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 review describes the syntheses and inhibition properties of pyrrolidine, piperidine, azepane, pyrrolizidine and indolizidine iminosugars, as well as iminosugar nucleotides and iminodi- and -oligosaccharides.
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
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.
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•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.
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
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.
: Facial telangiectasias is a prevalent cosmetic disorder that can be associated with several conditions such as rosacea. IPL (intensity pulsed light) therapy is commonly used for the treatment of ...vascular lesions. This study tested the efficacy of an IPL system emitting selected vascular chromophore-specific wavelengths in the range of 500-1200 nm for the treatment of vascular lesions.
: A total of 39 patients affected by different vascular lesions on their face were enrolled. The procedure consisted of three treatment sessions, spaced 1 month apart, using the IPL system with a 500-677 and 854-1200 nm filter. Follow-up was performed at 21-90 days (3 weeks-3 months) after the last IPL session. Three-dimensional and dermoscopic clinical photographs were captured and evaluated using a five-point scale. Adverse events were checked.
: In total, 21 patients achieved excellent improvement, 13 patients achieved good improvement, 3 patients achieved moderate improvement, 2 patients achieved mild improvement, and 0 patients achieved no improvement, with an overall good response to treatment. The photographic evaluation showed good results as soon as 3 days after the last IPL session. Relevant side effects were absent.
: The study device may represent a successful treatment to improve vascular lesions that are resistant to laser therapy.
Background and Objectives: For many years, fully ablative laser treatments, particularly those performed with a carbon dioxide (CO2) laser, were regarded as the gold standard for resurfacing. This ...study’s goal is to assess the depth that can be reached by a new CO2 scanner system, through a skin model with greater dermal thickness, to use in the treatment of deep scarring. Materials and Methods: Male human skin tissue was laser-treated using a CO2 fractional laser and a new scanning system, and all samples were fixed in 10% neutral buffered formalin, dehydrated using a series of crescent alcohol, embedded in paraffin, sectioned in series (4–5 µm thick), stained with haematoxylin and eosin (H&E), and then analysed under an optical microscope. Results: From the epidermis through the underlying papillary and reticular dermis to various depths of the dermis, microablation columns of damage and coagulated microcolumns of collagen were observed. The reticular dermis was fully penetrated up to 6 mm at higher energy levels (210 mJ/DOT), resulting in deeper tissue injury. Although the laser might penetrate further, the skin stops there, leaving just the fat and muscular tissue. Conclusions: The deep layers of the dermis can be penetrated by the CO2 laser system throughout the entire dermal thickness when using the new scanning system, suggesting that this laser’s potential impact, at the selected settings, covers all skin targets required to perform superficial or deep treatments on any dermatological issue. Finally, patients who have problems, such as morbid scar-deep complications, which affect their quality of life, are more likely to profit from this innovative technique.
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