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We present the new version (v14) of the BIRAIASB algorithm for the retrieval of formaldehyde (H2CO) columns from spaceborne UV-visible sensors. Applied to OMI measurements from Aura and to GOME-2 measurements from MetOp-A and MetOp-B, this algorithm is used to produce global distributions of H2CO representative of midmorning and early afternoon conditions. Its main features include (1) a new iterative DOAS scheme involving three fitting intervals to better account for the O2-O2 absorption, (2) the use of earthshine radiances averaged in the equatorial Pacific as reference spectra, and (3) a destriping correction and background normalisation resolved in the across-swath position. For the air mass factor calculation, a priori vertical profiles calculated by the IMAGES chemistry transport model at 09:30 and 13:30 LT are used. Although the resulting GOME-2 and OMI H2CO vertical columns are found to be highly correlated, some systematic differences are observed. Afternoon columns are generally larger than morning ones, especially in mid-latitude regions. In contrast, over tropical rainforests, morning H2CO columns significantly exceed those observed in the afternoon. These differences are discussed in terms of the H2CO column variation between mid-morning and early afternoon, using ground-based MAX-DOAS measurements available from seven stations in Europe, China and Africa. Validation results confirm the capacity of the combined satellite measurements to resolve diurnal variations in H2CO columns. Furthermore, vertical profiles derived from MAX-DOAS measurements in the Beijing area and in Bujumbura are used for a more detailed validation exercise. In both regions, we find an agreement better than 15% when MAX-DOAS profiles are used as a priori for the satellite retrievals. Finally, regional trends in H2CO columns are estimated for the 2004-2014 period using SCIAMACHY and GOME-2 data for morning conditions, and OMI for early afternoon conditions. Consistent features are observed, such as an increase of the columns in India and central-eastern China, and a decrease in the eastern US and Europe. We find that the higher horizontal resolution of OMI combined with a better sampling and a more favourable illumination at midday allow for more significant trend estimates, especially over Europe and North America. Importantly, in some parts of the Amazonian forest, we observe with both time series a significant downward trend in H2CO columns, spatially correlated with areas affected by deforestation. [ABSTRACT FROM AUTHOR]

We present an algorithm for retrieving tropospheric nitrogen dioxide (NO2) vertical column densities (VCDs) from ground-based zenith-sky (ZS) measurements of scattered sunlight. The method is based on a four-step approach consisting of (1) the differential optical absorption spectroscopy (DOAS) analysis of ZS radiance spectra using a fixed reference spectrum corresponding to low NO2 absorption, (2) the determination of the residual amount in the reference spectrum using a Langley-plot-type method, (3) the removal of the stratospheric content from the daytime total measured slant column based on stratospheric VCDs measured at sunrise and sunset, and simulation of the rapid NO2 diurnal variation, (4) the retrieval of tropospheric VCDs by dividing the resulting tropospheric slant columns by appropriate air mass factors (AMFs). These steps are fully characterized and recommendations are given for each of them. The retrieval algorithm is applied on a ZS data set acquired with a multi-axis (MAX-) DOAS instrument during the Cabauw (51.97° N, 4.93° E, sea level) Intercomparison campaign for Nitrogen Dioxide measuring Instruments (CINDI) held from 10 June to 21 July 2009 in the Netherlands. A median value of 7.9 × 1015 molec cm-2 is found for the retrieved tropospheric NO2 VCDs, with maxima up to 6.0 × 1016 molec cm-2. The error budget assessment indicates that the overall error σTVCD on the column values is less than 28 %. In the case of low tropospheric contribution, σTVCD is estimated to be around 39% and is dominated by uncertainties in the determination of the residual amount in the reference spectrum. For strong tropospheric pollution events, σTVCD drops to approximately 22% with the largest uncertainties on the determination of the stratospheric NO2 abundance and tropospheric AMFs. The tropospheric VCD amounts derived from ZS observations are compared to VCDs retrieved from off-axis and direct-sun measurements of the same MAX-DOAS instrument as well as to data from a co-located Système d'Analyse par Observations Zénithales (SAOZ) spectrometer. The retrieved tropospheric VCDs are in good agreement with the different data sets with correlation coefficients and slopes close to or larger than 0.9. The potential of the presented ZS retrieval algorithm is further demonstrated by its successful application on a 2-year data set, acquired at the NDACC (Network for the Detection of Atmospheric Composition Change) station Observatoire de Haute Provence (OHP; Southern France). [ABSTRACT FROM AUTHOR]

As an ubiquitous product of the oxidation of many volatile organic compounds (VOCs), formaldehyde (HCHO) plays a key role as a short-lived and reactive intermediate in the atmospheric photo-oxidation pathways leading to the formation of tropospheric ozone and secondary organic aerosols. In this study, HCHO profiles have been successfully retrieved from ground-based Fourier transform infrared (FTIR) solar spectra and UV-visible Multi-AXis Differential Optical Absorption Spectroscopy (MAX-DOAS) scans recorded during the July 2010-December 2012 time period at the Jungfraujoch station (Swiss Alps, 46.5° N, 8.0° E, 3580ma.s.l.). Analysis of the retrieved products has revealed different vertical sensitivity between both remote sensing techniques. Furthermore, HCHO amounts simulated by two state-of-the-art chemical transport models (CTMs), GEOSChem and IMAGES v2, have been compared to FTIR total columns and MAX-DOAS 3.6-8 km partial columns, accounting for the respective vertical resolution of each ground-based instrument. Using the CTM outputs as the intermediate, FTIR and MAX-DOAS retrievals have shown consistent seasonal modulations of HCHO throughout the investigated period, characterized by summertime maximum and wintertime minimum. Such comparisons have also highlighted that FTIR and MAX-DOAS provide complementary products for the HCHO retrieval above the Jungfraujoch station. Finally, tests have revealed that the updated IR parameters from the HITRAN 2012 database have a cumulative effect and significantly decrease the retrieved HCHO columns with respect to the use of the HITRAN 2008 compilation. [ABSTRACT FROM AUTHOR]

A 4-year data set of MAX-DOAS observations in the Beijing area (2008–2012) is analysed with a focus on NO2, HCHO and aerosols. Two very different retrieval methods are applied. Method A describes the tropospheric profile with 13 layers and makes use of the optimal estimation method. Method B uses 2–4 parameters to describe the tropospheric profile and an inversion based on a leastsquares fit. For each constituent (NO2, HCHO and aerosols) the retrieval outcomes are compared in terms of tropospheric column densities, surface concentrations and "characteristic profile heights" (i.e. the height below which 75% of the vertically integrated tropospheric column density resides). We find best agreement between the two methods for tropospheric NO2 column densities, with a standard deviation of relative differences below 10 %, a correlation of 0.99 and a linear regression with a slope of 1.03. For tropospheric HCHO column densities we find a similar slope, but also a systematic bias of almost 10% which is likely related to differences in profile height. Aerosol optical depths (AODs) retrieved with method B are 20% high compared to method A. They are more in agreement with AERONET measurements, which are on average only 5% lower, however with considerable relative differences (standard deviation ~25 %). With respect to near-surface volume mixing ratios and aerosol extinction we find considerably larger relative differences: 10±30, –23±28 and –8±33% for aerosols, HCHO and NO2 respectively. The frequency distributions of these near-surface concentrations show however a quite good agreement, and this indicates that near-surface concentrations derived from MAX-DOAS are certainly useful in a climatological sense. A major difference between the two methods is the dynamic range of retrieved characteristic profile heights which is larger for method B than for method A. This effect is most pronounced for HCHO, where retrieved profile shapes with method A are very close to the a priori, and moderate for NO2 and aerosol extinction which on average show quite good agreement for characteristic profile heights below 1.5 km. One of the main advantages of method A is the stability, even under suboptimal conditions (e.g. in the presence of clouds). Method B is generally more unstable and this explains probably a substantial part of the quite large relative differences between the two methods. However, despite a relatively low precision for individual profile retrievals it appears as if seasonally averaged profile heights retrieved with method B are less biased towards a priori assumptions than those retrieved with method A. This gives confidence in the result obtained with method B, namely that aerosol extinction profiles tend on average to be higher than NO2 profiles in spring and summer, whereas they seem on average to be of the same height in winter, a result which is especially relevant in relation to the validation of satellite retrievals. [ABSTRACT FROM AUTHOR]

A four year data set of MAX-DOAS observations in the Beijing area (2008-2012) is analysed with a focus on NO2, HCHO, and aerosols. Two very different retrieval methods are applied. Method A describes the tropospheric profile with 13 layers and makes use of the optimal estimation method. Method B uses 2-4 parameters to describe the tropospheric profile and an inversion based on a least-squares fit. For each constituent (NO2, HCHO and aerosols) the retrieval outcomes are compared in terms of tropospheric columns, surface concentrations, and "characteristic profile heights" (i.e. the height below which 75% of the vertically integrated tropospheric column resides). We find best agreement between the two methods for tropospheric NO2 columns, with a standard deviation of relative differences below 10%, a correlation of 0.99 and a linear regression with a slope of 1.03. For tropospheric HCHO columns we find a similar slope, but also a systematic bias of almost 10 % which is likely related to differences in profile height. Aerosol optical depths (AODs) retrieved with method B are 20% high compared to method A. They are more in agreement with AERONET measurements, which are on average only 5% lower, however with considerable relative differences (standard deviation ~ 25%). With respect to near surface volume mixing ratios and aerosol extinction we find considerably larger relative differences: 10 ± 30%, -23 ± 28% and - 8 ± 33% for aerosols, HCHO and NO2 respectively. The frequency distributions of these near-surface concentrations show however a quite good agreement, and this indicates that near-surface concentrations derived from MAX-DOAS are certainly useful in a climatological sense. A major difference between the two methods is the dynamic range of retrieved characteristic profile heights which is larger for method B than for method A. This effect is most pronounced for HCHO, where retrieved profile shapes with method A are very close to the a priori, and moderate for NO2 and aerosols which on average show quite good agreement for characteristic profile heights below 1.5 km. [ABSTRACT FROM AUTHOR]

Ground-based Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements of sulfur dioxide (SO2) have been performed at the Xianghe station (39.75° N, 116.96° E) located at ~50 km southeast of Beijing from March 2010 to February 2013. Tropospheric SO2 vertical profiles and corresponding vertical column densities (VCDs), retrieved by applying the Optimal Estimation Method to the MAX-DOAS observations, have been used to study the seasonal and diurnal cycles of SO2, in combination to correlative measurements from in situ instruments, as well as meteorological data. A marked seasonality was observed in both SO2 VCD and surface concentration, with a maximum in winter (February) and a minimum in summer (July). This can be explained by the larger emissions in winter due to the domestic heating and more favorable meteorological conditions for the accumulation of SO2 close to the ground during this period. Wind speed and direction are also found to be two key factors in controlling the level of the SO2-related pollution at Xianghe. In the case of east or southwest wind, the SO2 concentration rises with the increase of the wind speed, since heavy polluting industries are located to the east and southwest of the station. In contrast, when wind comes from other directions, the stronger the wind, the less SO2 is observed. Regarding the diurnal cycle, the SO2 amount is larger in the early morning and late evening and lower at noon, in line with the diurnal variation of pollutant emissions and atmospheric stability. The observed diurnal cycles of MAX-DOAS SO2 surface concentration are also in very good agreement (correlation coefficient close to 0.9) with those from collocated in-situ data, demonstrating the reliability and robustness of our retrieval. [ABSTRACT FROM AUTHOR]

Ground-based Multi-Axis Differential Optical Absorption Spectroscopy (MAX-DOAS) measurements of nitrous acid (HONO) and its precursor NO2 (nitrogen dioxide) as well as aerosols have been performed daily in Beijing city centre (39.98° N, 116.38° E) from July 2008 to April 2009 and at the suburban site of Xianghe (39.75° N, 116.96° E) located ~60 km east of Beijing from March 2010 to December 2012. This extensive dataset allowed for the first time the investigation of the seasonal cycle of HONO as well as its diurnal variation in and in the vicinity of a megacity. Our study was focused on the HONO and NO2 near-surface concentrations (0-200m layer) and total vertical column densities (VCDs) and also aerosol optical depths (AODs) and extinction coefficients retrieved by applying the Optimal Estimation Method to the MAX-DOAS observations. Monthly averaged HONO near-surface concentrations at local noon display a strong seasonal cycle with a maximum in late fall/winter (~0.8 and 0.7 ppb at Beijing and Xianghe, respectively) and a minimum in summer (~0.1 ppb at Beijing and 0.03 ppb at Xianghe). The seasonal cycles of HONO and NO2 appear to be highly correlated, with correlation coefficients in the 0.7-0.9 and 0.5-0.8 ranges at Beijing and Xianghe, respectively. The stronger correlation of HONO with NO2 and also with aerosols observed in Beijing suggests possibly larger role of NO2 conversion into HONO in the Beijing city center than at Xianghe. The observed diurnal cycle of HONO near-surface concentration shows a maximum in the early morning (about 1 ppb at both sites) likely resulting from night-time accumulation, followed by a decrease to values of about 0.1-0.4 ppb around local noon. The HONO/NO2 ratio shows a similar pattern with a maximum in the early morning (values up to 0.08) and a decrease to ~0.01-0.02 around local noon. The seasonal and diurnal cycles of the HONO near-surface concentration are found to be similar in shape and in relative amplitude to the corresponding cycles of the HONO total VCD and are therefore likely driven mainly by the balance between HONO sources and the photolytic sink, whereas dilution effects appear to play only a minor role. The estimation of OH radical production from HONO and O3 photolysis based on retrieved HONO near-surface concentrations and calculated photolysis rates indicate that in the 0-200m altitude range, HONO is by far the largest source of OH radicals in winter as well as in the early morning at all seasons, while the contribution of O3 dominates in summer from mid-morning until mid-afternoon. [ABSTRACT FROM AUTHOR]

We present intercomparison results for formaldehyde (HCHO) slant column measurements performed during the Cabauw Intercomparison campaign of Nitrogen Dioxide measuring Instruments (CINDI) that took place in Cabauw, the Netherlands, in summer 2009. During two months, nine atmospheric research groups simultaneously operated MAXDOAS (MultiAXis Differential Optical Absorption Spectroscopy) instruments of various designs to record UVvisible spectra of scattered sunlight at different elevation angles that were analysed using common retrieval settings. The resulting HCHO data set was found to be highly consistent, the mean difference between instruments generally not exceeding 15% or 7.5 × 1015 molec cm-2, for all viewing elevation angles. Furthermore, a sensitivity analysis was performed to investigate the uncertainties in the HCHO slant column retrieval when varying key input parameters such as the molecular absorption cross sections, correction terms for the Ring effect or the width and position of the fitting interval. This study led to the identification of potentially important sources of errors associated with crosscorrelation effects involving the Ring effect, O4, HCHO and BrO cross sections and the DOAS closure polynomial. As a result, a set of updated recommendations was formulated for HCHO slant column retrieval in the 336.5-359 nm wavelength range. To conclude, an error budget is proposed which distinguishes between systematic and random uncertainties. The total systematic error is estimated to be of the order of 20% and is dominated by uncertainties in absorption cross sections and related spectral cross-correlation effects. For a typical integration time of one minute, random uncertainties range between 5 and 30 %, depending on the noise level of individual instruments. [ABSTRACT FROM AUTHOR]

The trend in stratospheric NO2 column at the NDACC (Network for the Detection of Atmospheric Composition Change) station of Jungfraujoch (46.5° N, 8.0° E) is assessed using ground-based FTIR and zenith-scattered visible sunlight SAOZ measurements over the period 1990 to 2009 as well as a composite satellite nadir data set constructed from ERS-2/GOME, ENVISAT/SCIAMACHY, METOP-A/GOME-2 observations over the 1996-2009 period. To calculate the trends, a linear least squares regression model including explanatory variables for a linear trend, the mean annual cycle, the quasi-biennial oscillation (QBO), solar activity, stratospheric aerosol loading is used. For the 1990-2009 period, statistically indistinguishable trends of -3.7 ± 1.1% decade-1, -3.6 ± decade-11 are derived for the SAOZ and FTIR NO2 column time series, respectively. SAOZ, FTIR, satellite nadir data sets show a similar decrease over the 1996-2009 period, with trends of -2.4 ± 1.1% decade-11, -4.3 ± 1.4% decade-11, and -3.6 ± 2.2% decade-1, respectively. The fact that these declines are opposite in sign to the globally observed +2.5% decade-11 trend in N2O, suggests that factors other than N2O are driving the evolution of stratospheric NO2 at northern mid-latitudes. Possible causes of the decrease in stratospheric NO2 columns have been investigated. The most likely cause is a change in the NO2/NO partitioning in favor of NO, due to a possible stratospheric cooling and a decrease in stratospheric chlorine content, the latter being further confirmed by the negative trend in the ClONO2 column derived from FTIR observations at Jungfraujoch. Decreasing ClO concentrations slows the NO + ClO -> NO2 + Cl reaction and a stratospheric cooling slows the NO + O3 NO2 + O2 reaction, leaving more NOx in the form of NO. The slightly positive trends in ozone estimated from ground- and satellite-based data sets are also consistent with the decrease of NO2 through the NO2 + O3 -> NO3 + O2 reaction. Finally, we cannot rule out the possibility that a strengthening of the Dobson-Brewer circulation, which reduces the time available for N2O photolysis in the stratosphere, could also contribute to the observed decline in stratospheric NO2 above Jungfraujoch. [ABSTRACT FROM AUTHOR]

The article discusses the use of Multi-AXis differential optical absorption spectroscopy (DOAS) (MAXDOAS) technique for formaldehyde (HCHO) slant column measurements during the 2009 Cabauw Intercomparison Campaign of Nitrogen Dioxide measuring Instruments (CINDI) in the Netherlands. Sensitivity analysis was performed to examine the uncertainties in slant column. It mentions that recommendation was developed for HCHO slant column retrieval in the 336.5-359 nanometer (nm) wavelenght range.

The trend in stratospheric NO2 column at the NDACC (Network for the Detection of Atmospheric Composition Change) station of Jungfraujoch (46.5° N, 8.0° E) is assessed using ground-based FTIR and zenith-scattered visible sunlight SAOZ measurements over the period 1990 to 2009 as well as a composite satellite nadir data set constructed from ERS-2/GOME, ENVISAT/SCIAMACHY, and METOP-A/GOME-2 observations over the 1996--2009 period. To calculate the trends, a linear least squares regression model including explanatory variables for a linear trend, the mean annual cycle, the quasi-biennial oscillation (QBO), solar activity, and stratospheric aerosol loading is used. For the 1990--2009 period, statistically indistinguishable trends of -3.7±1.1 %/decade and -3.6±0.9 %/decade are derived for the SAOZ and FTIR NO2 column time series, respectively. SAOZ, FTIR, and satellite nadir data sets show a similar decrease over the 1996--2009 period, with trends of -2.4±1.1 %/decade, -4.3±1.4 %/decade, and -3.6±2.2 %/decade, respectively. The fact that these declines are opposite in sign to the globally observed +2.5%/decade trend in N2O, suggests that factors other than N2O are driving the evolution of stratospheric NO2 at northern mid-latitudes. Possible causes of the decrease in stratospheric NO2 columns have been investigated. The most likely cause is a change in the NO2/NO partitioning in favor of NO, due to a possible stratospheric cooling and a decrease in stratospheric chlorine content, the latter being further confirmed by the negative trend in the ClONO2 column derived from FTIR observations at Jungfraujoch. Decreasing ClO concentrations slows the NO+ClO ! NO2 +Cl reaction and a stratospheric cooling slows the NO+O3→NO2 +O2 reaction, leaving more NOx in the form of NO. The slightly positive trends in ozone estimated from ground- and satellite-based data sets are also consistent with the decrease of NO2 through the NO2 +O3→NO3 +O2 reaction. Finally, we cannot rule out the possibility that a strengthening of the Dobson-Brewer circulation, which reduces the time available for N2O photolysis in the stratosphere, could also contribute to the observed decline in stratospheric NO2 above Jungfraujoch. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the algorithm for the operational near real time retrieval of total and tropospheric nitrogen oxide columns from the Global Ozone Monitoring Experiment (GOME-2). It mentions that the authors used stratospheric air mass factors in computing nitrogen oxide columns. It states that tropospheric air mass factors are also being computed through collecting the monthly average profiles of nitrogen oxides.

The article presents a study on the recovery of aerosol optical attributes in several wavelengths of ground-based multi-axis differential absorption spectroscopy (MAXDOAS) in Beijing, China. The study involves the application of inversion algorithm at multiple wavelengths and calculation of aerosol optical depths (AODs). It assumes the correction factor in the measured differential slant column densities (DSCDs). Results of the study reveal the high quality of tetraoxygen (4) DSCDs.

The FRESCO (Fast Retrieval Scheme for Clouds from the Oxygen A-band) algorithm has been used to retrieve cloud information from measurements of the O2 Aband around 760 nm by GOME, SCIAMACHY and GOME- 2. The cloud parameters retrieved by FRESCO are the effective cloud fraction and cloud pressure, which are used for cloud correction in the retrieval of trace gases like O3 and NO2. To improve the cloud pressure retrieval for partly cloudy scenes, single Rayleigh scattering has been included in an improved version of the algorithm, called FRESCO+. We compared FRESCO+ and FRESCO effective cloud fractions and cloud pressures using simulated spectra and one month of GOME measured spectra. As expected, FRESCO+ gives more reliable cloud pressures over partly cloudy pixels. Simulations and comparisons with ground-based radar/lidar measurements of clouds show that the FRESCO+ cloud pressure is about the optical midlevel of the cloud. Globally averaged, the FRESCO+ cloud pressure is about 50 hPa higher than the FRESCO cloud pressure, while the FRESCO+ effective cloud fraction is about 0.01 larger. The effect of FRESCO+ cloud parameters on O3 and NO2 vertical column density (VCD) retrievals is studied using SCIAMACHY data and ground-based DOAS measurements. We find that the FRESCO+ algorithm has a significant effect on tropospheric NO2 retrievals but a minor effect on total O3 retrievals. The retrieved SCIAMACHY tropospheric NO2 VCDs using FRESCO+ cloud parameters (v1.1) are lower than the tropospheric NO2 VCDs which used FRESCO cloud parameters (v1.04), in particular over heavily polluted areas with low clouds. The difference between SCIAMACHY tropospheric NO2 VCDs v1.1 and groundbased MAXDOAS measurements performed in Cabauw, The Netherlands, during the DANDELIONS campaign is about -2.12x1014 molec cm-2. [ABSTRACT FROM AUTHOR]

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Various diseases are described as antecedents of Guillain-Barré syndrome (GBS), particularly gastroenteritis and respiratory infectious diseases, but epidemiological surveys are rare. This paper details a multicentre matched case-control study carried out within a well-defined Italian population. For each GBS case fulfilling the Asbury and Cornblath criteria, one control was recruited from a neurological (NC) ward and another from a non-neurological (NNC) ward, matched for age, sex, season of disease onset and area of residence. All cases and controls were administered a semistructured questionnaire. The OR was calculated according to the Mantel-Haenszel equation for triplets. Between 1 October 1996 and 30 September 1998, 75 triplets were included in the case-control study. The OR for flu-like syndrome was 7.14 (CI 95%, 3.28–15.52) and for gastroenteritis 3.57 (CI 95%, 1.31–9.72); no other factor reached significance. Our results, based on the clinical and anamnestic features of triplets of patients, support the possible role as risk factors for GBS of infectious diseases, particularly flu-like syndrome and gastroenteritis. [ABSTRACT FROM AUTHOR]

The role of para-chlorophenylalanine and α-methyl-DL-p-tyrosine in the antinociceptive effects of the intracerebroventricular administration of the antidepressant drugs clomipramine, zimelidine, imipramine and maprotiline was studied using the acetic acid writhing test in mice. The results demonstrated an antinociceptive effect for all these antidepressants. Pretreatment with para-chlorophenylalanine significantly reduced the antinociception induced by the ED50's of imipramine and maprotiline, and did not modify the effects of zimelidine and clomipramine, pretreatment with α-methyltyrosine did not modify the antinociception induced by these drugs except maprotiline. Pretreatment with para-chlorophenylanine plus α-methyltyrosine significantly reduced the antinociceptive effect of all the antidepressants tested. The main finding of the present study is that the association of para-chlorophenylanine plus α-methyltyrosine reduced the antinociceptive action of all the antidepressants. This means that critical levels of both 5-HT and NA are responsible for mediating the antinociceptive effects of antidepressants on the writhing test in mice. [ABSTRACT FROM AUTHOR]

Abstract The present work was designed to study the influence of testosterone and oestrogens on the benzodiazepine withdrawal syndrome in mice. Several withdrawal signs were induced by 15 mg/kg intraperitoneally of flumazenil in diazepam-treated mice. The most noticeable were jerks, usually accompanied by tail lifts, and seizures. The intensity of the diazepam withdrawal syndrome was significantly lower in male than in female mice, especially in relation to the incidence of seizures. Castrated male mice showed a significant increase in the intensity of withdrawal syndrome. In addition, diazepam produced a significant increase of body weight in males but not in females. The principal finding of the present work is that the incidence of seizures produced by the administration of flumazenil was significantly lower in male than in female diazepam-treated mice. This fact suggests that the mechanism of action of benzodiazepines is modulated by the action of sexual hormones, and that testosterone plays a relevant role. [ABSTRACT FROM AUTHOR]

The antinociceptive activity of nonsteroidal anti-inflammatory drugs (NSAIDs) has been explained mainly on the basis of their inhibition of the enzyme cyclooxygenase (COX); however, this inhibition is not enough to completely explain the analgesic efficacy of these drugs. The modulation exerted by serotonergic systems on antinociception is well known. The purpose of the present work was to further explore the role of serotonin in the antinociceptive activity of NSAIDs using the writhing test and the tail-flick test of the mice after the inhibition of serotonin biosynthesis with intraperitoneal p-chlorophenylalanine (p-CPA). Pretreatment with p-CPA produced a significant decrease in the antinociceptive activity of NSAIDs administered either by the intraperitoneal or intrathecal routes, in both algesiometric tests. These results suggest a complementary mechanism of antinociception for NSAIDs, independent of their ability to inhibit the activity of COX, involving the activation of descending serotonergic pathways. By the pharmacological nature of the study, one limitation was the absence of biochemical measurement of the synthesis of 5-HT, since the reduction of the brain 5-HT synthesis by pretreatment with p-CPA will be expressed as a disminished antinociceptive activity of NSAIDs, which would be a new argument to consider NSAIDs acting as central analgesic agents. [Copyright &y& Elsevier]

Background : Central neuropathic pain represents one of the most common symptoms in multiple sclerosis (MS) and it seriously affects quality of life. Spinal mechanisms may contribute to the pathogenesis of neuropathic pain in MS. Converging evidence from animal models and neurophysiological and clinical studies in humans suggests a potential effect of transcranial direct current stimulation (tc-DCS) on neuropathic pain. Spinal application of DCS, i.e., transcutaneous spinal DCS (ts-DCS), may modulate nociception through inhibition of spinal reflexes. Therefore, ts-DCS could represents an effective, safe and well-tolerated treatment for neuropathic pain in MS, a largely unexplored topic. This study is a pilot randomized double-blind sham-controlled trial to evaluate the efficacy of ts-DCS on central neuropathic pain in MS patients. Methods : Thirty-three MS patients with central neuropathic pain were enrolled and randomly assigned to two groups in a double-blind sham-controlled design: anodal ts-DCS group ( n = 19, 10 daily 20-min sessions, 2 mA) or sham ts-DCS group ( n = 14, 10 daily 20-min sessions, 0 mA). The following clinical outcomes were evaluated before ts-DCS treatment (T0), after 10 days of treatment (T1) and 1 month after the end of treatment (T2): neuropathic pain symptoms inventory (NPSI), Ashworth Scale (AS) for spasticity and Fatigue Severity Scale (FSS). A subgroup of patients treated with anodal ts-DCS ( n = 12) and sham ts-DCS ( n = 11) also underwent a parallel neurophysiological study of the nociceptive withdrawal reflex (NWR) and the NWR temporal summation threshold (TST), two objective markers of pain processing at spinal level. Results : Anodal ts-DCS group showed a significant improvement in NPSI at T1, which persisted at T2, while we did not detect any significant change in AS and FSS. Sham ts-DCS group did not show any significant change in clinical scales. We observed a non-significant trend towards an inhibition of NWR responses in the anodal ts-DCS group at T1 and T2 when compared to baseline. Conclusions : Anodal ts-DCS seems to have an early and persisting (i.e., 1 month after treatment) clinical efficacy on central neuropathic pain in MS patients, probably through modulation of spinal nociception. Clinical Trial Registration: www.ClinicalTrials.gov, identifier #NCT02331654.

Primary progressive multiple sclerosis (PPMS) and amyotrophic lateral sclerosis (ALS) seem to share some clinical and pathological features. MRI studies revealed the presence of grey matter (GM) atrophy in both diseases, but no comparative data are available. The objective was to compare the regional patterns of GM tissue loss in PPMS and ALS with voxel-based morphometry (VBM). Eighteen PPMS patients, 20 ALS patients, and 31 healthy controls (HC) were studied with a 1.5 Tesla scanner. VBM was performed to assess volumetric GM differences with age and sex as covariates. Threshold-free cluster enhancement analysis was used to obtain significant clusters. Group comparisons were tested with family-wise error correction for multiple comparisons (p < 0.05) except for HC versus MND which was tested at a level of p < 0.001 uncorrected and a cluster threshold of 20 contiguous voxels. Compared to HC, ALS patients showed GM tissue reduction in selected frontal and temporal areas, while PPMS patients showed a widespread bilateral GM volume decrease, involving both deep and cortical regions. Compared to ALS, PPMS patients showed tissue volume reductions in both deep and cortical GM areas. This preliminary study confirms that PPMS is characterized by a more diffuse cortical and subcortical GM atrophy than ALS and that, in the latter condition, brain damage is present outside the motor system. These results suggest that PPMS and ALS may share pathological features leading to GM tissue loss.

In this paper we present a new method for retrieving tropospheric NO2 Vertical Column Density (VCD) from zenith-sky Differential Optical Absorption Spectroscopy (DOAS) measurements using mobile observations. This method was used during three days in the summer of 2011 in Romania, being to our knowledge the first mobile DOAS measurements peformed in this country. The measurements were carried out over large and different areas using a mobile DOAS system installed in a car. We present here a step-by-step retrieval of tropospheric VCD using complementary observations from ground and space which take into account the stratospheric contribution, which is a step forward compared to other similar studies. The detailed error budget indicates that the typical uncertainty on the retrieved NO2tropospheric VCD is less than 25%. The resulting ground-based data set is compared to satellite measurements from the Ozone Monitoring Instrument (OMI) and the Global Ozone Monitoring Experiment-2 (GOME-2). For instance, on 18 July 2011, in an industrial area located at 47.03°N, 22.45°E, GOME-2 observes a tropospheric VCD value of (3.4 ± 1.9) × 1015 molec./cm2, while average mobile measurements in the same area give a value of (3.4 ± 0.7) × 10(15) molec./cm2. On 22 August 2011, around Ploiesti city (44.99°N, 26.1°E), the tropospheric VCD observed by satellites is (3.3 ± 1.9) × 10(15) molec./cm2 (GOME-2) and (3.2 ± 3.2) × 10(15) molec./cm2 (OMI), while average mobile measurements give (3.8 ± 0.8) × 10(15) molec./cm2. Average ground measurements over "clean areas", on 18 July 2011, give (2.5 ± 0.6) × 10(15) molec./cm2 while the satellite observes a value of (1.8 ± 1.3) × 10(15) molec./cm2.

To enhance analgesia, combination of analgesics drugs of proven efficacy is a strategy which is accompanied by a reduction of adverse effects. The present study was undertaken to characterize the antinociceptive interaction of morphine with different non-steroidal anti-inflammatory drugs (NSAIDs) using isobolographic analysis and the writhing test of mice. One of the possible mechanisms of action of spinally administered morphine with non-steroidal antiinflammatory drugs was investigated using the DOR antagonist naltrindole. The study demonstrated a synergistic antinociception of spinal administered combinations of morphine with the following NSAIDs agents: diclofenac, ketoprofen, meloxicam, metamizol, naproxen, nimesulide, parecoxib and piroxicam. The supraadditive effect seems to be independent of the selectivity of each NSAIDs to inhibit COX-1 or COX-2. The findings of the present work suggest that the combinations of opioids and non-steroidal anti-inflammatory drugs have a direct action on spinal processing of the nociceptive information, which may achieved by additional mechanisms independent of prostaglandin synthesis inhibition and/or activation of opioid receptors. The lack of effect of naltrindole to modify the analgesic activity of the combination of opioids and NSAIDs indicates that others pain regulatory systems are involved in this central action. Therefore, these combinations could be a viable alternative to clinical pain management, especially trough multimodal analgesia.

To enhance analgesia, the combinatorial use of analgesic drugs with proven efficacies is a widely-used strategy to reduce adverse side effects. The present study characterizes the antinociceptive interaction of intrathecal morphine co-administered with different NSAIDs using isobolographic analysis.Antinoceptive activity was evaluated using a model for acute visceral pain, the writhing test of mice. The possible involvement of opioid receptors in the mechanism of action of the intrathecal co-administration of morphine and NSAIDs was investigated using the non-selective receptor antagonist naltrexone. The study demonstrated a synergistic antinociception of intrathecal administered combinations of morphine with the following NSAIDs: diclofenac, ketoprofen, meloxicam, metamizol, naproxen, nimesulide, parecoxib and piroxicam. The supra additive effect was obtained with very low doses of each drug and it appeared to be independent of the COX-1 or COX-2 inhibition selectivity of each NSAID and was not significantly modified by intrathecal naltrexone. The findings of the present work suggest that the combination of opioids and NSAIDs has a direct action on spinal nociceptive processing, which may be achieved via mechanisms that are independent of the activation of opioid receptors. The ineffectiveness of naltrexone to reverse the analgesic activity of opioids + NSAIDs combinations indicates that other complex pain regulatory systems are involved in this effect.