Iminosugars are naturally occurring carbohydrate analogues known since 1967. These natural compounds and hundreds of their synthetic derivatives prepared over five decades have been mainly exploited ...to inhibit the glycosidases, the enzymes catalysing the glycosidic bond cleavage, in order to find new drugs for the treatment of type 2 diabetes and other diseases. However, iminosugars are also inhibitors of glycosyltransferases, the enzymes responsible for the synthesis of oligosaccharides and glycoconjugates. The selective inhibition of specific glycosyltransferases involved in cancer or bacterial infections could lead to innovative therapeutic agents. The synthesis and biological properties of all the iminosugars assayed to date as glycosyltransferase inhibitors are reviewed in the present article.
The nicotinamide phosphoribosyltransferase (NAMPT) is considered a very promising therapeutic target because it is overexpressed in pancreatic cancer. Although many inhibitors have been prepared and ...tested, clinical trials have shown that NAMPT inhibition may result in severe haematological toxicity. Therefore, the development of conceptually new inhibitors is an important and challenging task. We synthesized ten β-d-iminoribofuranosides bearing various heterocycle-based chains carbon-linked to the anomeric position starting from non-carbohydrate derivatives. They were then submitted to NAMPT inhibition assays, as well as to pancreatic tumor cells viability and intracellular NAD
depletion evaluation. The biological activity of the compounds was compared to that of the corresponding analogues lacking the carbohydrate unit to assess, for the first time, the contribution of the iminosugar moiety to the properties of these potential antitumor agents.
A cosmetic product is a substance or mixture intended to be applied on the outer surfaces of the human body or on teeth, on the mucous membranes of the mouth, with the purpose of cleaning, smelling, ...modifying, protecting, maintaining them in good condition. In order to prevent microbial proliferation in cosmetics, substances with antimicrobial activity are used, to inhibit the development of microorganisms. Among the most commonly used cosmetic contaminants, there are spore-forming bacteria, molds, yeasts and bacteria. In the following study through the challenge test, four cosmetics products were analyzed, including an ultra-moisturizing anti-aging facial cream, a biphasic tonic, an aqueous tanning gel and a hair wax. The main goal was to evaluate the conservative properties of products in catching any microbial contamination, that may occur as a result of use. The Challenge Test has proved to be useful and appropriate to predict the behavior of cosmetics in the event of bacterial contamination. Starting from a high microbial charge for all products, microbial growth after 7 days is stopped, thus demonstrating the good conservative properties of the analyzed products.
Antibiotic resistance represents a major threat worldwide. Gram-positive and Gram-negative opportunistic pathogens are becoming resistant to all known drugs mainly because of the overuse and misuse ...of these medications and the lack of new antibiotic development by the pharmaceutical industry. There is an urgent need to discover structurally innovative antibacterial agents for which no pre-existing resistance is known. This work describes the identification, synthesis and biological evaluation of a novel series of 1,5-diphenylpyrrole compounds active against a panel of ESKAPE bacteria. The new compounds show high activity against both wild type and drug-resistant Gram + ve and Gram-ve pathogens at concentrations similar or lower than levofloxacin. Microbiology studies revealed that the plausible target of the pyrrole derivatives is the bacterial DNA gyrase, with the pyrrole derivatives displaying similar inhibitory activity to levofloxacin against the wild type enzyme and retaining activity against the fluoroquinolone-resistant enzyme.
Display omitted
•Novel 1,5-diphenyl-pyrrole derivatives were synthesized.•The new compounds are endowed with high antibacterial activity.•The phenyl substituents at N1 and C5 of the pyrroles is essential for activity.•Protonatable guanidine/amino moieties improve the activity against Gram-ve bacteria.•Bacterial DNA gyrase was identified as a plausible target.
Despite the therapeutic relevance of δ-containing γ-aminobutyric acid type A receptors (GABAARs) and the need for δ-selective compounds, the structural determinants for the mode and molecular site of ...action of δ-selective positive allosteric modulator imidazo1,2-apyridine DS2 remain elusive. To guide the quest for insight, we synthesized a series of DS2 analogues guided by a structural receptor model. Using a fluorescence-based fluorometric imaging plate reader membrane potential assay, we found that the δ-selectivity and the pharmacological profile are severely affected by substituents in the 5-position of the imidazopyridine core scaffold. Interestingly, the 5-methyl, 5-bromo, and 5-chloro DS2 analogues, 30, 35, and 36, were shown to be superior to DS2 at α4β1δ as mid-high nanomolar potency δ-selective allosteric modulators, displaying 6–16 times higher potency than DS2. Of these, 30 also displayed at least 60-fold selectivity for α4β1δ over α4β1γ2 receptor subtypes representing a potential tool for the selective characterization of δ-containing GABAARs in general.
Objective. To evaluate in SSc, the frequency of digital lesions and the morphology, characteristics, natural course and time to healing of 1614 digital ulcers (DUs). Methods. One hundred SSc patients ...were followed up for 4 years. In the first step, the digital lesions were observed and classified at the time of presentation digital pitting scar (DPS); DU; calcinosis; gangrene. In the second step, DUs were divided into subsets according to their origin and main features. In the third step, the time to healing was recorded for each DU and the influence of DU main characteristics on time to healing was also evaluated. Results. In the first step, 1614 digital lesions were observed: DPS, 712 (44.1%) lesions; DU, 785 (48.6%); calcinosis, 110 (6.8%); and gangrene, 7 (0.8%). In the second step, DUs were subsetted as follows: DU developed on DPS (8.8%), pure DU; DU developed on calcinosis (60%); DU derived from gangrene. In the third step, the mean time to healing was 25.6 (15.6) days in DPS, 76.2 (64) days in pure DU, 93.6 (59.2) days in calcinosis ulcers and 281.1 (263.3) in gangrene. Conclusions. In SSc, digital lesions are represented by DPS, DU, calcinosis and gangrene, and provide an evidence-based DU subsetting according to their origin and main characteristics. Subsetting may be helpful for a precise DU evaluation and staging, and in randomized controlled trials for a precise identification of those DUs that are to be included in therapeutic studies.
The estimation of the body's center of mass (CoM) trajectory is typically obtained using force platforms, or optoelectronic systems (OS), bounding the assessment inside a laboratory setting. The use ...of magneto-inertial measurement units (MIMUs) allows for more ecological evaluations, and previous studies proposed methods based on either a single sensor or a sensors' network. In this study, we compared the accuracy of two methods based on MIMUs. Body CoM was estimated during six postural tasks performed by 15 healthy subjects, using data collected by a single sensor on the pelvis (Strapdown Integration Method, SDI), and seven sensors on the pelvis and lower limbs (Biomechanical Model, BM). The accuracy of the two methods was compared in terms of RMSE and estimation of posturographic parameters, using an OS as reference. The RMSE of the SDI was lower in tasks with little or no oscillations, while the BM outperformed in tasks with greater CoM displacement. Moreover, higher correlation coefficients were obtained between the posturographic parameters obtained with the BM and the OS. Our findings showed that the estimation of CoM displacement based on MIMU was reasonably accurate, and the use of the inertial sensors network methods should be preferred to estimate the kinematic parameters.
Background
The market requires ever‐faster techniques, in particular for pre‐rejuvenation condition.
Aim
The purpose of this study was to assess if a fractional CO2 scanner modality (called moveo) ...results in a faster full‐face rejuvenation treatment in comparison to the standard mode, currently existing in the scanner system.
Materials and Methods
A total of 12 female patients affected by fine lines participated in a split‐face clinical investigation and underwent to two sessions with a fractional CO2 laser system equipped with an existing and a faster dedicated scanner units. Pain was assessed using VAS. Three‐dimensional clinical photographs were captured before, immediately after, 3 days, 14 days after the first treatment and immediately after the second treatment and 1 months after the last one. The uniformity and aesthetic coverage of treatments were assessed using dermatoscopy. Global aesthetic improvement scale (GAIS) was used. The time taken to treat the two sides of the face and all possible side effects were monitored.
Results
Following only two treatment session with both scanner modes, the patient's skin texture improved significantly, with fine lines reduction. There is no statistically significant difference in perceived pain between patients. The GAIS score showed satisfactory results following both modalities. The time parameters indicated that with the faster scanner mode the full‐face treatment time was reduced by 30% compared to the standard one. No adverse effects were observed.
Conclusions
The moveo modality provide faster treatment and a better final dermal aesthetic outcome than the standard procedure while maintaining the same safety profile.
Background
Patients with keloids are often younger than 30 years old and have darker skin.
Aim
To evaluate the efficacy and safety of CO2 laser therapy in the management of earlobe and helix keloids ...in dark subjects.
Methods
A total of 21 dark patients (five men and 16 women) presented with the earlobe and ear helix keloids, with a mean age of 30.5 (±6.7) years and with phototype between III–VI, were enrolled. In order to improve their earlobe and helix keloids, all patients underwent a single session of CO2 laser therapy immediately followed by a pulsed Dye laser procedure. A single well‐experienced doctor performed all treatment sessions and the response to treatment. Patients were followed‐up for 6 months after termination of therapy. Clinical images were examined and collected: all patients were examined clinically and with Dermoscopy.
Results
The majority of the patients treated show complete remission of keloid lesions. Clinical photographs show a visible aesthetic improvement of several types of keloids in dark subjects.
Conclusions
Our data demonstrate that this combined laser therapeutic protocol appears to be effective and well tolerated for the management of earlobe and helix keloids in dark subjects, with no high recurrence rate and avoiding the adverse effects and lengthy recovery time.
PDF
