The effect of long-term exposure to combinations of growth promoters in Long Evans rats: part 1: Endocrine adrenal function

The aim of the study was to investigate whether the chronic administration (45 days) of clenbuterol (CB) at a growth promoting dose (1 mg kg(-1) bw) and/or dexamethasone (DEX: 0.1 mg kg(-1) bw) may cause the disruption of rat endocrine adrenal function. Blood samples were taken weekly during the whole experiment (S0-S7), and at different days of withdrawal (W0, W5, W10, W15 and W20). Hormone profiles were determined by RIA (ACTH) or EIA (corticosterone and catecholamines). ACTH showed significantly elevated concentrations from S1 until W5 (p<0.05) with CB administration. It began to decrease the day of DEX and CB-DEX administration. DEX showed significantly lowered ACTH concentrations from the day of drug injection (p<0.05). Corticosterone showed significantly elevated levels until W10 (p<0.01) with CB and CB+DEX. DEX showed lowered levels of corticosterone during the whole withdrawal period. Epinephrine presented significantly elevated plasma levels until W5 with CB and CB+DEX. With DEX, epinephrine was also elevated from W5 to W15 (p<0.05). Norepinephrine also presented significantly elevated plasma levels until S7 with CB and CB+DEX (p<0.001). With DEX no differences were found. Conclusion: Long-term administration of CB and/or DEX causes an endocrine adrenal disruption with changes in ACTH, glucocorticoid and catecholamine secretion.     

Contact Transcleral Ciliary Body Photodynamic Therapy with Verteporfin in Pigmented Rabbits: Effect of Repeated Treatments

We studied the effect on the intraocular pressure (IOP) and the ciliary body (CB) morphology after four consecutive contact transcleral photodynamic treatments of the ciliary body (CB-PDT) with verteporfin in pigmented rabbits. Twenty-two pigmented rabbits underwent CB-PDT (study group), performed once (six rabbits) or repeated for up to four times (16 rabbits). Six additional rabbits received only laser treatment without photosensitizer administration (control group). CB-PDT was performed in one eye in rabbits of the study group, with the fellow eye serving as internal control. Verteporfin dosage was 1 mg kg ⁻¹ as bolus injection and laser settings were 40 mW (600 μm core optical fiber) for 1.5 min per spot, for 10 spots. In repeated CB-PDT, treatments were performed in 4-day intervals. Daily IOP measurements were recorded. Histological studies were performed at selected time points. An IOP reduction, more sustained following repeated treatments, was detected in all treated eyes but not in fellow eyes or in the control group. On the average, the IOP was restored to pretreatment levels 4 days after the last treatment. No serious adverse events were observed and the CB architecture was intact at the end of the experiment. Repeated CB-PDT is safe and results in a short-term reduction of IOP. Induced CB alterations are reversible.     

Effects of exposure to dibutyltin dichloride on sperm density,viability and morphology in male mice

Experiments on the effects of 0.025–0.40 µg of dibutyltin dichloride (DBTCl) per kilogram body weight (kg bw), on sperm density, viability and morphology in mature mice were conducted by daily intraperitoneal injection for 7 days at 22 ± 2 °C and 12 h light–dark cycle conditions. The results demonstrated that DBTCl exhibited strong toxicity on sperm quality. Dosed with ≥ 0.05 µg DBTCl/kg bw groups, the testes weight, sperm density and the rate of survival of sperm decreased, whereas the rate of sperm abnormalities increased significantly. In addition, treatment with 0.05 µg DBTCl/kg bw resulted in increasing rate of sperm head abnormalities, whereas administration at 0.20 and 0.40 µg DBTCl/kg bw significantly increased the rate of sperm tail abnormalities. In the group treated at ≥ 0.10 µg DBTCl/kg bw, the mice body weights decreased. It appeared there was a noticeable dose–response relationship between DBTCl and the parameters studied. ED₅₀ values (7 days) of DBTCl for survival rate of sperm and density were 0.17 µg/kg bw and 0.19 µg/kg bw respectively. The present study provides a possibility for early diagnostic indicators and methods for sperm quality induced by organotin compounds (DBTCl) in mammals. Copyright © 2001 John Wiley & Sons, Ltd.     

Quality Parameters of Wheat Bread with the Addition of Untreated Cheese Whey

Τhe present study was carried out to evaluate wheat bread of three different flour compositions prepared by replacing water with untreated cheese whey (WCB). Bread prepared with water was taken as the control (CB). All breads were stored at 24 ± 1 °C for up to 6 days. Microbiological, physicochemical, and sensory analyses were determined as a function of storage time. WCB had lower total viable counts (TVC) (3.81 log cfu/g for CB and 2.78 log cfu/g for WCB on day 2 of storage) and showed delayed mold growth by 1 day (day 4 for CB and day 5 for WCB). WCB also had lower pH (5.91 for CB and 5.71 for WCB on day 0), higher titratable acidity values (TTA) (2.5–5.2 mL NaOH/10 g for CB and 4.5–6.8 mL NaOH/ 10 g for WCB), and higher protein content (PC) (PC 7.68% for CB and 8.88% for WCB). WCB was characterized by a more intense flavor, reduced hardness but similar cohesiveness, springiness, and adhesiveness compared to CB. Based primarily on sensory (appearance/mold formation) data, the shelf life of WCB was 4–5 days compared to 3–4 days for CB stored at 24 ± 1 °C. The proposed use of whey in bread preparation contributes decisively to the environmentally friendly management of whey.     

Orientational behavior of thermotropic liquid crystals on surfaces presenting electrostatically bound vesicular stomatitis virus

We report the orientational behavior of nematic phases of 4-cyano-4'-pentylbiphenyl (5CB) on cationic, anionic, and nonionic surfaces before and after contact of these surfaces with solutions containing the negatively charged vesicular stomatitis virus (VSV). The surfaces were prepared on evaporated films of gold by either adsorption of poly-L-lysine (cationic) or formation of self-assembled monolayers (SAMs) from HS(CH2)2SO3- (anionic) or HS(CH2)11(OCH2CH2)4OH (nonionic). Prior to treatment with virus, we measured the initial orientation of 5CB (delta epsilon = epsilon(parallel) - epsilon(perpendicular) > 0) to be parallel to the cationic surfaces (planar anchoring) but perpendicular (homeotropic) after equilibration for 5 days. A similar transition from planar to homeotropic orientation of 5CB was observed on the anionic surfaces. Only planar orientations of 5CB were observed on the nonionic surfaces. Because N-(4-methoxybenzylidene)-4-butylaniline (MBBA, delta epsilon = epsilon(parallel) - epsilon(perpendicular) < 0) exhibited planar alignment on all surfaces, the time-dependent alignment of 5CB on the ionic surfaces is consistent with a dipolar coupling between the 5CB and electrical double layers formed at the ionic interfaces. Treatment ofpoly-L-lysine-coated gold films (cationic) with purified solutions of VSV containing 10(8)-10(10) plaque-forming units per milliliter (pfu/mL) led to the homeotropic alignment of 5CB immediately after contact of 5CB with the surface. In contrast, treatment of anionic surfaces and nonionic surfaces with solutions of VSV containing approximately 10(10) pfu/mL did not cause immediate homeotropic alignment of 5CB. These results and others suggest that homeotropic alignment of 5CB on cationic surfaces treated with VSV of titer > or = 10(8) pfu/mL reflects the presence of virus electrostatically bound to these surfaces.     

Development and validation of a highly sensitive LC-MS/MS method for quantitation of dexlansoprazole in human plasma: application to a human pharmacokinetic study

A highly sensitive, specific and simple LC-MS/MS method was developed for the simultaneous estimation of dexlansoprazole (DEX) with 50 μL of human plasma using omeprazole as an internal standard (IS). The API-4000 LC-MS/MS was operated under multiple reaction-monitoring mode using electrospray ionization. A simple liquid-liquid extraction process was used to extract DEX and IS from human plasma. The total run time was 2.00 min and the elution of DEX and IS occurred at 1.20 min. This was achieved with a mobile phase consisting of 0.2% ammonia-acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X-terra RP 18 (50 × 4.6 mm, 5 μm) column. The developed method was validated in human plasma with a lower limit of quantitation of 2 ng/mL for DEX. A linear response function was established for the range of concentrations 2.00-2500.0 ng/mL (r > 0.998) for DEX. The intra- and inter-day precision values for DEX met the acceptance criteria as per FDA guidelines. DEX was stable in the battery of stability studies, viz. bench-top, auto-sampler and freeze-thaw cycles. The developed assay method was applied to an oral bioequivalence study in humans.     

Effect of compounding procedure on morphology and crystallization behavior of isotactic polypropylene/high‐density polyethylene/carbon black ternary composites

The effect of compounding procedure on morphology and crystallization behavior of isotactic polypropylene/high‐density polyethylene/carbon black (iPP/HDPE/CB) composite was investigated. iPP/HDPE/CB composites were prepared by four compounding procedures (A: iPP + HDPE + CB; B: iPP/HDPE + CB; C: HDPE/CB + iPP; D: iPP/CB + HDPE). Scanning electron microscopy observation showed that CB particles are mainly distributed in HDPE in all composites, and the phase morphology of composites was obviously affected by a compounding procedure. The size of the HDPE/CB domains in the composites prepared by procedures A and D decreased with the increase in CB content, whereas that of HDPE/CB in the composites prepared by procedures B and C rarely changed with the increase in CB content. The crystallization behaviors of the composites were significantly affected by their phase morphology, which resulted from the variation of compounding procedure. The isothermal crystallization rate of iPP in the composites prepared by procedures A and D was obviously increased, which may originate from the small HDPE/CB droplets dispersed in the iPP phase. The non‐isothermal crystallization curves of composites prepared by procedure D represented two peaks because the iPP component in these composites had the fastest crystallization rate, whereas the curves of composites prepared by other compounding sequences only exhibited one peak. Moreover, the crystallinity of HDPE almost increased by one time with the incorporation of only 1 phr CB because the CB particles selectively located in the HDPE phase, and the crystallinity of HDPE decreased with the further increase of CB content because of the strong restriction of CB on the HDPE chains. Copyright © 2011 John Wiley & Sons, Ltd.     

Modified graphitized carbon black as transducing material for reagentless H2O2 and enzyme sensors

Direct electron transfer between redox enzymes and electrodes is the basis for the third generation biosensors. We established direct electron transfer between quinohemoprotein alcohol dehydrogenase (PQQ-ADH) and modified carbon black (CBs) electrodes. Furthermore, for the first time, this phenomenon was observed for pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (PQQ-GDH). Reagentless enzyme biosensors suitable for the determination of ethanol, glucose and sensors for hydrogen peroxide were designed using CB electrodes and screen-printing technique. Aiming to create an optimal transducing material for biosensors, a set of CB batches was synthesized using the matrix of Plackett-Burman experimental design. Depending on the obtained surface functional groups as well as the nano-scale carbon structures in CBs batches, the maximal direct electron transfer current of glucose and ethanol biosensors can vary from 20 to 300 nA and from 30 to 6300 nA for glucose and ethanol, respectively. Using modified CB electrodes, an electrocatalytic oxidation of H₂O₂ takes place at more negative potentials (0.1-0.4 V versus Ag/AgCl). Moreover, H₂O₂ oxidation efficiency depends on the amount and morphology of fine fraction in the modified CBs.     

Nanostructured carbon black filled polypropylene/polystyrene blends containing styrene-butadiene-styrene copolymer: Influence of morphology on electrical resistivity

This paper is part of a comprehensive study on using selective localization of carbon black (CB) at the interface of immiscible polymer blends in order to reduce the percolation threshold concentration and enhance the conductivity of the blends. CB was successfully localized at the interface of polypropylene/polystyrene (PP/PS) blend by introducing styrene-butadiene-styrene (SBS) tri-block copolymer to the blend. In CB-PP/PS/SBS blends, CB has higher affinity for the polybutadiene (PBD) section of the SBS copolymer, whereas in CB-PP/PS blends, CB prefers the PS phase. PP/PS interface is one of the preferred locations for the SBS copolymer in the (PP/PS) blend; at which the PBD section of the SBS copolymer forms a few nanometers thick layer able to accommodate the CB nano-particles. The influence of SBS addition on the morphology and electrical properties of various PP/PS blends filled with 1 vol% CB were studied. SBS influence on the conductivity of PP/PS blends was found to be a function of the PP/PS volume ratio and SBS loading. The most dramatic increase in conductivity was found in the (60/40) and (70/30) PP/PS blends upon the addition of 5 vol% SBS. 5 vol% SBS was found to be the optimum loading for most blends. Using 10 vol% of SBS was reported to deteriorate electrical conductivity of the conductive co-continuous PP/PS blends. For all blends studied, SBS addition was found to compatibilize the blends. Finer morphologies were obtained by increasing SBS loading.     

Dielectric analysis of the interaction of nematic liquid crystals with carbon nanotubes

Multi-walled carbon nanotubes (MWCNTs) have been shown to self-organise, and when added as a guest to form a nanocomposite, their director couples with an organic liquid crystal (LC) host. Here, effects of MWCNTs on the low-frequency dielectric properties and Fréedericksz transition of the LC 4-cyano-4?-pentylbiphenyl (5CB) are studied. Anti-parallel electro-optic cells were filled with nanocomposites at weight percent concentrations of MWCNT to 5CB of: 0 (neat), 0.01, 0.10, 0.20, and 0.50. Low concentration was chosen to minimise Van der Waals attraction normally responsible for aggregation of MWCNTs. Dielectric relaxation spectroscopy was used to study interactions between MWCNTs and 5CB at frequencies from 20 Hz to 1 MHz. We propose a mechanism based upon measurements of the complex dielectric function which suggests that MWCNTs act as a slow-moving boundary within the sample cell at low frequencies and low applied electric fields, where the MWCNTs reorient along with the 5CB LC molecules. At higher frequencies and larger applied electric fields, the 5CB molecules rotate about their long axes while motion of the MWCNTs is frozen out.     

7-Acetylcytochalasin B: differential effects on sugar transport and cell motility.

Cytochalasin B (CB) is a potent inhibitor of sugar transport and cell motility in animal cells. We have synthesized and characterized the CB derivative 7-acetylcytochalasin B (CBAc) and have found that it has differential effects on transport and motile processes in fibroblasts. The derivative inhibited sugar transport in human red cells, 3T3 cells, and chicken embryo fibroblasts at micromolar concentrations, although it was less potent than its parent compound. Unlike CB, which causes fibroblasts to round up and arborize at less than 10 microM, CBAc had no effect on fibroblast morphology and membrane ruffling at concentrations as high as 90 microM. Competitive binding experiments using [3H] CB showed that the affinity of CBAc for sites related to sugar transport in the red cell membrane is about one-fourth of that of CB. In contrast, similar experiments using [3H] dihydrocytochalasin B (a derivative which inhibits cell motility but not sugar transport) showed that the affinity of CBAc for sites associated with red cell spectrin and actin is only about 1/20 of that of dihydrocytochalasin B. This study demonstrates that acetylation of the C-7 hydroxyl group of CB reduces its effect on cell morphology and motility much more than its ability to inhibit sugar transport. This observation, together with our earlier work with dihydrocytochalasin B, establishes that the pharmacologic effects of CB on fibroblasts result from the binding of the drug to two distinct classes of receptors and that these receptors interact with different parts of the cytochalasin molecule.     

Characterization of the interactions between synthetic nematic LCs and model cell membranes

Differential scanning calorimetry (DSC) was used to characterize interactions of synthetic LCs, 4-pentyl-4'-cyanobiphenyl (5CB) and TL205 (a mixture of cyclohexane-fluorinated biphenyls and fluorinated terphenyls) with simple mimics of cell membranes. The investigation was motivated by reports that living cells can be placed into contact with TL205 without apparent toxicity, whereas contact of cells with 5CB leads to cell death. The tendency was examined for 5CB and TL205 to spontaneously partition into and influence the organization for model cell membranes composed of phospholipids. Upon contact of an aqueous dispersion of DPPC liposomes with neat LC for 4 h, 5CB partitioned into the liposomes at a weight ratio of 5:1 DPPC:5CB, whereas TL205 partitioned at a ratio of 310:1 DPPC:TL205. DSC endotherms indicated that the 5CB spontaneously partitioned into the liposomes was far more perturbing than TL205. DSC endotherms of DPPC bilayers containing the same concentration of either 5CB or TL205 also revealed 5CB to be more perturbing than TL205. The effect of up to 7.8 wt % of TL205 was small, resulting in a shift in the melting transition from 41.4°C to 40.1°C and a minor change in peak width, indicating only minor effects on the organization of the bilayer. These effects are similar to those caused by cholesterol in DPPC bilayers. In contrast, 5CB shifted the DPPC melting transition from 41.4°C to ∼36°C and increased the width of the transition peak by a factor of ten, indicating a destabilization of the ordered phase in the bilayer and a disruption of the cooperative nature of the gel-to-LC transition of the phospholipid bilayer. Taken together, the results demonstrate that 5CB and TL205 differ significantly in their interactions with model cell membranes, which suggests one possible origin of their different toxicities toward cells.     

Study of nanocarbon black as synergist on improving flame retardancy of ethylene-vinyl acetate/brucite composites

Nanocarbon black (CB) was introduced into ethylene-vinyl acetate/brucite (EM) composites to investigate the synergistic effect of CB and metal hydroxide on improving the flame retardancy of EVA. Flammability properties of the as-prepared EVA composites were investigated by thermogravimetric analysis, limiting oxygen index (LOI), UL-94 test and cone calorimetry test. The results indicated that the optimum mass ratio of CB/brucite was 1/54, at which the EVA composites displayed dramatic improvement on thermal stability and flame retardancy. The LOI value was as high as 35.3%, the UL-94 passed the V-0 rating, and the peak heat release rate reduced 79% in comparison with pure EVA. Based on the morphology and structure analysis for residue chars, the flame-retardant mechanism was attributed mainly to the positive synergistic effect of CB and brucite on promoting the formation of better carbon protective layer during combustion.

     

Effects of ultrasonic extraction on the physical and chemical properties of polysaccharides from longan fruit pericarp

An ultrasonic technique was employed to extract polysaccharides from longan fruit pericarp (PLFP). Effects of ultrasonic power, time and temperature on the extraction of PLFP were examined. Different effects of ultrasonic time were observed at two different ultrasonic power of 120 and 300 W. A higher recovery rate of PLFP at an ultrasonic power of 300 W was obtained as compared with 120 W. The recovery rate of PLFP was slightly increased by elevating the ultrasonic temperature up to 60 °C. The highest recovery rate of PLFP was achieved at 120 W and 70 °C for 20 min. Furthermore, PLFP I and PLFP II-IV were prepared by hot-water extraction and ultrasonic extraction, respectively, and then used for the analyses of physical and chemical properties. Analysis by differential scanning calorimetry showed that the onset temperature, peak temperature, conclusion temperature and melting enthalpy (ΔH) of PLFP by hot-water extraction were lower than those by ultrasonic extraction. These results suggested that rearrangement of PLFP microstructure could occur and development of a higher proportion of crystalline regions might be induced by the ultrasonic treatments. The highest ΔH (8.02 J/g) and two endothermic peaks were observed in the thermogram of PLFP II. Scanning electron micrographs revealed more aggregated particles in PLFP III and IV compared with PLFP I and II. However, no apparent differences were found from the spectra of these four PLFP samples at a range of 195-550 nm, which indicated that ultrasonic treatment might not cause significant chemical modification of groups in the PLFP chain.     

Biodegradable microspheres containing poly(epsilon-caprolactone)-Pluronic block copolymers for temperature-responsive release of proteins

Temperature-responsive microspheres were fabricated for the purpose of releasing protein in responsive to surrounding temperature changes. Temperature-responsive polymer, Pluronic was synthesized into block copolymers of poly(epsilon-caprolactone)-Pluronic with two different chain lengths of poly(epsilon-caprolactone). Microspheres loaded with proteins were prepared by a W/O/W emulsion method. The surface morphology was examined by scanning electron microscopy, showing that microspheres with diblock copolymers had porous structures due to hydrophilicity of Pluronic blocks. After incubating the microsphere at 37 degrees C for 7 days, temperature-responsive protein release was monitored with alternating temperature changes between 20 and 37 degrees C. The protein release was attenuated when the microsphere was incubated at 20 degrees C but the release rate was recovered at 37 degrees C, confirming variable release rate according to the temperature changes. The variable release rate of protein was dependent on the length of poly(epsilon-caprolactone) blocks attached to Pluronic.     

Specific interaction of cytochalasins with muscle and platelet actin filaments in vitro

The cytochalasins (CE, CD, CB and H2CB) inhibit numerous cellular processes which require the interaction of actin with other structural and contractile proteins. In this report we describe the effects of the cytochalasins on the viscosity and morphology of muscle and platelet actin. The cytochalasins decreased the viscosity of F-actin solutions. The effect of H2CB, CB and CD ON F-actin viscosity was maximal at concentrations of 20-50 micro M and did not increase with time. In contrast, CE caused a progressive decrease in the viscosity of F-actin solutions which was dependent upon the concentration of CE and the duration of incubation of the CE-actin mixture. After two hours of incubation of drug-actin mixtures, the relative effectiveness of the cytochalasins in reducing the viscosity of F-actin was CE greater than CD greater than CB=H2CB. The effects of CD and CE were paralleled by morphologic changes in negatively stained actin filaments. The effects of the cytochalasins on the viscosity and morphology of muscle and platelet actin were the same whether the drugs were added before or after the polymerization of the protein. These studies show that the interaction of the cytochalasins with actin is highly specific. Because the relative potencies of these drugs for affecting motile processes and the relative affinities of the drugs for binding sites within a variety of cells are CE greater than CD greater than CB=H2CB, the effects of cytochalasins on actin described here may contribute to some of the biological effects of the drugs on motile processes.     

Electrical properties of conductive polymer composites prepared by an innovational method

<正>An innovational method that poly(styrene-co-maleic anhydride)(SMA),a compatibilizer of immiscible nylon6/polystyrene(PA6/PS) blends,was first reacted with carbon black(CB) and then blended with PA6/PS,has been employed to prepare the PA6/PS/(SMA-CB) composites of which CB localized at the interface.In PA6/PS/CB blends,CB was found to preferentially localize in the PA6 phase.However,in the PA6/PS/(SMA-CB) blends,it was found that CB particles can be induced by SMA to localize at the interface.The electrical porperties of PA6/PS/(SMA-CB) composites were investigated.The results showed that the composites exhibited distinct triple percolation behavior,i.e.the percolation is governed by the percolation of CB in SMA phase,the continuity of SMA-CB at the interface and the continuity of PA6/PS interface.The percolation threshold of PA6/PS/(SMA-CB) was only 0.15 wt%,which is much lower than that of PA6/PS/CB.Moreover,the PTC(positive temperature coefficient) intensity of PA6/PS/(SMA-CB) composites was stronger than that of PA6/PS/CB and the negative temperature coefficient(NTC) effect was eliminated.The electrical properties of PA6/PS/(SMA-CB) were explained in terms of its special interface morphology:SMA and CB localize at interphase to form the conductive pathways.     

Dexmedetomidine promotes the progression of hepatocellular carcinoma through hepatic stellate cell activation

Dexmedetomidine (DEX) is an anesthetic that is widely used in the clinic, and it has been reported to exhibit paradoxical effects in the progression of multiple solid tumors. In this study, we sought to explore the mechanism by which DEX regulates hepatocellular carcinoma (HCC) progression underlying liver fibrosis. We determined the effects of DEX on tumor progression in an orthotopic HCC mouse model of fibrotic liver. A coculture system and a subcutaneous xenograft model involving coimplantation of mouse hepatoma cells (H22) and primary activated hepatic stellate cells (aHSCs) were used to study the effects of DEX on HCC progression. We found that in the preclinical mouse model of liver fibrosis, DEX treatment significantly shortened median survival time and promoted tumor growth, intrahepatic metastasis and pulmonary metastasis. The DEX receptor (ADRA2A) was mainly expressed in aHSCs but was barely detected in HCC cells. DEX dramatically reinforced HCC malignant behaviors in the presence of aHSCs in both the coculture system and the coimplantation mouse model, but DEX alone exerted no significant effects on the malignancy of HCC. Mechanistically, DEX induced IL-6 secretion from aHSCs and promoted HCC progression via STAT3 activation. Our findings provide evidence that the clinical application of DEX may cause undesirable side effects in HCC patients with liver fibrosis.Subject terms: Cancer microenvironment, Cell growth     

Linagliptin,a Selective Dipeptidyl Peptidase-4 Inhibitor,Reduces Physical and Behavioral Effects of Morphine Withdrawal

(1) Background: Recent data indicate that receptors for GLP-1 peptide are involved in the activity of the mesolimbic system. Thus, the purpose of the present study was to examine the effect of the selective dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on morphine dependence in mice. (2) Methods: Morphine dependence in mice was obtained by administration of increasing doses of morphine for eight consecutive days, twice a day. On the 9th day of the experiment, the naloxone-induced (2 mg/kg, ip) morphine withdrawal signs (jumping) were assessed. Moreover, behavioral effects of short-term (60 h after morphine discontinuation) and long-term (14 days after morphine discontinuation) morphine withdrawal were observed. In terms of behavioral effects, the depressive effect in the forced swim test and anxiety in the elevated plus maze test were investigated. Locomotor activity of mice was also studied. (3) Results: The administration of linagliptin (10 and 20 mg/kg, ip) for 8 consecutive days before morphine injections significantly diminished the number of naloxone-induced morphine withdrawal signs (jumping) in mice. In addition, the cessation of morphine administration induced depressive behavior in mice which were observed during short- and long-term morphine withdrawal. Linagliptin administered during morphine withdrawal significantly reduced the depressive behavior in studied mice. Furthermore, the short-term morphine withdrawal evoked anxiety which also was reduced by linagliptin in mice. (4) Conclusions: The present study reveals that GLP-1 receptors are involved in morphine dependence. What is more, linagliptin might be a valuable drug in attenuating the physical symptoms of morphine dependence. It might be also a useful drug in reducing emotional disturbances which may develop during the morphine withdrawal period.     

Preparation of Polylactide/Poly(ether)urethane Blends with Excellent Electro-actuated Shape Memory via Incorporating Carbon Black and Carbon Nanotubes Hybrids Fillers

In this work, hybrid conductive fillers of carbon black(CB) and carbon nanotubes(CNTs) were introduced into polylactide(PLA)/thermoplastic poly(ether)urethane(TPU) blend(70/30 by weight) to tune the phase morphology and realize rapid electrically actuated shape memory effect(SME). Particularly, the dispersion of conductive fillers, the phase morphology, the electrical conductivities and the shape memory properties of the composites containing CB or CB/CNTs were comparatively investigated. The results suggested that both CB and CNTs were selectively localized in TPU phase, and induced the morphological change from the sea-island structure to the co-continuous structure. The presence of CNTs resulted in a denser CB/CNTs network, which enhanced the continuity of TPU phase.Because the formed continuous TPU phase provided stronger recovery driving force, the PLA/TPU/CB/CNTs composites showed better shape recovery properties compared with the PLA/TPU/CB composites at the same CB content. Moreover, the CB and CNTs exerted a synergistic effect on enhancing the electrical conductivities of the composites. As a result, the prepared composites exhibited excellent electrically actuated SME and the shape recovery speed was also greatly enhanced. This work demonstrated a promising strategy to achieve rapid electrically actuated SME via the addition of hybrid nanoparticles with self-networking ability in binary PLA/TPU blends over a much larger composition range.