Poly(3-hydroxyoctanoate) containing pendant carboxylic groups for the preparation of nanoparticles aimed at drug transport and release

Copolymers of poly(3-hydroxyoctanoate) (PHO) with carboxylic groups in lateral chains have been prepared by chemical modification of unsaturated bacterial polyesters. The oxidation of the pendant alkenes is complete and important loss in molecular weight of polymer was observed. The presence of repeating units containing pendant carboxy groups in the proportion of 25% has enhanced hydrophilicity of these new polymeric structures. Nanoparticles have been prepared from PHO and two functionalized derivatives, characterized by electronic microscopy and compared in view of bioactive molecules transport and release.     

Demonstration of functional CD40 in B-lineage acute lymphoblastic leukemia cells in response to T-cell CD40 ligand

Because activated T cells were previously shown to induce proliferation of human normal B-cell precursors (BCP) via the CD40 pathway, we investigated the effects of T cells on leukemic blasts isolated from patients with B-lineage acute lymphoblastic leukemia (BCP-ALL). An anti-CD3 activated human CD4+ T-cell clone was found to induce significant call proliferation in four of nine BCP-ALL samples analyzed. In one of these cases, the T-cell effect was clearly dependent on interaction between CD40 and its ligand. Accordingly, a more thorough analysis was performed on this particular leukemia (case 461, adult early pre-B-ALL, mBCR+, Philadelphia+, i(9q)+). Thus, autologous CD4+ T cells isolated from the patient were also able to induce CD40-dependent proliferation of the leukemic blasts. Analysis of the phenotype after coculture showed that, among the CD19+ cells, a proportion gradually lost expression of CD10 and CD34, whereas some cells acquired CD23. In addition, and in contrast with normal BCP, activated T cells promoted maturation of a subset of the case 461 leukemic cells into surface IgM+ cells. The leukemic origin of the cycling and the maturing cells was assessed by the presence of i(9q), a chromosomal abnormality associated with this leukemia and evidenced by fluorescence in situ hybridization. Taken together, these results show that leukemic BCP can be activated via CD40 but that not all cases display detectable stimulation in response to T cells despite their expression of CD40. In addition, the present data suggest that CD4+ T cells could potentially play a role in the physiology of BCP-ALL.     

A second generation of artificial cornea (Biokpro II)

The properties of a new second-generation colonizable artificial cornea were evaluated in humans. The prosthesis consisted of a peripheral rim of a translucent microporous fluorocarbon polymer (expanded polytetrafluoroethylene) fused with the polymer of the central optic. The optic was made of medical-grade polydimethylsiloxane coated with polyvinylpyrrolidone. Its refractive power was 42.2 diopters and it measured 7.0 mm in diameter and 0.55 mm in thickness. The geometry of the optic was tested by high-frequency ultrasound and intraocular pressure and distensibility were measured in an artificial chamber. Prostheses were implanted in one eye of 13 humans. The average follow-up was 6 months (range 3-9 months). Most of the eyes (11/13) were clinically stable after a 7 months follow up. Seven patients had visual acuity improvements. Mean corrected final visual acuity was 20/200 (range, 20/30 to light perception). Five anatomical failures occured (two extrusions, two retroprosthetic membranes, one endophthalmitis). The new optical core, junction, and surface properties of the polymers offer many advantages, quicker colonization of the supporting skirt, and an optical core with a geometry similar to that of a normal human cornea. Epithelial cells did not migrate over the interface and optical core. It seems that formation of an epithelium over the artificial device is essential for the long-term stability of the implant.     

The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.     

Epinephrine doses delivered from auto-injectors stored at excessively high temperatures

Context: Prompt injection of epinephrine (adrenaline) from epinephrine auto-injectors (EAIs) is the primary treatment for anaphylaxis in out-of-hospital settings. Storage of EAIs at room temperature (25?°C) is advised; however, storage at excessively high temperatures sometimes occurs. To our knowledge, there are no previous publications on the doses of epinephrine ejected from EAIs after storage at such temperatures.

Objective: We examined the epinephrine doses delivered from activated EAIs stored constantly or cyclically at 70?°C.

Methods: Twenty-five in-date EAIs were stored constantly or cyclically at 70?°C (excessive heat) or 25?°C (controls) for 5?d or 10?d. EAIs were activated and the epinephrine doses in the ejected solutions were measured using HPLC-UV. The enantiomeric purity of epinephrine was also measured by HPLC-UV.

Results: Control EAIs ejected a volume of 0.300?±?0.006?mL containing 103.7?±?3.3% of labeled dose (LD). After 5?d or 10?d of constant storage at 70?°C and activation at 70?°C, EAIs ejected a volume of 0.367?±?0.008?mL containing 96.8?±?3.8% LD and 0.373?±?0.007?mL containing 77.7?±?3.3% LD, respectively. After 5?d of cyclic storage at 70?°C and cooling to 25?°C before activation, EAIs ejected a volume of 0.311?±?0.008?mL containing 87.2?±?1.9% LD. Under the experimental conditions of this study, the resultant chromatographic peaks of epinephrine solutions from all EAIs represented only the pure l-enantiomer of epinephrine.

Conclusion: EAIs should be stored under recommended conditions of the manufacturer. EAIs stored at excessively high temperatures cannot be used to treat humans while still hot, and when cooled, cannot be relied on to deliver the labeled epinephrine dose in anaphylaxis.     

Stereoisomers composition of 4-[(1′-methylpropyl)-oxycarbonyl]-2-oxetanone and related compounds,as precursors of fuctional polyesters,determined by chiral gas chromatography

Summary The configurational analysis of racemic and optically active stereoisomers of 4-[(1-methylpropyl)oxycarbonyl]-2-oxetanone has been carried out by using chiral gas chromatography. This technique has been successful in the stereoisomers composition determination of these -substituted -lactones prepared by two different routes and used as monomers in the preparation of malic acid stereocopolymers. Result are in good agreement with those obtained from high resolution ¹H NMR, in the presence of an Europium salt, as chiral shift reagent. This method has been extended to 3-methyl-4-[(1,2,2-trimethyl propyl)oxycarbonyl]-2-oxetanone. The exact knowledge of precursors configurational structure is very important in regard to the obtention of the corresponding polystereoisomers with a strictly controlled enantiomeric or diastereoisomeric composition and consequently with predictable properties.     

Combining a new data classification technique and regression analysis to predict the Cost-To-Serve new customers

Identifying the Cost-To-Serve (CTS) of customers is one of the most challenging problems in Supply Chain Management because of the diversity in their business activities. For the particular case of the industrial gas business, we are interested in predicting the cost to deliver bulk (liquefied) gas to new customers using a multifactor linear regression model. Developing a single model, i.e. analyzing the observations all at once, produces poor prediction results. Therefore prior to the regression analysis, a new supervised learning technique is used to group customers who are similar in some sense. Classes of customers are represented by hyper-boxes and a linear regression model is subsequently built within each class. The combination of data classification and regression is proven to increase the accuracy of the prediction.Two Mixed-Integer-Linear Programming (MILP) models are developed for data classification purposes. Although we are dealing with a supervised learning method, classes are not predefined in our case. Rather, we input a continuous “classification” attribute that is optimally discretized by the MILP’s in order to minimize the number of misclassifications. Therefore our data classification model offers a broader range of applications. A number of illustrative examples are used to prove the effectiveness of the proposed approach.     

Deforestation and foreign transfers: a Stackelberg differential game approach

In this paper, our concern is with deforestation as a global environmental issue. Foreign transfers from developed or Northern countries to developing or Southern countries have been proposed to deal with that issue. We use a Stackelberg differential game approach where the two players are: a donor community (the leader) and a recipient country (the follower). We study the impact of different specifications for the transfer function, related to the different information structures the players can consider when playing the Stackelberg game. The different scenarios are compared both from the environmental and economic points of view.