Comparison Between Incremental and Single-Dose Allergen Administration in Bronchial Provocation Tests

To study the effect of different schedules of allergen administration on the early (EAR) and late allergic reaction (LAR), 15 asthmatic patients with dual response after allergen challenge were submitted to two consecutive bronchoprovocation tests (BPT). BPT₁ was carried out with semilogarithmic increase of allergen doses until a FEV₁ drop of 20% was recorded. BPT₂ was performed 2 weeks later using the highest allergen dose that had elicited the dual reaction in BPT₁. Both EAR and LAR were very similar for a given patient. As the allergen dose used in BPT₂ is smaller than the cumulative allergen dose administered in BPT₁, this protocol takes into account a possible influence on BPT₂ of bronchial hyperreactivity induced by BPT₁ performed 2 weeks before.     

Formation of a tablet: a site and bond percolation phenomenon.

The concepts of percolation theory are used to elucidate the formation of a tablet by compression of particulate matter. The process of compaction can be considered as a combination of site and bond percolation phenomena. Because of effects of different particle size and shape of the particles in a powder bed and effects of brittle fracture and plastic flow, moisture content of the powder, and finite size of the tablet, no sharp percolation thresholds are expected. Thus, it is interesting to test the validity of the fundamental equation of percolation theory: the power law X = S(p - pc)q, where X is the system property, S is the scaling factor, p is the site occupation or bond formation probability, and q is the critical exponent. This model is, in certain cases, only rigorously valid close to the percolation threshold (range, [+/- 0.1 pc]). Combination of the Heckel equation with an equation derived earlier for the properties (X) of tensile strength (sigma t) and deformation hardness (P) yields a power law with q = 1, S'(sigma t) = sigma tmax/(1 - pc), and S(P) = Pmax/(1 - pc). With respect to the simplifying assumptions made, the power law agrees well with the experimental results obtained. Substantial improvements in the interpretation of the compression-compaction process are possible with these findings, and some interpretations differ from previous ones in earlier publications.     

The application of percolation theory to the compaction of pharmaceutical powders

Based on the concepts of percolation theory the compaction process is interpreted as a site-bond percolation phenomenon. The combination of the Heckel equation with an equation derived earlier yields a simple relationship between the tensile strength σ_t, or the deformation hardness P and the relative density. This mathematical model is identical with the fundamental law of percolation theory i.e., X = s(p − p_c)^q with X= system property equivalent to tensile strength or deformation hardness, S = scaling factor, p = site occupation or bond formation probability corresponding to the relative density p,p_c = percolation threshold and critical exponent q = 1 according to percolation on a Bethe lattice. In the case of the tensile strength σ_t and the deformation hardness p, two percolation thresholds p_c(1) and p_c(2) corresponding to p_c(1) and p_c(2) could be identified. The relative density p_c(1) which is close to the relative poured or relative tapped density can be interpreted as a bond percolation threshold. The particles are bonded by weak interparticulate forces and form only loose compacts as used for filling of capsules. The relative density p_c(2) is the relative density where the first stable pharmaceutical compact is achieved which can no longer be disintegrated mechanically into its primary particles. It is of special interest that the above equation is also valid for the elastic modulus with the only percolation threshold p_c(1) = p_c(1).     

Analysis of Drug/Plasma Protein Interactions by Means of Asymmetrical Flow Field-Flow Fractionation

Purpose. The applicability of Asymmetrical Flow Field-Flow Fractionation (Asymmetrical Flow FFF) as an alternative tool to examine the distribution of a lipophilic drug (N-Benzoyl-staurosporine) within human plasma protein fractions was investigated with respect to high separation speed and loss of material on surfaces due to adsorption. Methods. Field-Flow Fractionation is defined as a group of pseudo-chromatographic separation methods, where compounds are separated under the influence of an externally applied force based on differences in their physicochemical properties. This method was used to separate human plasma in its protein fractions. The drug distribution in the fractions was investigated by monitoring the fractionated eluate for drug content by fluorescence spectroscopy. Results. Human plasma was separated into human serum albumin (HSA), high density lipoprotein (HDL), ₂-macroglobulin and low density lipoprotein (LDL) fractions in less than ten minutes. Calibration of the system and identification of the individual fractions was performed using commercially available protein reference standards. The influence of membrane type and carrier solution composition on the absolute recovery of N-Benzoyl-staurosporine and fluorescein-isothio-cyanate-albumin (FITC-albumin) was found to be quite significant. Both factors were optimized during the course of the investigations. N-Benzoyl-staurosporine was found to be enriched in the fraction containing HSA. Conclusions. If experimental conditions are thoroughly selected and controlled to suppress drug and plasma protein adsorption at the separation membrane, Asymmetrical Flow FFF shows high recoveries and fast separation of human plasma proteins, and can be a reliable tool to characterize drug / plasma protein interactions. For analytical purposes it has the potential to rival established technologies like ultracentrifugation in terms of ease-of-use, precision, and separation time.     

四氯偶氮苯在大鼠胆汁中的分泌和代谢

四氯偶氮苯（３,３’,４,４’ｔｅｔｒａｃｈｌｏｒｏａｚｏｂｅｎｚｅｎｅ,ＴＣＡＢ）和四氯氧化偶氮苯（３,３’,４,４’ｔｅｔｒａｃｈｌｏｒｏａｚｏｘｙｂｅｎｚｅｎｅ,ＴＣＡＯＢ）是在合成氯代或二氯代苯胺类除草剂时生成的污染废弃物。此类除草剂经...     

Phacoemulsification: technical initiation at what price?]

Phacoemulsification of the cataract is perhaps technically superior which is considered "classic". This technic consists however of a number of difficulties that may be mastered during an apprentiship. Considerable complications may arise during this initiation periods; imposing this surgical method on patients is thus an ethical problem. If the risks encountered during the apprentiship of phacoemulsification appear comparable to those during the classic extracapsular technique, phacoemulsification may be recommended with less reservation. We have compared 250 initial cases of classic extracapsular extraction with 250 "initial cases" of phacoemulsification, taking into account operative and post-operative complications and final functional results.     

Validity of annoyance scores for estimation of long term air pollution exposure in epidemiologic studies: the Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA)

In air pollution epidemiology, estimates of long term exposure are often based on measurements made at one fixed site monitor per area. This may lead to exposure misclassification. The present paper validates a questionnaire-based indicator of ambient air pollution levels and its applicability to assess their within-area variability. Within the framework of the SAPALDIA (Swiss Study on Air Pollution and Lung Diseases in Adults) cross-sectional study (1991), 9,651 participants reported their level of annoyance caused by air pollution on an 11-point scale. This subjective measure was compared with annual mean concentrations of particulate matter less than 10 microm in diameter (PM10) and nitrogen dioxide. The impact of individual factors on reported scores was evaluated. Nitrogen dioxide concentrations at home outdoors (measured in 1993), smoking, workplace dust exposure, and respiratory symptoms were found to be predictors of individual annoyance scores. Regression of population mean annoyance scores against annual mean PM10 and nitrogen dioxide concentrations (measured in 1993 and 1991, respectively) across areas showed a linear relation and strong correlations (r>0.85). Analysis within areas yielded consistent results. The observed associations between subjective and objective air pollution exposure estimates suggest that population mean scores, but not individual scores, may serve as a simple tool for grading air quality within areas. Reported annoyance due to air pollution should be considered an indicator for a complex environmental condition and thus might be used for evaluating the implementation of environmental policies.     

Antidoping: From health tests to the athlete biological passport

The athlete biological passport (ABP) was implemented by the International Cycling Union (UCI) in 2008. However, this improvement in the fight against doping was preceded with different milestones since 1996. In this paper, a detailed evolution of the ABP from traditional direct (urine) testing for antidoping purposes is presented. A chronological overview of the ABP including earlier non‐disclosed information and contemporary documentation are shown and documented. The strategic development from on‐site competition blood testing, called “health tests”, to the structure of the ABP is explained in this historical overview which provides information to the antidoping community and general public regarding the beginning of blood doping tests.     

Exposure to motor vehicle traffic and allergic sensitization. The Swiss Study on Air Pollution and Lung Diseases in Adults (SAPALDIA) Team

We examined the association between the presence of an allergic sensitization and seasonal allergic diseases or symptoms and the exposure to road traffic in Basel, Switzerland. Traffic counts at the domiciles of subjects ranged from 24 to 32,504 cars per 24 hours, with a median of 1,624. To investigate the relation of road traffic and allergies, we matched the data of the traffic inventory of Basel with those of the 820 participants of the SAPALDIA study (Swiss Study on Air Pollution and Lung Diseases in Adults), ages 18-60 years, who had completed a detailed respiratory health questionnaire and had undergone allergy testing (skin prick tests and serologic examinations). We observed a positive association with a sensitization to pollen that was most pronounced among persons with a duration of residence of at least 10 years. The odds ratios (adjusted for educational level, smoking behavior, number of siblings, age, sex, and family history of atopy) for cars, contrasting four exposure categories with the lowest quartile as referent category, were 1.99 [95% confidence interval (CI) = 0.91-4.38], 2.47 (95% CI = 1.06-5.73), and 2.83 (95% CI = 1.26-6.31). These results suggest that living on busy roads is associated with a higher risk for a sensitization to pollen and could possibly be interpreted as an indication for interactions between pollen and air pollutants. We did not, however, find a similar relation between motor vehicle traffic and hay fever or seasonal allergic symptoms, and we saw no trend that increasing traffic exposure was associated with a rise in sensitization rates to indoor allergens.     

Glial reactivity, an early feature of diabetic retinopathy

PURPOSE: To characterize early structural gliotic reactions in retinal Müller cells, astrocytes, and microglia in experimentally induced diabetes. METHODS: Rats were rendered diabetic by streptozotocin injection and killed after 2, 4, 12, or 20 weeks. Cell densities were determined in flatmounted retinas or transverse semithin sections. Expression of glial fibrillary acidic protein (GFAP) was localized on frozen sections or flatmounts by immunofluorescence and confocal microscopy, and GFAP content was evaluated by Western blot analysis. Microglial cells were visualized by binding of isolectin B4 or staining with antibodies to phosphotyrosine residues. The integrity of the blood-retinal barrier was assessed by intravenous injection of Evans blue. RESULTS: The density of Müller cells and microglia was significantly increased at 4 weeks of diabetes compared with nondiabetic controls. GFAP expression in Müller cells was not detected at 4 weeks but was prominent at 12 weeks. The number of astrocytes was significantly reduced at 4 weeks in the peripapillary and far peripheral retina. Shape changes of microglial cells indicated functional activation. Leakage of the blood-retinal barrier was observed at 2 weeks of hyperglycemia, the earliest time point investigated. CONCLUSIONS: The leakage of the blood-retinal barrier before glial reactivity suggests that glia are early targets of vascular hyperpermeability. The individual glial cell types react differentially to the diabetic state. Müller cells undergo hyperplasia preceding GFAP expression, and microglial cells are activated, whereas astrocytes regress. This glial behavior may contribute decisively to the onset and development of neuropathy in the diabetic retina.