Cancer risk of immunosuppressants in manufacturing

During the chemical and pharmaceutical production of active pharmaceutical substances which are intended for immunosuppressive therapy, the employees may be exposed to these substances via inhalation. Immunosuppressants are linked to development of certain types of cancers e.g., lymphoma or skin cancer in transplant patients. The development of these cancers in patients is linked to the level of immunosuppression needed for transplantation in order to avoid organ rejection. Below these levels, with the immune system functioning uninhibited, cancer is unlikely to develop.     

Preparation of clinical‐grade 89Zr‐panitumumab as a positron emission tomography biomarker for evaluating epidermal growth factor receptor‐targeted therapy

Panitumumab is a fully human monoclonal antibody approved for the treatment of epidermal growth factor receptor (EGFR) positive colorectal cancer. Recently, panitumumab has been radiolabeled with ⁸⁹Zr and evaluated for its potential to be used as immuno‐positron emission tomography (PET) probe for EGFR positive cancers. Interesting preclinical results published by several groups of researchers have prompted us to develop a robust procedure for producing clinical‐grade ⁸⁹Zr‐panitumumab as an immuno‐PET probe to evaluate EGFR‐targeted therapy. In this process, clinical‐grade panitumumab is bio‐conjugated with desferrioxamine chelate and subsequently radiolabeled with ⁸⁹Zr resulting in high radiochemical yield (>70%, n = 3) and purity (>98%, n = 3). All quality control (QC) tests were performed according to United States Pharmacopeia specifications. QC tests showed that ⁸⁹Zr‐panitumumab met all specifications for human injection. Herein, we describe a step‐by‐step method for the facile synthesis and QC tests of ⁸⁹Zr‐panitumumab for medical use. The entire process of bioconjugation, radiolabeling, and all QC tests will take about 5 h. Because the synthesis is fully manual, two rapid, in‐process QC tests have been introduced to make the procedure robust and error free. Copyright © 2013 John Wiley & Sons, Ltd.     

In-line solid state prediction during pharmaceutical hot-melt extrusion in a 12 mm twin screw extruder using Raman spectroscopy

The aim of this research was to use Raman spectroscopy for the in-line monitoring of the solid state of materials during pharmaceutical hot-melt extrusion in the die head of a 12 mm (development scale) twin-screw extruder during formulation development.A full factorial (mixed) design was generated to determine the influence of variations in concentration of Celecoxib (CEL) in Eudragit® E PO, three different screw configurations and varying barrel temperature profiles on the solid state, ‘melt temperature’ and die pressure of continuously produced extrudates in real-time. Off-line XRD and DSC analysis were used to evaluate the suitability of Raman spectroscopy for solid state predictions. First, principal component analysis (PCA) was performed on all in-line collected Raman spectra from the experimental design. The resulting PC 1 versus PC 2 scores plot showed clustering according to solid state of the extrudates, and two classes, one class where crystalline CEL is still present and a second class where no crystalline CEL was detected, were found. Then, a soft independent modelling of class analogy (SIMCA) model was developed, by modelling these two classes separately by disjoint PCA models. These two separate PCA models were then used for the classification of new produced extrudates and allowed distinction between glassy solid solutions of CEL and crystalline dispersions of CEL. All extrudates were classified similarly by Raman spectroscopy, XRD and DSC measurements, with exception of the extrudates with a 30% CEL concentration extruded at 130 °C. The Raman spectra of these experiments showed bands which were sharper than the amorphous spectra, but broader than the crystalline spectra, indicating the presence of CEL that has dissolved into the matrix and CEL in its crystalline state. XRD and DSC measurements did not detect this. Modifications in the screw configuration did not affect the solid state and did not have an effect on the solid state prediction of new produced extrudates.Secondly, the influence of variations in die pressure on the Raman spectra was examined. The applied drug concentration, processing temperature and feeder performance influence the die pressure, which is reflected in the Raman spectra as a change in spectral intensity. When applying PCA on the raw spectra from the experimental design, the first principal component describes the influence of die pressure on the spectra, which was seen as a decrease in Raman intensity of the whole spectrum when the pressure in the sample increased. Clustering according to processing temperature was found, although the temperature in the die remained constant, indicating that a difference in viscosity, resulting in a changed die pressure, was detected. When the feeder was stopped, the score values of the first principal component almost simultaneously decreased, and only stabilized once the die pressure became stable. Since Raman spectra collected in the extrusion die are influenced by changes in die pressure, disturbances upstream of the extrusion process can be observed and identified in the Raman measurements.     

丹莪妇康颗粒生产工艺研究简

目的 研究生产丹莪妇康颗粒的最佳生产工艺条件.方法 对剂型选择、提取工艺路线及制剂工艺技术等方面进行考察.结果 丹莪妇康颗粒的最佳生产工艺条件为将处方药材用70％乙醇浸渍24 h后,以3～5 mL/min渗漉,收集5倍量漉液,减压回收乙醇并浓缩至相对密度为1.30（50℃）;药渣与其余药材加8倍量水煎煮2次,2 h/次,合并煎液,滤过,滤液浓缩至相对密度为1.30（50℃）;合并稠膏,减压干燥成干膏,粉碎,过80目筛,得干膏粉,加入糊精和甜菊素适量,混均,以70％乙醇制软材,用16目筛制粒,干燥,过14目筛整粒,即得.结论 优选的丹莪妇康颗粒生产工艺,既保证了产品质量,又节约了能源,降低生产成本,适合于工业化大生产.     

The Effect of the Activation Process and Metal Oxide Addition (CaO,MgO, SrO) on the Catalytic and Physicochemical Properties of Natural Zeolite in Transesterification Reaction

This work provides valuable information about unexplored catalytic systems tested in the transesterification reaction of vegetable oil with methanol. It was demonstrated that natural zeolite treatment leads to enhanced catalytic activity and yield of biodiesel production. The activation of the catalytic material in a mixture of 5% H₂–95% Ar resulted in an improvement of the values of the TG conversion and fatty acid methyl esters (FAME) yield. In addition, it was proven that the incorporation of CaO, MgO and SrO oxides onto the natural zeolite surface improves the TG conversion and FAME yield values in the transesterification reaction.     

Green Approach to Develop Bee Pollen-Loaded Alginate Based Nanofibrous Mat

Green electrospun materials are gaining popularity in the quest for a more sustainable environment for human life. Bee pollen (BP) is a valuable apitherapeutic product and has many beneficial features such as antioxidant and antibacterial properties. Alginate is a natural and low-cost polymer. Both natural materials show good compatibility with human tissues for biomedical applications and have no toxic effect on the environment. In this study, bee pollen-loaded sodium alginate and polyvinyl alcohol (SA/PVA) nanofibrous mats were fabricated by the electrospinning technique. The green electrospun nanofibrous mats were analyzed by scanning electron microscopy (SEM), Fourier transforms infrared spectroscopy (FTIR), and differential scanning calorimeter (DSC). According to the findings of the study, the toxin-free electrospinning method is suitable for producing green nanomaterial. Because of the useful properties of the bee pollen and the favorable biocompatibility of the alginate fibers, the bee pollen-loaded SA/PVA electrospun mats have the potential for use in a variety of biomedical applications.     

Human Respiratory Syncytial Virus Infection in a Human T Cell Line Is Hampered at Multiple Steps

Human respiratory syncytial virus (HRSV) is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract, and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a human CD4⁺ T cell line. Using flow cytometry and fluorescent focus assay, we found that A3.01 cells are susceptible but virtually not permissive to HRSV infection. Dequenching experiments revealed that the fusion process of HRSV in A3.01 cells was nearly abolished in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by RT-qPCR showed that the replication of HRSV in A3.01 cells was considerably reduced. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, using fluorescence in situ hybridization, we found that the inclusion body-associated granules (IBAGs) were almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins colocalized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments were present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4⁺ T cells is virtually unproductive as compared to HEp-2 cells, as a result of defects at several steps of the viral cycle: Fusion, genome replication, formation of inclusion bodies, recruitment of cellular proteins, virus assembly, and budding.     

Effects of porcine follicle-stimulating hormone on the reproductive performance of female zebra finches (Taeniopygia guttata)

It has been suggested that follicle-stimulating hormone (FSH) may play a role in egg size/number trade-offs in oviparous vertebrates. We tested this hypothesis in an avian species by administering porcine FSH (pFSH) to intact, captive female zebra finches (Taeniopygia guttata) during egg formation. We predicted that (1) pFSH would increase the number of ovarian follicles recruited into rapid yolk development and so increase clutch size, (2) an increase in clutch size would lead to a reduction in egg size, and (3) doses of pFSH that were not sufficient to increase clutch size would increase yolk deposition and so increase egg mass. Although a range of pFSH doses decreased egg mass by ca. 10% in three separate experiments, the reduction in egg mass occurred in the absence of an increase in the number of eggs laid. Porcine FSH decreased mean clutch size significantly in one experiment and reduced median clutch size significantly in the other two experiments. The results of this study did not support the hypothesis that FSH mediates a trade-off between egg size and clutch size in birds.     

Congruent validity and inter-day reliability of two breath by breath metabolic carts to measure resting metabolic rate in young adults

Background & aims

Achieving high inter-day reliability is a key factor to analyze the magnitude of change in RMR, for instance after an intervention. The aims of this study were: i) to determine the congruent validity of RMR and respiratory quotient (RQ) with two breath by breath commercially available metabolic carts [CCM Express (CCM) and Ultima CardiO2 (MGU)]; and ii) to analyze the inter-day reliability of RMR and RQ measurements.

Where Does Research Occur in Geriatrics and Gerontology?

The International Plan of Action on Aging 2002 emphasized the need to promote and develop research on aging, especially in underdeveloped countries. This article aims at describing the current situation with regard to the international scientific production in the field of geriatrics and gerontology. All articles published in journals included in the categories "Geriatrics and Gerontology" of the Science Citation Index or "Gerontology" of the Social Science Citation Index in 2002 were analyzed. There is unquestionable predomination by the United States, which participates in 53.8% of the articles analyzed, followed by the United Kingdom (9.66%) and Canada (6.66%). The production of the 15 European Union countries together is 31.2%. When adjustments are made for economic or population factors, other countries show their importance: Israel and Sweden, for example. Authors from richer countries participate in more than 95% of the articles, whereas those in less-developed countries tend to publish less, and when they do so, it is through collaboration with more-developed countries. In general, only 10.5% of the articles are written in collaboration with institutions from different countries. One of the keys to stimulating research in less wealthy countries would seem to be precisely through collaboration. This would aid the transfer of knowledge and experience, allowing researchers in these countries to obtain autonomy to perform their own studies independently and to provide them with the ability to gain access for their publications at the international level.