Is Fentanyl Pectin Nasal Spray Safe and Effective for Patients with Breakthrough Cancer Pain?

OBJECTIVE: The objective of this systematic review is to determine whether fentanyl pectin nasal spray (FPNS) is safe and effective treatment for patients with breakthrough cancer pain. STUDY DESIGN: Review of three English language primary randomized controlled trials published 2010-2011. DATA SOURCES: Multicenter, randomized, double-blind, double-dummy, placebo-controlled trials comparing fentanyl pectin nasal spray, immediate-release morphine sulfate, and/or nasal spray placebo were found using PubMed, COCHRANE, and Medline databases. OUTCOME MEASURED: All three studies essentially used similar parameters to measure effectiveness and safety of fentanyl pectin nasal spray compared to oral immediate-release morphine sulfate and/or placebo. Baseline pain intensity was scored 0-10. Pain intensity (PI) and pain relief (PR) were measured at 5, 10, 15, 30, 45, 60 minutes in order to assess time intervals clinically meaningful pain relief and maximum pain relief has been achieved. Adverse events were also recorded through all phases of the studies, and objective nasal tolerability assessments were performed. RESULTS: Collectively, the results demonstrated that clinically meaningful pain relief was achieved by fentanyl pectin nasal spray in as early as 10 minutes when compared to the control. Furthermore, approximately half the breakthrough cancer pain episodes achieved maximum pain relief at 60 minutes with FPNS compared to just over one-third of patients with immediate-release morphine sulfate. No significant nasal effects were reported, and there were no nasal tolerability parameters reported at moderate to severe intensity. CONCLUSION: The three randomized-controlled trials demonstrate that fentanyl pectin nasal spray is both safe and effective for the treatment of BTCP episodes compared to the current gold standard of treatment and placebo. The efforts of the studies used have contributed to the FDA approval of this first intranasal option in 2011 for cancer patients suffering from inadequately managed breakthrough cancer pain

A simple atomistic model for the simulation of the gel phase of lipid bilayers

In this paper we present the results of a large-scale numerical investigation of structural properties of a model of cell membrane, simulated as a bilayer of flexible molecules in vacuum. The study was performed by carrying out extensive Molecular Dynamics simulations, in the (NVE) micro-canonical ensemble, of two systems of different sizes (2x32 and 2x256 molecules), over a fairly large set of temperatures and densities, using parallel platforms and more standard serial computers. Depending on the dimension of the system, the dynamics was followed for physical times that go from few hundred of picoseconds for the largest system to 5--10 nanoseconds for the smallest one. We find that the bilayer remains stable even in the absence of water and neglecting Coulomb interactions in the whole range of temperatures and densities we have investigated. The extension of the region of physical parameters that we have explored has allowed us to study significant points in the phase diagram of the bilayer and to expose marked structural changes as density and temperature are varied, which are interpreted as the system passing from a crystal to a gel phase.Comment: 41 pages, 13 figure

Cytogenetics in the Study of Chromosomal Rearrangement during Wheat Evolution and Breeding

Cytogenetic methods such as chromosome banding and in situ hybridization remain relevant in the post-genomic era, especially for allopolyploid species where genome duplication in some cases makes it difficult to assess the reorganization of chromosomes during evolution. In this review, we give a brief description of cytogenetic methods for the analysis of homoeological chromosomes in cereals. Emphasis is placed on the development of methods for the study of polyploid wheat and its progenitors and on tandem repeats and retrotransposons as markers to evaluate chromosome reorganization throughout evolution and breeding. The most effective cytological probes used for the identification of chromosomes in wheat and Triticeae species by fluorescence and genomic in situ hybridization are described. Particular attention is paid to ribosomal genes used as markers in phylogenetic studies and for chromosome identification. Utility of these cytogenetic methods in the evaluation of breeding lines is demonstrated. A strategy for cytological analysis of wheat hybrids according to the degree of relationships between the species involved in crosses is also discussed

Parallel computing and molecular dynamics of biological membranes

In this talk I discuss the general question of the portability of Molecular Dynamics codes for diffusive systems on parallel computers of the APE family. The intrinsic single precision arithmetics of the today available APE platforms does not seem to affect the numerical accuracy of the simulations, while the absence of integer addressing from CPU to individual nodes puts strong constraints on the possible programming strategies. Liquids can be very satisfactorily simulated using the "systolic" method. For more complex systems, like the biological ones at which we are ultimately interested in, the "domain decomposition" approach is best suited to beat the quadratic growth of the inter-molecular computational time with the number of elementary components of the system. The promising perspectives of using this strategy for extensive simulations of lipid bilayers are briefly reviewed.Comment: 4 pages LaTeX, 2 figures included, espcrc2.sty require

RESULTS FOR THE B-MESON DECAY CONSTANT FROM THE APE COLLABORATION

The decay constant for the B-meson in the static limit is calculated using the Wilson and clover actions at various lattice spacings. We show that both the contamination of our results by excited states and the effects finite lattice spacing are at most the order of the statistical uncertainties. A comparison is made of our results and those obtained in other studies. Values for $f^{stat}_{B_S}/f^{stat}_B$ and $M_{B_S} - M_B$ are also given.Comment: Contribution to Lattice'94, 3 pages PostScript, uuencoded compresse

A WIDE DISTRIBUTION OF A NEW VRN-B1c ALLELE OF WHEAT TRITICUM AESTIVUM L. IN RUSSIA, UKRAINE AND ADJACENT REGIONS: A LINK WITH THE HEADING TIME AND ADAPTIVE POTENTIAL

The adaptation of common wheat (T. aestivum L.) to diverse environmental conditions is greatly under the control of genes involved in determination of vernalization response (Vrn-1 genes). It was found that the variation in common wheat heading time is affected not only by combination of Vrn-1 homoeoalleles but also by multiple alleles at a separate Vrn-1 locus. Previously, we described the Vrn-B1c allele from T.aestivum cv. 'Saratovskaya 29' and found significant differences in the structure of the first (1st) intron of this allele when compared to another highly abundant Vrn-B1a allele, specifically, the deletion of 0.8 kb coupled with the duplication of 0.4 kb. We suggested that the changes in the intron 1 of Vrn-B1c allele caused earlier ear emergence in the near-isogenic line and cultivars, carrying this allele. In this study we investigate the distribution of the Vrn-B1c allele in a wide set of spring wheat cultivars from Russia, Ukraine and adjacent regions. The analysis revealed that 40% of Russian and 53% of Ukranian spring wheat cultivars contain the Vrn-B1c allele. The high distribution of the Vrn-B1c allele can be explained by a frequent using of 'Saratovskaya 29' in the breeding process inside the studied area. From the other hand, the predominance of the Vrn-B1c allele among cultivars cultivated in West Siberia and Kazakhstan may be due to the selective advantage of this allele for the region where there is a high risk of early fall frosts

The distribution of apolipoprotein E in mouse olfactory epithelium

Previous studies from our laboratory suggest that apolipoprotein (apoE), a lipid transporting protein, facilitates olfactory nerve regeneration. We have shown that apoE is enriched in the olfactory nerve and around the glomeruli of the olfactory bulb (OB). The studies reported herein were undertaken to identify possible sources of apoE in the olfactory epithelium (OE). Immunoblotting results revealed apoE expression in the OE of wild-type (WT) mice, but not in apoE deficient/knockout (KO) mice. Immunohistochemical studies revealed that the perikarya and processes of sustentacular (Sus) cells expressed apoE-like immunoreactivity. Minimal neuronal apoE immunostaining was seen, although apoE was observed in the interstial spaces between olfactory receptor neurons (ORN). Substantial apoE-like immunoreactivity was localized to the endfeet and terminal process of Sus cells surrounding the basal cells. Double labeling immunocytochemical studies confirmed that the cell bodies and endfeet of Sus cells expressed high levels of apoE. The endothelial cells of blood vessels were intensely stained for apoE in the lamina propria. Cells forming Bowman’s gland also immunostained for apoE. The apoE staining in the nerve fascicles was less intense, but was uniformly distributed throughout the core of the nerve bundles. Heavily stained cells, probably ensheathing glia, surrounded the nerve fascicles. These results revealed that apoE is expressed in the adult OE and lamina propria at strategic locations where it could facilitate the differentiation, maturation and axonal growth of the ORN, perhaps by recycling lipids from degenerating ORN for use by growing axons

Reconstitution of the Olfactory Epithelium Following Injury in ApoE-Deficient Mice

ApoE, a protein component of lipoproteins, is extensively expressed in the primary olfactory pathway. Because apoE has been shown to play a vital role in nerve repair and remodeling, we hypothesized that apoE expression will increase in the injured olfactory epithelium (OE), and that apoE deficiency in apoE knockout (KO) mice will lead to delayed/incomplete reconstitution of the OE following injury. To directly test this hypothesis, we compared OE regeneration in wild-type (WT) and KO mice following injury induced by intranasal irrigation of Triton X-100. OE was collected at 0, 3, 7, 21, 42, and 56 days post lesion. The amount and distribution of apoE in the regenerating OE was measured by immunoblotting and immunohistochemistry. Rate of OE reconstitution in WT and KO mice was assessed by using three independent measures: (1) OE thickness was measured in cresyl-violet stained sections, (2) basal cell proliferation was determined by using bromodeoxyuridine (BrdU) staining, and (3) differentiation and maturation of olfactory sensory neurons were measured by immunoblotting and immunohistochemical analysis of growth associated protein (GAP) 43 and olfactory marker protein (OMP). The results revealed that apoE expression in the OE is highly regulated during the entire course of OE reconstitution post injury, and that apoE deficiency in apoE KO mice leads to delayed recovery of mature OMP+ cells in the reconstituting OE. The data suggest that apoE production increases in the injured OE to facilitate maturation of olfactory sensory neurons

Cancer risk evaluation: Preliminary analysis of inflammatory biomarkers in farmers exposed to zoonotic agents

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