Megavoltage 2D topographic imaging: An attractive alternative to megavoltage CT for the localization of breast cancer patients treated with TomoDirect

PurposeTo show the usefulness of topographic 2D megavoltage images (MV2D) for the localization of breast cancer patients treated with TomoDirect (TD), a radiotherapy treatment technique with fixed-angle beams performed on a TomoTherapy system.MethodsA method was developed to quickly localize breast cancer patients treated with TD by registering the MV2D images produced before a TD treatment with reference images reconstructed from a kilovoltage CT simulation scanner and by using the projection of the beam-eye-view TD treatment field. Dose and image quality measurements were performed to determine the optimal parameters for acquiring MV2D images. A TD treatment was simulated on a chest phantom equipped with a breast attachment. MVCT and MV2D images were performed for 7 different shifted positions of the phantom and registered by 10 different operators with the simulation kilovoltage CT images.ResultsCompared to MVCT, MV2D imaging reduces the dose by a factor of up to 45 and the acquisition time by a factor of up to 49. Comparing the registration shift values obtained for the phantom images obtained with MVCT in the coarse mode to those obtained with MV2D, the mean difference is 1.0 ± 1.1 mm, −1.1 mm ± 1.1, and −0.1 ± 2.2 mm, respectively, in the lateral, longitudinal, and vertical directions.ConclusionsWith dual advantages (very fast imaging and a potentially reduced dose to the heart and contralateral organs), MV2D topographic images may be an attractive alternative to MVCT for the localization of breast cancer patients treated with TomoDirect.     

Validation of a method for “dose of the day” calculation in head-neck tomotherapy by using planning ct-to-MVCT deformable image registration

PurposeThe aim of this study was to test the feasibility and dosimetric accuracy of a method that employs planning CT-to-MVCT deformable image registration (DIR) for calculation of the daily dose for head and neck (HN) patients treated with Helical Tomotherapy (HT).MethodsFor each patient, the planning kVCT (CTplan) was deformably registered to the MVCT acquired at the 15th therapy session (MV15) with a B-Spline Free Form algorithm using Mattes mutual information (open-source software 3D Slicer), resulting in a deformed CT (CTdef). On the same day as MVCT15, a kVCT was acquired with the patient in the same treatment position (CT15). The original HT plans were recalculated both on CTdef and CT15, and the corresponding dose distributions were compared; local dose differences <2% of the prescribed dose (DD2%) and 2D/3D gamma-index values (2%-2 mm) were assessed respectively with Mapcheck SNC Patient software (Sun Nuclear) and with 3D-Slicer.ResultsOn average, 87.9% ± 1.2% of voxels were found for DD2% (on average 27 slices available for each patient) and 94.6% ± 0.8% of points passed the 2D gamma analysis test while the 3D gamma test was satisfied in 94.8% ± 0.8% of body’s voxels.ConclusionsThis study represents the first demonstration of the dosimetric accuracy of kVCT-to-MVCT DIR for dose of the day computations. The suggested method is sufficiently fast and reliable to be used for daily delivered dose evaluations in clinical strategies for adaptive Tomotherapy of HN cancer.     

First proof of bismuth oxide nanoparticles as efficient radiosensitisers on highly radioresistant cancer cells

This study provides the first proof of the novel application of bismuth oxide as a radiosensitiser. It was shown that on the highly radioresistant 9L gliosarcoma cell line, bismuth oxide nanoparticles sensitise to both kilovoltage (kVp) or megavoltage (MV) X-rays radiation. 9L cells were exposed to a concentration of 50 μg.mL⁻¹ of nanoparticle before irradiation at 125 kVp and 10 MV. Sensitisation enhancement ratios of 1.48 and 1.25 for 125 kVp and 10 MV were obtained in vitro, respectively. The radiation enhancement of the nanoparticles is postulated to be a combination of the high Z nature of the bismuth (Z = 83), and the surface chemistry. Monte Carlo simulations were performed to elucidate the physical interactions between the incident radiation and the nanoparticle. The results of this work show that Bi₂O₃ nanoparticles increase the radiosensitivity of 9L gliosarcoma tumour cells for both kVp and MV energies. Monte Carlo simulations demonstrate the advantage of a platelet morphology.     

Dosimetric comparison of RapidPlan and manually optimized plans in volumetric modulated arc therapy for prostate cancer

PurposeThis study evaluated whether RapidPlan based plans (RP plans) created by a single optimization, are usable in volumetric modulated arc therapy (VMAT) for patients with prostate cancer.MethodsWe used 51 previously administered VMAT plans to train a RP model. Thirty RP plans were created by a single optimization without planner intervention during optimization. Differences between RP plans and clinical manual optimization (CMO) plans created by an experienced planner for the same patients were analyzed (Wilcoxon tests) in terms of homogeneity index (HI), conformation number (CN), D_95%, and D_2% to planning target volume (PTV), mean dose, V_50Gy, V_70Gy, V_75Gy, and V_78Gy to rectum and bladder, monitor unit (MU), and multi-leaf collimator (MLC) sequence complexity.ResultsRP and CMO values for PTV D_95%, PTV D_2%, HI, and CN were significantly similar (p < 0.05 for all). RP mean dose, V_50Gy, and V_70Gy to rectum were superior or comparable to CMO values; RP V_75Gy and V_78Gy were higher than in CMO plans (p < 0.05). RP bladder dose-volume parameter values (except V_78Gy) were lower than in CMO plans (p < 0.05). MU values were RP: 730 ± 55 MU and CMO: 580 ± 37 MU (p < 0.05); and MLC sequence complexity scores were RP: 0.25 ± 0.02 and CMO: 0.35 ± 0.03 (p < 0.05).ConclusionsRP plans created by a single optimization were clinically acceptable in VMAT for patient with prostate cancer. Our simple model could reduce optimization time, independently of planner’s skill and knowledge.     

Découverte fortuite de fixations colorectales focales du FDG en TEP/TDM : corrélation aux données de la coloscopie

PurposeFDG-PET is an established tool for the diagnosis of recurrent or metastatic colorectal carcinoma. Several case series suggest that FDG-PET often detects incidental adenomatous polyps or colorectal adenocarcinomas. The aim of this study was to correlate unexpected colorectal foci of FDG uptake to pathology findings after systematic colonoscopy.Patients and methodsWe reviewed the records of 3541 patients who underwent FDG PET/CT in our institution over a 30-month period for the assessment of a known or suspected malignancy. In 85 of them, incidental, nodular shaped and well-circumscribed foci of abnormal uptake were identified in the area of the colon or rectum. Patients with segmental or diffuse abnormal colorectal uptake were excluded, as well as patients with known benign or malignant colorectal disease. Colonoscopy and complete pathology report was available in 29 patients. Maximal standardized uptake value (SUV_max) was measured in all lesions.ResultsUnexpected colorectal foci of FDG uptake were associated with colonoscopic abnormalities in 23 patients (true positive rate: 79 %). Adenocarcinomas were found in six patients (SUV_max = 7.3 ± 2.6), tubulous adenomas in four patients (SUV_max = 7.3 ± 4.9) and tubulovillous adenomas in 12 patients (SUV_max = 4.2 ± 1.1). Hyperplasic polyps with no sign of dysplasia were found in the last patient (SUV_max = 3.3). Concomitant CT abnormalities were found on PET/CT fusion in eight patients and consisted of wall thickening (n = 5) or nodular mass (n = 3). Conversely, PET was falsely positive in six patients (21 %), with no concomitant CT abnormalities and no abnormal findings at endoscopy (SUV_max = 6.2 ± 2.8, no significant difference with true positive lesions).ConclusionOur findings emphasize the need to perform a colonoscopy in front of incidental nodular colorectal foci of FDG uptake because malignant or pre-malignant neoplasms, which are not clinically apparent, are found in more than three-quarter of cases.     

Pharmacological evaluation of R(+)-pulegone on cardiac excitability: Role of potassium current blockage and control of action potential waveform

IntroductionR(+)-pulegone is a ketone monoterpene and it is the main constituent of essential oils in several plants. Previous studies provided some evidence that R(+)-pulegone may act on isolated cardiac myocytes. In this study, we evaluated in extended detail, the pharmacological effects of R(+)-pulegone on cardiac tissue.MethodsUsing in vivo measurements of rat cardiac electrocardiogram (ECG) and patch-clamp technique in isolated myocytes we determinate the influence of R(+)-pulegone on cardiac excitability.ResultsR(+)-pulegone delayed action potential repolarization (APR) in a concentration-dependent manner (EC₅₀ = 775.7 ± 1.48, 325.0 ± 1.30, 469.3 ± 1.91 μM at 10, 50 and 90% of APR respectively). In line with prolongation of APR R(+)-pulegone, in a concentration-dependent manner, blocked distinct potassium current components (transient outward potassium current (I_to), rapid delayed rectifier potassium current (I_Kr), inactivating steady state potassium current (I_ss) and inward rectifier potassium current (I_K1)) (EC₅₀ = 1441 ± 1.04; 605.0 ± 1.22, 818.7 ± 1.22; 1753 ± 1.09 μM for I_to, I_Kr, I_ss and I_K1, respectively). The inhibition occurred in a fast and reversible way, without changing the steady-state activation curve, but instead shifting to the left the steady-state inactivation curve (V_1/2 from −56.92 ± 0.35 to −67.52 ± 0.19 mV). In vivo infusion of 100 mg/kg R(+)-pulegone prolonged the QTc (∼40%) and PR (∼62%) interval along with reducing the heart rate by ∼26%.ConclusionTaken together, R(+)-pulegone prolongs the APR by inhibiting several cardiomyocyte K⁺ current components in a concentration-dependent manner. This occurs through a direct block by R(+)-pulegone of the channel pore, followed by a left shift on the steady state inactivation curve. Finally, R(+)-pulegone induced changes in some aspects of the ECG profile, which are in agreement with its effects on potassium channels of isolated cardiomyocytes.     

Dosimetric impact of 4DCT artifact in carbon-ion scanning beam treatment: Worst case analysis in lung and liver treatments

IntroductionWe evaluated the impact of 4DCT artifacts on carbon-ion pencil beam scanning dose distributions in lung and liver treatment.Methods & materials4DCT was performed in 20 liver and lung patients using area-detector CT (original 4DCT). 4DCT acquisition by multi-detector row CT was simulated using original 4DCT by selecting other phases randomly (plus/minus 20% phases). Since tumor position can move over the respiratory range in original 4DCT, mid-exhalation was set as reference phase. Total prescribed dose of 60 Gy (RBE) was delivered to the clinical target volume (CTV). Reference dose distribution was calculated with the original CT, and actual dose distributions were calculated with treatment planning parameters optimized using the simulated CT (simulated dose). Dose distribution was calculated by substituting these parameters into the original CT.ResultsFor liver cases, CTV-D95 and CTV-Dmin values for the reference dose were 97.6 ± 0.5% and 89.8 ± 0.6% of prescribed dose, respectively. Values for the simulated dose were significantly degraded, to 88.6 ± 14.0% and 46.3 ± 26.7%, respectively. Dose assessment results for lung cases were 84.8 ± 12.8% and 58.0 ± 24.5% for the simulated dose, showing significant degradation over the reference dose of 95.1 ± 1.5% and 87.0 ± 2.2%, respectively.Conclusions4DCT image quality should be closely checked to minimize degradation of dose conformation due to 4DCT artifacts. Medical staff should pay particular attention to checking the quality of 4DCT images as a function of respiratory phase, because it is difficult to recognize 4DCT artifact on a single phase in some cases     

Eye lens dose correlations with personal dose equivalent and patient exposure in paediatric interventional cardiology performed with a fluoroscopic biplane system

PurposeTo analyse the correlations between the eye lens dose estimates performed with dosimeters placed next to the eyes of paediatric interventional cardiologists working with a biplane system, the personal dose equivalent measured on the thorax and the patient dose.MethodsThe eye lens dose was estimated in terms of H_p(0.07) on a monthly basis, placing optically stimulated luminescence dosimeters (OSLDs) on goggles. The H_p(0.07) personal dose equivalent was measured over aprons with whole-body OSLDs. Data on patient dose as recorded by the kerma-area product (P_KA) were collected using an automatic dose management system. The 2 paediatric cardiologists working in the facility were involved in the study, and 222 interventions in a 1-year period were evaluated. The ceiling-suspended screen was often disregarded during interventions.ResultsThe annual eye lens doses estimated on goggles were 4.13 ± 0.93 and 4.98 ± 1.28 mSv. Over the aprons, the doses obtained were 10.83 ± 0.99 and 11.97 ± 1.44 mSv. The correlation between the goggles and the apron dose was R² = 0.89, with a ratio of 0.38. The correlation with the patient dose was R² = 0.40, with a ratio of 1.79 μSv Gy⁻¹ cm⁻². The dose per procedure obtained over the aprons was 102 ± 16 μSv, and on goggles 40 ± 9 μSv. The eye lens dose normalized to P_KA was 2.21 ± 0.58 μSv Gy⁻¹ cm⁻².ConclusionsMeasurements of personal dose equivalent over the paediatric cardiologist’s apron are useful to estimate eye lens dose levels if no radiation protection devices are typically used.     

Kinetic and thermodynamic analysis of the inhibitory effects of maltose,glucose, and related carbohydrates on wheat β-amylase

Inhibition of wheat β-amylase (WBA) by glucose and maltose was studied by kinetics and thermodynamics. The inhibitory effects of fructose, difructose, sucrose, trehalose, cellobiose, acarbose, and 1-deoxynojirimycin on WBA were also evaluated. The half maximal inhibitory concentrations (IC₅₀) of acarbose, maltose and glucose were 0.06 ± 0.01 M, 0.22 ± 0.09 M, and 1.41 ± 0.17 M, respectively. The inhibitor constant (K_i) and the thermodynamic parameters such as changes in Gibbs energy (ΔG), enthalpy (ΔH), and entropy (ΔS) of the dissociation reactions of the WBA-glucose and WBA-maltose complexes were temperature and pH-dependent. The dissociation reactions were endothermic and enthalpy-driven. Both glucose and maltose behaved as competitive inhibitors at pH 3.0 and 5.4 at a temperature of 25 °C with respective K_i values of 0.33 ± 0.02 M and 0.12 ± 0.03 M. In contrast, both sugars exhibited uncompetitive inhibition at pH 9 at a temperature of 25 °C with K_i values of 0.21 ± 0.03 M for glucose and 0.11 ± 0.04 M for maltose. The pH-dependence of the inhibition type and K_i values indicate that the ionizing groups of WBA influence drastically the interaction with these carbohydrates. This evidence enables us to consider temperature and pH in the WBA-catalyzed hydrolysis to manipulate the inhibition by end-product, maltose, and even by glucose.     

Clinical Markers Implying the Need for Treatment in Women with Gestational Diabetes Mellitus

ObjectiveTo assess the association of the point-of-care hemoglobin A_1c (POC A1C), fasting blood glucose (FBG), and BMI with fetal macrosomia and the need for medication in women with gestational diabetes (GDM).MethodsPOC A1C, FBG, and BMI values at GDM diagnosis and fetal weight at delivery were obtained for women identified from a prospective patient registry. These outcomes were compared between women who did not require medication for GDM and women who did require medication.ResultsMean values of POC A1C, FBG, and BMI in 67 patients who required medication were higher than those in 71 patients who did not require medication (POC A1C: 5.72 ± 0.45% vs 5.35 ± 0.46% [P < .001]; FBG: 97.4 ± 12.3 mg/dL vs 86.4 ± 9.5 mg/dL [P < .001]; BMI: 35.4 ± 6.4 kg/m2 vs 30.4 ± 6.2 kg/m2 [P < .001]). There was a modest correlation between POC A1C and FBG (Spearman rho 0.4, P < .001) and between POC A1C and BMI (Spearman rho 0.366, P < .001). Maternal POC A1C was not correlated with fetal weight at delivery (Spearman rho –0.010, P = .915).ConclusionsHigher POC A1C, FBG, and BMI values were associated with the need for medication in women with GDM. The use of clinical markers to assess glycemic control sooner in pregnancy may lead to the earlier identification of women at risk for GDM and earlier intervention to decrease the risk for complications. (Endocr Pract. 2012;18:62-65)     

Évaluation des paramètres et méthode de contrôle de qualité de la correction d’atténuation en tomographie par émission de positons

ObjectiveThe aim of this study is to evaluate the performance of the Computed Tomography based Attenuation Correction (CTAC) for Positron Emission Tomography (PET) data. Attenuation maps containing linear attenuation coefficients at 511 keV (LAC_511 keV) are calculated by trilinear conversion of Hounsfield Units (HU) obtained from CT slices after matrix size-reduction and gaussian filtering. Our work focusses on this trilinear conversion.Materials and methodsCT slices of an electron density phantom, composed of 17 cylindrical inserts made of different tissue-equivalent materials, were acquired using a Discovery ST4^® PET-CT. Data were processed with a customized version of CT quality control software, giving automatically the experimental conversion function: LAC_511 keV = f(HU). Furthermore, data from patient datasets were assessed using both smoothed CT slices and attenuation maps.ResultsLAC_511 keV extracted from phantom data are in good correlation with the expected theoretical values, except for the standard 10 mm diameter dense bone insert, where the obtained CTAC values are underestimated. Assuming a sample size issue, similar acquisitions were performed with a special 30 mm-diameter dense bone insert, confirming the underestimation as a consequence of the sample size. This effect, caused partly by a too smooth Gaussian filter of the CT images, could be limited by reducing the strength of the filter. Measurements from patients’ data showed the same underestimation of CAL_511 keV for high-density tissues.ConclusionWe assessed an underestimation of the CTAC obtained-values related to the sample size of the insert. A quality control was developed to this effect.     

Nonobese Young Females with Polycystic Ovary Syndrome Have Nutritive Microvascular Dysfunction: A Pilot Study

ObjectiveTo investigate nutritive microvascular function in young nonobese females with polycystic ovary syndrome (PCOS) and to correlate microvascular reactivity with sex steroids, inflammatory markers, and metabolic variables.MethodsFourteen nonobese females with PCOS (24.6 ± 2.7 years, body mass index [BMI] 23.7 ± 3.1 kg/ m²) and 13 age- and BMI-matched controls (22.8 ± 2.3 years, 22.5 ± 3.4kg/m2) underwent anthropometric, hormonal, and microvascular evaluations. The main outcome measures were capillary density, red blood cell velocity (RBCV) at resting and peak during postocclusive reactive hyperemia (RBCV_max), and time taken to reach RBCV_max (TRBCV_max).ResultsSubjects with PCOS had lower RBCV and higher TRBCV_max compared to controls, respectively (0.237 [0.220-0.324] vs. 0.362 [0.297-0.382] mm/s, F < .01) and (5 [5-6] vs. 4 [3-5] s, P < .05]. The free androgen index (FAI) and sex hormone-binding globulin (SHBG) level were different between groups. FAI correlated to RBCV_max (ρ = -0.49, P < .05) and to TRBCV_max (ρ = 0.41, P < .05). SHBG correlated with RBCV_max (ρ = 0.52, P < .01) while estradiol (E₂) levels correlated with RBCV (ρ = 0.80, P < .001) and RBCV_max (ρ = 0.46, P < .05).ConclusionMicrovascular dysfunction characterized by reduced RBCV_maxand prolonged TRBCV_maxwas present in young, nonobese PCOS subjects. FAI was associated with observed impairments, suggesting a possible common mechanism linking sex hormones and microvascular dysfunction. (Endocr Pract. 2014;20:1281-1289)     

Cytotoxic effects of stem bark extracts and pure compounds from Margaritaria discoidea on human ovarian cancer cell lines

Margaritaria discoidea (Baill.) G. L. Webster (Euphorbiaceae) is a well-known medicinal plant in Africa used for the treatment of various diseases. So far, no cytotoxic effects of plant extracts on cancer cell lines have been reported.Aim of the studyTo evaluate the cytotoxicity against human ovarian cancer cells of extracts of M. discoidea and characterize the major bioactive compounds.MethodsBoth organic and aqueous extracts of this plant were obtained by maceration. The sulforhodamine B cell proliferation assay was used for evaluation of their cytotoxic activities and the potential bioactive compounds were characterized by gas chromatography–mass spectrometry.ResultsThe organic extract of M. discoidea showed stronger cytotoxicity than the aqueous extract with IC₅₀ values of 14.4 ± 3.0, 14.2 ± 1.2 and 34.7 ± 0.5 µg/ml on OVCAR-8, A2780 and cisplatin-resistant A2780cis ovarian cancer cells, respectively. The organic extract was further subjected to bioassay-guided fractionation by partitioning with n-hexane, ethyl acetate, and n-butanol in water. The ethyl acetate fraction was the most potent on the three ovarian cancer cell lines. A GC–MS analysis of trimethylsilyl derivatives of this fraction indicated the presence of phenolic compounds such as gallic acid and the alkaloid securinine. The IC₅₀ values of these two compounds were determined to be in the range of 3–16 µM, which indicated that they could contribute to the cytotoxic activity of the extract of M. discoidea.ConclusionsThis study has evaluated the cytotoxicity of stem bark extracts of M. discoidea against ovarian cancer cells and provided a basis of further development of this plant for the treatment of ovarian cancer.     

The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat

AimThis study investigates the effects of montelukast sodium (MK) (CysLTLT1 receptor antagonist) on CCl₄induced hepatopathy on rat.Material and methodsWe worked on 4 groups of 10 Wistar male rats each. The groups received as follows: group I (control group) – saline, group II – MK 5 mg/kg/day i.p. for 5 days, group III – MK 5 mg/kg/day i.p., 1 day prior to and 4 days concomitantly with CCl₄ p.o., 0.3 ml/Kg/day and group IV – CCl₄, p.o., 0.3 ml/Kg/day for 4 days. One day after the last administration, samples of blood were taken and alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), malondialdehyde (MDA), catalase (CAT) as well as total antioxidant capacity (TAC) were determined. The histopathological exam was performed. We also determined superoxide dismutase (SOD), MDA, CAT and GSH in liver homogenate.ResultsCompared to group IV, group III exhibited statistically significant lower levels of ALT (318 ± 15.75 versus 203.14 ± 10.28 UI, p < 0.0001), TB (3.16 ± 0.30 versus 1.99 ± 0.08 mg/dl, p < 0.0001), MDA in blood and in liver homogenate (4.98 ± 1.71 versus 2.15 ± 1.18 nmol/ml, p = 0.0004) and higher levels of SOD and CAT. Histopathologically, group IV presented important macro- and micro-vesicular hepatic steatosis and group III preserved lobular histoarchitecture and had less severe cellular lesions.ConclusionMK exhibits a partial hepatoprotective effect on rats treated with CCl₄.     

Effect of pain location on spatial reorganisation of muscle activity

IntroductionWe aimed to determine whether the changes in muscle activity (in terms of both gross electromyography (EMG) and motor unit (MU) discharge characteristics) observed during pain are spatially organized with respect to pain location within a muscle which is the main contributor of the task.MethodsSurface and fine-wire EMG was recorded during matched low-force isometric plantarflexion from soleus (from four quadrants with fine-wire EMG and from the medial/lateral sides with surface EMG), both gastrocnemii heads, peroneus longus, and tibialis anterior. Four conditions were tested: two control conditions that each preceded contractions with pain induced in either the lateral (Pain_L) or medial (Pain_M) side of soleus.ResultsNeither the presence (p = 0.28) nor location (p = 0.19) of pain significantly altered gross muscle activity of any location (lateral/medial side of soleus, gastrocnemii, peroneus longus and tibialis anterior). Group data from 196 MUs show redistribution of MU activity throughout the four quadrants of soleus, irrespective of pain location. The significant decrease of MU discharge rate during pain (p < 0.0001; Pain_L: 7.3 ± 0.9–6.9 ± 1.1 Hz, Pain_M: 7.0 ± 1.1 to 6.6 ± 1.1 Hz) was similar for all quadrants of the soleus (p = 0.43), regardless of the pain location (p = 0.98). There was large inter-participant variation in respect to the characteristics of the altered MU discharge with pain.ConclusionResults from both surface and fine-wire EMG recordings do not support the hypothesis that muscle activity is reorganized in a simple systematic manner with respect to pain location.     

Synthesis and anti-parasitic activity of a novel quinolinone–chalcone series

A series of novel quinolinone–chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone–chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC₅₀ value of 1.3 ± 0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC₅₀ values of 2.1 ± 0.6 and 3.1 ± 1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC₅₀ values of 2.6 ± 0.1 and 3.3 ± 0.1 μM, respectively) as well as 6 and 9 (both having IC₅₀ values of <5 μM). Chemical modifications on the quinolinone–chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity.     

Alkaloids from the roots of Stemona javanica (Kunth) Engl. (Stemonaceae) and their anti-malarial,acetylcholinesterase inhibitory and cytotoxic activities

Two new protostemonine-type alkaloids, javastemonine A and B (3 and 4) have been isolated from the root extracts of Stemona javanica together with four known Stemona alkaloids, 13-demethoxy-11(S*),12(R*)-dihydroprotostemonine (1), isoprotostemonine (2), protostemonine and isomaistemonine. The structures and relative configurations of the new alkaloids were determined by spectroscopic analysis. The alkaloids 1 and 2 and protostemonine showed moderated antiplasmodial activities against the Plasmodium falciparum strains, TM4 (IC₅₀ values of 17.7 ± 3.7, 16.8 ± 5.4, 16.0 ± 4.2 μg/mL, respectively) and K1 (IC₅₀ values of 16.8 ± 3.1, 14.1 ± 3.7, 11.9 ± 3.3 μg/mL, respectively). These compounds showed no significant cytotoxicities against KB or Vero cells or acetylcholinesterase inhibitory activities.     

Increased Atherogenic Low-Density Lipoprotein Cholesterol in Untreated Subclinical Hypothyroidism

ObjectiveTo evaluate the effects of physiologic doses of levothyroxine replacement on the lipoprotein profile in patients with subclinical hypothyroidism (SCH).MethodsIn a prospective, double-blind, placebo- controlled study, we enrolled 120 patients—mostly, but not exclusively, premenopausal women—with SCH. Patients were randomly assigned to either a levothyroxine- treated group (n = 60) or a placebo (control) group (n = 60). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were measured before and 52 weeks after assignment to either group.ResultsIn the levothyroxine-treated group, the lipoprotein mean values before and after the 52-week study were as follows: TC, 5.05 ± 0.98 mmol/L versus 4.74 ± 0.87 mmol/L (P < .0001); LDL-C, 3.30 ± 0.90 mmol/L versus 2.89 ± 0.59 mmol/L (P < .01); TG, 1.18 ± 0.71 mmol/L versus 0.95 ± 0.53 mmol/L (P < .002); and HDL-C, 1.20 ± 0.33 mmol/L versus 1.19 ± 0.32 mmol/L (P = .29). In the control group, TC, HDL-C, and TG values remained unchanged after 52 weeks in comparison with baseline, but LDL-C mean values increased from 2.79 ± 0.60 mmol/L to 3.11 ± 0.77 mmol/L, a change that was statistically significant (P < .001). At the end of the study, the lipid profile changes between levothyroxine- treated and control groups were compared. Total cholesterol and LDL-C were significantly lower in the levothyroxine-receiving group (P < .029 and P < .0001, respectively) in comparison with the control group. The difference did not reach statistical significance for TG and HDL-C values.ConclusionIn premenopausal women, SCH has a negative effect on the lipoprotein profile and may translate into a sizable cardiovascular risk if left untreated. (Endocr Pract. 2008;14:570-575)     

Does gantry rotation time influence accuracy of volume computed tomography dose index (CTDIvol) in modern CT?

PurposeThe purpose of this study was to develop a gantry overrun corrected CTDI_vol (cCTDI_vol) dosimetry and evaluate the differences between the displayed CTDI_vol (dCTDI_vol), measured CTDI_vol (mCTDI_vol), and the cCTDI_vol.Methods and materialsThe each 8 rotation times between 275 and 1000 ms of two CT scanners were investigated. Rotation time (T_rot) and the beam-on time (T_beam) in axial scanning were measured accurately to determine the gantry overrun time (T_over) as T_beam − T_rot. Subsequently, mCTDI_vol was measured by using a 100 mm ionization chamber and CTDI phantoms. Furthermore, we introduced a gantry overrun correction factor (C_o = T_rot/T_beam) to obtain cCTDI_vol. Upon completion of the data acquisition, the dCTDI_vol and mCTDI_vol were compared with the cCTDI_vol.ResultsThe discrepancies of T_rot were 0.2 ± 0.2 ms as compared to the preset rotation times, and T_over was machine-specific and almost constant (22.4 ± 0.5 ms or 45.1 ± 0.3 ms) irrespective of the preset rotation time. Both dCTDI_vol and mCTDI_vol were increasingly overestimated compared to cCTDI_vol as the faster the preset rotation time was selected (1.7–23.5%).ConclusionThe rotation time influences the accuracy of CTDI_vol in modern CT, and should be taken into consideration when assessing the radiation output in modern CT.     

Possibility of limiting the un-justified irradiation in 131I therapy of Graves' disease: A thyroid mass-reduction based method for the optimum activity calculation

ObjectiveIn Graves' disease therapy, the amount of ¹³¹I is usually decided following two different modalities: the administration of a fixed activity or of an activity individually calculated based on a fixed value of target absorbed dose. Although the effectiveness of each of these approaches is good (about 80% of patients cured), the ALARA principle must be applied avoiding the un-justified radioactivity to the patient himself, the people living/working near him and the environment. In this paper a new approach to the ¹³¹I therapy in Graves' disease, based on the optimum value of the final thyroid mass, is presented.Design97 Graves' disease patients (29 males) were randomly assigned into three groups (GR1, GR2, GR3). In two of them (GR1, GR3) the radioiodine administering activity was calculated based on two fixed thyroid absorbed dose values (100 Gy for GR1; 400 Gy for GR3), in GR2 it was calculated based on the desired final optimum thyroid mass value m_f = 0.24 m₀/U₀ResultsThe rate of cured patients are 48% (GR1), 97% (GR2) (z-test, p < 0.001) and 97% (GR3). The average activity administered to GR2 (393 ± 157 MBq) is lower than that administrered to GR3 patients (524 ± 201 MBq) (p = 0.007, two-tails unpaired t-test); the thyroid absorbed dose in GR2 (262 ± 78 Gy) is lower than in GR3 patients (407 ± 23 Gy) (p < 0.001, two-tails unpaired t-test).ConclusionOur results demonstrate that the thyroid-mass based approach optimizes the treatment avoiding an un-justified excess or a not-effective too low activity without time and resources consuming.