Effective Dose Levels Research Articles

A REVIEW OF HUMAN HEALTH AND DISEASE CLAIMS FOR ELDERBERRY (SAMBUCUS NIGRA) FRUIT

European elder (Sambucus nigra) fruit has been used in folk medicine for centuries, but this use is not supported by experimental or clinical data. In recent years, however, dietary supplements, traditional herbal medicinal products (THMP) and other natural health products containing extracts, juices or syrups of European elderberry have become much more popular in the EU and the US as remedies for treating cold and flu symptoms. These are marketed primarily through natural food stores alongside other popular herbal remedies used for treatment or prevention of upper respiratory tract infections and symptoms associated with colds and flu. Several small clinical studies have been performed which indicate significantly faster recovery from symptoms associated with influenza compared with patients in the control group. However, no specified or effective dose level has been justified. In vitro studies have demonstrated a significant antioxidant capacity as determined by oxygen radical absorbing capacity (ORAC). Antiviral capacity is also demonstrated by inhibition of viral replication. Furthermore, immune-protective and immune-stimulatory activity was detected. Elderberry also increased production of the inflammatory and anti-inflammatory cytokines. There are a few reports of poisonings from the fresh juice of some Sambucus species.

Effective Dose Levels from Computed Tomography of the Head during Contrast Studies in Nigeria

Background: Diagnostic reference levels for a number of common diagnostic radiological exami- nations against which individual centres could compare their performance have been recom- mended by relevant international agencies. Due to variations in different populations globally, lo- cal and national diagnostic reference levels are more reliable. To the best of our knowledge, no centre-specific study has been carried out and national surveys are not available. Objective: To establish a preliminary local and national diagnostic reference level in Nigeria. Methods: A pros- pective and cross-sectional study involving 30 conscious paediatrics and adult patients referred for head computed tomography scan. They were positioned supine and scanned according to the standard protocol for head computed tomography with manual mA selection. The total dose- length products were recorded at the end of the pre-contrast and post-contrast sequences respec- tively. The pre-contrast dose was taken into cognizance in the determination of the post-contrast value. The effective dose was established by multiplying the dose-length product by 0.0023 mSv∙mGy −1 ∙cm −1 , a conversion coefficient for brain tissue adopted from the European Commission. Statistical Package for Social Sciences version 17.0 was used to analyze the data. Results: 30 pae- diatrics and adult patients of mixed gender participated in the study. Their ages ranged from 1 to 74 years with a mean age of 41.47 ± 23.30 years. The pre-contrast effective dose ranged from 1.93 mSv to 3.32 mSv with mean of 2.56 ± 0.51 mSv and 75 th percentile of 3.11 mSv while the post- contrast effective dose ranged from 4.06 mSv to 6.97 mSv with mean of 5.27 ± 0.97 mSv and 75 th percentile of 6.13 mSv. The mean effective dose from this work and two other isolated studies was * Corresponding author.

Sub-chronic exposure of non-observable adverse effect dose of terbufos sulfone: neuroinflammation in diabetic and non-diabetic rats.

Neuroinflammation (NI) contributes to the pathogenesis of several neurodegenerative disorders. Epidemiological and a few animal studies have shown that chronic exposure of organophosphorus compounds (OPC) may cause neuronal injury and predispose to neuro- as well as psychotic disorders in conjunction with NI. However, in vivo studies are meager and do not represent the entire toxicologically diversified OPC. The present study aimed to investigate the result of non-observable adverse effect level dose of a highly toxic OPC, terbufos sulfone (TBS), on sub-chronic exposure on the status of proinflammatory cytokines; interleukin-1β, interleukin-6 and tumor necrosis factor-α in rats brain. In addition, lactate dehydrogenase, nitric oxide and reduced glutathione were also determined in brain. Red blood cell acetylcholinesterase was measured weekly. Total of four groups' saline control, diabetes control, non-diabetes TBS and diabetes treated with TBS were employed in the study. Control groups received saline and the experimental groups were injected with TBS intraperitonealy for fifteen days daily. Twenty four hours after the last injection, the animals were euthanized for collection of brain and serum samples. The study showed significant elevation of interleukin-6, tumor necrosis factor-α and lactate dehydrogenase in brain of TBS treated groups, while the presence of interleukin-1β was significantly greater in the non-diabetes TBS treated group when compared with saline control. The increase was observed to be independent of acetylcholinesterase level and diabetes condition. The change in reduced glutathione was modest as compared with control. Based on the findings, the study concludes that the non-observable adverse effect level dose of TBS has potential to cause NI and subsequent neurodegeneration, a remarkable sign of many chronic neuronal and psychotic disorders. Further studies with prolonged exposure and other neurodegenerative parameters are warranted.

Evaluation of an iterative model-based reconstruction algorithm for low-tube-voltage (80kVp) computed tomography angiography.

The objective of this study was to investigate the improvement in diagnostic quality of an iterative model-based reconstruction (IMBR) algorithm for low-tube-voltage (80-kVp) and low-tube-current in abdominal computed tomography angiography (CTA). A total of 11 patients were imaged on a 256-slice multidetector computed tomography for visualization of the aorta. For all patients, three different reconstructions from the low-tube-voltage data are generated: filtered backprojection (FBP), IMBR, and a mixture of both [Formula: see text]. To determine the diagnostic value of IMBR-based reconstructions, the image quality was assessed. With IMBR-based reconstructions, image noise could be significantly reduced, which was confirmed by a highly improved contrast-to-noise ratio. In the image quality assessment, radiologists were able to reliably detect more third-order and higher aortic branches in the IMBR reconstructions compared to FBP reconstructions. The effective dose level was, on average, 3.0mSv for 80-kVp acquisitions. Low-tube-voltage CTAs significantly improve vascular contrast as presented by others; however, this effect in combination with IMBR enabled yet another substantial improvement of diagnostic quality. For IMBR, a significant improvement of image quality and a decreased radiation dose at low-tube-voltage can be reported.

Efeito da dessecação com etefão na produção e qualidade da soja

The desiccation is done with the objective of controlling weeds, causing defoliation of the crop, anticipate and uniform the harvest and obtain seeds with better quality. The objective was to evaluate the yield and quality of soybean seeds desiccated with ethephon. The cultivar MSOY 7211 RR was desiccated at the R7.0 stage using ethephon at the doses of 0, 100, 200 and 300 ppm ha-1. The experiment was conducted in a randomized complete block design with three replications. It was evaluated the number of plants per meter (NP), plant height (PH), number of nodes (NN), height of the first pod (AIPV), 100 seed weight (P100), production and water content of the seeds were all rated at harvest. The seeds physiological quality and vigor was assessed by testing first count, germination, growth analysis, sand emergence velocity index emergency and dry matter of roots and shoots. Analyses of variance were processed and, when significant, the means were compared by Tukey test at 5% probability. There were no differences (p> 0.5) for NP, AP, NN, AIPV, P100 and production. There was an interaction (p <0.05) between the dose and the number of days after drying and the content of water in the grain parameter which, after identity testing, the time to effect dose levels adjusted to the linear model simple (R2 = 0.98). No difference was observed for germination and seed vigor. Although not significant, the increase in the dose of ethephon reduced the weight of hundred seeds and productivity. However, seed quality was not affected.

Inactivation of Candida albicans following exposure to 624-nanometer light from a supraluminous diode array.

To determine the potential for visible light (405 or 624 nm) to produce an inhibitory effect on Candida albicans. In addition, the study sought to evaluate a series of doses in terms of their respective inhibiting capabilities. The authors have studied the effect of blue light on Staphylococcus aureus and found that a bactericidal outcome can be obtained with low doses of blue light. Candida albicans was tested because of its common appearance in human skin and mucous membrane infections. The organism was treated in vitro with 405-nm (blue) and with 624-nm (red) light emitted from a supraluminous diode array. Doses of 3, 9, 15, 30, and 60 J/cm(2) were used. Colony counts were performed and compared with untreated controls using Student t tests and 1-way analysis of variance with Tukey post hoc analysis. The results revealed no inhibition produced by 405 nm on C albicans (F4,20 = 0.901; P = .482). However, 624 nm did inhibit growth of C albicans at 3, 9, and 30 J/cm(2) (F4,20 = 6.064; P = .002). Appropriate doses of 624-nm light from a supraluminous diode array can inhibit the growth of C albicans in vitro. Three, 9, and 30 J/cm(2) are all effective dose levels.

Assessment of individual organ doses in a realistic human phantom from neutron and gamma stimulated spectroscopy of the breast and liver.

Understanding the radiation dose to a patient is essential when considering the use of an ionizing diagnostic imaging test for clinical diagnosis and screening. Using Monte Carlo simulations, the authors estimated the three-dimensional organ-dose distribution from neutron and gamma irradiation of the male liver, female liver, and female breasts for neutron- and gamma-stimulated spectroscopic imaging. Monte Carlo simulations were developed using the Geant4 GATE application and a voxelized XCAT human phantom. A male and a female whole body XCAT phantom was voxelized into 256 × 256 × 600 voxels (3.125 × 3.125 × 3.125 mm(3)). A monoenergetic rectangular beam of 5.0 MeV neutrons or 7.0 MeV photons was made incident on a 2 cm thick slice of the phantom. The beam was rotated at eight different angles around the phantom ranging from 0° to 180°. Absorbed dose was calculated for each individual organ in the body and dose volume histograms were computed to analyze the absolute and relative doses in each organ. The neutron irradiations of the liver showed the highest organ dose absorption in the liver, with appreciably lower doses in other proximal organs. The dose distribution within the irradiated slice exhibited substantial attenuation with increasing depth along the beam path, attenuating to ~15% of the maximum value at the beam exit side. The gamma irradiation of the liver imparted the highest organ dose to the stomach wall. The dose distribution from the gammas showed a region of dose buildup at the beam entrance, followed by a relatively uniform dose distribution to all of the deep tissue structures, attenuating to ~75% of the maximum value at the beam exit side. For the breast scans, both the neutron and gamma irradiation registered maximum organ doses in the breasts, with all other organs receiving less than 1% of the breast dose. Effective doses ranged from 0.22 to 0.37 mSv for the neutron scans and 41 to 66 mSv for the gamma scans. Neutron and gamma irradiation of a primary target organ was found to impart the majority of the total dose to the primary target organ (and other large organs) within the beam plane and considerably lower dose to proximal organs outside of the beam. These results also indicate that despite the use of a highly scattering particle such as a neutron, the dose from neutron stimulated emission computed tomography scans is on par with other clinical imaging techniques such as x-ray computed tomography (x-ray CT). Given the high nonuniformity in the dose across an organ during the neutron scan, care must be taken when computing average doses from neutron irradiations. The effective doses from neutron scanning were found to be comparable to x-ray CT. Further technique modifications are needed to reduce the effective dose levels from the gamma scans.

Evaluation of the natural gamma radiation level in residential zones and determination of annual effective exposure dose in the residents of Hamadan province, Iran, 2012

Background and Aim: Human is always exposed to natural background ionizing radiation which may have harmful effects; therefore, measurement of the natural background radiation is important. In this study, was measured the dose of effective natural background gamma radiation in indoor residential zones of Hamadan Province. Material and Methods: In this cross-sectional study, we selected four stations along the main geographic directions and one in the center of city for measurement of the indoor dose rate in each of the cities in Hamadan Province. Based on the household numbers, some houses were selected randomly in every station and natural background indoor dose was measured by using RDS-110 survey meter. Then, using the results of our previous study about measuring the level of outdoor natural gamma radiation in this province, we determined the level of annual effective exposure dose from natural gamma radiation in Hamadan residents. Results: In Hamadan province cities, maximum and minimum indoor natural background radiation (gamma ray) belonged to Razan City (1.41±0.079 mSv) and Asadabad City (0.955±0.044 mSv), respectively. Mean annual equivalent indoor dose in Hamadan Province was 1.20±0.070 mSv. Also the maximum indoor natural background radiation dose (gamma ray) in the buildings with the age of more and less than 25 years were 1.42±0.219 mSv and 1.44±0.149 mSv, respectively. According to the results of this study and our previous study about outdoor gamma natural background radiation, the annual effective dose in Hamadan Province residents was 0.83 mSv. Conclusion: According to the results of this study, it seems that annual effective equivalent dose due to indoor gamma radiation in Hamadan Province exceeded the mean external exposure amount reported by UNSCEAR (0.5 mSv). Also the annual effective dose due to gamma background radiation in Hamadan Province residents is 0.83 mSv, which is higher than the global average (0.48 mSv) reported by UNSCEAR - 2000. Therefore epidemiological studies to assess the prevalence of chronic diseases associated with natural radiation exposure among Hamadan Province residents are recommended.

Measurement of the Space Radiation Dose for the Flight Aircrew at High-Altitude

This paper describes an experimental approach to evaluate the effective doses of space radiations at high-altitude by combining the measured data from the Liulin-6K spectrometer loaded onto the air-borne RC-800 cockpit and the calculated data from CARI-6M code developed by FAA. In this paper, 15 exposed dose experiments for the flight missions at a high-altitude above 10 km and 3 experiments at a normal altitude below 4 km were executed over the Korean Peninsula in 2012. The results from the high-altitude flight measurements show a dramatic change in the exposed doses as the altitude increases. The effective dose levels (an average of <TEX>$15.27{\mu}Sv$</TEX>) of aircrew at the high-altitude are an order of magnitude larger than those (an average of <TEX>$0.30{\mu}Sv$</TEX>) of the normal altitude flight. The comparison was made between the measure dose levels and the calculated dose levels and those were similar each other. It indicates that the annual dose levels of the aircrew boarding RC-800 could be above 1 mSv. These results suggest that a proper procedure to manage the exposed dose of aircrew is required for ROK Air Force.

Confirmation and Control of Triazine and 4-Hydroxyphenylpyruvate Dioxygenase-Inhibiting Herbicide-Resistant Palmer Amaranth (Amaranthus palmeri) in Nebraska

Palmer amaranth is a difficult-to-control broadleaf weed that infests corn and soybean fields in south-central and southwestern Nebraska and several other states in the United States. The objectives of this research were to confirm triazine and 4-hydroxyphenylpyruvate dioxygenase (HPPD)-inhibiting herbicide-resistant Palmer amaranth in Nebraska and to determine sensitivity and efficacy of POST-applied corn herbicides for control of resistant and susceptible Palmer amaranth biotypes. Seeds from a putative HPPD-resistant Palmer amaranth biotype from Fillmore County, NE were collected from a seed corn production field in fall 2010. The response of Palmer amaranth biotypes to 12 rates (0 to 12×) of mesotrione, tembotrione, topramezone, and atrazine was evaluated in a dose–response bioassay in a greenhouse. On the basis of the values at the 90% effective dose (ED90) level, the analysis showed a 4- to 23-fold resistance depending upon the type of HPPD-inhibiting herbicide being investigated and susceptible biotype used for comparison. This biotype also had a 9- to 14-fold level of resistance to atrazine applied POST. Results of a POST-applied herbicide efficacy study suggested a synergistic interaction between atrazine and HPPD-inhibiting herbicides that resulted in &gt; 90% control of all Palmer amaranth biotypes. The resistant biotype had a reduced sensitivity to acetolactate synthase inhibiting herbicides (halosulfuron and primisulfuron), a photosystem-II inhibitor (bromoxynil), and a protoporphyrinogen oxidase inhibitor (fluthiacet-methyl). Palmer amaranth biotypes were effectively controlled (≥ 90%) with glyphosate, glufosinate, and dicamba, whereas 2,4-D ester provided 81 to 83% control of the resistant biotype and &gt; 90% control of both susceptible biotypes.

Annual effective dose from environmental gamma radiation in Bushehr city

BackgroundPresent study was an attempt to measure outdoor and indoor gamma dose rates in Bushehr city to determine corresponding annual effective dose and, to assess effect of active nuclear power plant located in Bushehr city on background radiation level of this city.MethodsAll measurements were performed by G.M (Geiger Muller) detector (X5C plus) calibrated in Iran Atomic Energy Agency. In order to avoid effects of ground on outdoor and indoor measurements, G.M detector was placed one meter higher than ground level. Also, during the outdoor measurements, G.M detector was used at least six meters away from the walls of any building nearby to avoid unwanted effects of the materials used in the buildings on measurements.ResultsAverage gamma dose rates of outdoor and indoor measurements were determined as 51.8 ± 8.8 nSv/h and 60.2 ± 7.2 nSv/h, respectively. Annual effective dose due to background gamma radiation was calculated as 0.36 mSv which was lower than average global level.ConclusionsThe average annual effective dose from background gamma radiation in Bushehr city was less than global level. Comparison of the results of present study, as follow up, with previous attempt performed in 2004 to determine effective dose of environmental gamma radiation in Bushehr province revealed that, during eight years, nuclear power plant located in this city has not significantly increased level of annual effective dose of Bushehr city.

Radiation Exposure of Patients by Cone Beam CT during Endobronchial Navigation - A Phantom Study

Rationale: Cone Beam Computed Tomography imaging has become increasingly important in many fields of interventional therapies. Objective: Lung navigation study which is an uncommon soft tissue approach. Methods: As no effective organ radiation dose levels were available for this kind of Cone Beam Computed Tomography application we simulated in our DynaCT (Siemens AG, Forchheim, Germany) suite 2 measurements including 3D acquisition and again for 3D acquisition and 4 endobronchial navigation maneuvers under fluoroscopy towards a nodule after the 8th segmentation in the right upper lobe over a total period of 20 minutes (min). These figures reflect the average complexity and time in our experience. We hereby describe the first time the exact protocol of lung navigation by a Cone Beam Computed Tomography approach. Measurement: The hereby first time measured body radiation doses in that approach showed very promising numbers between 0,98-1,15mSv giving specific lung radiation doses of 0,42-0,38 mSv. Main results: These figures are comparable or even better to other lung navigation systems. Cone Beam Computed Tomography offers some unique features for lung interventionists as a realtime 1-step navigation system in an open structure feasible for endobronchial and transcutaneous approach. Conclusions: Due to this low level of radiation exposure Cone Beam Computed Tomography is expected to attract interventionists interested in using and guiding endobronchial or transcutaneous ablative procedures to peripheral endobronchial and other lung lesions.

Radiation dose evaluation of dental cone beam computed tomography using an anthropomorphic adult head phantom

Dental cone beam computed tomography (CBCT) provides high-resolution tomographic images and has been gradually used in clinical practice. Thus, it is important to examine the amount of radiation dose resulting from dental CBCT examinations. In this study, we developed an in-house anthropomorphic adult head phantom to evaluate the level of effective dose. The anthropomorphic phantom was made of acrylic and filled with plaster to replace the bony tissue. The contour of the head was extracted from a set of adult computed tomography (CT) images. Different combinations of the scanning parameters of CBCT were applied. Thermoluminescent dosimeters (TLDs) were used to measure the absorbed doses at 19 locations in the head and neck regions. The effective doses measured using the proposed phantom at 65, 75, and 85kVp in the D-mode were 72.23, 100.31, and 134.29µSv, respectively. In the I-mode, the effective doses were 108.24, 190.99, and 246.48µSv, respectively. The maximum percent error between the doses measured by the proposed phantom and the Rando phantom was l4.90%. Therefore, the proposed anthropomorphic adult head phantom is applicable for assessing the radiation dose resulting from clinical dental CBCT.

Molecular Imaging of Death Receptor 5 Occupancy and Saturation Kinetics In Vivo by Humanized Monoclonal Antibody CS-1008

CS-1008 (tigatuzumab; phase I/II), an antihuman death receptor 5 (DR5) agonist, induces apoptosis and has cytotoxic activity against human cancer cell lines. This study reports on the preclinical validation of (111)In-labeled anti-DR5 humanized antibody CS-1008 as a diagnostic tool to study the DR5 occupancy in patients with cancer and establish dose ranges for receptor saturation kinetics in vivo. CS-1008 was radiolabeled and characterized for DR5 binding and labeling efficiency on TRAIL-sensitive DR5-positive colorectal cancer cells (COLO 205 and WiDr). Pharmacokinetic and biodistribution studies were conducted in BALB/c nu/nu mice bearing COLO 205, WiDr, or DR5-negative CT26 colon tumors. Planar gamma camera imaging and computerized tomography (CT) images were obtained to study receptor occupancy in vivo. Scatchard analysis showed high and specific binding affinity (Kd, 1.05 ± 0.12 nmol/L) of (111)In-labeled CS-1008. (111)In-labeled CS-1008 was specifically taken up in mice bearing COLO 205 and WiDr tumors with prolonged tumor retention (26.25 ± 2.85%ID/g vs. 12.20 ± 2.24 at 168 hours post injection; n = 5, SD), and uptake correlated both with DR5 expression on tumor cells and antitumor activity. DR5 saturation was shown in vivo via both biodistribution studies and planar gamma camera imaging/CT imaging of (111)In-labeled CS-1008. Saturation of DR5 corresponded to maximal in vivo antitumor efficacy. Imaging of DR5 receptor occupancy in vivo correlates with tumor concentration and in vivo efficacy, and is a novel molecular imaging technique that can be used to determine receptor occupancy and effective dose levels of DR5 agonist antibodies in the clinic.

Combining in vitro embryotoxicity data with physiologically based kinetic (PBK) modelling to define in vivo dose–response curves for developmental toxicity of phenol in rat and human

In vitro assays are often used for the hazard characterisation of compounds, but their application for quantitative risk assessment purposes is limited. This is because in vitro assays cannot provide a complete in vivo dose-response curve from which a point of departure (PoD) for risk assessment can be derived, like the no observed adverse effect level (NOAEL) or the 95% lower confidence limit of the benchmark dose (BMDL). To overcome this constraint, the present study combined in vitro data with a physiologically based kinetic (PBK) model applying reverse dosimetry. To this end, embryotoxicity of phenol was evaluated in vitro using the embryonic stem cell test (EST), revealing a concentration-dependent inhibition of differentiation into beating cardiomyocytes. In addition, a PBK model was developed on the basis of in vitro and in silico data and data available from the literature only. After evaluating the PBK model performance, effective concentrations (ECx) obtained with the EST served as an input for in vivo plasma concentrations in the PBK model. Applying PBK-based reverse dosimetry provided in vivo external effective dose levels (EDx) from which an in vivo dose-response curve and a PoD for risk assessment were derived. The predicted PoD lies within the variation of the NOAELs obtained from in vivo developmental toxicity data from the literature. In conclusion, the present study showed that it was possible to accurately predict a PoD for the risk assessment of phenol using in vitro toxicity data combined with reverse PBK modelling.

Novel use of the ultra-short-acting intravenous β1-selective blocker landiolol for supraventricular tachyarrhythmias in patients with congestive heart failure

The purpose of this study was to find a safe dosing regimen for landiolol, an ultra-short-acting β-adrenergic blocking agent, to rapidly control supraventricular tachyarrhythmias (SVTs) in patients with heart failure (HF). Landiolol is reported to have good effects in the treatment of SVTs after cardiac surgery. We evaluated 52 patients with SVT and symptoms of HF (NYHA class III/IV, 10/42; EF 32 ± 12 %) on admission because of ischaemic disease (n = 10), non-ischaemic cardiomyopathy (n = 32), or valvular disease (n = 10). Paroxysmal/persistent atrial fibrillation and atrial tachycardia were present in 16 (30 %), 23 (45 %), and 13 (25 %) patients, respectively. The patients first underwent conventional therapy with carperitide, dobutamine, or milrinone. Intravenous landiolol was administered at an infusion rate of 1 μg/kg/min and, if no adverse effects developed, the maintenance dose, titrated to HR and blood pressure response, was increased. At an average dose of 10.8 ± 9.4 μg/kg/min, mean HR significantly decreased significantly from 133 ± 27 to 82 ± 15 beats/min (P < 0.01), whereas systolic blood pressure did not differ from baseline to attainment of an effective dose level (105 ± 21 vs. 101 ± 19 mmHg, P = ns). Within 60 min after initiation of therapy, all patients had achieved a 20 % reduction in HR at the maintenance dose. Transient asymptomatic hypotension requiring cessation of landiolol therapy occurred in three patients. Intravenous administration of landiolol was both effective in rapidly controlling HR for up to 24 h and useful as bridging treatment to additional therapy of oral β blockade, pulmonary vein catheter ablation, or cardiac resynchronisation therapy in patients with HF.

OP0043 Twenty-Four Weeks of Treatment with a Novel Anti-IL-6 Receptor Nanobody® (ALX-0061) Resulted in 84% ACR20 Improvement and 58% DAS28 Remission in a Phase I/Ii Study in RA

BackgroundALX-0061 is a monovalent IL-6R targeting Nanobody. It inhibits signalling via soluble and membrane IL-6R. PK/PD modelling resulted in a condensed study design, combining single ascending dose (SAD), multiple ascending...

Anticonvulsant, Anxiolytic and Neurotoxicity Profile of Aqarqarha (&amp;lt;i&amp;gt;Anacyclus pyrethrum&amp;lt;/i&amp;gt;) DC (Compositae) Root Ethanolic Extract

Ethnopharmacological relevance: Aqarqarha (Anacyclus pyrethrum) DC root has long been used as a traditional an-tiepileptic remedy in Unani system of medicine over centuries. Aim of the Study: To rationalize the ethnomedical claim and screen for anxiolytic and neurotoxicity profile of ethanolic extract of Aqarqarha (Anacyclus pyrethrum) root (APE). Materials and Methods: The anticonvulsant and anxiolytic potential of APE (100-800 mg/kg) was evaluated against Pentylenetetrazole (PTZ), Bicuculline (BCL), Increasing current electroshock (ICES) and Elevated plus maze(EPM) models. Rotarod test was employed as neurotoxicity model including an additional higher dose (1600 mg/kg). Results: The APE showed significant anticonvulsant activity (p i.p.) in a dose-dependent manner but against BCL (30 mg/kg, i.p.) at the dose 800 mg/kg only (p 0.05). The extract also showed anxiolytic behaviour in EPM (p Conclusions: The results suggested significant anticonvulsant activity of APE against PTZ and BCL but failure against ICES. Moreover, APE also exhibited anxiolytic potential without any evidence of neurotoxicity at the effective dose level. We concluded that anticonvulsant effect of APE is probably mediated by enhancing GABAergic neurotransmission.

Непараметрическое оценивание эффективных доз по данным бинарных откликов

For the quantal response model we propose a new direct method for nonpara- metric estimation of the effective dose level ���� 100�� (0 < �� < 1). This method yields a simple and reliable monotone estimate of the effective dose level curve �� → ���� 100�� and is appealing to users of conventional smoothing methods of kernel estimates. Moreover, it is computationally very efficient, because it does not require a numerical inversion of the estimate of the quantile dose response curve. We prove asymptotic normality of this new estimator and compare it with the DNP-estimator.

Dose Reduction or Intermittent Administration of Erlotinib: Which Is Better for Patients Suffering from Intolerable Toxicities?

Erlotinib is an epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor that is widely used in the treatment of non-small cell lung cancer. Skin rashes and diarrhea are frequent side effects of erlotinib therapy. When these toxicities become intolerable, dose reduction is commonly performed. However, dose reduction may not maintain the effective dose levels in some specific situations, such as in cases of wild-type EGFR tumors or central nervous system metastases. We speculate that intermittent administration is better than dose reduction to simultaneously maintain the effective dose levels and reduce toxicities in such situations. We herein present four cases of patients who successfully received intermittent administration of erlotinib.