An increasing number of peptides with specific binding affinity to various protein and even non-protein targets are being discovered from phage display libraries. The power of this method lies in its ...ability to efficiently and rapidly identify ligands with a desired target property from a large population of phage clones displaying diverse surface peptides. However, the search for the needle in the haystack does not always end successfully. False positive results may appear. Thus instead of specific binders phage with no actual affinity toward the target are recovered due to their propagation advantages or binding to other components of the screening system, such as the solid phase, capturing reagents, contaminants in the target sample or blocking agents, rather than the target. Biopanning experiments on different targets performed in our laboratory revealed some previously identified and many new target-unrelated peptide sequences, which have already been frequently described and published, but not yet recognized as target-unrelated. Distinguishing true binders from false positives is an important step toward phage display selections of greater integrity. This article thoroughly reviews and discusses already identified and new target-unrelated peptides and suggests strategies to avoid their isolation.
Diabetes mellitus is a major healthcare problem. It is not only characterized by hyperglycemia and chronic complications, but in longer lasting diabetes and a longer living population, it is also ...associated with accelerated arterial ageing, which importantly contributes to cardiovascular complications. The accelerated arterial ageing in patients with diabetes should be considered separately from arterial ageing in patients without diabetes. Basic and clinical research have allowed better insight into the mechanisms of arterial ageing. In a simplified mechanistic way, it could be considered that the three tightly connected cornerstone characteristics of arterial ageing in patients with diabetes are: phenotypic presentation as endothelial dysfunction and arterial stiffness, and the underlying basic ageing-facilitating mechanism represented as the impaired expression of genetic longevity pathways. Currently, specific drugs for preventing/treating arterial ageing are not available. Therefore, we aimed to review the capacity of available drugs, particularly antidiabetic drugs, to interfere with the arterial ageing process. In the near future, these characteristics could help to guide therapy in patients with diabetes. Overall, it appears that arterial ageing could become a new target in diabetes. The expanding knowledge regarding the capability of antidiabetic drugs and other available drugs to inhibit/delay arterial aging is therefore essential.
The world population is aging and the number of old people is continuously increasing. Arterial structure and function change with age, progressively leading to arterial stiffening. Arterial ...stiffness is best characterized by measurement of pulse wave velocity (PWV), which is its surrogate marker. It has been shown that PWV could improve cardiovascular event prediction in models that included standard risk factors. Consequently, it might therefore enable better identification of populations at high-risk of cardiovascular morbidity and mortality. The present review is focused on a survey of different pharmacological therapeutic options for decreasing arterial stiffness. The influence of several groups of drugs is described: antihypertensive drugs (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, beta-blockers, diuretics, and nitrates), statins, peroral antidiabetics, advanced glycation end-products (AGE) cross-link breakers, anti-inflammatory drugs, endothelin-A receptor antagonists, and vasopeptidase inhibitors. All of these have shown some effect in decreasing arterial stiffness. Nevertheless, further studies are needed which should address the influence of arterial stiffness diminishment on major adverse cardiovascular and cerebrovascular events (MACCE).
Allergen-specific immunotherapy represents the only available curative approach to allergic diseases. The treatment has proven effective, but it requires repetitive administrations of allergen ...extracts over 3-5 years and is often associated with adverse events. This implies the need for novel therapeutic strategies with reduced side effects and decreased treatment time, which would improve patients' compliance. Development of vaccines that are molecularly well defined and have improved safety profile in comparison to whole allergen extracts represents a promising approach. Molecular allergy vaccines are based on major allergen proteins or allergen-derived peptides. Often, such vaccines are associated with lower immunogenicity and stability and therefore require an appropriate delivery vehicle. In this respect, viruses, bacteria, and their protein components have been intensively studied for their adjuvant capacity. This article provides an overview of the microbial delivery vehicles that have been tested for use in allergy immunotherapy. We review
and
data on the immunomodulatory capacity of different microbial vehicles for allergens and allergen-derived peptides and evaluate their potential in development of allergy vaccines. We also discuss relevant aspects and challenges concerning the use of microbes and their components in immunotherapy of allergic diseases.
Objective
To explore the effects of oral semaglutide on glycaemic parameters, body weight, and satisfaction in the first recipient patients with type 2 diabetes mellitus in Slovenia, in a real-world ...clinical practice setting.
Methods
The first consecutive adult patients with type 2 diabetes who were eligible for oral semaglutide treatment were included in this prospective, open-label interventional study. Patients received increasing doses of oral semaglutide and were evaluated at inclusion, at 1 month, then 3–5 months after starting treatment. Fasting blood glucose, glycosylated haemoglobin (HbA1c), body weight, patient satisfaction with oral semaglutide treatment (using the validated Treatment Satisfaction Questionnaire for Medication), and adverse effects, were analysed. Statistical analyses were performed using one-way analysis of variance, and, when significant interactions were found, Bonferroni post-hoc test. A P-value <0.05 was considered statistically significant.
Results
Twenty patients (11 male: 9 female; mean age, 59.9 ± 1.5 years; mean diabetes duration, 8.5 ± 1.4 years) were included. Oral semaglutide (7 and 14 mg) significantly decreased HbA1c (from 9.4 ± 0.3% to 8.2 ± 0.2% and 7.8 ± 0.2%, respectively) and fasting plasma glucose (from 11.2 ± 0.5 mmol/L to 9.2 ± 0.7 mmol/L and 8.9 ± 0.4 mmol/L, respectively). Oral semaglutide (14 mg) significantly decreased body weight (from 100.9 ± 2.7 kg to 92.7 ± 2.4 kg). Patients reported that treatment was easy to use and expressed high global satisfaction. Mild and transient, mostly gastrointestinal, adverse effects were reported in 10 patients.
Conclusions
Oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, was effective and safe, and associated with high patient satisfaction, in its first recipients in Slovenia. The results are important for daily clinical practice involving patients with type 2 diabetes, however, due to the small study population, lack of placebo control, and short exposure to oral semaglutide, the effectiveness of oral semaglutide in clinical practice requires further investigation.
Deteriorated arterial function and high incidence of cardiovascular events characterise diabetes mellitus. Metformin and recent antidiabetic drugs, SGLT2 inhibitors, reduce cardiovascular events. We ...explored the possible effects of empagliflozin's effect on top of metformin treatment on endothelial function and arterial stiffness parameters in type 1 diabetes mellitus (T1DM) patients.
Forty T1DM patients were randomised into three treatment groups: (1) empagliflozin (25 mg daily), (2) metformin (2000 mg daily) and (3) empagliflozin/metformin (25 mg daily and 2000 mg daily, respectively). The fourth group received placebo. Arterial function was assessed at inclusion and after 12 weeks treatment by: endothelial function brachial artery flow-mediated dilation (FMD), reactive hyperaemia index (RHI), arterial stiffness pulse wave velocity (PWV) and common carotid artery stiffness (β-stiffness). For statistical analysis one-way analysis of variance with Bonferroni post-test was used.
Empagliflozin on top of metformin treatment significantly improved endothelial function as did metformin after 12 weeks of treatment: FMD 2.6-fold (P < 0.001) vs. 1.8-fold (P < 0.05) and RHI 1.4-fold (P < 0.01) vs. 1.3-fold (P < 0.05). Empagliflozin on top of metformin treatment was superior to metformin in improving arterial stiffness parameters; it significantly improved PWV and β-stiffness compared to metformin by 15.8% (P < 0.01) and by 36.6% (P < 0.05), respectively. Metformin alone did not influence arterial stiffness.
Empagliflozin on top of metformin treatment significantly improved arterial stiffness compared to metformin in T1DM patients. Endothelial function was similarly improved in all treatment groups. Empagliflozin seems to possess a specific capacity to decrease arterial stiffness, which could support its cardioprotective effects observed in large clinical studies. Trial registration Clinical trial registration: NCT03639545.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims
Telemedicine improves glycemic and perinatal outcomes when used as an adjunct to standard care in gestational diabetes (GDM). Little is known about its effectiveness when used instead of ...standard care. We aimed to compare the outcomes of telemedicine care and the standard care in women with GDM.
Methods
In a single-center, parallel, randomized controlled trial, women were randomized to: (1) a telemedicine group, sending glucose readings via an application installed on a smartphone and monthly individual video calls replacing on-site visits or (2) standard care group with routine monthly on-site visits. The primary outcome was the effectiveness of glycemic control. The secondary outcomes were gestational weight gain (GWG) and perinatal data, including birth weight, gestational age, the incidence of the offspring large for gestational age, preterm birth, preeclampsia and cesarean section.
Results
A total of 106 women were randomized to the telemedicine (
n
= 54) and the standard care group (
n
= 52). The telemedicine group demonstrated less postprandial measurements above the glycemic target (10.4% 3.9–17.9 vs. 14.6% 6.5–27.1;
p
= 0.015), together with lower average postprandial glucose (5.6 ± 0.3 vs. 5.9 ± 0.4;
p
= 0.004). Percentage of cesarean section was lower in the telemedicine group (9 (17.3%) vs. 18 (35.3%);
p
= 0.038).
Conclusions
Telemedicine offers an effective alternative to delivering care to women with GDM.
Trial registration
NCT05521893, ClinicalTrials.gov Identifier URL:
https://www.clinicaltrials.gov/ct2/show/NCT05521893?term=NCT05521893&draw=2&rank=1
Zaviralci natrij-glukoznega koprenašalnega sistema-2 (SGLT-2) se vse pogosteje predpisujejo tako v diabetologiji kot tudi v drugih internističnih strokah. Primarno ugodno vplivajo na presnovne ...dejavnike, tj. parametre glikemije in na telesno maso. Poleg tega omogočajo zaščito tarčnih organov, srčno-žilnega sistema in ledvic, pri osebah s sladkorno boleznijo ali brez nje. Neželeni učinki ob zdravljenju z zaviralci SGLT-2 so redki, večinoma nenevarni in jih lahko preprečimo. Zelo redek, a življenje ogrožajoč zaplet je lahko pojav diabetične ketoacidoze. Dejavnikov, ki povečajo tveganje za njen nastanek, še niso popolnoma raziskali. V prispevku so opisani diabetična ketoacidoza in njene posebnosti ob zdravljenju z zaviralci SGLT-2 ter možni vzročni dejavniki zanjo. Poznavanje slednjih je predvsem pomembno zaradi možnosti aktivnega preprečevanja diabetične ketoacidoze. Najpogosteje se pojavi hkrati z zdravljenjem z zaviralci SGLT-2 ob okužbah, sladkorni bolezni tipa 1, opustitvi inzulinskega zdravljenja ter v primerih stradanja. Prispevek vključuje tudi prikaz serije primerov, ki so bili hospitalizirani na našem kliničnem oddelku zaradi diabetične ketoacidoze ob zdravljenju z zaviralci SGLT-2, ob različni sočasni antidiabetični terapiji.
Type 1 (T1D) and type 2 diabetes (T2D) are determinants of health-related outcomes including health-related quality of life (HRQOL). We aimed to determine differences in HRQOL between older adults ...with T1D and T2D and specific factors influencing HRQOL in this age group. This study used a cross-sectional design with 56 age- and HbA1c-matched T1D and T2D patients (aged 68.9 ± 7.8 years; 55% had T2D). We employed several validated questionnaires (Short Form-36 (SF-36) and the EuroQol-5 Dimensions/Visual Analog Scale (VAS)) to investigate the relationships between HRQOL domains and diabetes type, glycemic control, complications, and comorbidities. T1D was associated with better self-reported general health (assessed with the SF-36 general health domain (
= 0.048) and the EuroQol-5 VAS (
= 0.002), whereas no significant differences in the other SF-36 domains, self-reported diabetes distress, anxiety, or depression were found. Most HRQOL domains were not associated with HbA1c or the presence of diabetes complications. The most significant reduction in HRQOL was experienced by patients with higher BMIs, irrespective of the diabetes type. The obtained HRQOL data could be used in clinical settings for evidence-based patient education focused on specific subgroups of patients, as well as in national healthcare policies, e.g., interventions designed to alleviate obesity.
In Diabetes Mellitus (DM), hyperglycaemia and insulin resistance progressively lead to both microvascular and macrovascular complications. Whereas the incidence of microvascular complications is ...closely related to tight glycaemic control, this does not apply to macrovascular complications. Hyperglycaemia influences many interweaving molecular pathways that initially lead to increased oxidative stress, increased inflammation and endothelial dysfunction. The latter represents the initial in both types of vascular complications; it represents the "obligatory damage" in microvascular complications development and only "introductory damage" in macrovascular complications development. Other risk factors, such as arterial hypertension and dyslipidaemia, also play an important role in the progression of macrovascular complications. All these effects accumulate and lead to functional and structural arterial wall damage. In the end, all factors combined lead to the promotion of atherosclerosis and consequently major adverse cardiovascular events. If we accept the pivotal role of vascular wall impairment in the pathogenesis and progression of microvascular and macrovascular complications, treatment focused directly on the arterial wall should be one of the priorities in prevention of vascular complications in patients with DM. In this review, an innovative approach aimed at improving arterial wall dysfunction is described, which may show efficacy in clinical studies. In addition, the potential protective effects of current treatment approaches targeting the arterial wall are summarised.
PDF
