Topically applied methyl nicotinate evokes a temporary inflammation on human skin

Some challengers such as methylnicotinate (MN) have been used in human models to study the anti-inflammatory effect of topical formulations. However, MN skin responses are still poorly understood and widely varied. In the present study we aim to contribute to better characterise those responses. Eight healthy participants were selected. All procedures were approved by the institutional Ethics Committee. Two aqueous MN dilutions (0.5% and 1.0%) were left in contact for 1 minute in the anterior forearm skin. Following exposure, skin reactions were clinically and biometrically assessed at 30, 60 and 120 minutes and compared with baseline. Measurements involved the ICDRG clinical score scale and select analytical technologies - laser Doppler flowmetry, Polarised Spectroscopy, Transepidermal Water Loss Meter, and High Resolution Sonography. Results have shown that MN application evoked a maximal response at 30 minutes with an increase in the ICDRG score between 1-2. Significant changes in TEWL and microcirculation were observed, as was an increased dermal hypoecogenicity (edema), detected by HRS. These effects are compatible with a localised short-duration inflammation and reinforce the interest of MN to be used as a safe and controllable challenger in human models.

Nitric oxide release and related light-induced cytotoxicity of ruthenium nitrosyls with coordinated nicotinate derivatives

The synthetic approaches for the preparation of trans(NO,OH)-cis(NO2,NO2)-[RuNO(L)2(NO2)2OH], where L = ethyl nicotinate (I) and methyl nicotinate (II) are reported. The structures of the complexes are characterized by X-Ray diffraction...

Studies on the effect of Dielectric constants of Aquo-DMF Solvent- System of the Solvolysis Products of Nicotinates

From the eenhancement observed in G* values with simultaneous decrease in the values of H and S* of the reaction, it is concluded that the organic co-solvent dimethyl formamide (DMF) acts as entropy controller and enthalpy stimulator solvent for alkali catalysed solvolysis of Methyl nicotinate. Form the evaluated values of water molecules associated with the activated complex of the reaction which are found to increase with increase in the temperature of the reaction, it is inferred that the bimolecular mechanistic path is changed to unimolecular in presence of the organic component (DMF) of the reaction media. The numerical value of Iso-Kinetic temperature of the reaction which comes to be nearly 287.5 (below 300) indicates that there is weak but considerable solvent-solute interaction in the aquo-DMF solvent system.

The effects of sustained fitness improvement on the gut microbiome: A longitudinal, repeated measures case-study approach

ObjectiveThe composition and metabolic function of the gut microbiome in the elite athlete differs from that of non-athletes. However, short-term fitness improvement in the sedentary adult does not replicate the microbiome characteristics seen in the athlete. Whether sustained fitness improvement over a prolonged period can lead to pronounced and beneficial alteration in the gut microbiome is unknown. The objective was to explore this possibility.MethodsThis study used a repeated-measures, case-study approach to explore changes in the gut microbiome of two unfit volunteers undertaking progressive exercise training over a 6-month period. Training was to culminate in the completion of a marathon or Olympic-distance triathlon. The volunteers were sampled every two weeks for six months and microbiome, metabolome, diet, body composition, and cardiorespiratory fitness data were recorded.ResultsBoth participants completed their respective goals with improved body composition and fitness parameters over the training period. Increases in α-diversity of the gut microbiota occurred with sustained training and fluctuations occurred in response to training events (e.g., injury, illness and training peaks). Participants’ fat mass and BMI reduced during the study and was significantly associated with increased urinary measurements of N-methyl nicotinate (P value < 0.001) and hippurate (P value < 0.05), and decreased phenylacetylglutamine (P value < 0.05).ConclusionThese results suggest that sustained fitness improvements result in alterations to gut microbiota and physiologically-relevant metabolites. This study provides longitudinal analysis of the response of the gut microbiome to real-world events during progressive fitness training, including intercurrent illness and injury.