143 research outputs found
Natural products as novel scaffolds for the design of glycogen synthase kinase 3Ī² inhibitors
Introduction: The different and relevant roles of GSK-3 are of critical importance since they deal with development, metabolic homeostasis, cell polarity and fate, neuronal growth and differentiation as well as modulation of apoptotic potential. Given their involvement with different diseases, many investigations have been undertaken with the aim of discovering new and promising inhibitors for this target. In this context, atural products represent an invaluable source of active molecules. Areas covered: In order to overcome issues such as poor pharmacokinetic properties or efficacy, frequently associated with natural compounds, different GSK-3Ī² inhibitors belonging to alkaloid or flavonoid classes have been subjected to structural modifications in order to obtain more potent and safer compounds. Herein, the authors report the results obtained from studies where natural compounds have been used as hits with the aim of providing new kinase inhibitors endowed with a better inhibitory profile. Expert opinion: Structurally modification of natural scaffolds is a proven approach taking advantage of their pharmacological characteristics. Indeed, whatever the strategy adopted is and, despite the limitations associated with the structural complexity of natural products, the authors recommend the use of natural scaffolds as a promising strategy for the discovery of novel and potent GSK-3Ī² inhibitors
Prevalence of positivity for diabetes-associated autoantibodies in individuals with type 2 diabetes and their further characterisation: cross-sectional study from Slovakia
Background
Individuals initially diagnosed with type 2 diabetes (T2D) might exhibit positivity for diabetes-associated autoantibodies (DAAā+). We investigated the prevalence of DAA positivity in a group of individuals with T2D who were referred to a tertiary diabetes centre within a pre-specified period of time. We aimed to identify characteristics linked with DAA positivity by comparing DAAā+āindividuals with their DAA-negative counterparts.
Methods
This was a cross-sectional study into which all T2D patients referred to the National Institute of Endocrinology and Diabetology, ĽubochÅa, Slovakia, between 1 January and 30 June 2016 were included. Data onā>ā70 participantsā characteristics, including antibodies against glutamic acid decarboxylase (anti-GAD65), insulinoma-associated antigen IA-2 (IA-2A) and insulin (IAA), were collected.
Results
Six hundred and ninety-two individuals (387, 55.6% female) with a median (range) age of 62 (24ā83) years, HbA1c of 8.9 (5.0ā15.7)% [74 (31ā148 mmol/mol)] and diabetes duration of 13.0 (0ā42) years were analysed. One hundred and forty-five (145/692, 21.0%) tested positive for at least one DAA; 136/692 (19.7%) were positive for anti-GAD65, 21/692 (3.0%) were positive for IA-2A and 9/692 (1.3%) were positive for IAA. Only 84.9% of the DAAā+āindividuals agedā>ā30 years at the time of diabetes diagnosis met the current diagnostic criteria for latent autoimmune diabetes of adults (LADA). DAAā+ādiffered from DAA ā individuals in multiple characteristics, including the incidence of hypoglycaemia.
Conclusion
Several pathological processes linked with distinct types of diabetes can develop in parallel, including insulin resistance and autoimmune insulitis. In this single-centre cross-sectional study from Slovakia, we report a higher than previously published prevalence of DAA positivity in a group of individuals with a formal diagnosis of T2D
Biomaterial strategies for alleviation of myocardial infarction
World Health Organization estimated that heart failure initiated by coronary artery disease and myocardial infarction (MI) leads to 29 per cent of deaths worldwide. Heart failure is one of the leading causes of death in industrialized countries and is expected to become a global epidemic within the twenty-first century. MI, the main cause of heart failure, leads to a loss of cardiac tissue impairment of left ventricular function. The damaged left ventricle undergoes progressive āremodellingā and chamber dilation, with myocyte slippage and fibroblast proliferation. Repair of diseased myocardium with in vitro-engineered cardiac muscle patch/injectable biopolymers with cells may become a viable option for heart failure patients. These events reflect an apparent lack of effective intrinsic mechanism for myocardial repair and regeneration. Motivated by the desire to develop minimally invasive procedures, the last 10 years observed growing efforts to develop injectable biomaterials with and without cells to treat cardiac failure. Biomaterials evaluated include alginate, fibrin, collagen, chitosan, self-assembling peptides, biopolymers and a range of synthetic hydrogels. The ultimate goal in therapeutic cardiac tissue engineering is to generate biocompatible, non-immunogenic heart muscle with morphological and functional properties similar to natural myocardium to repair MI. This review summarizes the properties of biomaterial substrates having sufficient mechanical stability, which stimulates the native collagen fibril structure for differentiating pluripotent stem cells and mesenchymal stem cells into cardiomyocytes for cardiac tissue engineering
Polarization investigation of a tunable high-speed short-wavelength bulk-micromachined MEMS-VCSEL
We report the investigation of the state of polarization (SOP) of a tunable vertical-cavity surface-emitting laser (VCSEL) operating near 850 nm with a mode-hop free single-mode tuning range of about 12 nm and an amplitude modulation bandwidth of about 5 GHz. In addition, the effect of a sub-wavelength grating on the device and its influence on the polarization stability and polarization switching has been investigated. The VCSEL with an integrated sub-wavelength grating shows a stable SOP with a polarization mode suppression ratio (PMSR) more than 35 dB during the tuning
Tuneable VCSEL aiming for the application in interconnects and short haul systems
Widely tunable vertical cavity surface emitting lasers (VCSEL) are of high interest for optical communications, gas spectroscopy and fiber-Bragg-grating measurements. In this paper we present tunable VCSEL operating at wavelength around 850 nm and 1550 nm with tuning ranges up to 20 nm and 76 nm respectively. The first versions of VCSEL operating at 1550 nm with 76 nm tuning range and an output power of 1.3mW were not designed for high speed modulation, but for applications where only stable continious tuning is essential (e.g. gas sensing). The next step was the design of non tunable VCSEL showing high speed modulation frequencies of 10 GHz with side mode supression ratios beyond 50 dB. The latest version of these devices show record output powers of 6.7mW at 20 Ā°C and 3mW at 80 Ā°C. The emphasis of our present and future work lies on the combination of both technologies. The tunable VCSEL operating in the 850 nm-region reaches a modulation bandwidth of 5.5GHz with an output power of 0.8mW
Clinical outcomes and electrolyte balance factors in complex cardiac operations in adults; del nido versus custodiol cardioplegia solutions: A randomized controlled clinical trial
Background: Cardioplegia is used for protection of myocardium during cardiac operations. Del Nido (DN) and Custodiol cardioplegia solutions are used for prolonged protection of the myocardium during cardiopulmonary bypass (CPB). Custodiol cardioplegia (CC) solution is gaining popularity for myocardial protection during cardiopulmonary bypass. Objectives: This study aimed to compare the effects of Custodiol with another cardioplegia solution, Del Nido, on myocardial protection during cardiopulmonary bypass. Methods: In a randomized controlled clinical trial, forty patients were randomly allocated to DN and Custodiol (CC) groups. Patients in both groups received a normal anesthesia protocol. For cardioplegia, in the DN group, the DN solution was administered every 90 minutes by the antegrade route. In the Custodiol group, the Custodiol solution was administered in the same way at the beginning of the cardioplegia. Demographic information, blood chemistry parameters and other related perioperative and postoperative clinical indices were recorded. Results: Frequency of female patients was 14/21 (66.66) in the DN and 12/19 (63.15) in the CC group (P = 0.816), age was 57.14 ĆĀ± 12.48 years in the DN and 59.47 ĆĀ± 11.96 years in the CC group (P = 0.551), weight was 70.95 ĆĀ± 9.56 kilograms in the DN and 69.63 ĆĀ± 7.64 kilograms in the CC group (P = 0.635), CPB time was103.19 ĆĀ± 23.43 minutes in the DN versus 97.36 ĆĀ± 16.7 minutes in the CC group (P = 0.376), and cross-clamp time was 73.76 ĆĀ± 19.66 minutes in the DN and 83.95 ĆĀ± 16.14 minutes in the CC group (P = 0.083). Blood chemistry and blood gas analysis revealed a similar trend between the two groups in these parameters (P > 0.05) except for higher sodium levels after cardioplegia (P = 0.016) and end of CPB (P = 0.002), potassium levels after cardioplegia (P = 0.029), and bicarbonate anions at the end of bypass (P = 0.03) in the custodiol group. Conclusions: In conclusion, CC and DN offer effective myocardial protection during cardiopulmonary bypass. It is recommended to restrict the use of CC in patients susceptible to electrolyte disturbances. ĆĀ© 2018, Author(s)
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