Sol/gel transition of thermoresponsive Hyaluronan: From liquids to elastic and sticky materials.

Thermoassociating copolymers were prepared by grafting temperature responsive poly(N-isopropylacrylamide-stat-N-tert-butylacrylamide) telomers onto hyaluronan. By varying the composition of LCST side chains, from 50 to 100 wt% of NIPAM units, it is shown that the sol/gel transition of entangled solutions can be accurately controlled in the range of 10 to 35 °C with an abrupt transition and reversible properties. Complementary experiments, performed by DSC and NMR, demonstrate the close relationship between thermoassociation of LCST grafts, forming microdomains of low mobility, and macroscopic properties. Moreover, by performing tack experiments during heating we demonstrate that hyaluronan formulations abruptly switch from a weak adhesive viscous behavior to an elastic adhesive profile in the gel regime. As LCST side-chains form concentrated micro-domains of low mobility, physical gels can resist to dissociation above their sol/gel transition for relatively long periods when immersed in excess physiological medium. The thermoassociative behavior of these copolymers, whose properties can be finely tuned in order to form sticky gels at body temperature, clearly demonstrates their potential in biomedical applications such as injectable gels for drug delivery or tissue engineering.

Neutron reflectivity measurements at the oil/water interface for the study of stimuli-responsive emulsions⋆.

Stable stimuli-responsive emulsions between oil and water are formed with an amphiphilic block copolymer bearing polystyrene (PS) and poly(dimethylaminoethyl methacrylate) (PDMAEMA) moieties. Different kinds of emulsions like direct, multiple or inverse ones are reproducibly formed as a function of chemical parameters such as p H and salt concentration. To test the correlation between the different nature of the emulsion and the conformation of the polymer chain at the interface, neutron reflectometry at the oil/water interface was carried out. An original sample cell was built and the procedure to get reliable results with it on the FIGARO reflectometer at the Institut Laue-Langevin is described. Results show that for direct emulsions, the copolymer is much more extended on the water side than on the oil side. In the case where multiple emulsions are stabilized, the conformation is strongly modified and is compatible with a more equilibrated extension of the chain on both sides. The inverse case shows that the extension in oil is stronger than in water. These results are discussed in term of polymer brushes (charged or neutral) extension with respect to salt addition and hydrophobic interactions.

Correction: Breaking of the Bancroft rule for multiple emulsions stabilized by a single stimulable polymer.

Correction for 'Breaking of the Bancroft rule for multiple emulsions stabilized by a single stimulable polymer' by L. Besnard et al., Soft Matter, 2014, 10, 7073-7087.

Breaking of the Bancroft rule for multiple emulsions stabilized by a single stimulable polymer.

We investigated emulsions of water and toluene stabilized by (co)polymers consisting of styrene (S) and 2-(dimethylamino)ethyl methacrylate (DMAEMA) monomer units with different compositions and structures such as a PDMAEMA homopolymer, a P(S-co-DMAEMA) random copolymer and various PS-b-PDMAEMA and PS-b-(S-co-DMAEMA) block copolymers. The model system is used to study the fundamental conditions under which the different kinds of polymer-stabilized emulsions (direct oil in water, inverse water in oil and multiple emulsions) are stabilized or destabilized by pH change (at constant temperature). Polymer properties like chain conformation at the toluene-water interface as probed by SANS and neutron reflectivity at the liquid-liquid interface, the oil-water partitioning of the polymer chains (Bancroft's rule of thumb) as determined by UV spectroscopy and interfacial tensions measured by the rising and spinning drop techniques are determined. Overall, results evidence that the curvature sign, as defined by positive and negative values as the chain segments occupy preferentially the water and toluene sides of the interface respectively, reliably predicts the emulsion kind. In contrast, the Bancroft rule failed at foreseeing the emulsion type. In the region of near zero curvature the crossover from direct to inverse emulsions occurs through the formation of either unstable coexisting direct and inverse emulsions (i) or multiple emulsions (ii). The high compact adsorption of the chains at the interface as shown by low interfacial tension values does not allow to discriminate between both cases. However, the toluene-water partitioning of the polymeric emulsifier is still a key factor driving the formation of (i) or (ii) emulsions. Interestingly, the stabilization of the multiple emulsions can be tuned to a large extent as the toluene-water polymer partitioning can be adjusted using quite a large number of physico-chemical parameters linked to polymer architecture like diblock length ratio or polymer total molar mass, for example. Moreover, we show that monitoring the oil-water partitioning aspect of the emulsion system can also be used to lower the interfacial tension at low pH to values slightly higher than 0.01 mN m(-1), irrespective of the curvature sign.

Infrared spectrometry and Raman microprobe in the analysis of urinary calculi.

Infrared spectrophotometry and Raman spectroscopy, thanks to the laser molecular microsond (MOLE), are two analytical techniques particularly well suited to a precise analysis of the composition and structure of urinary calculi. They both showed noteworthy efficiency in their ability to recognize the various crystalline or amorphous mineral and organic species. The MOLE permits analysis of crystals 1 mu in size, demonstrating its usefulness in the study of calculi nuclei as well as in the study of urinary crystals. These analyses are a very important source of information about conditions of crystalline nucleation and growth as well as about ions and molecules which can take place in the formation and the evolution of the diverse crystalline phases. On the clinical level, these data can contribute to a better comprehension of the formation of every stone.

[Study of spontaneous crystalluria using infrared spectroscopy. Research on correlations between crystals, calculi, bacteria and the sex of the patients]. / Etude de la cristallurie spontanée par spectroscopie infrarouge. Recherche de corrélations entre les cristaux, les calculs, les germes et le sexe des malades.

6 100 specimens of urine were examined according to classical cytobacteriological techniques for the presence of crystals and the possible correlations with the bacteria identified and the sex of the patients. When crystals were present, the urine was centrifuged and the deposit was dried in a filter with low porosity, scraped away and incorporated in a tablet of potassium bromide and then examined by infra-red spectrophotometry. Positive crystalluria was found in 6.4% of urines from patients without lithiasis and in 59% of cases with lithiasis. Only 50% of cases had a pure mineral type. Struvite was the most common (34.3%), then weddellite (33.1%), carbapatite (23.1%), amorphous calcium phosphate (22.7%) and ammonium urate (18.3%). Any of these compounds could be found pure or in combination with others. The other constituents were appreciably less common. All in all, 76 types of crystalluria were demonstrated. Important differences in crystallurias and the bacteria identified were detected as a function of the sex of the patients. Positive correlations were found between a number of bacteria and the crystals with which they are associated. The distribution and the composition of the cases of crystalluria were compared with those of urinary calculi.

[Detection and diagnosis of drug induced lithiasis]. / Dépistage et diagnostic des lithiases médicamenteuses.

Drug-induced calculi are often mis-diagnosed because of inadequate analysis of the urinary calculi. These stones can only be characterized unambiguously by global physical methods like infra-red spectrophotometry. From a series of 2,000 calculi analysed under infra-red, we identified 22, i.e. 1.1% of cases, which contained, partly or entirely, drug products. Ten other cases are still being studied. Amongst the products identified we found metabolites of glafenine (Glifanan) in 7 cases, triamterene and its derivatives (Cycloteriam) in 7 cases, metabolites of phenazopyridine (Pyridium) in 4 cases, sulphonamides in 2 cases : N-acetylsulphamethoxazole hydrochloride (Bactrim) and N-acetylsulphaguanidine (Guanidan), flumequine (Apurone) in 1 case and calcite (Cal-Mag-Na) in 1 case. The authors estimate that about 100,000 calculi are excreted in France each year and that at least 1,000 of these potentially contain drugs and are not diagnosed. Early recognition of drug induced stones is essential in order to protect the patient from recurrences, the risks of renal complications or, more simply, from useless therapeutic or dietetic regimes.

[Renal toxicity of glafenine in man: renal stones and acute renal failure]. / Toxicité rénale de la glafénine chez l'homme: calculs rénaux et insuffisance rénale aiguë.

The role of glafenine in certain cases of acute renal failure was described several years ago, but very little work has been done on the intratubular precipitates generally responsible for these manifestations. We have been able to study 6 cases of acute poisoning and 5 cases of glafenine renal stones which have shown that several mechanisms are likely to be involved. In 4 cases, the acute poisoning resulted in reversible oliguria which resolved after several days. In 3 of the 5 cases of renal stones, variable amounts of glafenine were found in the zone of nucleation. Infrared spectrophotometric and chromatographic examination of the first urine after the return of diuresis in the oliguric subjects and in the patients with renal stones, revealed that several metabolites of glafenine could be implicated in the development of these renal precipitates. In the different cases, free metabolites and conjugated derivatives were found to be responsible. The authors discuss the relationship between the products detected and the clinical manifestations observed.

[Triamterene induced nephrolithiasis (author's transl)]. / Lithiase urinaire médicamenteuse. Calculs composés de triamtérène.

Various studies have demonstrated a relationship between nephrolithiasis and the ingestion of certain drugs. We are particularly interested in the effects of triamterene. Five published case studies on patients of both sexes between 43 and 60 years of age have proven that a regular consumption of normal doses of triamterene has a direct effect upon the formation of renal stones. The stones analysed by infra-red spectrophotometry during the above observations contained from 20 to 100% of triamterene and it's metabolite hydroxytriamterene, following a daily consumption of 150 to 350 mg during a period of 6 to 38 months. It has been confirmed that triamterene and it's metabolite hydroxytriamterene are very poorly soluble and super-saturate the urine for a brief period following the ingestion of the drug. Triamterene might also intervene in the initial phenomena of nucleation. It is therefore recommended that triamterene be used with caution in those patients presenting a history of nephrolithiasis. The existence of drug induced nephrolithiasis reinforces the importance of the technique of renal stone analysis, and the necessity of a systematic study of all renal stones found. This will allow us to develop the study of the correlations between the different episodes of renal stone disease, the nature of the treatment undertaken and the systematic analysis, layer by layer, of the stone.

[Triamterene and renal calculi]. / Triamtérène et lithiases rénales.

The authors report the detailed analysis of 4 calculi containing triamterene observed between 1979 and 1981. The composition of drug layers is almost the same in the 4 calculi and shows a mixture of triamterene (estimated at 35% of iatrogenic components) and 7 metabolites among them p-hydroxy-triamterene (5-10%) and mainly p-hydroxytriamterene estersulfate (40-55%). The authors hypothesize a metabolic or physicochemical relation between triamterene and uric acid which are frequently associated in these calculi that represent 0.4% of all lithiasis. An estimated 150 to 200 calculi with triamterene are probably eliminated though not detected every year in France. The interest of a fine analysis of calculi by appropriate physical methods, such as infrared spectrometry, is emphasized.

[Renal pelvis stones made of glafenic acid in two patients under prolonged treatment with analgesics (author's transl)]. / Calculs pyéliques d'acide glafénique chez deux patientes traitées de façon prolongée par des analgésiques.

Two women aged 62 and 69 years who had been taking glafenine at normal dosage over a period of 4 years developed a renal calculus. In the first case, 6 small slightly radioopaque stones were extracted by pyelotomy, presenting a crystalline surface and yellow, soft, and amorphous section. They consisted of 50% calcium oxalate, 33% glafenic acid, and 10% proteins. In the second case, pyelography showed a sizable round and radiotransparent defect in the renal pelvis. At pyelotomy, a large, soft, and greenish stone was extracted, presenting a yellow and amorphous section, without calcium, but consisting of 75% glafenic acid, and 25% proteins. Through IR spectrography, glafenine metabolites found in the stones represented 33% in our first case and 75% in our second case. Through other methods, such as UV spectrophotometry and chromatography, 26% and 61% are respectively found. The metabolites are glafenic acid and hydroglafenic acid, in an identical proportion of 9 to 1 in both cases.

Analysis of urinary calculi in adults. Attempt of correlations between morphology and composition.

The analysis of 322 urinary calculi in adults by microdissection, infrared spectromorphometry and microchemistry has shown that stones could be classified in several groups according to their morphology and composition: 8 morphological types have been defined (2 for the oxalic, 2 for the uric, 2 for the phosphatic and 2 for the cystinic stones). Correlations between morphology and composition have been established dividing the calculi into 10 categories, 4 for the pure forms and 6 for the mixed forms; the total includes approximately 94% of the calculi analyzed. An 11th category gathering various lithiases (rare or with multiple components) represents 6% of the cases. Moreover, the study of the localization of the component in stones emphasizes the high frequency of Ca phosphates in the nucleus of oxalic lithiases: 80% in mixed forms, in which the oxalate is the main constituent.

[Analysis of gallstones by infrared spectrophotometry. Advantages and limits of the method (author's transl)]. / Analyse des calculs par spectrophotométrie infrarouge. Avantages et limites de la méthode.

Numerous clinicians criticise the insufficiency and imprecision, and the incoherency of the analyses of biological calculations by the usual clinical methods and thus frequently avoid prescribing such an examination. The authors propose the application of a physical method, infrared spectrophotometry for the qualitative and semi-quantitative determination of the composition of stones of all origins. They recall the often heterogeneous structure of the stones and emphasise the importance which they attribute of differential analysis by separate zones during careful dissection, the results of which may orient the therapeutic attitude of the clinician. The differentiation of a few crystalline structures and the study of complex mixtures are dealt with in the form of characteristic infrared spectra. The advantages and limits of the method compared with other technics of analysis are discussed.