Aerosol inhalation delivery of cefazolin in mice: Pharmacokinetic measurements and antibacterial effect.

Aerosol inhalation delivery of cefazolin, a broad-spectrum first-generation cephalosporin antibiotic, was investigated. Inhalation system based on ultrasonic nebulizer was developed for the generation of dry cefazolin aerosol within mean particle diameter range 0.5-3.0 µm and mass concentration 0.01-3 µg/cm3. Pharmacokinetic measurements were carried out for the aerosolized form of cefazolin delivered in mice using nose-only chamber. Cefazolin concentrations in blood serum and in the lungs of mice were measured as a function of time by means of high performance liquid chromatography. Body-delivered dose depending on particle size, concentration and inhalation time as well as other pharmacokinetic parameters were determined. The antibacterial effect of aerosolized cefazolin was assessed through the aerosol inhalation treatment of mice infected with Klebsiella pneumoniae. Survival rate for infected mice after the treatment with cefazolin aerosol demonstrated high antibacterial efficiency of the inhalation delivery of cefazolin in comparison with intraperitoneal delivery.

Excipient-free isoniazid aerosol administration in mice: Evaporation-nucleation particle generation, pulmonary delivery and body distribution.

Excipient-free isoniazid aerosol formation and pulmonary delivery in mice are studied. An evaporation-nucleation route is used for the generation of isoniazid aerosol. Particle diameters and number concentrations are measured with an aerosol spectrometer consisting of a diffusion battery, condensation chamber, and photoelectric counter. The pulmonary delivery of isoniazid particles is studied in both nose-only (NO) and whole-body (WB) inhalation chambers for the particle mean diameter and number concentration to be 600 nm and 6 × 106 cm-3, respectively. It is found that the rate of drug systemic absorption in the WB chamber is 27% higher than that for the NO one because of an additional consumption of drug orally from the fur in the WB chamber. The particle deposition efficiency ε in the mouse respiratory tract is measured as a function of mean diameter. The quantity ε is equal to 0.7 for the particle diameter d = 10 nm and decreases to 0.2 with the diameter increasing to 300 nm, and then, at d > 300 nm the deposition efficiency increases with diameter to 0.5 at d = 2000 nm. The bioavailability of the aerosol form of isoniazid (72 ±â€¯10%) is very close to that for the per-oral form (61 ±â€¯10%).

Key Issues for Seamless Integrated Chemistry-Meteorology Modeling.

Online coupled meteorology-atmospheric chemistry models have greatly evolved in recent years. Although mainly developed by the air quality modeling community, these integrated models are also of interest for numerical weather prediction and climate modeling, as they can consider both the effects of meteorology on air quality and the potentially important effects of atmospheric composition on weather. This paper summarizes the main conclusions from the "Symposium on Coupled Chemistry-Meteorology/Climate Modelling: Status and Relevance for Numerical Weather Prediction, Air Quality and Climate Research," which was initiated by the European COST Action ES1004 "European Framework for Online Integrated Air Quality and Meteorology Modelling (EuMetChem)." It offers a brief review of the current status of online coupled meteorology and atmospheric chemistry modeling and a survey of processes relevant to the interactions between atmospheric physics, dynamics, and composition. In addition, it highlights scientific issues and emerging challenges that require proper consideration to improve the reliability and usability of these models for three main application areas: air quality, meteorology (including weather prediction), and climate modeling. It presents a synthesis of scientific progress in the form of answers to nine key questions, and provides recommendations for future research directions and priorities in the development, application, and evaluation of online coupled models.

Role of ion-pair states in the predissociation dynamics of Rydberg states of molecular iodine.

Using femtosecond pump-probe ion imaging spectroscopy, we establish the key role of I(+) + I(-) ion-pair (IP) states in the predissociation dynamics of molecular iodine I2 excited to Rydberg states. Two-photon excitation of Rydberg states lying above the lowest IP state dissociation threshold (1st tier) is found to be followed by direct parallel transitions into IP states of the 1st tier asymptotically correlating to a pair of I ions in their lowest states I(+)((3)P2) + I(-)((1)S0), of the 2nd tier correlating to I(+)((3)P0) + I(-)((1)S0), and of the 3rd tier correlating to I(+)((1)D2) + I(-)((1)S0). Predissociation via the 1st tier proceeds presumably with a delay of 1.6-1.7 ps which is close to the vibrational period in the 3rd tier state (3rd tier-mediated process). The 2nd tier IP state is concluded to be the main precursor for predissociation via lower lying Rydberg states proceeding with a characteristic time of 7-8 ps and giving rise to Rydberg atoms I(5s(2)5p(4)6s(1)). The channel generating I((2)P3/2) + I((2)P1/2) atoms with total kinetic energy corresponding to one-photon excitation is found to proceed via a pump - dump mechanism with dramatic change of angular anisotropy of this channel as compared with earlier nanosecond experiments.

Ultrasensitive detection of inhaled organic aerosol particles by accelerator mass spectrometry.

Accelerator mass spectrometry (AMS) was shown to be applicable for studying the penetration of organic aerosols, inhaled by laboratory mice at ultra-low concentration ca. 10(3) cm(-3). We synthesized polystyrene (PS) beads, composed of radiocarbon-labeled styrene, for testing them as model organic aerosols. As a source of radiocarbon we used methyl alcohol with radioactivity. Radiolabeled polystyrene beads were obtained by emulsifier-free emulsion polymerization of synthesized (14)C-styrene initiated by K2S2O8 in aqueous media. Aerosol particles were produced by pneumatic spraying of diluted (14)C-PS latex. Mice inhaled (14)C-PS aerosol consisting of the mix of 10(3) 225-nm particles per 1 cm(3) and 5·10(3) 25-nm particles per 1 cm(3) for 30 min every day during five days. Several millions of 225-nm particles deposited in the lungs and slowly excreted from them during two weeks of postexposure. Penetration of particles matter was also observed for liver, kidneys and brain, but not for a heart.

[TESTICULAR FUNCTION AND LIPID METABOLISM IN MALE MICE WITH HEREDITARY PREDISPOSITION TO OBESITY].

Parameters of spermatogenesis, androgen status and lipid metabolism (amount of abdominal fat, cholesterol and triglycerides plasma levels) in male mice with the mutation yellow at the locus agouti (Ay mice), which results in obesity after puberty were studied. Their lean littermate's mice of standard C57BL/6J strain genotype (a/a mice) were used as a control. At the age of 15 and 30 weeks the body weight, triglyceride levels, and at the age of 30 weeks - abdominal fat mass in Ay males were higher than that of a/a males. These data confirm the development of obesity and disturbance of lipid metabolism in Ay males. There were no changes in the number of sperm in the caudal epididymis, the proportion of mobile and morphologically abnormal sperm, the concentration of testosterone and its content in the testes in Ay mice at the reproductively active period (age 15 and 30 weeks). It is assumed that the ectopic expression of agouti protein in Ay males may be involved in the protection of the testicular function from the negative impact of obesity.

[STUDY RELATIVE EXPRESSION OF GENES THAT CONTROL GLUCOSE METABOLISM IN THE LIVER IN MICE WITH DEVELOPMENT OF MELANOCORTIN OBESITY].

The relative gene expressions of glucose-6-phosphatase (G6P), phosphoenolpyruvate carbo- xykinase (PEPCK)--markers of gluconeogenesis, glucokinase (GK)--a marker of glycolysis, glucose transporter type 2 (GLUT2)--a marker of input and output of glucose in the liver were measured during the development of melanocortin (MC) obesity in male mice of C57BL/6J strain with mutation yellow in the Agouti locus (Ay/a mice). The mutation decreases MC receptor activity and induces hyperphagia and MC obesity. The males of the same line with mutation nonagouti were used as control. Tissue samples were taken at age 10 (before obesity), 15 (moderate obesity) and 30 (developed obesity) weeks. It has been shown that Ay/a mice had decreased glucose tolerance since 10-week age. There were age-related changes in mRNA levels in the liver of Ay/a mice, unlike a/a mice. In Ay/a mice the mRNA GLUT2 levels at the age of 10 weeks, mRNA GK levels at the age of 15 weeks, and mRNA G6P levels at the age of 3O weeks were higher than those in Ada mice of other ages. InAYfa mice the mRNA GK levels at the age of 15 weeks and mRNA G6F levels at the age of 30 weeks were increased relatively to those in a/a mice. Thus, Ay/a mice before the development of MK obesity had changes in the mRNA levels genes of proteins that regulate hepatic glucose metabolism, which may contribute to the compensation of glucose metabolism disorders caused by a hereditary decrease of MK system activity

Predissociation dynamics of lithium iodide.

The predissociation dynamics of lithium iodide (LiI) in the first excited A-state is investigated for molecules in the gas phase and embedded in helium nanodroplets, using femtosecond pump-probe photoionization spectroscopy. In the gas phase, the transient Li(+) and LiI(+) ion signals feature damped oscillations due to the excitation and decay of a vibrational wave packet. Based on high-level ab initio calculations of the electronic structure of LiI and simulations of the wave packet dynamics, the exponential signal decay is found to result from predissociation predominantly at the lowest avoided X-A potential curve crossing, for which we infer a coupling constant VXA = 650(20) cm(-1). The lack of a pump-probe delay dependence for the case of LiI embedded in helium nanodroplets indicates fast droplet-induced relaxation of the vibrational excitation.

[Staged correction of spinal deformity in a patient with incontinentia pigmenti syndrome].

Case presentation of staged surgical treatment of patients with spinal deformity in incontinentia pigmenti syndrome. As a result of surgical procedure proper sagittal balance of the body was restored.

An hourly PM10 diagnosis model for the Bilbao metropolitan area using a linear regression methodology.

There is extensive evidence of the negative impacts on health linked to the rise of the regional background of particulate matter (PM) 10 levels. These levels are often increased over urban areas becoming one of the main air pollution concerns. This is the case on the Bilbao metropolitan area, Spain. This study describes a data-driven model to diagnose PM10 levels in Bilbao at hourly intervals. The model is built with a training period of 7-year historical data covering different urban environments (inland, city centre and coastal sites). The explanatory variables are quantitative-log [NO2], temperature, short-wave incoming radiation, wind speed and direction, specific humidity, hour and vehicle intensity-and qualitative-working days/weekends, season (winter/summer), the hour (from 00 to 23 UTC) and precipitation/no precipitation. Three different linear regression models are compared: simple linear regression; linear regression with interaction terms (INT); and linear regression with interaction terms following the Sawa's Bayesian Information Criteria (INT-BIC). Each type of model is calculated selecting two different periods: the training (it consists of 6 years) and the testing dataset (it consists of 1 year). The results of each type of model show that the INT-BIC-based model (R(2) = 0.42) is the best. Results were R of 0.65, 0.63 and 0.60 for the city centre, inland and coastal sites, respectively, a level of confidence similar to the state-of-the art methodology. The related error calculated for longer time intervals (monthly or seasonal means) diminished significantly (R of 0.75-0.80 for monthly means and R of 0.80 to 0.98 at seasonally means) with respect to shorter periods.

[Surgical treatment of patients with spinal deformities with shortening of the lower limb].

AIM: Determination of the optimal diagnostic and treatment strategy in patients with scoliosis and having an anatomic shortening of the lower limb. PATIENTS AND METHODS: Surgical correction of scoliosis held 8 to patients with lower limb shortening caused by congenital dislocation of the hip (n = 3), anatomic shortening of the lower extremities due to the hip (n = 1), the shin bone (n = 4). Shortening before correction and fixation of scoliosis ranged from 6 to 14 cm, after surgery on the spine has been reduced by 2-4 cm achieved reduction or removal of pelvic obliquity. The second stage, after 8-12 months, performed surgery to address shortening of the lower extremity. Osteotomy of the femur with the imposition of a spoke - rod device held 4 tibial osteotomy with the imposition of external fixation device Spoke - and 4 patients and in the subsequent limb lengthening was performed by compression-distraction osteosynthesis. RESULTS: After the dorsal stabilization and fixation of the spine scoliosis correction averaged 64% (from 76 to 27 degrees), the value of breast/thoracolumbar kyphosis after surgery failed to bring to the physiological (average 43 degrees). Misalignment of the pelvis is reduced by 67% (from 24 to 8 degrees), which reduced the shortening of the lower limb by an average of 3 cm (compensation relative shortening by reducing or eliminating the distortion of the pelvis). Further compensation shortening held on the second stage of treatment, representing an osteotomy and subsequent elongation of the femur or tibia bones by transosseous compression-distraction osteosynthesis by Ilizarov. CONCLUSIONS: Multi-stage treatment reduced the degree of spinal deformity, to normalize the balance of the body, restore the function of distance without the use of orthotic devices and means of support.

Experimental study of homogeneous nucleation from the bismuth supersaturated vapor: evaluation of the surface tension of critical nucleus.

The homogeneous nucleation of bismuth supersaturated vapor is studied in a laminar flow quartz tube nucleation chamber. The concentration, size, and morphology of outcoming aerosol particles are analyzed by a transmission electron microscope (TEM) and an automatic diffusion battery (ADB). The wall deposit morphology is studied by scanning electron microscopy. The rate of wall deposition is measured by the light absorption technique and direct weighting of the wall deposits. The confines of the nucleation region are determined in the "supersaturation cut-off" measurements inserting a metal grid into the nucleation zone and monitoring the outlet aerosol concentration response. Using the above experimental techniques, the nucleation rate, supersaturation, and nucleation temperature are measured. The surface tension of the critical nucleus and the radius of the surface of tension are determined from the measured nucleation parameters. To this aim an analytical formula for the nucleation rate is used, derived from author's previous papers based on the Gibbs formula for the work of formation of critical nucleus and the translation-rotation correction. A more accurate approach is also applied to determine the surface tension of critical drop from the experimentally measured bismuth mass flow, temperature profiles, ADB, and TEM data solving an inverse problem by numerical simulation. The simulation of the vapor to particles conversion is carried out in the framework of the explicit finite difference scheme accounting the nucleation, vapor to particles and vapor to wall deposition, and particle to wall deposition, coagulation. The nucleation rate is determined from simulations to be in the range of 10(9)-10(11) cm(-3) s(-1) for the supersaturation of Bi(2) dimers being 10(17)-10(7) and the nucleation temperature 330-570 K, respectively. The surface tension σ(S) of the bismuth critical nucleus is found to be in the range of 455-487 mN/m for the radius of the surface of tension from 0.36 to 0.48 nm. The function σ(S) changes weakly with the radius of critical nucleus. The value of σ(S) is from 14% to 24% higher than the surface tension of a flat surface.

Evaluation of surface tension and Tolman length as a function of droplet radius from experimental nucleation rate and supersaturation ratio: metal vapor homogeneous nucleation.

Zinc and silver vapor homogeneous nucleations are studied experimentally at the temperature from 600 to 725 and 870 K, respectively, in a laminar flow diffusion chamber with Ar as a carrier gas at atmospheric pressure. The size, shape, and concentration of aerosol particles outcoming the diffusion chamber are analyzed by a transmission electron microscope and an automatic diffusion battery. The wall deposit is studied by a scanning electron microscope (SEM). Using SEM data the nucleation rate for both Zn and Ag is estimated as 10(10) cm(-3) s(-1). The dependence of critical supersaturation on temperature for Zn and Ag measured in this paper as well as Li, Na, Cs, Ag, Mg, and Hg measured elsewhere is analyzed. To this aim the classical nucleation theory is extended by the dependence of surface tension on the nucleus radius. The preexponent in the formula for the vapor nucleation rate is derived using the formula for the work of formation of noncritical embryo [obtained by Nishioka and Kusaka [J. Chem. Phys. 96, 5370 (1992)] and later by Debenedetti and Reiss [J. Chem. Phys. 108, 5498 (1998)]] and Reiss replacement factor. Using this preexponent and the Gibbs formula for the work of formation of critical nucleus the dependence of surface tension on the radius R(S) of the surface of tension is evaluated from the nucleation data for above-mentioned metals. For the alkali metals and Ag the surface tension was determined to be a strong function of R(S). For the bivalent metals (Zn, Hg, and Mg) the surface tension was independent of radius in the experimental range. A new formula for the Tolman length delta as a function of surface tension and radius R(S) is derived by integration of Gibbs-Tolman-Koenig equation assuming that delta is a monotonic function of radius. The formula derived is more correct than the Tolman formula and convenient for the elaboration of experimental data. Using this formula the values of delta are determined as a function of R(S) from the experimental nucleation data. It is determined that all the metals considered are characterized by strong dependence of delta on radius; for the bivalent metals delta changes sign.

Iron monoxide photodissociation.

The photodissociation of (56)FeO was studied by means of the velocity map imaging technique. A molecular beam of iron atoms and iron monoxide molecules was created using an electrical discharge with an iron electrode in a supersonic expansion of molecular oxygen. The ground state iron atom Fe((5)D(4)) and FeO concentrations in the molecular beam have been estimated. The dissociation energy of the FeO X (5)Delta ground electronic state was found to be D(0) (0)(FeO)=4.18+/-0.01 eV. The effective absorption cross section of FeO at 252.39 nm (vac), leading to the Fe((5)D(4))+O((3)P) dissociation channel, is approximately 1.2 x 10(-18) cm(2). A (1+1) resonantly enhanced multiphoton ionization spectrum of (56)FeO in the region 39 550-39 580 cm(-1) with rotational structure has been observed, but not assigned. Angular distributions of Fe((5)D(4)) and Fe((5)D(3)) products for the channel FeO-->Fe((5)D(4,3))+O((3)P) have been measured at several points in the 210-260 nm laser light wavelength region. The anisotropy parameter varies strongly with wavelength for both channels.

Assessment of potential atmospheric transport and deposition patterns due to Russian Pacific Fleet operations.

A probabilistic analysis of atmospheric transport and deposition patterns from two nuclear risk sites-Kamchatka and Vladivostok-situated in the Russian Far East to countries and geographical regions of interest (Japan, China, North and South Koreas, territories of the Russian Far East, State of Alaska, and Aleutian Chain Islands, US) was performed. The main questions addressed were the following: Which geographical territories are at the highest risk from hypothetical releases at these sites? What are the probabilities for radionuclide atmospheric transport and deposition on different neighboring countries in case of accidents at the sites? For analysis, several research tools developed within the Arctic Risk Project were applied: (1) isentropic trajectory model to calculate a multiyear dataset of 5-day forward trajectories that originated over the site locations at various altitudes; (2) DERMA long-range transport model to simulate 5-day atmospheric transport, dispersion, and deposition of 137Cs for 1-day release (at the rate of 10(10) Bq/s); and (3) a set of statistical methods (including exploratory, cluster, and probability fields analyses) for evaluation of trajectory and dispersion modeling results. The possible impact (on annual, seasonal, and monthly basis) of selected risk sites on neighboring geographical regions is evaluated using a set of various indicators. For trajectory modeling, the indicators examined are: (1) atmospheric transport pathways, (2) airflow probability fields, (3) fast transport probability fields, (4) maximum possible impact zone, (5) maximum reaching distance, and (6) typical transport time fields. For dispersion modeling, the indicators examined are: (1) time integrated air concentration, (2) dry deposition, and (3) wet deposition. It was found for both sites that within the boundary layer the westerly flows are dominant throughout the year (more than 60% of the time), increasing with altitude of free troposphere up to 85% of the time. For the Kamchatka site, the US regions are at the highest risk with the average times of atmospheric transport ranging from 3 to 5.1 days and depositions of 10(-1) Bq/m2 and lower. For the Vladivostok site, the northern China and Japan regions are at the highest risk with the average times of atmospheric transport of 0.5 and 1.6 days, respectively, and depositions ranging from 10(0) to 10(+2) Bq/m2. The areas of maximum potentially impacted zones are 30 x 10(4) km2 and 25 x 10(4) km2 for the Kamchatka and Vladivostok sites, respectively.

Can the confidence in long range atmospheric transport models be increased? The pan-european experience of ensemble.

Is atmospheric dispersion forecasting an important asset of the early-phase nuclear emergency response management? Is there a 'perfect atmospheric dispersion model'? Is there a way to make the results of dispersion models more reliable and trustworthy? While seeking to answer these questions the multi-model ensemble dispersion forecast system ENSEMBLE will be presented.

Methodology for evaluation of possible consequences of accidental atmospheric releases of hazardous matter.

Sites exist with high levels of risk of accidental atmospheric releases. These releases can be hazardous nuclear, chemical, and biological matter. Such accidents may occur during transport of waste, or they may be due to natural hazards, human errors, terror acts or various operations at high risk. Considering the operation of lifting and transport of the sunken Kursk nuclear submarine as an example, a methodology for risk assessment is described. This methodology includes two approaches: (1) probabilistic analysis of possible atmospheric transport pathways using trajectory modelling, and (2) evaluation of possible contamination and consequences using real-time operational atmospheric dispersion modelling. The first approach can be applied in advance of an operation during the preparation stage, the second in real time during the operation stage. For the cases considered in this study, the results of trajectory modelling are supported by the operational dispersion modelling, i.e., the westerly flow is dominant during fall occurring 79% of the time. Hence, September-October 2001 was more appropriate for the lifting and transport of the Kursk nuclear submarine in comparison with summer months, when atmospheric transport toward the populated regions of the Kola and Scandinavian Peninsulas was dominant. The suggested methodology may be applied to any potentially dangerous object involving a risk of atmospheric release of hazardous material of nuclear, chemical or biological nature.

Atmospheric transport patterns and possible consequences for the European North after a nuclear accident.

The main purpose of this study is to examine possible impacts and consequences of a hypothetical accident at the Kola nuclear plant in north-west Russia on different geographical regions: Scandinavia, central Europe, European FSU and Taymyr. The period studied is 1991-1996. An isentropic trajectory model has been used to calculate forward trajectories that originated over the nuclear accident region. Atmospheric transport patterns were identified using the isentropic trajectories and a cluster analysis technique. From the trajectory model results, a number of cases were chosen for examination in detail using more complete transport models. For this purpose, the models MATHEW/ADPIC, DERMA and a newly developed FOA Random Displacement Model have been used to simulate the radionuclide transport and contamination in the case of a nuclear accident and their results have been compared with those of the trajectory modelling. Estimation of the long-term consequences for populations after an accident has been performed for several specific dates by empirical models and correlation between fallout and doses to humans on the basis of the Chernobyl accident exposures in Scandinavia.

Correlation between sagittal plane changes and adjacent segment degeneration following lumbar spine fusion.

Adjacent segment degeneration following lumbar spine fusion remains a widely acknowledged problem, but there is insufficient knowledge regarding the factors that contribute to its occurrence. The aim of this study is to analyse the relationship between abnormal sagittal plane configuration of the lumbar spine and the development of adjacent segment degeneration. Eighty-three consecutive patients who underwent lumbar fusion for degenerative disc disease were reviewed retrospectively. Patients with spondylolytic spondylolisthesis and degenerative scoliosis were not included in this study. Mean follow-up period was 5 years. Results were analysed to determine the association between abnormal sagittal configuration and post operative adjacent segment degeneration. Thirty-one out of 83 patients (36.1%) showed radiographic evidence of adjacent segment degeneration. Patients with normal C7 plumb line and normal sacral inclination in the immediate post operative radiographs had the lowest incidence of adjacent level change compared with patients who had abnormality in one or both of these parameters. The difference was statistically significant (P<0.02). There was no statistically significant difference in the incidence of adjacent level degeneration between male and female patients; between posterior fusion alone and combined posterolateral and posterior interbody fusions; and between fusions extending down to the sacrum and fusions stopping short of the sacrum. It was concluded was that normality of sacral inclination is an important parameter for minimizing the incidence of adjacent level degeneration. Retrolisthesis was the most common type of adjacent segment change. Patients with post operative sagittal plane abnormalities should preferably be followed-up for at least 5 years to detect adjacent level changes.