Rheological and drug‐release behaviour of a scleroglucan gel matrix at different drug loadings

The aim of this study was to investigate the drug‐loading effects on release and mechanical properties of a scleroglucan gel, with the intention of considering them in delivery systems formulations. The rheological and kinetic properties of a 2 % w/w scleroglucan gel matrix loaded with 0, 0.02, 0.04, 0.06, 0.2 and 0.4 % w/w of theophylline (Th, used as a model drug) were investigated. Rheological measurements were performed in a controlled‐stress rotational‐shear rheometer under isothermal conditions. For theophylline release from the gel a flat Franz cell was used and the kinetic parameters were derived applying a semi‐empirical power law. The influence of scleroglucan molar weight on kinetic and rheological behaviour was also studied. Results suggest two possible effects of drug loading on the gel network: in the 0.04–0.06 % w/w Th range a plasticizing effect and in the 0.2–0.4 % w/w Th range a rigidization effect. In the first range mentioned, the changes in the gel structural properties tested by means of rheological measurements are coincident with changes in drug‐release kinetics. Copyright © 2005 Society of Chemical Industry     

"What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex": Correction.

Reports an error in "What is in a word? No versus Yes differentially engage the lateral orbitofrontal cortex" by Nelly Alia-Klein, Rita Z. Goldstein, Dardo Tomasi, Lei Zhang, Stephanie Fagin-Jones, Frank Telang, Gene-Jack Wang, Joanna S. Fowler and Nora D. Volkow (Emotion, 2007[Aug], Vol 7[3], 649-659). The supplemental materials link should appear as follows: http://dx.doi.org/10.1037/1528-3542.7.3.649.supp. (The following abstract of the original article appeared in record 2007-11660-018.) The words "No" and "Yes" are involved in conditioning to prohibit or encourage behavior, respectively. The authors, therefore, hypothesized that these words would be attributed to endogenous valence, activating neuronal circuits involved with valence and emotional control. Functional MRI (fMRI) at 4 Tesla was used to record regional brain activity while participants were exposed to emphatic vocalizations of the words. Results showed that No and Yes were associated with opposite brain-behavior responses; while No was negatively valenced, produced slower response times, and evoked a negative signal in the right lateral orbitofrontal cortex (OFC), Yes was positively valenced, produced faster response times, and evoked a positive signal in a contiguous region of the OFC. Attribution of negative valence to No and trait anger control were associated with increased responsivity of the OFC to No. Inasmuch as sensitivity to the prohibitive command No develops during childhood through interaction with primary caregivers as the first social objects, our findings may implicate the lateral OFC in the neurobiology of emotion regulation and subsequent social development. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Energy efficiency, carbon emissions and economic development in Venezuela

Venezuela's vast natural resource base has largely shaped the nation's economic and energy-use patterns. Major opportunities exist for improving the efficiency of energy use in Venezuela and, consequently, restraining the growth of energy-related carbon emissions. This paper presents a detailed report of one potential development path for Venezuela and estimates the ensuing levels of energy demand and CO₂ emissions associated with pursuing this path through the year 2025. The results indicate that by adopting a development strategy that incorporates structural changes in the economy, fuel-switching measures and improved end-use efficiencies, Venezuela can introduce energy efficiency and carbon restraints as part of its economic development process.     

Matching treatment focus to patient social investment and support: 18-month follow-up results.

Patients were randomly assigned to 1 of 3 treatments: brief broad-spectrum (BBS), extended relationship enhancement (ERE), or extended cognitive–behavioral (ECB). A hierarchical latent growth model was used to analyze the data of 188 patients (82%) followed for 18 months. ERE treatment was significantly more effective in increasing abstinence of patients entering treatment with a network unsupportive of abstinence or with a low level of investment in their network, whereas BBS treatment was more effective for patients with either (a) both a social network unsupportive of abstinence and a low level of network investment or (b) high investment in a network supportive of abstinence. ECB outcomes were neither as good as those matched nor as bad as those mismatched to the different exposures of relationship enhancement. This suggests that dose of relationship enhancement should be determined after assessing patient relationships. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement of adenovirus-mediated gene transfer to human bone marrow cells

Adenovirus infection of CD34+ hematopoietic stem/progenitor cells is dependent on the multiplicity of infection (MOI), time of incubation, the volume in which the co-incubation occurs and the presence or absence of growth factors. Studies revealed that a brief co-incubation (1-8 hours), resulted in low levels of transgene expression, suggesting that adenovirus infection of CD34+ cells occurs slowly, and optimal transduction requires a 24 hour exposure to adenovirus. Infection by Ad/beta-gal or Ad/p53 at a MOI of 500:1 provided a high transduction efficiency but inhibited hematopoietic function. However, treatment at a MOI of 50-100 resulted in efficient transduction (10.7-15.7% positive) without detectable toxicity. Secondary proof of adenovirus transgene expression was demonstrated by detection of mRNA for p53 in Ad/p53 infected stem cells. We conclude that a 24 hour exposure to recombinant adenovirus encoding p53 or beta-gal, at a MOI of 50-100 is optimal for in vitro gene transfer to BM cells and has no significant effect on hematopoietic function. Adenovirus-mediated transduction of BM cells can also be modulated by growth factors (IL-3, GM-CSF and G-CSF) with improved gene delivery and maintenance of hematopoietic function. In summary, adenovirus vectors can be used to transiently transduce stem cells, and conditions have been defined to maximize expression and limit inhibitory effects on CD34+ cells. These data support continued investigation of this vector for local cytokine delivery and purging of stem cell products.     

Visceral Adipose Tissue Displays Unique Metabolomic Fingerprints in Obesity,Pre-Diabetes and Type 2 Diabetes

Visceral adipose tissue (VAT) metabolic profiling harbors the potential to disentangle molecular changes underlying obesity-related dysglycemia. In this study, the VAT exometabolome of subjects with obesity and different glycemic statuses are analyzed. The subjects (n = 19) are divided into groups according to body mass index and glycemic status: subjects with obesity and euglycemia (Ob+NGT, n = 5), subjects with obesity and pre-diabetes (Ob+Pre-T2D, n = 5), subjects with obesity and type 2 diabetes under metformin treatment (Ob+T2D, n = 5) and subjects without obesity and with euglycemia (Non-Ob, n = 4), used as controls. VATs are incubated in culture media and extracellular metabolite content is determined by proton nuclear magnetic resonance (¹H-NMR). Glucose consumption is not different between the groups. Pyruvate and pyroglutamate consumption are significantly lower in all groups of subjects with obesity compared to Non-Ob, and significantly lower in Ob+Pre-T2D as compared to Ob+NGT. In contrast, isoleucine consumption is significantly higher in all groups of subjects with obesity, particularly in Ob+Pre-T2D, compared to Non-Ob. Acetate production is also significantly lower in Ob+Pre-T2D compared to Non-Ob. In sum, the VAT metabolic fingerprint is associated with pre-diabetes and characterized by higher isoleucine consumption, accompanied by lower acetate production and pyruvate and pyroglutamate consumption. We propose that glucose metabolism follows different fates within the VAT, depending on the individuals’ health status.