A Ciprofloxacin Extended Release Tablet Based on Swellable Drug Polyelectrolyte Matrices

The aim of this work was the development of extended release tablets of 500 mg of ciprofloxacin based on swellable drug polyelectrolyte matrices (SDPM). A set of complexes of carbomer, ciprofloxacin and sodium, (CB–Cip)₅₀Na _x , having a molar ratio Cip/CB acid groups of 0.5 and variable proportions of Na⁺ was used to prepare SDPM. Characterization of complexes by FT-IR, powder X-ray diffraction and thermal analysis revealed that Cip, in its protonated form, is ionically bonded to the functional groups of CB. Rates of fluid uptake of (CB–Cip)₅₀Na _x matrices as well as Cip release in simulated gastric fluid were modulated by changes in the proportion of Na⁺ incorporated in the complexes. A direct correlation between fluid uptake and delivery rate was observed along the series of matrices. Release rates were modulated from 1.4 mg/min to 25 mg/min in going from (CB–Cip)₅₀Na₁₀ to (CB–Cip)₅₀Na₁₄. The analysis of kinetic data suggest that rates of swelling, ionic pair dissociation and drug diffusion play a role in the kinetic control of delivery. Complexes were satisfactorily prepared and processed together with small amounts of antiadherent and lubricant excipients to obtain a series of extended release SDPM tablets through the current tableting technology processes. Cip release from matrices was widely modulated by the composition of the complexes yielding a flexible system that allows selecting a composition that releases in 120 min 90% of the dose in simulated gastric fluid.     

HSP-72 Accelerated Expression in Mononuclear Cells Induced In Vivo by Acetyl Salicylic Acid Can Be Reproduced In Vitro when Combined with H2O2

Background

Among NSAIDs acetyl salicylic acid remains as a valuable tool because of the variety of benefic prophylactic and therapeutic effects. Nevertheless, the molecular bases for these responses have not been complete understood. We explored the effect of acetyl salicylic acid on the heat shock response.

Results

Peripheral blood mononuclear cells from rats challenged with acetyl salicylic acid presented a faster kinetics of expression of HSP-72 messenger RNA and protein in response to in vitro heat shock. This effect reaches its maximum 2 h after treatment and disappeared after 5 h. On isolated peripheral blood mononuclear cells from untreated rats, incubation with acetyl salicylic acid was ineffective to produce priming, but this effect was mimicked when the cells were incubated with the combination of H₂O₂+ ASA.

Conclusions

Administration of acetyl salicylic acid to rats alters HSP-72 expression mechanism in a way that it becomes more efficient in response to in vitro heat shock. The fact that in vitro acetyl salicylic acid alone did not induce this priming effect implies that in vivo other signals are required. Priming could be reproduces in vitro with the combination of acetyl salicylic acid+H₂O₂.     

Morphological assessment of the Octopus vulgaris species complex evaluated in light of molecular‐based phylogenetic inferences

Cryptic species are common in the ocean, particularly among marine invertebrates such as octopuses. Delineating cryptic species is particularly problematic in octopus taxonomy where the plasticity recorded among taxonomic characters often results in low resolution at the species level. This study investigated the morphological relationships among seven phylogenetic clades (identified using cytochrome c oxidase subunit I) of the broadly distributed Octopus vulgaris species complex and close relatives. Morphological analyses in this study were successful in delimiting O. sinensis, Brazilian O. vulgaris and O. vulgaris sensu stricto, which was congruent with the molecular findings of this study. Analyses based on male morphology were successful in distinguishing 14 of 15 total pairwise comparisons and proved to be a more reliable indicator of species‐level relationships in comparison with female morphology. The majority of characters with the greatest discriminatory power were male sexual traits. Significant morphological differences were also recorded among sampling localities of conspecifics, with phenotype showing correlation with local environmental data. The findings of this study support the hypothesis that multiple O. vulgaris‐like species are currently being incorrectly treated under a single species name, O. vulgaris. Octopuses being exported globally under the name O. vulgaris are of extremely high fisheries market value and profile. Our findings have potentially significant implications for the naming and conservation of commercially harvested members of this species complex throughout their ranges.     

<Superscript>1</Superscript>H, <Superscript>15</Superscript>N,and <Superscript>13</Superscript>C resonance assignments of <Emphasis Type="Italic">Staphylococcus aureus</Emphasis> extracellular adherence protein domain 4

The pathogenic bacterium Staphylococcus aureus has evolved to actively evade many aspects of the human innate immune system by expressing a series of secreted inhibitory proteins. Among these, the extracellular adherence protein (Eap) has been shown to inhibit the classical and lectin pathways of the complement system. By binding to complement component C4b, Eap is able to inhibit formation of the CP/LP C3 pro-convertase. Secreted full-length, mature Eap consists of four ~98 residue domains, all of which adopt a similar beta-grasp fold, and are connected through a short linker region. Through multiple biochemical approaches, it has been determined that the third and fourth domains of Eap are responsible for C4b binding. Here we report the backbone and side-chain resonance assignments of the 11.3 kDa fourth domain of Eap. The assignment data has been deposited in the BMRB database under the accession number 26726.     

Ferns and Melastomataceae as indicators of vascular plant composition in rain forests of Colombian Amazonia

In a case-study from Colombian Amazonia, species information from ferns and Melastomataceae was used to explain the compositional patterns of other vascular plant species in 40 widely distributed 0.1-ha plots. Canonical correspondence analysis was applied to regress vascular plant species composition in the forests against information from these two indicator groups (summarized as axes of principal coordinate analyses), together with that from soils, landscape, and the spatial sampling design. In total, 53,941 individuals of 2480 vascular plant species were recorded. Of these, 17,473 individuals and 132 species were from ferns and Melastomataceae. In 19 well-drained upland (tierra firme) plots 19,622 vascular plant individuals and 1716 species were found, with 3793 plants and 91 species from ferns and Melastomataceae. In both the set of all landscapes and the subset of tierra firme forests the principal PCoA axes of the two indicator groups were highly related to the main patterns of forest species composition. In principle, therefore, ferns and Melastomataceae can be used to detect and forecast changes in the forest composition of the study area. However, evidence was not obtained that ferns and Melastomataceae show more potential to predict the main patterns in species composition of forests than soil, landscape, and spatial variables. The partioning of the total variation in forest composition showed that the correlation of ferns and Melastomataceae with other forest plants was quite independent from that of soil, landscape, and space. Direct effects of ferns and Melastomataceae on other plants might be obtained from experimental studies of between-plant interactions, concentrating on the seedling or juvenile stages of trees and lianas, both above-ground as well as in the rooting environment.     

Overactive and underactive bladder dysfunction is reflected by alterations in urothelial ATP and NO release

ATP and NO are released from the urothelium in the bladder. Detrusor overactivity (DO) following spinal cord injury results in higher ATP and lower NO release from the bladder urothelium. Our aim was to study the relationship between ATP and NO release in (1) early diabetic bladders, an overactive bladder model; and (2) "diuretic" bladders, an underactive bladder model. To induce diabetes mellitus female rats received 65mg/kg streptozocin (i.v.). To induce chronic diuresis rats were fed with 5% sucrose. At 28 days, in vivo open cystometry was performed. Bladder wash was collected to analyze the amount of ATP and NO released into the bladder lumen. For in vitro analysis of ATP and NO release, a Ussing chamber was utilized and hypoosmotic Krebs was perfused on the urothelial side of the chamber. ATP was analyzed with luminometry or HPLC-fluorometry while NO was measured with a Sievers NO-analyzer. In vivo ATP release was increased in diabetic bladders and unchanged in diuretic bladders. In vitro release from the urothelium followed the same pattern. NO release was unchanged both in vitro and in vivo in overactive bladders whereas it was enhanced in underactive bladders. We found that the ratio of ATP/NO, representing sensory transmission in the bladder, was high in overactive and low in underactive bladder dysfunction. In summary, ATP release has a positive correlation while NO release has a negative correlation with the bladder contraction frequency. The urinary ATP/NO ratio may be a clinically relevant biomarker to characterize the extent of bladder dysfunction.     

Understanding the laminated layer of larval Echinococcus II: immunology

The laminated layer (LL) is the massive carbohydrate-rich structure that protects Echinococcus larvae, which cause cystic echinococcosis (hydatid disease) and alveolar echinococcosis. Increased understanding of the biochemistry of the LL is allowing a more informed analysis of its immunology. The LL not only protects the parasite against host attack but also shapes the overall immune response against it. Because of its dense glycosylation, it probably contains few T-cell epitopes, being important instead in T-cell independent antibody responses. Crucially, it is decoded in non-inflammatory fashion by innate immunity, surely contributing to the strong immune-regulation observed in Echinococcus infections. Defining the active LL molecular motifs and corresponding host innate receptors is a feasible and promising goal in the field of helminth-derived immune-regulatory molecules.     

Deforestation Induced Climate Change: Effects of Spatial Scale

Deforestation is associated with increased atmospheric CO₂ and alterations to the surface energy and mass balances that can lead to local and global climate changes. Previous modelling studies show that the global surface air temperature (SAT) response to deforestation depends on latitude, with most simulations showing that high latitude deforestation results in cooling, low latitude deforestation causes warming and that the mid latitude response is mixed. These earlier conclusions are based on simulated large scal land cover change, with complete removal of trees from whole latitude bands. Using a global climate model we examine the effects of removing fractions of 5% to 100% of forested areas in the high, mid and low latitudes. All high latitude deforestation scenarios reduce mean global SAT, the opposite occurring for low latitude deforestation, although a decrease in SAT is simulated over low latitude deforested areas. Mid latitude SAT response is mixed. In all simulations deforested areas tend to become drier and have lower SAT, although soil temperatures increase over deforested mid and low latitude grid cells. For high latitude deforestation fractions of 45% and above, larger net primary productivity, in conjunction with colder and drier conditions after deforestation cause an increase in soil carbon large enough to produce a net decrease of atmospheric CO₂. Our results reveal the complex interactions between soil carbon dynamics and other climate subsystems in the energy partition responses to land cover change.