Conscious and anaesthetised Göttingen mini-pigs as an in-vivo model for buccal absorption – pH-dependent absorption of metoprolol from bioadhesive tablets

The potential of buccal mucosa as a site for systemic absorption has attracted increased attention in recent years creating a need for new predictive in-vivo models. The aim of this study was to evaluate anaesthetised and conscious Göttingen mini-pigs as a model for buccal drug absorption by testing pH-dependent absorption of metoprolol from a solid dosage form. Buccal tablets buffered to pH 6.2 and pH 8.9, oral liquid and intravenous injection were tested in four conscious and anaesthetised Göttingen mini-pigs in a non-randomised cross-over study. Blood samples were collected and processed before analysis by ultra-performance liquid chromatography with tandem mass spectrometry detection. An ex-vivo flow retention model was applied to study release and retention of the bioadhesive buccal tablets. The T_max obtained from the two buccal conscious groups (55?±?5 and 35?±?5?min) were significantly different to the buccal anaesthetised groups (120?±?0 and 165?±?15?min) for buccal tablet pH 6.2 and pH 8.9, respectively. Also, the absolute bioavailability from the anaesthetised buccal tablet pH 8.9 (20.7?±?4.0%) had a significant increase compared to all other buccal tablet groups. In conclusion, this study showed a pH-dependent absolute bioavailability of metoprolol when administrated as bioadhesive buccal tablets to anaesthetised mini-pigs. The anaesthesia was found to delay the time to reach maximal plasma concentration of metoprolol as compared to the conscious pig model when administrated as buccal tablets.     

On the failure of scientific research: an analysis of SBIR projects funded by the U.S. National Institutes of Health

Scientometrics - The Small Business Innovation Research (SBIR) program is the primary source of public funding in the United States for research by small firms on new technologies, and the National...     

面向LED照明的低压交流应用

低压交流照明系统 在过去的30年中,低压交流照明设备已日趋普及。如今,从室内局部照明到一般性的活动式投射灯照明,再到如花园和景观等户外应用照明中,此类照明系统随处可见。像宜家家居和美国家得宝这样的家居零售卖场和住宅美化商场极大推进了该技术在消费人群中的使用。这类低压照明系统采用特殊低压编码规则,终端用户可自行安装而无需外部承包商。因此,这些系统相对便宜且易于安装。     

Intermittent Hypoxic Therapy Inhibits Allogenic Bone-Graft Resorption by Inhibition of Osteoclastogenesis in a Mouse Model

Systemic Intermittent Hypoxic Therapy (IHT) relies on the adaptive response to hypoxic stress. We investigated allogenic bone-graft resorption in the lumbar spine in 48 mice. The mice were exposed to IHT for 1 week before surgery or 1 week after surgery and compared with controls after 1 and 4 weeks. Complete graft resorption was observed in 33–36% of the animals in the control group, but none in the preoperative IHT group. Increased bone-graft volume was demonstrated by micro-computed tomography in the preoperative IHT group after 1 week (p = 0.03) while a non-significant difference was observed after 4 weeks (p = 0.12). There were no significant differences in the postoperative IHT group. Increased concentration of immune cells was localized in the graft area, and more positive tartrate-resistant acid phosphatase (TRAP) staining was found in controls compared with IHT allogenic bone grafts. Systemic IHT resulted in a significant increase of the major osteoclast inhibitor osteoprotegerin as well as osteogenic and angiogenic regulators Tgfbr3, Fst3l, Wisp1, and Vegfd. Inflammatory cytokines and receptor activator of nuclear factor kappa-B ligand (RANKL) stimulators IL-6, IL-17a, IL-17f, and IL-23r increased after 1 and 4 weeks, and serum RANKL expression remained constant while Ccl3 and Ccl5 decreased. We conclude that the adaptive response to IHT activates numerous pathways leading to inhibition of osteoclastic activity and inhibition of allogenic bone-graft resorption.     

Bacterial communities in commercial aircraft high‐efficiency particulate air (HEPA) filters assessed by PhyloChip analysis

Abstract  Air travel can rapidly transport infectious diseases globally. To facilitate the design of biosensors for infectious organisms in commercial aircraft, we characterized bacterial diversity in aircraft air. Samples from 61 aircraft high‐efficiency particulate air (HEPA) filters were analyzed with a custom microarray of 16S rRNA gene sequences (PhyloChip), representing bacterial lineages. A total of 606 subfamilies from 41 phyla were detected. The most abundant bacterial subfamilies included bacteria associated with humans, especially skin, gastrointestinal and respiratory tracts, and with water and soil habitats. Operational taxonomic units that contain important human pathogens as well as their close, more benign relatives were detected. When compared to 43 samples of urban outdoor air, aircraft samples differed in composition, with higher relative abundance of Firmicutes and Gammaproteobacteria lineages in aircraft samples, and higher relative abundance of Actinobacteria and Betaproteobacteria lineages in outdoor air samples. In addition, aircraft and outdoor air samples differed in the incidence of taxa containing human pathogens. Overall, these results demonstrate that HEPA filter samples can be used to deeply characterize bacterial diversity in aircraft air and suggest that the presence of close relatives of certain pathogens must be taken into account in probe design for aircraft biosensors.

Practical Implications

A biosensor that could be deployed in commercial aircraft would be required to function at an extremely low false alarm rate, making an understanding of microbial background important. This study reveals a diverse bacterial background present on aircraft, including bacteria closely related to pathogens of public health concern. Furthermore, this aircraft background is different from outdoor air, suggesting different probes may be needed to detect airborne contaminants to achieve minimal false alarm rates. This study also indicates that aircraft HEPA filters could be used with other molecular techniques to further characterize background bacteria and in investigations in the wake of a disease outbreak.

     

Salivary Amylase Induction by Tannin-Enriched Diets as a Possible Countermeasure Against Tannins

Tannins are characterized by protein-binding affinity. They have astringent/bitter properties that act as deterrents, affecting diet selection. Two groups of salivary proteins, proline-rich proteins and histatins, are effective precipitators of tannin, decreasing levels of available tannins. The possibility of other salivary proteins having a co-adjuvant role on host defense mechanisms against tannins is unknown. In this work, we characterized and compared the protein profile of mice whole saliva from animals fed on three experimental diets: tannin-free diet, diet with the incorporation of 5% hydrolyzable tannins (tannic acid), or diet with 5% condensed tannins (quebracho). Protein analysis was performed by one-dimensional gel electrophoresis combined with Matrix-Assisted Laser Desorption Ionization-Time of Flight mass spectrometry to allow the dynamic study of interactions between diet and saliva. Since abundant salivary proteins obscure the purification and identification of medium and low expressed salivary proteins, we used centrifugation to obtain saliva samples free from proteins that precipitate after tannin binding. Data from Peptide Mass Fingerprinting allowed us to identify ten different proteins, some of them showing more than one isoform. Tannin-enriched diets were observed to change the salivary protein profile. One isoform of α-amylase was overexpressed with both types of tannins. Aldehyde reductase was only identified in saliva of the quebracho group. Additionally, a hypertrophy of parotid salivary gland acini was observed by histology, along with a decrease in body mass in the first 4 days of the experimental period. G. da Costa and E. Lamy have contributed equally to this work.     

Egg Consumption Modulates HDL Lipid Composition and Increases the Cholesterol-Accepting Capacity of Serum in Metabolic Syndrome

We recently demonstrated that daily whole egg consumption during moderate carbohydrate restriction leads to greater increases in plasma HDL-cholesterol (HDL-C) and improvements in HDL profiles in metabolic syndrome (MetS) when compared to intake of a yolk-free egg substitute. We further investigated the effects of this intervention on HDL composition and function, hypothesizing that the phospholipid species present in egg yolk modulate HDL lipid composition to increase the cholesterol-accepting capacity of subject serum. Men and women classified with MetS were randomly assigned to consume either three whole eggs (EGG, n = 20) per day or the equivalent amount of egg substitute (SUB, n = 17) throughout a 12-week moderate carbohydrate-restricted (25–30 % of energy) diet. Relative to other HDL lipids, HDL-cholesteryl ester content increased in all subjects, with greater increases in the SUB group. Further, HDL-triacylglycerol content was reduced in EGG group subjects with normal baseline plasma HDL-C, resulting in increases in HDL-CE/TAG ratios in both groups. Phospholipid analysis by mass spectrometry revealed that HDL became enriched in phosphatidylethanolamine in the EGG group, and that EGG group HDL better reflected sphingomyelin species present in the whole egg product at week 12 compared to baseline. Further, macrophage cholesterol efflux to EGG subject serum increased from baseline to week 12, whereas no changes were observed in the SUB group. Together, these findings suggest that daily egg consumption promotes favorable shifts in HDL lipid composition and function beyond increasing plasma HDL-C in MetS.     

Isolation of adipophilin and butyrophilin from bovine milk and characterization of a cDNA encoding adipophilin

The milk fat globule membrane-associated proteins adipophilin (alias adipocyte differentiation-related protein) and butyrophilin were purified from bovine milk by reverse-phase chromatography. The nucleotide sequence of bovine adipophilin was obtained via peptide mapping and sequencing of a mammary gland cDNA clone, which comprises 1841 nucleotides and has an open reading frame of 450 amino acids. By peptide mapping, 19% of the amino acid sequence was confirmed. The obtained amino acid sequence has 87 and 80% identical residues with human and mouse adipophilin, respectively. Alignment with the proteins perilipin and TIP47 revealed two highly conserved segments, which may assemble into amphipathic alpha-helices.     

MIMO Systems in Random Uncorrelated,Correlated and Deterministic Radio Channels

The paper discusses the BER and spectral efficiency of different MIMO systems in random uncorrelated, correlated and deterministic environments, and more specifically uncorrelated and correlated Rayleigh and Ricean fading channels. It is known that the so-called MIMO eigenmode transmission assumes channel knowledge at the transmitter for pre-coding, whereas V-BLAST and STC do not assume the channel knowledge at the transmitter, instead they use it at the receiver for recovering the transmitted information. It is shown that for the same spectral efficiency, the BER performance of the MIMO eigenmode transmission outperforms MIMO systems like V-BLAST and STBC. In fully correlated random environment, transmitting through the largest eigenmode exploits the full transmitter-receiver array gain and diversity order, giving the maximal possible performance in terms of reducing the BER. In any of the scenarios, transmitting through the largest eigenmode gives better performance in terms of reducing the BER compared with STBC systems. Spatial multiplexing through the so-called eigensets (sets which consist of transmission modes with significant channel gain) outperforms systems like V-BLAST. In this context, adaptive modulation has been used to minimize the overall BER for a given spectral efficiency.     

Study of taste-active compounds in the water-soluble extract of mature Cheddar cheese

The chemical composition of the water-soluble extracts of mature Cheddar cheese were identified, with the emphasis on understanding the interplay of compounds contributing to the savoury taste in Cheddar. The ultra-filtered water-soluble extracts of two mature Cheddar cheeses were fractionated by gel permeation chromatography (GPC). By sensory evaluation, two taste-active GPC fractions were identified from each cheese. On the basis of chemical profiling of these fractions, aqueous model tastant mixtures were prepared and sensory omission tests carried out. Glutamic acid, organic acids and mineral salts were the main tastants, whereas the other amino acids had a limited impact on taste. The characteristic umami taste was explained by a synergistic effect of glutamic acid and salts. Matching umami taste intensities were obtained from different concentrations of glutamic acid and salts. Unmasking of a bitter or sweet taste from mixtures of sub-threshold concentrations of amino acids without glutamic acids was also observed.