Effect of pancreatico-biliary secretions and GI transit time on the absorption and pharmacokinetic profile of ranitidine in humans

PURPOSE: Ranitidine plasma concentration vs. time profiles and the extent of ranitidine absorption were examined in the presence and absence of pancreatico-biliary secretions in order to elucidate factors which may contribute to secondary peaks after oral ranitidine administration. METHODS: Ranitidine solution (300 mg) was administered to 4 fasting healthy subjects via an indwelling small-bore oroenteric tube located approximately 16 cm distal to the pylorus On 3 consecutive days, subjects randomly received ranitidine alone (control), ranitidine 10 min after 0.04 micrograms/kg IV cholecystokinin (CCK) sufficient to cause gall bladder emptying into the duodenum, and ranitidine 30 min after inflation of an occlusive duodenal balloon located approximately 10 cm distal to the pylorus to prevent pancreatico-biliary secretions from reaching the dosing port or beyond. Small bowel transit time (SBTT; min) was measured by breath H2. Serial blood samples, obtained over 12 hours in each treatment, were analyzed by HPLC to determine ranitidine AUC0-12 (ng*h/mL), as well as Cmax (ng/mL) and Tmax (min) of the first and subsequent peaks, if subsequent peaks were observed. RESULTS: Ranitidine AUC0-12 and Cmax were not altered significantly by treatments; treatment effects on SBTT varied. Secondary peaks were observed in subjects #1 and #3 during the control treatment and subjects #2 and #4 during the CCk treatment. No secondary peaks were observed in any subject during the balloon treatment, and Tmax1 was delayed. CONCLUSIONS: Results support the hypothesis that pancreatico-biliary secretions (present in the intestinal lumen during control or CCK treatment) and gastrointestinal transit time may influence the occurrence of secondary peaks in ranitidine concentration vs. time profiles.     

Lidar measurements taken with a large-aperture liquid mirror. 1. Rayleigh-scatter system

A lidar system has been built to measure atmospheric-density fluctuations and the temperature in the upper stratosphere, the mesosphere, and the lower thermosphere, measurements that are important for an understanding of climate and weather phenomena. This lidar system, the Purple Crow Lidar, uses two transmitter beams to obtain atmospheric returns resulting from Rayleigh scattering and sodium-resonance fluorescence. The Rayleigh-scatter transmitter is a Nd:YAG laser that generates 600 mJ/pulse at the second-harmonic frequency, with a 20-Hz pulse-repetition rate. The sodium-resonance-fluorescence transmitter is a Nd:YAG-pumped ring dye laser with a sufficiently narrow bandwidth to measure the line shape of the sodium D(2) line. The receiver is a 2.65-m-diameter liquid-mercury mirror. A container holding the mercury is spun at 10 rpm to produce a parabolic surface of high quality and reflectivity. Test results are presented which demonstrate that the mirror behaves like a conventional glass mirror of the same size. With this mirror, the lidar system's performance is within 10% of theoretical expectations. Furthermore, the liquid mirror has proved itself reliable over a wide range of environmental conditions. The use of such a large mirror presented several engineering challenges involving the passage of light through the system and detector linearity, both of which are critical for accurate retrieval of atmospheric temperatures. These issues and their associated uncertainties are documented in detail. It is shown that the Rayleigh-scatter lidar system can reliably and routinely measure atmospheric-density fluctuations and temperatures at high temporal and spatial resolutions.     

Sheared-beam imaging: an evaluation of its optical compensation of thick atmospheric turbulence

Sheared-beam imaging (SBI) should compensate the effects of an idealized layer of turbulence located either in a transmitter/detector plane or in an object plane. This motivated the study of optical compensation of SBI in the presence of uniformly distributed turbulence over long horizontal paths in the cases of ideally smooth and ideally rough extended objects. The phase error along a one-dimensional wave front resulting from SBI observation is computed numerically in the long-path regime and is compared with that of an equivalent conventional system for the case of a large smooth object. It is found that for the conditions considered the phase errors of the SBI system are greater than those of a conventional system. In the case of an ideally rough object the extra information furnished by the SBI observations does not lead to data that can be inverted to compute an image by the conventional shearing-interferometric algorithm. The phase errors in imaging a point reflector, however, are perfectly compensated.     

Unusual Lipid A from a Cold‐Adapted Bacterium: Detailed Structural Characterization

Colwellia psychrerythraea 34H is a Gram‐negative cold‐adapted microorganism that adopts many strategies to cope with the limitations associated with the low temperatures of its habitat. In this study, we report the complete characterization of the lipid A moiety from the lipopolysaccharide of Colwellia. Lipid A and its partially deacylated derivative were completely characterized by high‐resolution mass spectrometry, NMR spectroscopy, and chemical analysis. An unusual structure with a 3‐hydroxy unsaturated tetradecenoic acid as a component of the primary acylation pattern was identified. In addition, the presence of a partially acylated phosphoglycerol moiety on the secondary acylation site at the 3‐position of the reducing 2‐amino‐2‐deoxyglucopyranose unit caused tremendous natural heterogeneity in the structure of lipid A. Biological‐activity assays indicated that C. psychrerythraea 34H lipid A did not show an agonistic or antagonistic effect upon testing in human macrophages.     

Comparative chemical composition,antioxidant and hypoglycaemic activities of Juniperus oxycedrus ssp. oxycedrus L. berry and wood oils from Lebanon

Juniper (Juniperus oxycedrus) is used in European cuisine for its distinguishing flavour. J. oxycedrus ssp. oxycedrus berry and wood essential oils were tentatively identified by GC and GC/MS. Fifty compounds were identified in the berry oil and 23 compounds were identified in the wood oil. The J. oxycedrus ssp. oxycedrus berry oil was characterised by high contents of α-pinene (27.4%) and β-myrcene (18.9%). Other important compounds were α-phellandrene (7.1%), limonene (6.7%), epi-bicyclosesquiphellandrene (2.3%) and δ-cadinene (2.2%) while, in the wood oil, δ-cadinene (14.5%) is a major main component, together with cis-thujopsene (9.2%) and α-muurolene (4.9%). In vitro evaluation of antioxidant activity by the DPPH method showed a significant activity for both oils with IC₅₀ values of 1.45 μl/ml for wood and 7.42 μl/ml for berries. Hypoglycaemic activity was investigated through the inhibition of α-amylase. The results revealed that oil obtained by hydrodistillation from J. oxycedrus ssp. oxycedrus wood exhibits an interesting activity with IC₅₀ of 3.49 μl/ml.     

Exosite Binding in Thrombin: A Global Structural/Dynamic Overview of Complexes with Aptamers and Other Ligands

Thrombin is the key enzyme of the entire hemostatic process since it is able to exert both procoagulant and anticoagulant functions; therefore, it represents an attractive target for the developments of biomolecules with therapeutic potential. Thrombin can perform its many functional activities because of its ability to recognize a wide variety of substrates, inhibitors, and cofactors. These molecules frequently are bound to positively charged regions on the surface of protein called exosites. In this review, we carried out extensive analyses of the structural determinants of thrombin partnerships by surveying literature data as well as the structural content of the Protein Data Bank (PDB). In particular, we used the information collected on functional, natural, and synthetic molecular ligands to define the anatomy of the exosites and to quantify the interface area between thrombin and exosite ligands. In this framework, we reviewed in detail the specificity of thrombin binding to aptamers, a class of compounds with intriguing pharmaceutical properties. Although these compounds anchor to protein using conservative patterns on its surface, the present analysis highlights some interesting peculiarities. Moreover, the impact of thrombin binding aptamers in the elucidation of the cross-talk between the two distant exosites is illustrated. Collectively, the data and the work here reviewed may provide insights into the design of novel thrombin inhibitors.     

Development and validation of a grouping method for pesticides analysed in foodstuffs

The cost effective monitoring of hundreds of pesticide residues in foodstuffs of vegetable origin involves the definition of groups of analytes associated with homogeneous performance parameters of the used analytical method. The performance of the analytical method only needs to be tested on a daily base for some of these group’s compounds. This work proposes a strategy for defining groups of compounds with homogeneous physical–chemical properties based on the evaluation of the similarity of the multivariate pattern of five of these properties namely: molar mass, melting point, vapour pressure at 20 °C, n-octanol–water partition coefficient and solubility in water at 20 or 25 °C. Three independent and competing multivariate analysis tools, namely Principal Component Analysis, Hierarchical Clustering and K-Mean Clustering were used. This strategy was successfully used to group 100 pesticides into nine clusters, with 1–40 pesticides, represented by a compound with within group average properties. The developed grouping method was validated using physical–chemical data from other references or compounds and produced groups consistent with the performance of the studied determination of pesticide residues in dried red bean. The mean analyte recoveries of groups with larger dimension are statistically different for a confidence level of 95%. The within group coefficients of variance of mean analyte recoveries of larger groups ranged from 6.7% to 8.5%. This grouping method can reduce the number of recovery tests performed for the validation of the analytical method or test quality control.     

Technical Properties of Regenerated Plastic Material Bars Produced from Recycled Agricultural Plastic Film

The increased use of plastic material in many different agricultural applications causes high volumes of waste. The mechanical recycling of postconsumption plastic is a suitable system for the recovery of these materials. With the aim of evaluating the mechanical and physical characteristics of plastic bars’ profiles, obtained by recycling different polymeric mixtures of agricultural plastic film. Experimental tests were performed on different blends of heterogeneous material. Bars, made from recycled agricultural plastic film were produced through mechanical recycling, mixed with calcium carbonate, high density polyethylene, ‘densified’ polyethylene from scrap material, wood powder, and glass fibers.     

Microbial polysaccharide‐based membranes: Current and future applications

Microbial polysaccharides are characterized by high molecular structure variability which translates into a wide range of different properties offering interesting opportunities for application in many different areas, including membrane‐based products and processes. Due to their new or improved properties, microbial polysaccharides can replace plant, algae, and animal products, either in their traditional or in new applications. The main constraint to their wider use is the production costs that are still higher than that of other natural and synthetic polymers. The current applications of microbial polysaccharide membranes in medical, food, and industrial processes are outlined. The limitations still faced by these membranes and the requirements for obtaining innovative products and processes are also addressed. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci., 2014 , 131, 40047.