in the aortic arch resulted in smaller, macrophage-rich plaques with intraplaque hemorrhage and increased apoptosis. In keeping with the latter, in vitro studies revealed augmented polarization toward pro-inflammatory macrophages after irradiation and reduced efferocytosis by anti-inflammatory macrophages. In addition, considerably more lesions in irradiated mice were enriched in pro-inflammatory macrophages. CONCLUSIONS: Irradiation of existing atherosclerotic lesions led to smaller but more inflamed plaques, with increased numbers of apoptotic cells, most likely due to a shift toward pro-inflammatory macrophages in the plaque.

Profuse mediastinal hemorrhage due to mediastinitis after a sternal infection.

A 79-year-old female patient was admitted because of profuse bleeding from a skin defect in the anterior chest due to a deep sternal wound infection. Eighteen years earlier, she had undergone irradiation to treat a sternal metastasis from breast cancer. Computed tomography (CT) showed the extravasation of iodinated contrast material from the ascending aorta. The patient underwent an immediate thoracotomy and recovered. This report presents a very rare case of massive bleeding from the thoracic aorta due to a mediastinal infection after irradiation for sternal metastasis from breast cancer.

[Effect of Korargin on reactivity of isolation aorta of adult and old irradiated rats].

Introduction to the diet of adult (7-8 months) and old (24-26 months) male rats for 30 days after a single R-irradiation at a dose of 5 Gy of preparation "Korargin" (whose active ingredients are L-arginine, contributing to the prevention of endothelial dysfunction, and inosine) in old irradiated rats significantly increased the relaxation of isolated segments of thoracic aorta by the action of acetylcholine, sodium nitroprusside and insulin. In adults irradiated animals this effect was not observed. Vasoconstriction response of isolated segments of thoracic aorta to norepinephrine was decreased in isolated segments of thoracic aorta by adults and old irradiated rats compared with controls, and application of korargin had no significant effect. Thus, in old irradiated rats, in contrast to adult irradiated animals, the use of korargin increased of vascular sensitiveness to act of endothelial-dependent and endothelial-nondependent vazodilatators, helped to preserve of endothelial function and increase the capacity of vazodilatator potential.

The BK(Ca) channels deficiency as a possible reason for radiation-induced vascular hypercontractility.

It is likely that large-conductance Ca²âº-activated K⁺ (BK(Ca)) channels channelopathy tightly involved in vascular malfunctions and arterial hypertension development. In the present study, we compared the results of siRNAs-induced α-BK(Ca) gene silencing and vascular abnormalities produced by whole-body ionized irradiation in rats. The experimental design comprised RT-PCR and patch clamp technique, thoracic aorta smooth muscle (SM) contractile recordings and arterial blood pressure (BP) measurements on the 30th day after whole body irradiation (6Gy) and following siRNAs KCNMA1 gene silencing in vivo. The expression profile of BK(Ca) mRNA transcripts in SM was significantly decreased in siRNAs-treated rats in a manner similar to irradiated SM. In contrast, the mRNA levels of K(v) and K(ATP) were significantly increased while L-type calcium channels mRNA transcripts demonstrated tendency to increment. The SMCs obtained from irradiated animals and after KCNMA1 gene silencing showed a significant decrease in total K⁺ current density amplitude. Paxilline (500 nM)-sensitive components of outward current were significantly decreased in both irradiated and gene silencing SMCs. KCNMA1 gene silencing increased SM sensitivity to norepinephrine while Ach-induced relaxation had decreased. The silencing of KCNMA1 had no significant effect on BP while radiation produced sustained arterial hypertension. Therefore, radiation alters the form and function of the BK(Ca) channel and this type of channelopathy may contribute to related vascular abnormalities. Nevertheless, it is unlikely that BK(Ca) can operate as a crucial factor for radiation-induced arterial hypertension.

[The endothelium-derived hyperpolarization factor as a reserve defence mechanism of vasodilatation under conditions of ionizing radiation].

The goal of this study was to determine the cellular mechanisms of vascular endothelial dysfunction in rats irradiated with gamma-rays. Acetylcholine (Ach)-induced relaxation of rat thoracic aorta rings was measured as a test of endothelial integrity and function. The data obtained allow suggest that endothelial function is impaired in aorta from g-irradiated rats mainly due to the loss of EDRF/NO-dependent, but not EDHF-dependent relaxation. It has been shown that r-irradiation reduced the Ach-induced NO-release measured as nitrite anion content. Experiments on isolated rat aortic smooth muscle cells using whole-cell patch clamp technique demonstrated that irradiation led to a significant decrease in outward potassium currents. However, gamma-ray irradiation was without effect on K(+)-current carried through apamine-sensitive channels while the current through charybdotoxin-sensitive channels was increased as compared to cells from control animals. The data suggest that EDHF is resistant to ionized radiation and may constitute a crucial reserve mechanism for maintenance of blood flow under radiation. Therefore, it is likely that the subsequent studies related to EDHF identification will be important for new drugs development and targeted pharmacological intervention at endothelium dysfunction in case of radiation impact.

Segmentation of the heart and great vessels in CT images using a model-based adaptation framework.

Recently, model-based methods for the automatic segmentation of the heart chambers have been proposed. An important application of these methods is the characterization of the heart function. Heart models are, however, increasingly used for interventional guidance making it necessary to also extract the attached great vessels. It is, for instance, important to extract the left atrium and the proximal part of the pulmonary veins to support guidance of ablation procedures for atrial fibrillation treatment. For cardiac resynchronization therapy, a heart model including the coronary sinus is needed. We present a heart model comprising the four heart chambers and the attached great vessels. By assigning individual linear transformations to the heart chambers and to short tubular segments building the great vessels, variable sizes of the heart chambers and bending of the vessels can be described in a consistent way. A configurable algorithmic framework that we call adaptation engine matches the heart model automatically to cardiac CT angiography images in a multi-stage process. First, the heart is detected using a Generalized Hough Transformation. Subsequently, the heart chambers are adapted. This stage uses parametric as well as deformable mesh adaptation techniques. In the final stage, segments of the large vascular structures are successively activated and adapted. To optimize the computational performance, the adaptation engine can vary the mesh resolution and freeze already adapted mesh parts. The data used for validation were independent from the data used for model-building. Ground truth segmentations were generated for 37 CT data sets reconstructed at several cardiac phases from 17 patients. Segmentation errors were assessed for anatomical sub-structures resulting in a mean surface-to-surface error ranging 0.50-0.82mm for the heart chambers and 0.60-1.32mm for the parts of the great vessels visible in the images.

Concomitant trastuzumab with thoracic radiotherapy: a morphological and functional study.

BACKGROUND: The purpose of this study is to elucidate if there is an additive or supra-additive toxic effects of radiotherapy (RT) and trastuzumab (T) on vascular structures when used concomitantly. METHODS: Female Wistar albino rats were treated with either 8 or 15 Gy of thoracic RT. T was applied i.p. with a dose of 6 mg/kg 2 h before RT. Four rats in each arm were killed at 6th h, 21st and 70th days after irradiation and thoracic aorta of each animal was dissected for electron microscopy. In addition, functional studies for evaluating the relaxation and contraction were carried out 21 days after RT. RESULTS: Only 15-Gy RT dose groups showed significant difference in terms of functional deterioration as more contraction than the others (P < 0.05) without any difference between RT and RT + T. However, T produced additional deficit in relaxation when added to RT, which was considered near significant (P: 0.0502). Electron microscopy showed endothelial and subendotelial damage signs in 15-Gy dose groups. T + 15-Gy arm showed more pronounced endothelial cell damage than 15-Gy RT-only arm, 70 days after RT. CONCLUSION: T and high-dose RT may lead to vascular damage that seems at least additive.