Comparison of gastrointestinal pH in cystic fibrosis and healthy subjects

The primary objective of this study was to define the pH conditions under which supplemental pancreatic enzyme preparations must function in the upper gastrointestinal tract. The hypothesis was that normal or greater gastric acid output in patients with cystic fibrosis (CF), combined with low pancreatic bicarbonate output, results in an acidic duodenal pH, compromising both dosage-form performance and enzyme activity. Gastrointestinal pH profiles were obtained in 10 CF and 10 healthy volunteers under fasting and postprandial conditions. A radiotelemetric monitoring method, the Heidelberg capsule, was used to continuously monitor pH. Postprandial duodenal pH was lower in CF than in healthy subjects, especially in the first postprandial hour (mean time greater than pH 6 was 5 min in CF, 11 min in healthy subjects, P <0.05). Based on the dissolution pH profiles of current enteric-coated pancreatic enzyme products, the duodenal postprandial pH in CF subjects may be too acidic to permit rapid dissolution of current enteric-coated dosage forms. However, the pH was above 4 more than 90% of the time on the average, suggesting that irreversible lipase inactivation in the duodenum is not likely to be a significant limitation to enzyme efficacy. Overall results suggest that slow dissolution of pH-sensitive coatings, rather than enzyme inactivation, may contribute to the failure of enteric-coated enzyme supplements to normalize fat absorption.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44403/1/10620_2005_Article_BF01296029.pd

Evidence for the stability of the West Antarctic Ice Sheet divide for 1.4 million years

Past fluctuations of the West Antarctic Ice Sheet (WAIS) are of fundamental interest because of the possibility of WAIS collapse in the future and a consequent rise in global sea level. However, the configuration and stability of the ice sheet during past interglacial periods remains uncertain. Here we present geomorphological evidence and multiple cosmogenic nuclide data from the southern Ellsworth Mountains to suggest that the divide of the WAIS has fluctuated only modestly in location and thickness for at least the last 1.4 million years. Fluctuations during glacial–interglacial cycles appear superimposed on a long-term trajectory of ice-surface lowering relative to the mountains. This implies that as a minimum, a regional ice sheet centred on the Ellsworth-Whitmore uplands may have survived Pleistocene warm periods. If so, it constrains the WAIS contribution to global sea level rise during interglacials to about 3.3 m above present

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Early Christianity in East Africa and Red Sea/Indian Ocean Commerce

The ancient East African kingdom of Aksum gradually adopted Christianity from the early- to mid-fourth-century reign of Ezana onwards. The well-known narrative of the late Roman church-historian Rufinus relates a top-down process of conversion, starting with the ruler himself. The report, corroborated by the adoption of Christian symbolism on Ezana’s late coinage, and monotheistic as well as overtly Christian references in royal inscriptions, is generally considered trustworthy. While not challenging the significance of charismatic and powerful individuals, this article argues that Christianity was present in the region before Ezana, and that the introduc- tion of Christianity should be situated within the context of early Red Sea/Indian Ocean commerce. Trade was the carrier of ideological impulses from communities in the Indian Ocean and Mediterranean worlds and created the social infrastructure that expatriate believers, early converts, and later, church officials and local elites could draw upon

Liposomal budesonide for dry powder inhaler: Preparation and stabilization

The purpose of the study was to prepare stable liposomally entrapped budesonide (BUD) for a dry powder inhaler (DPI) formulation. BUD liposomes composed of egg phosphatidyl choline and cholesterol were prepared by lipid film hydration technique and sonicated to have the desired size (<5 μm). A rapid method was used for separation of free drug by centrifugation at a lower centrifugal force (G value). Liposomal dispersion was subjected to lyophilization after blending BUD with cryoprotectant in varying bulk and mass ratios, and percent drug remaining entrapped after lyophilization was optimized. Comparative drug retention studies on storage of DPI formulations were carried out in accordance with International Conference on Harmonization guidelines. Critical relative humidity of the formulations was determined and reported as one of the manufacturing controls. Sucrose was found to be the most effective cryoprotectant when present on both sides of the lamellae of liposomes in a bulk strength of 500 mM and mass ratio of lipid:sugar; 1∶10. Blending of sorbolac before lyophilization showed better retention of encapsulated drug (95.59%). The respirable fraction of the product (20.69±1.50%) was comparable with that of the control (26.49±1.52%), suggesting that the liposomal BUD can be successfully delivered throughout the broncho-pulmonary tree. The findings demonstrate that liposome of BUD can be prepared with a high entrapment value, stabilized by lyophilization, and delivered as an aerosolized DPI. The stability studies of lyophilized product suggests a shelf-life of one year when stored under refrigeration (2°C–8°C)

Comparison of Spray Freeze Drying and the Solvent Evaporation Method for Preparing Solid Dispersions of Baicalein with Pluronic F68 to Improve Dissolution and Oral Bioavailability

The objective of this study was to prepare solid dispersions consisting of baicalein and a carrier with a low glass transition/melting point (Pluronic F68) by spray freeze drying (SFD). We compared these powders to those produced from the conventional solvent evaporation method. In the SFD process, a feeding solution was atomized above the surface of liquid nitrogen following lyophilization, which resulted in instantaneously frozen microparticles. However, solid dispersions prepared by the solvent evaporation method formed a sticky layer on the glass flask with crystalline baicalein separated out from the carrier. The powder samples were characterized by scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), surface area measurement, differential scanning calorimetry, and Fourier transform infrared spectrometry. SEM and PXRD results suggested that the majority of baicalein in the SFD-processed solid dispersion was in the amorphous state, which has a higher specific surface area than pure baicalein. However, the majority of baicalein was recrystallized in the solid dispersion at the same composition prepared by the solvent evaporation method, which showed a similar dissolution rate to the physical mixture. SFD product was physically and chemically stable after being stored at 40°C with low humidity for 6 months. After enzyme hydrolysis, baicalein in the SFD product displayed a significantly shorter Tmax and higher Cmax than pure baicalein after oral dosing. The relative bioavailability of the SFD product versus pure baicalein determined by comparing the AUC0–12 was 233%, which demonstrated the significantly improved oral bioavailability of baicalein produced by the SFD technique