Hybridization of Poly(oxazoline) and Poly(ethylene oxide)-Based Amphiphilic Copolymers into Thermosensitive Mixed Micelles of Tunable Cloud Point.

This paper reports the development in aqueous solution of mixed micelles of tunable cloud point temperature through blending in various proportions of two copolymers of different chemical natures. For that purpose, a lipid-b-poly(2-isopropyl-2-oxazoline) (lipid-b-P(iPrOx)) copolymer, self-assembling into thermosensitive micelles that phase-separate above a cloud point temperature of 38 °C, was blended in various proportions with commercial C18-b-PEOx. The latter was constituted of a hydrophobic saturated C18 chain and a hydrophilic poly(ethylene oxide) (PEO) block with varying polymerization degrees (x) and does not have any thermosensitive properties on the studied temperature range for any value of x. The different blends were thoroughly characterized by light scattering and UV-visible spectroscopy, revealing that hybridization between both copolymers always occurred, independent of the PEO block length. The resulting mixed micelles present TCP values progressively increasing with the C18-b-PEOx proportion, from 38 to 61 °C. This study demonstrates the relevance of the blending approach to tune the phase separation of micellar systems by formulation rather than by more tedious synthetic efforts. Shifting TCP through this approach extends the range of temperature where lipid-b-P(iPrOx) can find an application.

Effect of hydrophobicity and molar mass on the capacity of chitosan and κ-carrageenan to stabilize water in water emulsions.

A range of commercial chitosan samples with different molar masses and degrees of acetylation was tested for their capacity to stabilize water in water (W/W) emulsions formed by mixing aqueous solutions of dextran and poly (ethylene oxide). To further understand the effect of the acetylation degree, commercial samples were acetylated and deacetylated to different degrees. The effect of pH and chitosan concentration on the stability was investigated. The lowest investigated degree of acetylation (6%) was sufficient to inhibit coalescence, but higher degrees that were studied (up to 50%) led to faster stabilization resulting in smaller stable dispersed droplets that did not sediment for at least one week. The effect of hydrophobic acetyl units on the stability was confirmed for κ-carrageenan that could stabilize the W/W emulsion only after acetylation. For chitosan it was shown that the molar mass should be above a critical value independent of the degree of acetylation.

Analysis of risk factors for complications and adverse obstetrical outcomes in women with Takayasu arteritis: a French retrospective study and literature review.

OBJECTIVE: Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed. METHODS: All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015. RESULTS: The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study. CONCLUSION: This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

Mixed iota and kappa carrageenan gels in the presence of both calcium and potassium ions.

The effect was studied of adding both KCl and CaCl2 on gelation of solutions of ι-carrageenan, κ-carrageenan and mixtures of both types. The gel temperature (Tg) of ι-car was found to be determined by the CaCl2 concentration and Tg of κ-car by the KCl concentration. At a given salt concentration, ι-car was stiffest with pure CaCl2, but κ-car gels and mixed carrageenan gels were stiffer when both KCl and CaCl2 were present. Gelation of κ-car increased the turbidity of mixed carrageenan gels in the presence of KCl or CaCl2, but when both salts were present it led to a drop of the turbidity. In mixed salt, K+ induces formation of a homogeneous κ-car network that causes the mixed network to become more homogeneous. Rheological and structural properties of carrageenan gels can be tuned for a given polymer and salt concentration by adding both KCl and CaCl2 to κ-car/ι-car mixtures.

Stabilization of Water-In-Water Emulsions by Linear Homo-Polyelectrolytes.

The effect of adding a small quantity of linear polymers on the stability of water-in-water (W/W) emulsions was studied for emulsions of dextran-rich droplets in a continuous poly(ethylene oxide) (PEO) phase (D/P) and vice versa (P/D). It was found that out of 16 different polymers that were tested, three had a significant effect: chitosan (Chit), diethyl aminoethyl dextran (DEAED), and propylene glycol alginate (PGA). In the presence of Chit or PGA, P/D emulsions were much less stable than D/P emulsions, but DEAED stabilized both types of emulsion. Interactions of these polymers with PEO or dextran were investigated with light scattering, and the microstructure of the emulsions was studied with confocal laser scanning microscopy. The effect of pH, polymer concentration, interfacial tension, and ionic strength on the stability was investigated and was found to be different for the three polymer types. The results suggest that stabilization of W/W emulsions by linear polymers requires that they contain both charged and hydrophobic units.

Impact of backbone stiffness and hydrophobic chain length of modified xanthan on oil in water emulsion stabilization.

The impact of xanthan chemical modification under both ordered and disordered conformations on oil-in-water (O/W) emulsion stabilization was investigated. While both hydrophobically modified xanthan (HMX) are able to stabilize the O/W interface, a dramatic difference was observed macroscopically. When HMXord (ordered conformation) could produce stable emulsions at concentrations down to 0.2% w/w, HMXdis (disordered conformation) led to unstable systems mostly by creaming whatever the concentration studied. Moreover, in the case of HMXdis, the role of the grafted chain length was investigated and two different behaviors were observed depending on the grafting unit. It was demonstrated that the cornerstone of these emulsion stability was the rheological properties of the continuous phase which was governed by two main factors: the partitioning of HMXdis between the interface and the continuous phase and the viscosifying ability of the polymer, the latter being directly linked to the backbone stiffness.

Hydrophobically modified xanthan: Thickening and surface active agent for highly stable oil in water emulsions.

Oil-in-water (O/W) emulsions were prepared using exclusively a hydrophobically modified xanthan (HMX) under ordered conformation without any surfactant. A series of HMX differing in grafting density were utilized at different concentrations. It was demonstrated that HMX stabilizes O/W emulsions where pristine xanthan do not. Indeed, in some cases, emulsions with HMX proved to be homogeneous and stable over months. Emulsions microstructure and rheological properties were investigated over time as a function of HMX concentration and grafting density in order to determine the mechanisms governing this efficient stability. The higher the HMX concentration is, the better the emulsions stability. However, unexpectedly, increasing the HMX grafting density leads to faster destabilization. The whole set of results demonstrate that the stability of the emulsions against coalescence and creaming is explained by partitioning of HMX molecules between bulk and interface, thus split between viscosifying the aqueous phase and stabilizing the interface.

Chemical modification of xanthan in the ordered and disordered states: An open route for tuning the physico-chemical properties.

The impact of the chain stiffness on physicochemical properties has been studied by chemical modification of xanthan under both ordered and disordered conformations. Corresponding rheological properties were studied and results showed that amphiphilic xanthan exhibited completely different behaviors depending on its conformation during modification. Xanthan, when modified under ordered conformation, exhibits similar behavior to non-modified one, only the chain relaxation being strongly slowed down. Therefore, the high stiffness of xanthan helices does not allow hydrophobic moieties to associate. Oppositely, xanthan modified under its disordered conformation displayed a chemical gel-like behavior without any relaxation of the chain within the studied frequency range nor with temperature, which is unexpected for this length of alkyl chains. These different viscoelastic properties can be correlated to the regioselectivity of the grafting; the latter can be controlled by the conformation of xanthan during modification, thus by the synthesis conditions.

Long-term efficacy and safety of rituximab in IgG4-related disease: Data from a French nationwide study of thirty-three patients.

OBJECTIVES: To assess efficacy and safety of rituximab (RTX) as induction therapy, maintenance of remission and treatment of relapses in a cohort of IgG4-related disease (IgG4-RD) patients. METHODS: Nationwide retrospective multicenter study of IgG4-RD patients treated with at least one course of RTX. Clinical, biological and radiological response, relapse rate and drug tolerance were analyzed. Kaplan-Meier curves were plotted and risk factors for relapse studied with a Cox regression model. RESULTS: Among 156 IgG4-RD patients included in the French database, 33 received rituximab. Clinical response was noted in 29/31 (93.5%) symptomatic patients. Glucocorticoids withdrawal was achieved in 17 (51.5%) patients. During a mean follow-up of 24.8 ±21 months, 13/31 (41.9%) responder patients relapsed after a mean delay of 19 ±11 months after RTX. Active disease, as defined by an IgG4-RD Responder Index >9 before RTX, was significantly associated with relapse (HR = 3.68, 95% CI: 1.1, 12.6) (P = 0.04), whereas maintenance therapy with systematic (i.e. before occurrence of a relapse) RTX retreatment was associated with longer relapse-free survival (41 versus 21 months; P = 0.02). Eight severe infections occurred in 4 patients during follow-up (severe infections rate of 12.1/100 patient-years) and hypogammaglobulinemia ≤5 g/l in 3 patients. CONCLUSION: RTX is effective for both induction therapy and treatment of relapses in IgG4-RD, but relapses are frequent after B-cell reconstitution. Maintenance therapy with systematic RTX infusions is associated with longer relapse-free survival and might represent a novel treatment strategy. Yet, the high rate of infections and the temporary effect of RTX might be hindrances to such strategy.

Ophthalmic manifestations in IgG4-related disease: Clinical presentation and response to treatment in a French case-series.

IgG4-related disease (IgG4-RD) is characterized by variable tissue or organ involvements sharing common pathological findings. Orbital or orbital adnexa involvement of the disease has been reported in a few case series. The aim of our study was to characterize and analyze ophthalmic manifestations from a nationwide French case-series.Patients with IgG4-RD and orbital or orbital adnexa involvement included in the French multicentric IgG4-RD case-registry were identified. Only patients fulfilling "modified" comprehensive diagnostic criteria with pathological documentation were retained for the study. Clinical, biological, pathological, radiological findings and data regarding the response to treatment were retrospectively analyzed.According to our data registry, the frequency of IgG4-related ophthalmic disease (IgG4-ROD) was 17%. Mean age at diagnosis was 55.1 ±â€Š7.1 years with a male/female ratio of 2.2. The 19 cases of IgG4-ROD consisted of lacrimal gland (68.4%), soft tissue (57.9%), extra-ocular muscles (36.8%), palpebral (21.1%), optical nerve (10.5%), orbital bone (10.5%), and mononeuritis (V1 and/or V2, 10.5%) involvements. IgG4-ROD was bilateral in 57.9% of cases. Extra-ophthalmic manifestations were reported in 78.9% of cases. All patients responded to prednisone but two-thirds of patients relapsed within a mean (SD) of 9.8 (3.5) months and 72.2% required long-term glucocorticoids and/or immunosuppressive agents. Eight patients were treated by rituximab with a favorable response in 87.5% of cases.Lacrimal involvement is the most frequent ophthalmic manifestation of IgG4-RD and is frequently associated with extra-orbital manifestations. Despite initial favorable response to steroids, the long-term management of relapsing patients needs to be improved.

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers.

It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.

Effect of salt on turbulent drag reduction of xanthan gum.

The turbulent flow of an aqueous KCl solution driven by a rotating disc in a closed chamber showed significant drag reduction (DR) when a small amount of xanthan gum (XG) was added. The effects of the experimental parameters (XG and KCl concentrations, and time) on the drag reduction efficiency were examined. While the DR efficiency of XG decreased with increasing salt (KCl) concentration, the time-dependent DR efficiency was found to be fitted well using Brostow model equation.

Hydrophobically modified xanthan: an amphiphilic but not associative polymer.

Hydrophobic octyl moieties have been grafted in various densities onto the carboxylic acid functions of xanthan under its ordered conformation. The outcoming amphiphilic and associative properties were studied by fluorescence spectroscopy and rheology. Results showed that the conformation of xanthan is not affected by the chemical modification and remains the same as the native one. Additionally, xanthan derivatives do not show any viscoelastic enhancement; nevertheless, their dynamics is strongly slowed down: the higher the grafting density, the slower the relaxation. We proved that hydrophobically modified xanthan, even being amphiphilic, does not exhibit any additional associating properties compared to the unmodified xanthan. The high stiffness of xanthan helices does not allow the derivatives to adopt the organization usually observed for flexible amphiphilic polymers. On the basis of these observations, a model depicting such a singular behavior is proposed.

[Management of the hunger strike in prison]. / Prise en charge médicale de la grève de la faim en milieu carcéral.

INTRODUCTION: Entering prison can feed pre-existent behavior of demands or generate them. Several means of expression are then used. Hunger strike is an average privileged act. It belongs to prison culture. OBJECTIVE: Estimate how practitioners working in prison take care of the hunger strikers. METHODOLOGY: The study, realised in 2008, was led with all the Units of Consultations and Ambulatory Care in France. It is a declarative investigation where a medical testimony by unit was asked. RESULTS: From 174 "maisons d'arrêt" and establishments for punishment in France, 95 answers were obtained. This situation was already seen by 98,8% of the doctors. The motives for hunger strike were mainly judicial for "maisons d'arrêt" (70,1%) and prison motives for detention centers (68,7%). Mainly, doctors opted for a neutral attitude (63% of the cases). The hunger strikes were mostly brief (less than a week in 85% of the cases). Only 5,5% of the doctors proposed written information concerning the risks incurred during a fast. A doctor in 4 approximately (23%) was already witness to complications due to fasting. The fact that a patient may refuse care makes the medical approach difficult. Faced with such a situation, 45% of the doctors privileged their duty of care, 28% respected the patient's wishes, and 27% did not pronounce. From a therapeutic point of view, the place of treatment using vitamins was rarely recognized (32,7%). DISCUSSION: Hunger strike is rarely severe, but it is rather frequent in prison so that every doctor working there will be confronted with it. The refeeding syndrome seems often ignored. The coverage of hunger strike is governed by the law, but ethical questions stay in the appreciation of every doctor.

Transient gelation and glass formation of reversibly cross-linked polymeric micelles.

Poly(ethylene oxide) (PEO) end-capped with a hexadecyl group at one (alpha-PEO) or both ends (alpha,omega-PEO) are highly asymmetric diblock or triblock copolymers that form spherical micelles in aqueous solution. alpha,omega-PEO can bridge between two micelles leading to reversible association of the micelles. At a first critical concentration (C(p)), the micelles percolate and a transient network is formed with an elastic modulus determined by the concentration of alpha,omega-PEO. C(p) increases with increasing fraction of alpha-PEO and is insensitive to the temperature. At a second critical concentration (C(c)), a liquid-solid transition occurs. C(c) is independent of the fraction of alpha-PEO and increases with increasing temperature. There are indications that the solid state is formed by nucleation and growth of domains of dynamically arrested micelles. The properties of the transient network are almost the same in the liquid and in the solid state.

Structure and viscoelasticity of mixed micelles formed by poly(ethylene oxide) end capped with alkyl groups of different length.

Poly(ethylene oxide) (PEO) end capped with an alkyl group is a highly asymmetric diblock copolymer that forms spherical micelles in aqueous solution resembling multiarm star polymers. The effect of varying the length of the alkyl end group on the structure and viscoelasticity was investigated for pure and mixed micelle suspensions. The aggregation number (p) of the micelles increased and the critical association concentration (CAC) decreased with increasing the length of the end group. At high concentrations a discontinuous reversible liquid-solid transition was observed below a critical temperature (Tc) that increased with increasing length of the end group. Mixing end-capped PEO with different alkyl lengths led first to formation of the micelles by polymers with the lowest CAC into which the other polymers were incorporated when the concentration was increased. The viscoelastic properties at high concentrations are the same for pure systems and mixtures with the same average length of the alkyl end group.