In vivo visualization of hyaluronic acid injection by high spatial resolution T2 parametric magnetic resonance images

BACKGROUND/PURPOSE: In recent years, increasing use of injectable resorbable fillings has been reported for facial wrinkle treatment. However, the physiological processes involved such as the localization and subsequent diffusion of the injected product in skin tissues are poorly documented. This may be noninvasively achieved using quantitative magnetic resonance imaging (MRI), which is duly presented in this pilot study. METHODS: Hyaluronic acid (HA) was injected intradermally in the forearm of a young male volunteer. High-resolution MRI scans using a surface antenna were performed just after injection, and after 2, 4 and 9 months. Morphological images were compared with transverse relaxation time (T(2)) images computed from a pixel-by-pixel analysis. RESULTS: On high-resolution morphological MR images the HA injection is barely visible, but with quantitative MRI the zone of injection is clearly seen. This is due to HA having a distinctly different transverse relaxation time, T(2) approximately 600 ms, compared with dermal and hypodermal tissues, 35 and 80 ms, respectively. CONCLUSION: These preliminary results demonstrate the ability of the T(2) images for in vivo visualization of the filler agent and also for characterization of tissue modifications. In addition, the diffusion and progressive degradation of the filler agent can be monitored by T(2) measurements over time.     

Dilution of the 75-g oral glucose tolerance test increases postprandial glycemia: implications for diagnostic criteria

BACKGROUND: Dilution has been noticed to increase the glycemic response to various sugars, including glucose. This effect may contribute to the poor reproducibility of the oral glucose tolerance test (OGTT). To test this hypothesis we assessed the effect of diluting a 75-g OGTT on 2-hour postprandial blood glucose based diagnostic outcomes, incremental glycemia and area under the glucose curve. METHODS: On 3 different occasions, 10 subjects (mean age 40 [and standard error of the mean (SEM) 3.2] years; mean body mass index 27.2 [and SEM 1.2] kg/m2) without previously diagnosed dysglycemia were given a 300-mL, 600-mL or 900-mL 75-g OGTT in random order. The protocol followed the American Diabetes Association's guidelines. Finger-prick capillary blood samples were obtained at fasting and then 15, 30, 45, 60, 90 and 120 minutes after the start of the test. RESULTS: At 30, 45 and 60 minutes, incremental glycemic concentrations were significantly higher with the 900-mL meal (means [and SEMs]: 4.9 [0.4] mmol/L, 5.1 [0.6] mmol/L and 4.6 [0.8] mmol/L, respectively) than with the 600-mL (means [and SEMs]: 4.0 [0.3] mmol/L, 4.2 [0.6] mmol/L and 3.6 [0.7] mmol/L, respectively) and the 300-mL meals (means and [SEMs]: 3.8 [0.5] mmol/L, 4.0 [0.5] mmol/L and 3.2 [0.6] mmol/L, respectively) (p < 0.05). The same was true for peak incremental blood glucose, regardless of time (p < 0.05). The area under the curve for the 900-mL meal (mean [and SEM] 404 [57] min.mmol/L) was significantly higher than for the 600-mL (mean [and SEM] 331 [51] min.mmol/L) and 300-mL meals (mean [and SEM] 280 [48] min.mmol/L) (p < 0.05). No other significant differences were observed. INTERPRETATION: Dilution of the 75-g OGTT will likely not affect current screening practices that use 2-h postprandial glucose levels as the basis for diagnosis. It may, however, bias the interpretation of older criteria that rely on intermediate time points because these midpoints appear to be sensitive to alterations in the total volume of the meal ingested.     

Antimicrobial and antioxidant activities of amines derived from vanillin as potential preservatives: Impact of the substituent chain length and polarity

The stability of cosmetic products in terms of microbial safety or oxidation is a major challenge when faced with consumer's expectations for less controversial compounds used in their formulation. In this context, we present new vanillin derivatives synthesized in a two steps one-pot process. The synthesis was based on the reductive amination reaction between vanillin and a selected panel of amines with different structural units such as alkyl chains, halogens and aromatics. The different molecules were designed to bring a better understanding of the structure-preservative activity relationships in vanillin-based molecules. Most compounds exhibited strong antioxidant activities in DPPH, ABTS and FRAP assays. The antibacterial and antifungal properties were evaluated on several strains known to be responsible for the contamination of cosmetic products. Some of these vanillin compounds derived with a p-ethylaniline (2c), with a p-butylaniline (2d), with a p-hexylaniline (2e) and a p-iodoaniline (3b) showed a promising level of antibacterial activity against Bacillus subtilis and Micrococcus luteus. In particular, 2d was very active against most of the tested bacterial and fungal strains and showed very promising antibacterial and antifungal capabilities while displaying among the highest antioxidant capacity and no cytotoxic effect on human fibroblasts. We investigated if a correlation between the hydrophobicity and biological activities of the compounds could be established and we highlighted that the presence of aliphatic chains grafted on the aromatic amine ring is associated to the highest antimicrobial activities. The structure-activity relationships highlighted in this study allow paving the way for future applications of these compounds in cosmetics as alternative to controversial molecules.     

Design and characterization of a chitosan-enriched fibrin hydrogel for human dental pulp regeneration

Objective

Regenerating a functional dental pulp in the pulpectomized root canal has been recently proposed as a novel therapeutic strategy in dentistry. To reach this goal, designing an appropriate scaffold able to prevent the growth of residual endodontic bacteria, while supporting dental pulp tissue neoformation, is needed. Our aim was to create an innovative cellularized fibrin hydrogel supplemented with chitosan to confer this hydrogel antibacterial property.

Suppression of rat and human growth hormone and prolactin secretion by a novel somatostatin/dopaminergic chimeric ligand

As cotreatment of somatostatin (SRIF) and dopamine (DA) agonists reduces GH in acromegaly more effectively than either agonist alone, SRIF and DA receptors (SSTR and DAR) may interact with enhanced functional activity. The selective SSTR2 agonist, BIM-23023 (50% effective dose, 0.42), and the DAR2 agonist, BIM-53097 (50% effective dose, 22.1), dose- dependently inhibited GH secretion in cultured primary rat and human fetal as well as in human pituitary tumor cells derived from GH-secreting adenomas. The combination of individual SSTR2 and DAR2 agonists was additive for suppressing GH secretion in both rat and human pituitary cells. BIM-23A387 is a chimeric compound that contains structural elements of both SRIF and DA in a single molecule and retains potent, selective binding to DAR2 and SSTR2. BIM-23A387 (50% effective dose, 0.16 for SSTR2 and 24.5 for DAR2), displayed similar efficacy in suppressing GH secretion from rat pituitary cells as the combination of the two individual agonists. In contrast, the chimeric molecule was more potent than individual selective analogs in suppressing GH secretion by human fetal pituitary and GH-secreting adenoma cells (P < 0.05). Although the DAR2 antagonist, sulpiride, reversed BIM-23A387-induced GH suppression, blockade of SSTR2 by the selective SSTR antagonist, BIM-23454, did not block BIM-23A387-suppressed GH secretion. These results indicate that mechanisms by which the chimeric molecule suppresses pituitary GH secretion may not be mediated by individual SSTR2 or DAR2 signaling, respectively. Functional interaction of the two receptors may explain the clinical observation that more effective GH suppression is achieved when DAR2 and SSTR2 agonists are administered in combination. The SRIF/DA chimeric molecule, BIM-23A387, represents a novel tool for effective drug treatment of acromegaly and for prolactinomas otherwise resistant to dopaminergic therapy.     

Comparison of Fracture Risk Prediction among Individuals with Reduced and Normal Kidney Function

Background and objectives

The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function.

Design, setting, participants, & measurements

The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged ≥40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR<60 ml/min per 1.73 m² [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus ≥60 ml/min per 1.73 m²) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus).

Results

There were 320 individuals with an eGFR<60 ml/min per 1.73 m² and 1787 with an eGFR≥60 ml/min per 1.73 m². The mean age was 67±10 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR<60 ml/min per 1.73 m², which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR<60 ml/min per 1.73 m² versus ≥60 ml/min per 1.73 m² (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38).

Conclusions

This study showed that FRAX was able to predict major osteoporotic fractures in individuals with reduced kidney function; further study is needed before FRAX should be routinely used in individuals with reduced kidney function.