Embodied Deviance,Gender, and Epistemologies of Ignorance: Re-Visioning Drugs Use in a Neurochemical,Unjust World

The paper develops key notions needed for a feminist embodiment approach to drugs, their use and users. First, the term embodied deviance is defined in relationship to women drug users. Second, the bodily tasks of gendered drug use are defined to show how “normal” embodiment is foreclosed to women drug users. Third, disease regimes and epistemologies of ignorance are introduced. Fourth, another piece is inserted into the feminist embodiment puzzle –emotions. Simply, we look at some of the practices that emerge from the affective dimensions of gendered drug use. In the concluding section of my paper, I ask, “Where do we go from here?”     

Formulation Development,Optimization, and In Vitro–In Vivo Characterization of Natamycin-Loaded PEGylated Nano-Lipid Carriers for Ocular Applications

The present study aimed at formulating and optimizing natamycin (NT)-loaded polyethylene glycosylated nano-lipid carriers (NT-PEG-NLCs) using Box-Behnken design and investigating their potential in ocular applications. Response surface methodology computations and plots for optimization were performed using Design-Expert^® software to obtain optimum values for response variables based on the criteria of desirability. Optimized NT-PEG-NLCs had predicted values for the dependent variables which are not significantly different from the experimental values. NT-PEG-NLCs were characterized for their physicochemical parameters; NT's rate of permeation and flux across rabbit cornea was evaluated, in vitro, and ocular tissue distribution was assessed in rabbits, in vivo. NT-PEG-NLCs were found to have optimum particle size (<300 nm), narrow polydispersity index, and high NT entrapment and NT content. In vitro transcorneal permeability and flux of NT from NT-PEG-NLCs was significantly higher than that of Natacyn^®. NT-PEG-NLC (0.3%) showed improved delivery of NT across the intact cornea and provided concentrations statistically similar to the marketed suspension (5%) in inner ocular tissues, in vivo, indicating that it could be a potential alternative to the conventional suspension during the course of fungal keratitis therapy.     

InVitro,Ex Vivo,and In Vivo Evaluation of a Dual pH/Redox Responsive Nanoliposomal Sludge for Transdermal Drug Delivery

A dual pH/redox responsive copper-glyglycine-prednisolone succinate–loaded nanoliposomal (NL) sludge was successfully synthesized and optimized using a Box-Behnken design of experiments. Preformulation design variables indicated that relative ratios of phospholipids, considerably influences NL size, thus altering the degree of drug loading in the formulation. In vitro evaluation further confirmed optimum release kinetics of the NL sludge, corresponding closely to ex vivo permeation studies, demonstrating effective transdermal delivery of prednisone succinate (PS) through a pig skin model, which closely resembles human skin anatomy. The pH/redox stimuli responsiveness of the NL sludge further demonstrated superior properties in vivo using a Sprague-Dawley rat model. The NL sludge displayed the greatest release of PS within 24 h of evaluation, falling within the acceptable therapeutic range of PS dose efficiency. In vivo results further displayed the greatest absorption of PS under inflammatory induced conditions, thus confirming the unique pH/redox responsive properties of the NL sludge. It was thus confirmed that the copper-glyglycine-prednisolone succinate–loaded NL sludge has significant potential for application in chronic inflammatory conditions such as tumor necrosis factor receptor–associated periodic syndrome (TRAPS), designed to release an effective dose of corticosteroid, as a transdermal drug delivery formulation, for effective therapeutic efficacy.     

The integration of multi-platform MS-based metabolomics and multivariate analysis for the geographical origin discrimination of Oryza sativa L.

For the authentication of white rice from different geographical origins, the selection of outstanding discrimination markers is essential. In this study, 80 commercial white rice samples were collected from local markets of Korea and China and discriminated by mass spectrometry-based untargeted metabolomics approaches. Additionally, the potential markers that belong to sugars & sugar alcohols, fatty acids, and phospholipids were examined using several multivariate analyses to measure their discrimination efficiencies. Unsupervised analyses, including principal component analysis and k-means clustering demonstrated the potential of the geographical classification of white rice between Korea and China by fatty acids and phospholipids. In addition, the accuracy, goodness-of-fit (R²), goodness-of-prediction (Q²), and permutation test p-value derived from phospholipid-based partial least squares-discriminant analysis were 1.000, 0.902, 0.870, and 0.001, respectively. Random Forests further consolidated the discrimination ability of phospholipids. Furthermore, an independent validation set containing 20 white rice samples also confirmed that phospholipids were the excellent discrimination markers for white rice between two countries. In conclusion, the proposed approach successfully highlighted phospholipids as the better discrimination markers than sugars & sugar alcohols and fatty acids in differentiating white rice between Korea and China.     

Improvement of nutritional components and in vitro antioxidative properties of soy-powder yogurts using Lactobacillus plantarum

This research was the first to demonstrate changes in nutritional compositions (isoflavone and CLA) from the 50% methanol extracts of soy-powder milk (SPM) and soy-powder yogurt (SPY) through fermentation using Lactobacillus plantarum S48 and P1201 strains. The radical scavenging activities and protective effects against oxidative stress in LLC-PK₁ cells were also investigated. The average physicochemical characteristics including acidity and viable cell number as well as β-glucosidase activity increased with 0.2 → 0.7%, 7.5 → 9.8 log cfu/mL, and 0.0 3 → 1.75 U/g in SPYs. Total average isoflavones were considerably reduced (3180.3 → 2018.3 μg/g) with the increase of aglycone contents (191.8 → 770.2 μg/g), especially, daidzein exhibited the most remarkable increase rate (98.6 → 460.9 μg/g; > 4.8 times) during fermentation. The CLA and total phenolics also increased with significant differences (ND → 1.6 mg/g; 2.4 → 3.6 mg/GAE/g) between SPM and SPY. Interestingly, the cis-9, trans-11 CLA showed approximately 90% in total content. Moreover, the scavenging capacities against three radicals markedly increased with about 30% in SPYs, as the following order: ABTS > hydroxyl > DPPH. The protective effects on oxidative stress (pyrogallol: O₂^-, SNP: NO, and SIN-1: ONOO^?) were also observed high cell viabilities (>10%) under LLC-PK₁ cellular system. Our results suggest that SPY may be utilized as a potent source regarding natural antioxidants and beneficial components for health food and medical uses.     

Metabolic disorders and cardiovascular consequences of HIV infection and antiretroviral therapy

Metabolic disturbances associated with HIV disease have become an important factor in patient management and have important implications for long-term outcomes, both in regards to mortality and healthcare burden. Recent research has implicated both HIV infection itself and specific antiretroviral therapies in the development of these disorders. This review examines recent findings from research into insulin and glucose dysregulation, serum lipid abnormalities, adipose tissue and derangements in bone metabolism. This review then describes the cardiovascular consequences and management of these metabolic disorders, and summarizes current thinking on the pathogenesis and effects of antiretroviral therapy. Finally, the review raises some questions regarding ongoing challenges and unmet needs in this field of research.     

Development,Characterization, and In Vitro Testing of Co-Delivered Antimicrobial Dry Powder Formulation for the Treatment of Pseudomonas aeruginosa Biofilms

Pseudomonas aeruginosa is an opportunistic bacteria responsible for recurrent lung infections. Previously, we demonstrated that certain materials improved the activity of tobramycin (Tob) against P. aeruginosa biofilms in vitro. We aimed to develop prototype dry powder formulations comprising Tob and a mixture of excipients and test its aerodynamic properties and antimicrobial activity. First, we evaluated different combinations of excipients with Tob in solution against P. aeruginosa biofilms. We selected the compositions with the highest activity, to prepare dry powders by spray drying. The powders were characterized by morphology, bulk density, water content, and particle size distributions. Finally, the antimicrobial activity of the powders was tested. The combinations of Tob (64 μg/mL) with l-alanine and l-proline (at 10 and 20 mM; formulations 1 and 2, respectively) and with l-alanine and succinic acid (at 20 mM; formulation 3) showed the highest efficacies in vitro and were prepared as dry powders. Formulation 1 had the best aerodynamic performance as indicated by the fine particle fraction and the best in vitro activity against P. aeruginosa biofilms. Formulation 3 represents a good candidate for further optimization because it demonstrated good dispersibility potential and optimization of the particle size distribution may achieve high delivery efficiencies.     

An investigation of the olive phenols activity as a natural medicine

The natural antioxidants of olive oil have phenolic structure and their activities are related to the formation of stable derivatives. In this study, the single components of the phenolic fraction of olive oil (1,4-hydroquinone, Semiquinone and 1,4-benzoquinone) have been studied as theoretical by using DFT (Density functional Theory). The behaviors of phenolic compounds of olive against to the alkyl peroxy radicals were investigated. Our data show that 1,4-benzoquinone is the best electron transfer agent in primary metabolic processes to human life. The frontier orbital gap, namely HOMO (highest occupied molecular orbital)–LUMO (lowest unoccupied molecular orbital) gap is the smallest for 1,4-benzoquinone. Hence, it is more stable than the others in blood. The natural phenolic compound's mechanism of many plants can be explained by using DFT method without consuming time and money. In this study, we have indicated the behaviors of natural antioxidants of olive oil's single components phenolic structure in blood phase.     

Potential of Cationic-Polymeric Nanoparticles for Oral Delivery of Naringenin: In Vitro and In Vivo Investigations

The objective of the study was to improve the bioavailability and anticancer potential of naringenin (NRG) by developing a drug-loaded polymeric nanodelivery system. NRG-loaded eudragit E100 nanoparticle (NRG-EE100-NPs) system was developed and physicochemically characterized. In vivo pharmacokinetic and in vitro cytotoxicity abilities of the NRG-EE100-NPs were investigated. In vivo anticancer activity was evaluated in murine BALB/c mice-bearing colorectal tumor. The NRG-EE100-NPs had an optimum mean particle size (430.42 ± 5.78 nm), polydispersity index (0.283 ± 0.089) with percent entrapment efficiency (68.83 ± 3.45%). The NRG-EE100-NPs demonstrated significant higher bioavailability (～96-fold; p <0.05) as well as cytotoxicity (～16-fold; p <0.001) as compared to free NRG. Furthermore, NRG-EE100-NPs indicated significant tumor suppression (p <0.01) subsequently improvement in survival rate compared to free NRG in vivo. Thus, the physicochemical properties and colorectal cancer efficacy of NRG were improved by successful encapsulating in cationic-polymeric nanoparticle system.     

Proliferation,Metabolic Activity,and Adipogenic Differentiation of Human Preadipocytes Exposed to 2 Surfactants In Vitro

Fat grafting is a pivotal technique for tissue repair. Adipose stromal cells, including preadipocytes, play a major role in the regenerative effects attributed to fat grafting. But the benefits are impaired by the low survival of the graft due to mechanical stress during harvesting, hypoxia, and nutrient deprivation. Nonionic surfactant molecules demonstrated their efficacy in preventing and repairing mechanical damage on the cellular membrane, but it is poorly understood if and how they affect cellular viability, proliferation, and differentiation. We investigated the influence of 2 nonionic surfactants, Kolliphor^®P188 and Kolliphor^®EL, on cultured human preadipocytes. We analyzed their effects on metabolic activity, cell number, adipogenic differentiation, and secretion of growth factors. Kolliphor^®P188 increased metabolic activity, while it did not influence proliferation and differentiation as well as growth factors release. Kolliphor^®EL confirmed its cytotoxic effect at the highest concentrations applied. Contrariwise, treatment with lower concentrations significantly raised metabolic activity, induced adipogenesis, and increased insulin-like growth factor-1 and vascular endothelial growth factor secretion. The effect on differentiation was inhibited by blocking peroxisome proliferator-activated receptor gamma. Our results revealed important effects of surfactants on preadipocytes' survival, proliferation, death, and the interplay with their environment. Particularly Kolliphor^®EL provides modes of action, which could recommend it for novel treatment to improve fat graft viability.     

In Vitro and In Vivo Correlation of Hepatic Fraction of Metabolism by P450 in Dogs

1-Aminobenzotriazole (ABT) has been widely used as a nonspecific mechanism-based inhibitor of cytochrome P450 (P450) enzymes. It is extensively used in preclinical studies to determine the relative contribution of oxidative metabolism mediated by P450 in vitro and in vivo. The aim of present study was to understand the translation of fraction metabolized by P450 in dog hepatocytes to in vivo using ABT, for canagliflozin, known to be cleared by P450-mediated oxidation and UDP-glucuronosyltransferases–mediated glucuronidation, and 3 drug discovery project compounds mainly cleared by hepatic metabolism. In a dog hepatocyte, intrinsic clearance assay with and without preincubation of ABT, 3 Lilly compounds exhibited a wide range of fraction metabolized by P450. Subsequent metabolite profiling in dog hepatocytes demonstrated a combination of metabolism by P450 and UDP-glucuronosyltransferases. In vivo, dogs were pretreated with 50 mg/kg ABT or vehicle at 2 h before intravenous administration of canagliflozin and Lilly compounds. The areas under the concentration-time curve (AUC) were compared for the ABT-pretreated and vehicle-pretreated groups. The measured AUC_ABT/AUC_veh ratios were correlated to fraction of metabolism by P450 in dog hepatocytes, suggesting that in vitro ABT inhibition in hepatocytes is useful to rank order compounds for in vivo fraction of metabolism assessment.     

Bioequivalence of Torad tablet 5 mg to Torem tablet 5 mg (torasemide 5 mg)

The purpose of the present study was to evaluate the bioequivalence of two torasemide tablets, Torem (Roche Korea Co., Ltd., Korea, reference drug) and Torad (Samchundang Pharmaceutical Co., Ltd., Korea, test drug) tablet, according to the guidelines of Korea Food and Drug Administration (KFDA). Twenty-eight healthy male Korean volunteers, 23.68 ± 1.79 years in age and 67.59 ± 9.87 kg in body weight, were divided into two groups and received each medicine at the torasemide dose of 10 mg in a randomized 2 × 2 crossover study. After a single administration, blood samples were taken at predetermined time intervals and the serum concentrations of torasemide were monitored by an HPLC–UV. The in vitro dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUC_t (the area under the serum concentration–time curve from time zero to 12 h), C_max (maximum serum drug concentration), and T_max (time to reach C_max) were calculated, and computer programs (equiv test and K-BE test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed AUC_t and C_max. The results showed that the differences between two formulation based on the reference drug, ?2.84, ?1.22 and 15.91 % for AUC_t, C_max, and T_max, respectively. No significant sequence effect was found for all of the bioavailability parameters indicating that the crossover design was properly performed. The 90 % confidence intervals using logarithmically transformed data were within the acceptance range of log0.80 to log1.25 (e.g., log0.9305?log1.0043 and log0.9422?log1.0903 for AUC_t and C_max, respectively). Thus, the criteria of the KFDA guidelines for the bioequivalence was satisfied, indicating Torad tablet and Torem tablet are bioequivalent.     

Bioaccumulation and physiological effects of mercury in Pteris vittata and Nephrolepis exaltata

Anatomical, histochemical and biochemical approaches were used to study mercury uptake and phytotoxicity as well as anti-oxidative responses in two species of ferns [Chinese brake fern (Pteris vittata) and Boston fern (Nephrolepis exaltata)], grown in a hydroponic system. The roots of both cultivars accumulated large amounts of mercury, but exhibited limited mercury translocation to shoots. Mercury exposure led to more pronounced phytotoxicity accompanied by stronger oxidative stress in the shoots of P. vittata than in N. exaltata. N. exaltata established a more effective anti-oxidative system against mercury-induced oxidative stress than did P. vittata. The activity of anti-oxidative enzymes (superoxide dismutase, catalase and glutathione reductase) increased. The reduced ascorbate (ASA) and oxidized ascorbate (DHA) are regulated. Mercury exposure led to an increase in the concentration of glutathione (GSH) in both fern species. The present study suggests that N. exaltata is more tolerant to mercury exposure than P. vittata, which has been also reported to be more tolerant to arsenic exposure. N. exaltata may thus have potential for phytostabilization of soils or phytofiltration of waste water contaminated with mercury.     

Approaches to the pharmacological treatment of obesity

Obesity is a global health crisis resulting in major morbidity and premature death. The need for safe and efficacious drug therapies is great, and presently unmet. The two drugs currently licensed in the USA for the long-term treatment of obesity, orlistat and sibutramine, provide only modest weight-loss benefits and are associated with high attrition rates owing to side effects. This review summarizes current concepts in the neuroendocrine control of energy homeostasis and major pharmacological treatments for obesity in the pipeline.     

Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year

Rationale

Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment.

Objectives

The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year.

Method

From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N?=?78), ziprasidone (N?=?62), or quetiapine (N?=?62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy.

Results

The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole?=?43.6 %, ziprasidone?=?66.1 % and quetiapine?=?82.3 %) (χ ²?=?22.545; p?<?0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ ²?=?19.436; p?<?0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank?=?30.732 p?<?0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants.

Conclusions

First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.     

Preparation of Ibuprofen Microparticles by Antisolvent Precipitation Crystallization Technique: Characterization,Formulation, and In Vitro Performance

This study demonstrates the preparation and characterization of ibuprofen (IBP) microparticles with some excipients by a controlled crystallization technique with improved dissolution performance. Using the optimum concentrations pluronic F127, hydroxypropyl methyl cellulose, D-mannitol, and l-leucine in aqueous ethanol, the IBP microparticles were prepared. The dissolution tests were performed in phosphate buffer saline using a United States Pharmacopoeia dissolution tester at 37°C. The Raman spectroscopy was used to investigate the interactions and distribution of the IBP with the additives in the microcrystals. The prepared IBP microparticles showed higher dissolution compared to that of the smaller sized original IBP particles. The Raman data revealed that the excipients with a large number of hydroxyl groups distributed around the IBP particle in the crystal enhanced the dissolution of the drug by increasing the drug-solvent interaction presumably through hydrogen bonding. The Raman mapping technique gave an insight into the enhanced dissolution behavior of the prepared IBP microparticles, and such information will be useful for developing pharmaceutical formulations of hydrophobic drugs. The controlled crystallization was a useful technique to prepare complex crystals of IBP microparticles along with other additives to achieve the enhanced dissolution profile.     

A simple and robust quantitative analysis of retinol and retinyl palmitate using a liquid chromatographic isocratic method

Vitamin A is a vital nutritional substances that regulates biological activities including development, but is also associated with disease onset. The extent of vitamin A intake influences the retinoid content in the liver, the most important organ for the storage of vitamin A. Measurement of endogenous retinoid in biological samples is important to understand retinoid homeostasis. Here we present a reliable, highly sensitive, and robust method for the quantification of retinol and retinyl palmitate using a reverse-phase HPLC/UV isocratic method. We determined the impact of chronic dietary vitamin A on retinoid levels in livers of mice fed an AIN-93G semi-purified diet (4 IU/g) compared with an excess vitamin A diet (1000 IU/g) over a period from birth to 10 weeks of age. Coefficients of variation for intra-assays for both retinoids were less than 5%, suggesting a higher reproducibility than any other HPLC/UV gradient method. Limits of detection and quantification for retinol were 0.08 pmol, and 0.27 pmol, respectively, which are remarkably higher than previous results. Supplementation with higher doses of vitamin A over the study period significantly increased liver retinol and retinyl palmitate concentrations in adult mice. The assays described here provide a sensitive and rigorous quantification of endogenous retinol and retinyl palmitate, which can be used to help determine retinoid homeostasis in disease states, such as toxic hepatitis and liver cancer.