Drug-Phospholipid Complex-loaded Matrix Film Formulation for the Enhanced Transdermal Delivery of Quercetin

A novel quercetin-phospholipid-complex(QPLC)-loaded matrix film for improved transdermal delivery of quercetin was developed. The QPLC formulation, prepared using a solvent-evaporation method, was optimized using a central-composite design. The optimized QPLC formulation was characterized by particle size and zeta potential analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and proton nuclear magnetic resonance spectroscopy (1H-NMR). QPLC formulation was functionally evaluated for solubility and in vitro dissolution of quercetin. Matrix films of pure quercetin (Q-MF)or QPLC QPLC-MF) were prepared using a solvent casting method. The prepared Q-MF and QPLC-MF were characterized for weight uniformity, folding endurance, moisture content, and moisture uptake. The films were also functionally characterized for in vitro diffusion of quercetin through a dialysis membrane and ex vivo permeability of quercetin across rat skin. Finally, the anti-inflammatory activity of the films was evaluated on carrageenan-induced paw edema in Wistar albino rats. The experimental design identified the optimal formulation and process variables for the preparation of QPLC. The validation of the obtained model using these values confirmed the suitability and robustness of the model. The physical-chemical characterization of the prepared QPLC supported the formation of a stable complex. The solubility analysis of QPLC showed a 22-fold increase in quercetin aqueous solubility, compared to pure quercetin. The dissolution results exhibited a significantly higher rate and extent of quercetin dissolution from QPLC compared to that of pure quercetin. The permeability of quercetin from Q-MF and QPLC-MF across rat skin mirrored those obtained from the dissolution studies. Topical application of QPLC-MF exhibited a significant (p\u3c0.05) inhibition of carrageenan-induced paw edema in rats compared to that of Q-MF. This study provides a promising combination approach, i.e., phospholipid-based complexation and transdermal film formulation for improved transdermal delivery of quercetin and similar pharmacologically active phytoconstituents

Seed priming with endophytes on physiological, biochemical and antioxidant activity of hybrid maize (Zea mays l.) COH (M) 8 seeds

Endophytes are important microorganisms that enhance the plant's stability through a symbiotic relationship, without any harmful effects and symptoms in the host plant. To study the effect of endophytes on overall performance of COH(M)8 hybrid maize seeds, the present study was conducted with different endophytic seed priming for  12 hrs duration with Beauveria bassiana @ 5% (T2), Metarhizium anisopliae @ 5% (T3) and Bacillus subtilis @ 8% (T4) along with hydro priming (T1) and untreated control (T0).  The seed priming treatments with all the above three endophytes enhanced the seed quality parameters, among which M. anisopliae @ 5% (T3) registered maximum increase of germination (4.34%), shoot length (20.73%), root length (15.04%), dry matter production (15.22%) and vigour index (22.68%) over control. Similarly, the seeds primed with M. anisopliae @ 5% (T3) recorded the highest value of dehydrogenase activity (0.441 OD value), α- amylase activity (2.06 mg maltose min-1) and antioxidant activity viz., catalase (1.55 μmol H2O2 min-1 g-1 protein) and peroxidase  (0.87 U mg-1protein min-1). Results of this study revealed that the endophytes can enhance overall the seed quality in maize

Zoledronate Prevents Simulated Weightlessness-Induced Bone Loss in the Cancellous Compartment While Blunting the Efficacy of a Mechanical Loading Countermeasure

Astronauts using high-force resistance training while weightless show a high-turnover remodeling state within the skeletal system, with resorption and formation biomarkers being elevated. One countermeasure for the skeletal health of astronauts includes an antiresorptive of the bisphosphonate (BP) drug class. We asked, does the combination of an anti-resorptive and high-force exercise during weightlessness have negative effects on bone remodeling and strength? In this study, we developed an integrated model to mimic the mechanical strain of exercise via cyclical loading (CL) in mice treated with the BP Zoledronate (ZOL) combined with hind limb unloading (HU) to simulate weightlessness. We hypothesized that ZOL prevents structural degradation from simulated weightlessness and that CL and ZOL interact to render CL less effective. Thirty-two C57BL/6 mice (male, 16 weeks old, n=8/group) were exposed to 3 weeks of either HU or normal ambulation (NA). Cohorts of mice received one subcutaneous injection of ZOL (45g/kg), or saline vehicle (VEH), prior to the start of HU. The right tibia was axially compressed in vivo 60x/day to 9N (+1200strain on the periosteal surface) and repeated 3x/week during HU. Left tibiae served as a within subject, non-compressed control. Ex vivo CT was performed on all subjects to determine cancellous and cortical architectural parameters. Static and dynamic histomorphometry were carried out for the left and right tibiae to determine osteoclast- and osteoblast relevant surfaces. Further, micro damage was assessed in select groups by basic-fuchsin staining to test whether CL had an effect. For all assays, a multivariate (2x2x2) ANCOVA model was used to account for body weight changes. Additionally, for the tibiae, we incorporated a random effect for the subject (hence, a mixed model) to account for observations of both left and right tibiae within each subject. P < 0.05 was considered significant. In the cancellous compartment of the proximal tibial metaphysis, we observed a main effect from each independent variable, as determined by structural and histomorphometric assays. Specifically, as expected, ZOL showed an increase in the cancellous bone volume to total volume fraction (BV/TV, +32%) and trabecular number (+18%) compared to the VEH. As expected, ZOL decreased osteoclast surface (OC/BS) by -45% compared to VEH. Surprisingly, ZOL reduced mineralizing surface (MS/BS) and bone formation rate (BFR), indicators of osteoblast activity, by -40% and -54%, respectively, compared to VEH. Altogether, ZOL-treated mice displayed a low turnover state of remodeling in the metaphysis. In the context of skeletal aging, we speculate that ZOL prevented age-related cancellous strut loss during the experiment. As a main effect, as expected, HU decreased BV/TV by - 31% via reductions in both trabecular thickness (-11%) and number (-22%) compared to NA controls. Additionally, HU decreased MS/BS by -38% and bone formation rate (BFR) by -50% compared to NA controls. Altogether, these data are consistent with structural degradation resulting from imbalanced remodeling that favors resorption. As a main effect, CL increased BV/TV by +15% via increased trabecular thickness (+12%) compared to the noncompressed limb. As expected, CL increased MS/BS (+20%) and BFR (+24%), indicating osteoblast mineralization contributed to bone gains. These data show that CL provided an anabolic stimulus to the cancellous tissue. We observed unique interactions in ZOL*CL and HU*CL. First, ZOL prevented CL-induced increases in BV/TV and trabecular number, as compared to VEH. In the context of skeletal aging, these data suggest no added benefit from CL in the ZOL-treated mice. Interestingly, no microdamage was observed in mice that were unloaded and treated with ZOL (independent of CL). Secondly, HU prevented CL-induced increases in BFR, as compared to NA controls. These data suggest that either exercise is less effective or the kinetics of formation are slower during simulated weightlessness. Osteoclast surface was unchanged by either treatment. Thus, in contrast to exercising astronauts, these data do not suggest a high-turnover state in the metaphysis. To assess mechanical properties as a function of HU or ZOL, we tested the left femur in three-point bending ex vivo. As expected, HU decreased stiffness (-30%) compared to NA, and ZOL increased stiffness compared to VEH (+28%). Interestingly, HU increased the post-yield displacement, related to collagenous tensile loading, compared to NA (+20%). ZOL increased yield force (+11%) and ultimate force (+17%), which seems to explain the significant effect of ZOL increasing total energy (work-to-fracture, +15%), while not affecting the post yield displacement. Taken together, ZOL did not have detrimental affect on mechanical properties. Our integrated model simulates the combination of weightlessness, exercise-induced mechanical strain, and anti-resorptive treatment that astronauts experience during space missions. We conclude that Zoledronate was an effective countermeasure against weightlessness-induced bone loss, though zoledronate, as well as weightlessness, rendered exercise-related mechanical loading less effective

Ligament Tissue Engineering and Its Potential Role in Anterior Cruciate Ligament Reconstruction

Tissue engineering is an emerging discipline that combines the principle of science and engineering. It offers an unlimited source of natural tissue substitutes and by using appropriate cells, biomimetic scaffolds, and advanced bioreactors, it is possible that tissue engineering could be implemented in the repair and regeneration of tissue such as bone, cartilage, tendon, and ligament. Whilst repair and regeneration of ligament tissue has been demonstrated in animal studies, further research is needed to improve the biomechanical properties of the engineered ligament if it is to play an important part in the future of human ligament reconstruction surgery. We evaluate the current literature on ligament tissue engineering and its role in anterior cruciate ligament reconstruction

Inverted porphyrins and expanded porphyrins: an overview

Porphyrins and metallopophyrins have attracted the attention of chemists for the past 100 years or more owing to their widespread involvement in biology. More recently, synthetic porphyrins and porphyrin-like macrocycles have attracted the attention of researchers due to their diverse applications as sensitizers for photodynamic therapy, MRI contrasting agents, and complexing agents for larger metal ions and also for their anion binding abilities. The number of π-electrons in the porphyrin ring can be increased either by increasing the numberof conjugated double bonds between the pyrrole rings or by increasing the number of heterocyclic rings. Thus, 22π sapphyrins, 26π rubyrins, 30π heptaphyrins, 34π octaphyrins and higher cyclic polypyrrole analogues containing 40π, 48π, 64π, 80π and 96π systems have recently been reported in the literature. These macrocycles show rich structural diversity where normal and different kinds of inverted structures have been identified. In this review, an attempt has been made to collect the literature of the inverted porphyrins and expanded porphyrins reported until December 2001. Since themeso aryl expanded porphyrins have tendency to form both inverted and non-inverted structures more emphasis has been given to meso aryl expanded porphyrins

The Importance of Being Psychologically Empowered: Buffering the Negative Effects of Employee Perceptions of Leader-Member Exchange Differentiation

Although differentiated relationships among leaders and their followers are fundamental to Leader-Member Exchange (LMX) theory, research provides limited knowledge about whether employees’ responses to individual perceptions of LMX differentiation are uniform. In a field study, we examined whether individual-level psychological empowerment buffers the negative relationship between perceived LMX differentiation and job satisfaction, and found that the negative relationship is strongest under low employee psychological empowerment conditions, as compared to high psychological empowerment. Furthermore, in a multi-wave field study and an experiment, we extended these initial findings by investigating employees’ perceptions of supervisory fairness as a mediator of this moderated relationship. We found that the indirect effect between perceived LMX differentiation and job satisfaction, through supervisory fairness perceptions, is strongest under low employee psychological empowerment, as compared to high psychological empowerment. Collectively, our findings showcase the importance of psychological empowerment as a tool for employees to use to counteract the negative effect of perceived differentiated contexts

In silico analysis of lipopolysaccharide and β-1, 3-glucan binding protein (LGBP) gene from the haemocytes of Indian white shrimp Fenneropenaeus indicus

Lipopolysaccharide and β-1,3-glucan binding protein (LGBP) gene are involved in the pattern recognition mechanism of invertebrates, it induces the cell and humoral mediated immune responses like encapsulation, phagocytosis, nodule formation, clotting, synthesis of antimicrobial peptides and activation of the prophenoloxidase (proPO) system. The current study focuses to model the three-dimensional structure of novel immune related gene LGBP from the Indian white shrimp Fenneropeneaus indicus (F.indicus) by in silico homology modeling and its motif prediction. Fenneropeneaus indicus lipopolysaccharide and β-1,3-glucan binding protein (Fein-LGBP) consists of glycosylated regions which come under the glucanase family. Two conserved putative integrin-binding motif (cell adhesion sites), bacterial glucanase motif (GM) and two polysaccharide recognition motifs for the polysaccharide binding motif (PsBM) and β- glucan recognition motif (β-GRM) were conserved in the novel sequences of Fein-LGBP. Prediction of motifs, patterns, disulfide bridges and secondary structure were performed for functional characterization of the Fein-LGBP. Three dimensional structure of the Fein-LGBP was generated by Modeller9V8, Swiss Model and validated using NIH server. Results revealed that the modelled structure of Fein-LGBP was 75.7% of residues in allowed region. Theoretical model of Fein- LGBP facilitates to the discovery of new synthetic immune related peptides, agonists that could be useful to  understand the mechanism of LGBP involvement in the prophenoloxidase activating system of crustaceans. The tertiary structure prediction of the immune related gene Fein- LGBP will assist to explore more knowledge in immune system of crustaceans

Comment on "Is the nonlinear Meissner effect unobservable?"

In a recent Letter (Phys. Rev. Lett. 81, p.5640 (1998), cond-mat/9808249 v3), it was suggested that nonlocal effects may prevent observation of the nonlinear Meissner effect in YBCO. We argue that this claim is incorrect with regards to measurements of the nonlinear transverse magnetic moment, and that the most likely reason for a null result lies elsewhere.Comment: 1 pag

Circadian and circannual changes in the testicular function of adult rhesus monkeys

The endocrine and gametogenic status of the testes were studied in 9 healthy adult rhesus monkeys of proven fertility throughout a one-year period. Testosterone levels were estimated by radioimmunoassay in blood samples collected at 4 h intervals over a 24 h period once a month. Semen samples and testicular biopsies were also examined once a month. A well-defined circandian rhythm was evident in serum levels of testosterone. The rhythmicity was less pronounced in February and September. The 24 h mean levels of serum testosterone were high between the months of August to March and low in the months of May to July. All animals did not uniformly respond to electro-ejaculation in April and May. Semen volume and total number of spermatozoa were maximal between September and March and least from April to August. Testicular biopsies indicated that all stages of spermatogenesis were evident between September and March and the spermatogenic activity was less evident between April and August. The contents of Sertoli cells showed a seasonal cyclicity; they were laden with lipid droplets during April to August when spermatogenesis was quiescent and vacuolated during September to March when spermatogenesis was active. These studies indicate that the testing of contraceptive drugs needs to be restricted to months of September to March in male rhesus monkeys otherwise, it is possible that the naturally occurring reproductive quiscence may be attributed to the effect of the drug being tested. The data accrued from the present studies also provide quantitative information on circulating levels of testosterone which could be used as a reference background while evaluating the contraceptive drug-effects in male rhesus monkeys