Polymyxin B-Enriched Exogenous Lung Surfactant: Thermodynamics and Structure.

The use of an exogenous pulmonary surfactant (EPS) to deliver other relevant drugs to the lungs is a promising strategy for combined therapy. We evaluated the interaction of polymyxin B (PxB) with a clinically used EPS, the poractant alfa Curosurf (PSUR). The effect of PxB on the protein-free model system (MS) composed of four phospholipids (diC16:0PC/16:0-18:1PC/16:0-18:2PC/16:0-18:1PG) was examined in parallel to distinguish the specificity of the composition of PSUR. We used several experimental techniques (differential scanning calorimetry, small- and wide-angle X-ray scattering, small-angle neutron scattering, fluorescence spectroscopy, and electrophoretic light scattering) to characterize the binding of PxB to both EPS. Electrostatic interactions PxB-EPS are dominant. The results obtained support the concept of cationic PxB molecules lying on the surface of the PSUR bilayer, strengthening the multilamellar structure of PSUR as derived from SAXS and SANS. A protein-free MS mimics a natural EPS well but was found to be less resistant to penetration of PxB into the lipid bilayer. PxB does not affect the gel-to-fluid phase transition temperature, Tm, of PSUR, while Tm increased by ∼+ 2 °C in MS. The decrease of the thickness of the lipid bilayer (dL) of PSUR upon PxB binding is negligible. The hydrophobic tail of the PxB molecule does not penetrate the bilayer as derived from SANS data analysis and changes in lateral pressure monitored by excimer fluorescence at two depths of the hydrophobic region of the bilayer. Changes in dL of protein-free MS show a biphasic dependence on the adsorbed amount of PxB with a minimum close to the point of electroneutrality of the mixture. Our results do not discourage the concept of a combined treatment with PxB-enriched Curosurf. However, the amount of PxB must be carefully assessed (less than 5 wt % relative to the mass of the surfactant) to avoid inversion of the surface charge of the membrane.

Optimizing Rule Weights to Improve FRBS Clustering in Wireless Sensor Networks.

Wireless sensor networks (WSNs) are usually composed of tens or hundreds of nodes powered by batteries that need efficient resource management to achieve the WSN's goals. One of the techniques used to manage WSN resources is clustering, where nodes are grouped into clusters around a cluster head (CH), which must be chosen carefully. In this article, a new centralized clustering algorithm is presented based on a Type-1 fuzzy logic controller that infers the probability of each node becoming a CH. The main novelty presented is that the fuzzy logic controller employs three different knowledge bases (KBs) during the lifetime of the WSN. The first KB is used from the beginning to the instant when the first node depletes its battery, the second KB is then applied from that moment to the instant when half of the nodes are dead, and the last KB is loaded from that point until the last node runs out of power. These three KBs are obtained from the original KB designed by the authors after an optimization process. It is based on a particle swarm optimization algorithm that maximizes the lifetime of the WSN in the three periods by adjusting each rule in the KBs through the assignment of a weight value ranging from 0 to 1. This optimization process is used to obtain better results in complex systems where the number of variables or rules could make them unaffordable. The results of the presented optimized approach significantly improved upon those from other authors with similar methods. Finally, the paper presents an analysis of why some rule weights change more than others, in order to design more suitable controllers in the future.

Thermodynamic and Structural Study of Budesonide-Exogenous Lung Surfactant System.

The clinical benefits of using exogenous pulmonary surfactant (EPS) as a carrier of budesonide (BUD), a non-halogenated corticosteroid with a broad anti-inflammatory effect, have been established. Using various experimental techniques (differential scanning calorimetry DSC, small- and wide- angle X-ray scattering SAXS/WAXS, small- angle neutron scattering SANS, fluorescence spectroscopy, dynamic light scattering DLS, and zeta potential), we investigated the effect of BUD on the thermodynamics and structure of the clinically used EPS, Curosurf®. We show that BUD facilitates the Curosurf® phase transition from the gel to the fluid state, resulting in a decrease in the temperature of the main phase transition (Tm) and enthalpy (ΔH). The morphology of the Curosurf® dispersion is maintained for BUD < 10 wt% of the Curosurf® mass; BUD slightly increases the repeat distance d of the fluid lamellar phase in multilamellar vesicles (MLVs) resulting from the thickening of the lipid bilayer. The bilayer thickening (~0.23 nm) was derived from SANS data. The presence of ~2 mmol/L of Ca2+ maintains the effect and structure of the MLVs. The changes in the lateral pressure of the Curosurf® bilayer revealed that the intercalated BUD between the acyl chains of the surfactant's lipid molecules resides deeper in the hydrophobic region when its content exceeds ~6 wt%. Our studies support the concept of a combined therapy utilising budesonide-enriched Curosurf®.

Loss of 15-Lipoxygenase in Retinodegenerative RCS Rats.

Retinitis pigmentosa (RP) is a retinal degenerative disease associated with a diversity of genetic mutations. In a natural progression study (NPS) evaluating the molecular changes in Royal College of Surgeons (RCS) rats using lipidomic profiling, RNA sequencing, and gene expression analyses, changes associated with retinal degeneration from p21 to p60 were evaluated, where reductions in retinal ALOX15 expression corresponded with disease progression. This important enzyme catalyzes the formation of specialized pro-resolving mediators (SPMs) such as lipoxins (LXs), resolvins (RvDs), and docosapentaenoic acid resolvins (DPA RvDs), where reduced ALOX15 corresponded with reduced SPMs. Retinal DPA RvD2 levels were found to correlate with retinal structural and functional decline. Retinal RNA sequencing comparing p21 with p60 showed an upregulation of microglial inflammatory pathways accompanied by impaired damage-associated molecular pattern (DAMP) clearance pathways. This analysis suggests that ALXR/FPR2 activation can ameliorate disease progression, which was supported by treatment with an LXA4 analog, NAP1051, which was able to promote the upregulation of ALOX12 and ALOX15. This study showed that retinal inflammation from activated microglia and dysregulation of lipid metabolism were central to the pathogenesis of retinal degeneration in RP, where ALXR/FPR2 activation was able to preserve retinal structure and function.

Hamstring muscle architecture and myotonometer measurements in elite professional football players with a prior strained hamstring.

The purpose of this study was to compare the fascicle length, angle pennation and mechanical properties of the biceps femoris long head (BFlh) in dominant and non-dominant limbs in previously injured and uninjured professional football players. Fifteen professional football players were recruited to participate in this study. Seven players had suffered a BFlh injury during the previous season. Myotonometry mechanical properties were measured in the proximal, common tendon and distal BFlh using MyotonPRO, and angle pennation and fascicle length were also measured. We observed significantly higher distal BFlh frequency, stiffness, decrement, relaxation and creep than in the common tendon and proximal BFlh. The previously injured players showed significantly higher frequency and stiffness, and lower relaxation and creep in the dominant BFlh than did uninjured players. There were no significant differences between the fascicle length and angle pennation in previously injured and uninjured BFlh. Myotonometric measurement provides a quick and inexpensive way to check the properties of the BFlh in professional football players. Professional football players with previous BFlh injury showed higher intrinsic tension and a poorer capacity to deform than did players with no injury to the BFlh.

Cloning, expression, solubilization, and purification of a functionally active recombinant cAMP-dependent protein kinase catalytic subunit-like protein PKAC1 from Trypanosoma equiperdum.

The gene encoding the cAMP-dependent protein kinase (PKA) catalytic subunit-like protein PKAC1 from the Venezuelan TeAp-N/D1 strain of Trypanosoma equiperdum was cloned, and the recombinant TeqPKAC1 protein was overexpressed in bacteria. A major polypeptide with an apparent molecular mass of ∼38 kDa was detected by SDS-polyacrylamide gel electrophoresis, and immunoblotting using antibodies against the human PKA catalytic subunit α. Unfortunately, most of the expressed TeqPKAC1 was highly insoluble. Polypeptides of 36-38 kDa and 45-50 kDa were predominantly seen by immunoblotting in the bacterial particulate and cytosolic fractions, respectively. Since the incorporation of either 4% Triton X-100 or 3% sarkosyl or a mixture of 10 mM MgCl2 and 1 mM ATP (MgATP) improved the solubilization of TeqPKAC1, we used a combination of Triton X-100, sarkosyl and MgATP to solubilize the recombinant protein. TeqPKAC1 was purified by first reconstituting a hybrid holoenzyme between the recombinant protein and a mammalian poly-His-tagged PKA regulatory subunit that was immobilized on a Ni2+-chelating affinity resin, and then by eluting TeqPKAC1 using cAMP. TeqPKAC1 was functional given that it was capable of phosphorylating PKA catalytic subunit substrates, such as kemptide (LRRASLG), histone type II-AS, and the peptide SP20 (TTYADFIASGRTGRRNSIHD), and was inhibited by the peptide IP20 (TTYADFIASGRTGRRNAIHD), which contains the inhibitory motif of the PKA-specific heat-stable inhibitor PKI-α. Optimal enzymatic activity was obtained at 37 °C and pH 8.0-9.0; and the order of effectiveness of nucleotide triphosphates and divalent cations was ATP ¼ GTP â‰… ITP and Mg2+ â‰… Mn2+ â‰… Fe2+ ¼ Ca2+ â‰… Zn2, respectively.

Decarbonisation of calcium carbonate in sodium hydroxide solutions under ambient conditions: effect of residence time and mixing rates.

The decarbonisation of CaCO3 is essential for the production of lime (Ca(OH)2 and CaO), which is a commodity required in several large industries and the main precursor for cement production. CaCO3 is usually decarbonised at high temperatures, generating gaseous CO2 which will require post-process capture to minimise its release into the environment. We have developed a new process that can decarbonise CaCO3 under ambient conditions, while sequestering the CO2 as Na2CO3·H2O or Na2CO3 in the same stage. Here, the effects of increasing stirring rates and residence times on reaction efficiency of the key reaction occurring between CaCO3 and NaOH solution are studied. It is shown that the reaction is enhanced at lower stirring rates and longer residence times up to 300 seconds of contact between the reactants. The mass balance performed for Ca and CO2 revealed that up to the 95% of the process CO2 embodied in CaCO3 was sequestered, with maximum capture rate assessed at nn moles CO2 captured per second of reaction progress. A deeper insight into the precipitation of Na2CO3·H2O or Na2CO3 under different reaction conditions was gained, and SEM-EDX analysis enabled the observation of the reaction front by detection of Na migrating towards inner regions of partially-reacted limestone chalk particles.

Three-Dimensional Pinecone-like Binder-Free Pt-TiO2 Nanorods on Ti Mesh Structures: Synthesis, Characterization and Electroactivity towards Ethanol Oxidation.

We report here the synthesis of binderless and template-less three-dimensional (3D) pinecone-shaped Pt/TiO2/Ti mesh structure. The TiO2 hydrothermally synthesized onto Ti mesh is composed of a mixture of flower-like nanorods and vertically aligned bar-shaped structures, whereas Pt film grown by pulsed laser deposition displays a smooth surface. XRD analyses reveal an average crystallite size of 41.4 nm and 68.5 nm of the TiO2 nanorods and Pt, respectively. In H2SO4 solution, the platinum oxide formation at the Pt/TiO2/Ti mesh electrode is 180 mV more negative than that at the Pt/Ti mesh electrode, indicating that TiO2 provides oxygeneous species at lower potentials, which will facilitate the removal of CO-like intermediates and accelerate an ethanol oxidation reaction (EOR). Indeed, the Pt/TiO2/Ti mesh catalyst exhibits current activity of 1.19 mA towards an EOR at a remarkably superior rate of 4.4 times that of the Pt/Ti mesh electrode (0.27 mA). Moreover, the presence of TiO2 as a support to Pt delivers a steady-state current of 2.1 mA, with an increment in durability of 6.6 times compared to Pt/Ti mesh (0.32 mA). Pt is chosen here as a benchmark catalyst and we believe that with catalysts that perform better than Pt, such 3D pinecone structures can be useful for a variety of catalytic or photoelectrochemical reactions.

A Common Endocrine Signature Marks the Convergent Evolution of an Elaborate Dance Display in Frogs.

AbstractUnrelated species often evolve similar phenotypic solutions to the same environmental problem, a phenomenon known as convergent evolution. But how do these common traits arise? We address this question from a physiological perspective by assessing how convergence of an elaborate gestural display in frogs (foot-flagging) is linked to changes in the androgenic hormone systems that underlie it. We show that the emergence of this rare display in unrelated anuran taxa is marked by a robust increase in the expression of androgen receptor (AR) messenger RNA in the musculature that actuates leg and foot movements, but we find no evidence of changes in the abundance of AR expression in these frogs' central nervous systems. Meanwhile, the magnitude of the evolutionary change in muscular AR and its association with the origin of foot-flagging differ among clades, suggesting that these variables evolve together in a mosaic fashion. Finally, while gestural displays do differ between species, variation in the complexity of a foot-flagging routine does not predict differences in muscular AR. Altogether, these findings suggest that androgen-muscle interactions provide a conduit for convergence in sexual display behavior, potentially providing a path of least resistance for the evolution of motor performance.

Role of the Cholinergic Anti-Inflammatory Reflex in Central Nervous System Diseases.

In several central nervous system diseases, it has been reported that inflammation may be related to the etiologic process, therefore, therapeutic strategies are being implemented to control inflammation. As the nervous system and the immune system maintain close bidirectional communication in physiological and pathological conditions, the modulation of inflammation through the cholinergic anti-inflammatory reflex has been proposed. In this review, we summarized the evidence supporting chemical stimulation with cholinergic agonists and vagus nerve stimulation as therapeutic strategies in the treatment of various central nervous system pathologies, and their effect on inflammation.

Comparison of a Brucella Enzyme Immunoassay and the Standard Agglutination with 2-Mercaptoethanol Test in the Diagnosis and Monitoring of Brucellosis in Mexican Patients.

BACKGROUND: The diagnosis of human brucellosis is difficult based on clinical grounds alone. Thus, the diagnosis is based on microbiological and serological tests. Therefore, the diagnosis relies predominantly on laboratory testing. The objective of this study was to determine the most efficient test for the diagnosis and monitoring of patients treated for brucellosis by comparing the standard agglutination test in a tube with 2-mercaptoethanol (SAT-2Me) to an enzyme-linked immunosorbent assay for the detection of antibodies against Brucella IgM (IgM ELISA). METHODS: A retrospective chart review was performed. A total of 108 patients with brucellosis were analyzed at diagnosis and at the first and second follow-ups after treatment. The data were captured and analyzed using the SPSS 18.0 program. Frequencies, percentages, the Pearson's chi-square test, the kappa coefficient, sensitivity, specificity, predictive values, odds ratio, and conditional odds ratio (OR and COR) were calculated. RESULTS: Diagnostic test: the IgM ELISA showed 96.3% sensitivity vs. 73.1% sensitivity for the SAT-2Me (p < 0.001). First follow-up: the IgM ELISA presented significant differences vs. the SAT-2Me in sensitivity (97.2% vs. 72.2%) and specificity (89.7% vs. 44.1%). Additionally, the second follow-up data showed significant differences in the sensitivity (85.7% vs. 71.4%) and specificity (82.8% vs. 41.4%) for the IgM ELISA vs. the SAT-2Me, re-spectively. In addition, the IgM ELISA showed significant concordance (0.836, p < 0.001 and 0.563, p < 0.001) at the first and second follow-ups, respectively, vs. the SAT-2Me. CONCLUSIONS: The IgM ELISA is a more reliable and useful assay for the diagnosis and monitoring of brucellosis patients than the SAT-2 Me, avoiding up to 45.6% of unnecessary treatments. The SAT-2Me showed lower efficiency for diagnosis than the IgM ELISA and limited relevance for monitoring.

SQ109 inhibits proliferation of Leishmania donovani by disruption of intracellular Ca2+ homeostasis, collapsing the mitochondrial electrochemical potential (ΔΨm) and affecting acidocalcisomes.

Leishmania donovani is the causative agent of visceral leishmaniasis. Annually, 500 million new cases of infection are reported mainly in poor communities, decreasing the interest of the pharmaceutical industries. Therefore, the repositioning of new drugs is an ideal strategy to fight against these parasites. SQ109, a compound in phase IIb/III of clinical trials to treat resistant Mycobacterium tuberculosis, has a potent effect against Trypanosoma cruzi, responsible for Chagas' disease, and on Leishmania mexicana, the causative agent of cutaneous and muco-cutaneous leishmaniasis. In the latter, the toxic dose against intramacrophagic amastigotes is very low (IC50 ~ 11 nM). The proposed mechanism of action on L. mexicana involves the disruption of the parasite intracellular Ca2+ homeostasis through the collapse of the mitochondrial electrochemical potential (ΔΨm). In the present work, we show a potent effect of SQ109 on L. donovani, the parasite responsible for visceral leishmaniasis, the more severe and uniquely lethal form of these infections, obtaining a toxic effect on amastigotes inside macrophages even lower to that obtained in L. mexicana (IC50 of 7.17 ± 0.09 nM) and with a selectivity index > 800, even higher than in L. mexicana. We also demonstrated for first time that SQ109, besides collapsing ΔΨm of the parasite, induced a very rapid damage to the parasite acidocalcisomes, essential organelles involved in the bioenergetics and many other important functions, including Ca2+ homeostasis. Both effects of the drug on these organelles generated a dramatic increase in the intracellular Ca2+ concentration, causing parasite death.

A Distributed Clustering Algorithm Guided by the Base Station to Extend the Lifetime of Wireless Sensor Networks.

Clustering algorithms are necessary in Wireless Sensor Networks to reduce the energy consumption of the overall nodes. The decision of which nodes are the cluster heads (CHs) greatly affects the network performance. The centralized clustering algorithms rely on a sink or Base Station (BS) to select the CHs. To do so, the BS requires extensive data from the nodes, which sometimes need complex hardware inside each node or a significant number of control messages. Alternatively, the nodes in distributed clustering algorithms decide about which the CHs are by exchanging information among themselves. Both centralized and distributed clustering algorithms usually alternate the nodes playing the role of the CHs to dynamically balance the energy consumption among all the nodes in the network. This paper presents a distributed approach to form the clusters dynamically, but it is occasionally supported by the Base Station. In particular, the Base Station sends three messages during the network lifetime to reconfigure the s k i p value of the network. The s k i p , which stands out as the number of rounds in which the same CHs are kept, is adapted to the network status in this way. At the beginning of each group of rounds, the nodes decide about their convenience to become a CH according to a fuzzy-logic system. As a novelty, the fuzzy controller is as a Tagaki-Sugeno-Kang model and not a Mandami-one as other previous proposals. The clustering algorithm has been tested in a wide set of scenarios, and it has been compared with other representative centralized and distributed fuzzy-logic based algorithms. The simulation results demonstrate that the proposed clustering method is able to extend the network operability.

Pathological Response to Neoadjuvant Chemotherapy and the Molecular Classification of Locally Advanced Breast Cancer in a Latin American Cohort.

BACKGROUND: The majority of patients with breast cancer in Colombia are admitted into oncological centers at locally advanced stages of the disease (53.9%). The aim of this study was to describe the pathological response obtained with neoadjuvant chemotherapy (NACT) according to the molecular classification of breast cancer in patients with locally advanced tumors treated within the National Cancer Institute (NCI) Functional Breast Cancer Unit (FBCU) in Bogotá, Colombia. MATERIALS AND METHODS: This was an observational, descriptive, historical cohort study of patients with locally advanced breast cancer treated within the NCI FBCU. RESULTS: We included 414 patients who received NACT and surgical management. Most patients had luminal B HER2-negative tumors (n = 134, 32.4%). The overall rate of pathological complete response (pCR) ypT0/ypN0 was 15.2% (n = 63). Tumors that presented the highest rate of pCR were pure HER2, at 40.5% (n = 15; odds ratio [OR], 6.7); however, with a follow-up of 60 months, only the triple negative tumors presented a statistically significant difference for event-free survival (EFS; median recurrence time, 18 months; range, 1-46) and overall survival (OS; median follow-up, 31 months; range 10-57). The molecular subtype that most recurrences presented was luminal B HER2 negative, at 38.3% (n = 28). The majority of recurrences (93.2 %; n = 68; OR, 5.9) occurred in patients in whom no pathological response was obtained (Chevallier 3 and 4). CONCLUSION: Pathological response in locally advanced tumors is related to the molecular subtype of breast cancer, finding higher pCR rates in pure HER2 and triple-negative tumors. A direct relationship was found between disease recurrences and the pathological response, evidencing greater tumor recurrence in patients who did not respond to NACT (Chevallier 3 and 4). EFS and OS were greater in patients with pCR, with statistical significance only in triple-negative tumors. IMPLICATIONS FOR PRACTICE: This research article is of scientific interest, because it describes the clinical and pathological features and analyzes the correlation between pathological response to neoadjuvant chemotherapy and the molecular classification of locally advanced breast cancer in patients treated in the National Cancer Institute in Bogotá, Colombia. It was found that pathological response is related to the molecular subtype of breast cancer. In addition, there is a direct relationship between disease recurrences and pathological response. The survival results were greater in patients with pathological complete response.

pH-Sensitive N,N-Dimethylalkane-1-amine N-Oxides in DNA Delivery: From Structure to Transfection Efficiency.

pH-sensitive liposomes composed of homologues of series of N,N-dimethylalkane-1-amine N-oxides (CnNO, n = 8-18, where n is the number of carbon atoms in the alkyl substituent) and neutral phospholipid dioleoylphosphatidylethanolamine (DOPE) were prepared at two molar ratios (CnNO/DOPE = 0.4:1 and 1:1) and tested for their in vitro transfection activity. Several techniques (SAXS/WAXS, UV-vis, zeta potential measurements, confocal microscopy) were applied to characterize the system in an effort to unravel the relationship among the transfection efficiency, structure, and composition of the lipoplexes. The transfection efficiency of CnNO/DOPE for plasmid DNA in U2OS cells follows a quasi-parabolic dependence on CnNO's alkyl substituent length with a maximum at n = 16. The transfection efficiency of CnNO/DOPE (n = 12-18) lipoplexes was found to be higher than that of commercially available Lipofectamine 2000. C16NO/DOPE also positively transfected HEK 293T and HeLa cells. Small-angle X-ray scattering (SAXS) shows large structural diversity depending on the complex's composition and pH. Transfection efficiencies mediated by two structures, either a condensed lamellar (Lαc) or epitaxially connected Lαc and a condensed inverted hexagonal (HIIc) phase (Lαc & HIIc), were found to be very similar. The change in pH from acidic to neutral induces phase transition Lαc & HIIc → QII + Lα, with cubic phase QII of the Pn3m space group. QII detected in lipoplexes of most efficient composition CnNO/DOPE (n = 16 and 18) facilitates DNA release and promotes its internalization in the cell.

A New Centralized Clustering Algorithm for Wireless Sensor Networks.

Clustering is presently one of the main routing techniques employed in randomly deployed wireless sensor networks. This paper describes a novel centralized unequal clustering method for wireless sensor networks. The goals of the algorithm are to prolong the network lifetime and increase the reliability of the network while not compromising the data transmission. In the proposed method, the Base Station decides on the cluster heads according to the best scores obtained from a Type-2 Fuzzy system. The input parameters of the fuzzy system are estimated by the base station or gathered from the network with a careful design that reduces the control message exchange. The whole network is controlled by the base station in a rounds-based schedule that alternates rounds when the base station elects cluster heads, with other rounds in which the cluster heads previously elected, gather data from their contributing nodes and forward them to the base station. The setting of the number of rounds in which the Base Station keeps the same set of cluster heads is another contribution of the present paper. The results show significant improvements achieved by the proposal when compared to other current clustering methods.

A new evidence-based risk stratification system for cutaneous squamous cell carcinoma into low, intermediate, and high risk groups with implications for management.

Most primary cutaneous squamous cell carcinomas are cured with surgery. A subset, however, may develop local and nodal metastasis that may eventuate in disease-specific; death. This subset has been variably termed high risk. Herein, we review; an emerging body of data on the risks of these outcomes and propose an evidence-based; risk stratification for low-, intermediate-, and high-risk tumors that takes into; account both tumor and patient characteristics. Finally, we discuss a framework for; management of these tumors on the basis of data, when available, and our; recommendations when data are sparse.

Parylene scaffold for cartilage lesion.

Evaluate parylene scaffold feasibility in cartilage lesion treatment, introducing a novel paradigm combining a reparative and superficial reconstructive procedure. Fifteen rabbits were used. All animals had both knees operated and the same osteochondral lesion model was created bilaterally. The parylene scaffold was implanted in the right knee, and the left knee of the same animal was used as control. The animals were euthanized at different time points after surgery: four animals at three weeks, three animals at six weeks, four animals at nine weeks, and four animals at 12 weeks. Specimens were analyzed by International Cartilage Repair Society (ICRS) macroscopic evaluation, modified Pineda histologic evaluation of cartilage repair, and collagen II immunostaining. Parylene knees were compared to its matched contra-lateral control knees of the same animal using the Wilcoxon matched-pairs signed rank. ICRS mean ± SD values for parylene versus control, three, six, nine and twelve weeks, respectively: 7.83 ± 1.85 versus 4.42 ± 1.08, p = 0.0005; 10.17 ± 1.17 versus 6.83 ± 1.17, p = 0.03; 10.89 ± 0.60 versus 7.33 ± 2.18, p = 0.007; 10.67 ± 0.78 versus 7.83 ± 3.40, p = 0.03. Modified Pineda mean ± SD values for parylene versus control, six, nine and twelve weeks, respectively: 3.37 ± 0.87 versus 6.94 ± 1.7, p < 0.0001; 5.73 ± 2.05 versus 6.41 ± 1.7, p = 0.007; 3.06 ± 1.61 versus 6.52 ± 1.51, p < 0.0001. No inflammation was seen. Parylene implanted knees demonstrated higher collagen II expression via immunostaining in comparison to the control knees. Parylene scaffolds are a feasible option for cartilage lesion treatment and the combination of a reparative to a superficial reconstructive procedure using parylene scaffolds led to better results than the reparative procedure alone.

Oseltamivir phosphate interaction with model membranes.

Oseltamivir belongs to the neuraminidase inhibitors, developed against the influenza virus, and registered under the trademark Tamiflu. Despite its long-term acquaintance, there is limited information in the literature about its physicochemical and structural properties in a lipid-water system. We present an experimentally determined partition coefficient with structural information on the interaction of oseltamivir with the model membrane, its possible location, and its effect on the membrane thermodynamics. The hydrophobic part of the lipid bilayer is affected to a moderate extent, which was proved by slight changes in thermal and structural properties. Hereby, interaction of oseltamivir with the phospholipid bilayer induces concentration dependent decrease of lateral pressure in the bilayer acyl chain region. Oseltamivir charges the bilayer surface positively, which results in the zeta potential increase and changes in anisotropic properties studied by the polarised light microscopy. At the highest oseltamivir concentrations studied, the multilamellar structure is extensively disturbed, likely due to electrostatic repulsion between the adjacent bilayers.