Effect of electron-withdrawing fluorine and cyano substituents on photovoltaic properties of two-dimensional quinoxaline-based polymers.

In this study, strong electron-withdrawing fluorine (F) and cyano (CN) substituents are selectively incorporated into the quinoxaline unit of two-dimensional (2D) D-A-type polymers to investigate their effects on the photovoltaic properties of the polymers. To construct the 2D polymeric structure, electron-donating benzodithiophene and methoxy-substituted triphenylamine are directly linked to the horizontal and vertical directions of the quinoxaline acceptor, respectively. After analyzing the structural, optical, and electrochemical properties of the resultant F- and CN-substituted polymers, labeled as PBCl-MTQF and PBCl-MTQCN, respectively, inverted-type polymer solar cells with a non-fullerene Y6 acceptor are fabricated to investigate the photovoltaic performances of the polymers. It is discovered that the maximum power conversion efficiency of PBCl-MTQF is 7.48%, whereas that of PBCl-MTQCN is limited to 3.52%. This significantly reduced PCE of the device based on PBCl-MTQCN is ascribed to the formation of irregular, large aggregates in the active layer, which can readily aggravate the charge recombination and charge transport kinetics of the device. Therefore, the photovoltaic performance of 2D quinoxaline-based D-A-type polymers is significantly affected by the type of electron-withdrawing substituent.

Comparative evaluation of the concentration-dependent effect of proton-pump inhibitor in association with calcium hydroxide and chlorhexidine on Enterococcus faecalis: An in vitro study.

BACKGROUND: Enterococcus faecalis is the most persistent organism in the root canal which resists most of the intracanal medicaments. There is always a constant attempt to eliminate this endodontic pathogen from the root canal system. AIM: The aim of this study was to evaluate the efficacy of the association of different concentrations of proton-pump inhibitor (PPI) (Lansoprazole) with calcium hydroxide (CH) and chlorhexidine (CHX) against E. faecalis using a broth dilution method. MATERIALS AND METHODS: E. faecalis was inoculated into brain-heart infusion broth at 37°C for 5 h. The master broth was then treated with CH (Group 1); CH + 2% CHX (Group 2); CH + PPI 6.25 µg/ml (Group 3A); CH + PPI 25 µg/ml (Group 3B); 2% CHX + PPI 6.25 µg/ml (Group 4A); 2% CHX + PPI 25 µg/ml (Group 4B); CH + 2% CHX + PPI 6.25 µg/ml (Group 5A), and CH + 2% CHX + PPI 25 µg/ml (Group 5B). The groups were spectrophotometrically analyzed at 630 nm at 24 h to determine the group with the least optical density. STATISTICAL ANALYSIS: Comparison between the groups was done by the one-way analysis of variance and Kruskal-Wallis test for multiple comparisons. RESULTS: The mean percentage inhibition of E. faecalis by Group 5A (CH + 2% CHX + PPI 6.25 µg/ml) was the highest compared to other groups. The lowest mean value was observed in Group 3A (CH + PPI 6.25 µg/ml) indicating least efficiency. CONCLUSION: There was a concentration-dependent effect of PPI on CH and CHX against E. faecalis. The maximum efficacy was found when the lower concentration of PPI was associated with CH/CHX mixture.

Cytokine responses in pigs after natural infection with classical swine fever virus.

Classical swine fever (CSF) is a highly contagious viral infection that affects domestic and wild pig population. The classical swine fever virus (CSFV) targets immune cells which perturb the immune functions causing immunopathological disorders such as immunosuppression, leukopenia and haemorrhage. In the present study, ELISA and quantitative real-time reverse transcription PCR (qRT-PCR) analysis was employed to determine cytokine profiles in pigs naturally infected with CSFV using whole blood assay (WBA) under field conditions. Significantly higher TNF-α, IL-10, and IL-6 expression levels were found in unvaccinated pigs infected with CSFV (group B) compared to vaccinated pigs that recovered after CSF (group A), the difference being statistically significant (p = 0.001). However, the expression of IFN-γ was significantly higher in group A compared to group B (p = 0.001). The findings of this field-supported study will help us to understand the immune biology of CSFV infection in infected pigs. The WBA technique can be used as a reliable, fast and feasible in vitro method to assess porcine cellular immune responses as it imitates the porcine blood conditions. Such studies could be of some value in determining the immune status of the ailing animals infected with CSFV. Keywords: classical swine fever virus; immune response; field conditions; interleukin; IFN-γ; TNF-α.

Microporous organic polymers involving thiadiazolopyridine for high and selective uptake of greenhouse gases at low pressure.

A new core of [1,2,5]-thiadiazolo-[3,4-c]-pyridine was employed for the fabrication of microporous organic polymers exhibiting a very high CO2 uptake of 5.8 mmol g-1 (25.5 wt%) at 273 K and 1 bar. The presence of CO2-philic active sites and microporosity confer the high uptake and superior selectivity (61) towards CO2 over N2.

Slope climbing challenges, fear of heights, anxiety and time of the day.

When exposed to an unfamiliar open space, animals experience fear and attempt to find an escape route. Anxiety emerges when animals are confronted with a challenging obstacle to this fear motivated escape. High anxiety animals do not take risks; they avoid the challenge. The present experiments investigated this risk avoidant behavior in mice. In experiment 1, BALB/c, C57BL/6J and CD-1 mice were exposed to a large platform with downward inclined steep slopes attached on two opposite sides. The platform was elevated 75 and 100cm from the ground, in a standard (SPDS) and in a raised (RPDS) configuration, respectively. In experiment 2, the platform was elevated 75cm from the ground. Mice had to climb onto a stand at the top of upward inclined slopes (SPUS). In experiment 3, BALB/c mice were exposed to SPDS with steep or shallow slopes either in early morning or in late afternoon. In all 3 test configurations, mice spent more time in the areas adjacent to the slopes than in the areas adjacent to void, however only C57BL/6J and CD-1 crossed onto the slopes in SPDS, and crossed onto the stands in SPUS whereas BALB/c remained on the platform in SPDS and explored the slopes in SPUS. Elevation of the platform from the ground reduced the crossings onto the slopes in C57BL/6J and CD-1, and no differences were observed between BALB/c and C57BL/6J. BALB/c mice demonstrated no difference in anxiety when tested early morning or late afternoon; they crossed onto shallow slopes and avoided the steep one.

Pre-training in a radial arm maze abolished anxiety and impaired habituation in C57BL6/J mice treated with dizocilpine.

Familiarity can imply a reduction of fear and anxiety, which may render learning and memory performance insensitive to NMDA receptor antagonism. Our previous study indicates that MK-801 (dizocilpine), NMDA antagonist, increased anxiety and prevented the acquisition of a spatial memory task. Here, we examined whether MK-801 will produce anxiety in mice that were familiar with the test environment. Male C57BL/6J mice were exposed, one session a day for 7days, to a 3D maze, which consisted of nine arms attached to upward inclined bridges radiating from a nonagonal platform. In this maze, high anxiety mice avoid the arms in the first sessions. One group of mice received saline (SAL) while a second group received MK-801 (MKD1), both on day one. A third group received saline in the first 3 sessions, and MK 801 in subsequent sessions (MKD4). Saline and MK-801 (0.1mg/kg) were administered intraperitoneally 30min before the test. MKD4 mice demonstrated an increase in bridge and arm visits, and reached arm/bridge entries ratio close to 1 in session 5. SAL mice also crossed frequently onto the arms, and reached a comparable ratio, but this was achieved with a lower number of arm visits. MKD1 mice demonstrated a reduced number of arm visits in each session compared to SAL and MKD4 mice. Dizocilpine produced anxiety in mice treated from day 1 of the test, but not in those treated from day 4. It also impaired habituation in animals familiar with the test environment; it produced sustained non-habituating hyperactivity.

Effects of chronic fluoxetine treatment on anxious behaviour of BALB/c mice in a 3-dimensional maze.

Here we used a 3-dimensional (3D) maze, a modification of the radial maze, to assess the effects of treatment for two weeks with a single daily dose of fluoxetine (20 mg/kg, i.p.) on anxiety in male BALB/c mice. We examined whether anxiolytic effects of fluoxetine can be detected over three daily test sessions. We examined also whether repeated handling associated with chronic treatment interferes with effects of fluoxetine on anxiety responses. The 3D maze comprises nine arms, each connected to an upward inclined bridge radiating from a central platform. In this maze, BALB/c mice cross frequently into the bridges but avoid the arms. This avoidance is used as an index of anxiety. Two separate groups received once a day either saline (SALCH, n = 8) or fluoxetine (FLUCH, n = 8) for 14 days, and up to 30 min before the test during the subsequent 3 days. A third group received saline (SALAC, n = 8) 30 min before the test, once a day for 3 days. SALAC mice did not cross into the arms, and continued this avoidance over 3 sessions. SALCH mice avoided the arms in session 1 whereas FLUCH mice did cross into the arms, and like SALCH mice, increased number of crossings into and time on the arms in subsequent sessions. Fluoxetine evidently had an anxiolytic effect but only in the first session. These results indicate that handling experience decreased fear and anxiety in the mice, which may have masked the anxiolytic effect of fluoxetine in the second and third test sessions.

Evaluation of antihepatotoxic potential of Solanum xanthocarpum fruit extract against antitubercular drugs induced hepatopathy in experimental rodents.

OBJECTIVE: To assess the hepatoprotective effect of Solanum xanthocarpum (S. xanthocarpum) fruit extract against antitubercular drug-induced liver toxicity in experimental animals. METHODS: Ethanolic (50%) fruit extract of S. xanthocarpum (100, 200 and 400 mg/kg bw) was administered daily for 35 days in experimental animals. Liver toxicity was induced by combination of three antitubercular drugs [isoniazid (I) 7.5 mg/kg, rifampicin (R) 10 mg/kg and pyrazinamide (P) 35 mg/kg] given orally as suspension for 35 days in rats. The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatise (ALP), total bilirubin (TBL), albumin (ALB), total protein (TP), lactate dehydroginase (LDH), and serum cholesterol (CHL). Meanwhile, in vivo antioxidant activities as lipid peroxidation (LPO), reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) were measured in rat liver homogenate. The biochemical observations were supplemented by histopathological examination. RESULTS: The results demonstrated that treatment with S. xanthocarpum significantly (P<0.05-P<0.001) and dose-dependently prevented drug induced increase in serum levels of hepatic enzymes. Furthermore, S. xanthocarpum significantly (up to P<0.001) reduced the LPO in the liver tissue and restored activities of defence antioxidant enzymes GSH, SOD and CAT towards normal levels. Histopathology of the liver tissue showed that S. xanthocarpum attenuated the hepatocellular necrosis and led to reduction in inflammatory cells infiltration. CONCLUSIONS: The results of this study strongly indicate the protective effect of S. xanthocarpum against liver injury which may be attributed to its hepatoprotective activity, and thereby scientifically support its traditional use.

Polysaccharide nanogel delivery of a TNF-alpha and RANKL antagonist peptide allows systemic prevention of bone loss.

We report here a nanogel-mediated peptide drug delivery system. Low stability is a major drawback towards clinical application of peptide drugs. The W9-peptide, a TNF-alpha and RANKL antagonist, was used as a model for testing the feasibility of cholesterol-bearing pullulan (CHP)-nanogel as the drug delivery system. We found CHP-nanogel could form complex with the W9-peptide and prevents its aggregation in vitro. Murine bone resorption model using low dietary calcium was used to investigate the in vivo effect. Two-time-injection of 24 mg/kg W9-peptide per day with or without CHP-nanogel was given for 7 days. Thereafter, radiological, and histological assessments were performed. The injections of the W9-peptide (24 mg/kg) with CHP-nanogel prevented the reduction in bone mineral density whereas the same dose without CHP-nanogel could not show any inhibitory effect. Histomorphometric analysis of tibiae showed significant decrease of osteoclast number and surface in CHP-W9 complex treated group and the levels of urinary deoxypyridinoline reflected these decrease of bone resorption parameters. Taken together these data shows that CHP-nanogel worked as a suitable carrier for the W9-peptide and it prevented aggregation and increased the stability of the W9-peptide. This study reveals the feasibility of CHP-nanogel-mediated peptide delivery in preventing bone resorption in vivo.

Preparation and release of ibuprofen from polyacrylamide gels.

The conditions of preparation of polyacrylamide (polyAC) gels, the incorporation of ibuprofen (IB), and the kinetics of IB release under various conditions have been evaluated. Transparent, opaque, or elastic gels were prepared depending on the concentration of acrylamide (AC) and the cross-linking agent, N,N'-methylenebisacrylamide (BIS). Release studies in media below pH 5.0 resulted in opaque gels. The kinetics of IB release was a function of the AC, BIS, and the pH of the medium, but the optimum composition, in terms of gel integrity and release characteristics, was 7% AC cross-linked with BIS at a 50:1 ratio. Modulation of the release rate was possible with the incorporation of 10% of certain polymers. The amount of IB that could be incorporated per gram of transparent gel was a function of the amount of polymer initiator N,N,N',N'-tetramethylene diamine (TEMED) used per gram of gel. More than 200 mg of IB could be incorporated per gram of transparent gel by using 100 microliters of TEMED. The release of IB obeyed matrix/swelling-controlled kinetics and 70-80% of the IB was released from gels containing 10 to 40 mg IB per gram of gel in 5 hr at pH 7.4 and 37 degrees C.

Kinetic interactions of lidocaine, diphenhydramine, and verapamil with diltiazem. A study using isolated perfused rat liver.

The effect of several tertiary amines, which are known enzyme inhibitors, on the disposition of diltiazem (DZ) was evaluated using a single-pass isolated rat liver perfusion system. Coinfusion of lidocaine (LID) or diphenhydramine (DPH) at the steady state of DZ resulted in a sharp increase in the perfusate concentration of DZ, which was followed by a decline to a new steady-state concentration (Cnss) that was higher than the original Cnss value (46 and 45%, respectively). The initial sharp increase in DZ concentration was attributed to the displacement of DZ from its tissue binding sites; the higher Css values were due to the inhibition of N-oxidation and O-demethylation, and some unknown primary metabolic pathways. The kinetics of LID were altered by DZ; the steady-state extraction ratio of LID was reduced and the characteristic maximum in the concentration-time profile of its N-deethylated metabolite, MEGX, was abolished. These results suggest that DZ and LID share common isozymes in their disposition and that the two drugs are also capable of inactivating similar enzymes. The effect of enzyme inactivation on DZ disposition was evaluated by intraperitoneal pretreatment of rats with either saline (0.4 ml) or 1 of the 4 drugs--DZ (20 mg/kg), LID (30 mg/kg), DPH (20 mg/kg), and verapamil (10 mg/kg)--daily for at least 3 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanisms of time-dependent kinetics of diltiazem in the isolated perfused rat liver.

The time-dependent mechanisms of diltiazem (DZ) disposition were studied in a single-pass isolated perfused rat liver system. DZ (2-100 microM) was infused continuously until a steady state was achieved. The time required to achieve steady state (Tss) ranged from 15 to 75 min and was inversely related to infusion concentration. Steady-state extraction (E) of DZ decreased from 0.98 to 0.73 as the outlet concentration increased from 0.03 to 26.34 microM. This reduction of E is not related to the saturation of the primary deacetylation and N-demethylation pathways of metabolism. The N-demethylated metabolite went through a characteristic maximum prior to reaching a steady state, indicating enzyme inactivation. During a second DZ infusion, spaced with a 30-min washout period (stop-infusion experiment), the concentration vs. time profile of DZ was similar to that of the first one. Washout data from stop-infusion and [3H]DZ infusion studies showed that DZ and its metabolites were tightly bound to liver proteins. This observation is consistent with the unusually long Tss of DZ. Infusion studies with [3H]DZ showed that 669.5 +/- 156.5 and 974.2 +/- 99.2 nmol of DZ and its metabolites (calculated as DZ) were bound and/or distributed/g of liver at inlet concentrations of 35.5 +/- 3.2 and 67.2 +/- 3.4 microM, respectively. The amounts of DZ and its metabolites bound irreversibly to the whole liver, hepatic microsomal and hepatic cytosolic proteins were not different at the two inlet concentrations studied and were 24.5 +/- 6.6, 48.8 +/- 11.8, and 23.7 +/- 5.8 pmol/mg of protein, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacokinetics of diltiazem in patients undergoing coronary artery bypass grafting.

The pharmacokinetics of oral diltiazem (DZ) were studied in 10 patients on the day before cardiac surgery and on the next day during surgery and cardiopulmonary bypass (CPB). Six patients were taking DZ 60 mg q.i.d. and four patients were taking DZ 90 mg q.i.d. All had been receiving DZ treatment for at least 3 months. The plasma concentration profile of DZ on the day before surgery was assumed to reflect the steady-state condition. DZ showed dose-dependent kinetics. On the day of surgery, the levels of total DZ (TDZ) at 15 min and 1 h after the initiation of CPB were significantly reduced (approximately 50%) when compared with the pre-CPB level. The levels of unbound DZ (FDZ) and the two major metabolites, N-demethyl DZ (MA) and deacetyl-DZ (M1) were not changed significantly by CPB. The plasma unbound fraction value increased sharply from 0.43 +/- 0.12 before the onset of CPB to a peak value of 0.83 +/- 0.12 during CPB, and returned to baseline level 24 h after dosing. We conclude that CPB decreases the TDZ concentration but has little effect on FDZ, MA, and M1 levels. The lack of effect of CPB on FDZ was related to the reduction of plasma protein binding of DZ.

Simple and sensitive high-performance liquid chromatographic method for the determination of diltiazem and six of its metabolites in human plasma.

A sensitive, specific and reproducible high-performance liquid chromatographic technique is described for the simultaneous determination in human plasma of diltiazem (DZ) and six of its primary and secondary metabolites which are products of N- and O-demethylation, deacetylation and N-oxidation. The method involves addition of excess KHCO3 to 1 ml of plasma, followed by extraction with 4 ml of ethyl acetate. The organic layer was extracted with 0.01 M HCl and the aqueous layer was dried under nitrogen and then reconstituted with 0.002 M HCl. DZ and its metabolites were free from interference and wer baseline-separated. Calibration curves were linear in the concentration range studied (5-500 ng/ml for all the species). The lower limit of quantification of the assay was 5 ng/ml for DZ and the metabolites. Inter-day and intra-day coefficients of variation were less than 10%. The applicability of this procedure is shown by evaluating the kinetics of DZ and its metabolites in three patients receiving chronic DZ therapy. N-Demethyldiltiazem, deacetyldiltiazem and N-demethyldeacetyldiltiazem were found to be the major metabolites, as previously described. Deacetyldiltiazem N-oxide was found in two of the patients. The other two known but unreported metabolites in human, O-demethyldeacetyldiltiazem and N,O-didemethyldeacetyldiltiazem, were found in the plasma of all three patients.