Photochemically Activated 3D Printing Inks: Current Status, Challenges, and Opportunities.

3D printing with light is enabled by the photochemistry underpinning it. Without fine control over the ability to photochemically gate covalent bond formation by the light at a certain wavelength and intensity, advanced photoresists with functions spanning from on-demand degradability, adaptability, rapid printing speeds, and tailored functionality are impossible to design. Herein, recent advances in photoresist design for light-driven 3D printing applications are critically assessed, and an outlook of the outstanding challenges and opportunities is provided. This is achieved by classing the discussed photoresists in chemistries that function photoinitiator-free and those that require a photoinitiator to proceed. Such a taxonomy is based on the efficiency with which photons are able to generate covalent bonds, with each concept featuring distinct advantages and drawbacks.

The impact of low mineral content water on cardiac function in diabetic rats: focus on oxidative stress.

The aim of this study was to estimate the effects of natural low mineral water from the source "Sneznik-1/79" in Serbia on glycemia as well as heart function in rats with diabetes mellitus type 2 (T2DM), with the special emphasis on the role of the oxidative stress. Twenty Wistar albino rats (males, 4 weeks old at the beginning of the study, body weight 180 ± 20 g) were included in the study. Rats were divided randomly into 2 groups (10 animals per group): T2DM: rats with diabetes mellitus type 2 with free access to tap water; T2DM + SW: rats with diabetes mellitus type with free access to natural mineral water from "Sneznik-1/79". Glucose level, ex vivo cardiac function as well as systemic and cardiac redox state were assessed. At the end of the study protocol, glucose level was lower in diabetic rats who consumed mineral water. Moreover cardiac function wasn't affected by mineral water intake, however, significant antioxidant effects were observed. Our study suggests that 4-week consumption of low mineral water from the spring "Sneznik-1/79" has important role in regulation of glycemia and altering redox state in favor of elevated antioxidant capacity without affecting heart function. Based on our findings we may assume that low mineral water from the spring "Sneznik-1/79" has the potential to be used either as preventive strategy or as additional therapeutic strategy in management of T2DM.

Effects of rivaroxaban and dabigatran on global hemostasis in patients with atrial fibrillation.

: The study was aimed to evaluate the effects of two standard doses of rivaroxaban and dabigatran on global hemostatic assays in patients with atrial fibrillation. The study included 52 patients treated with rivaroxaban (15/20 mg), 50 on dabigatran (110/150 mg) and 20 healthy individuals. Platelet-poor plasma was used for determination of three global hemostatic assays, namely endogenous thrombin potential (ETP), calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP). Rivaroxaban and dabigatran reduced ETP (P < 0.01) although OHP (P < 0.05) was diminished only by dabigatran. Strong correlations were noticed between ETP parameters and the plasma concentrations of rivaroxaban (ETP, r = -0.51; c-max, r = -0.85; t-lag, r = 0.83; t-max, r = 0.66) as well as with plasma concentration of dabigatran (ETP, r = -0.75; c-max, r = -0.74; t-lag, r = 0.73; t-max, r = 0.52). Analysis of dabigatran concentrations under 50 ng/ml showed that ETP parameter has area under the concentration-time curve-receiver operating characteristic value of 0.879 (95% confidence interval 0.776-0.980). Dabigatran treatment paradoxically increased area under the concentration-time curve and peak values although rivaroxaban decreased peak values (P < 0.01). However, significant correlation between CAT parameters and plasma concentration of both direct oral anticoagulants was not observed. We confirmed that the CAT assay is inappropriate for estimation of dabigatran effects and is not fully sensitive as regards rivaroxaban. The ETP assay can potentially be the appropriate method for estimation of global hemostatic capacity as regards both direct oral anticoagulants. The role of OHP needs to be confirmed in additional studies. ETP parameter of chromogenic assay has promising potential in exclusion of high plasma concentrations of dabigatran.

High-protein diet and omega-3 fatty acids improve redox status in olanzapine-treated rats.

The present study aimed to estimate the effects of high-protein diet (PD)-isolated whey protein and omega-3 fatty acids-docosahexaenoic and eicosapentaenoic acid on oxidative parameters of rats treated with Olanzapine (OLZ). Experiments were carried out on 8-week-old Wistar albino male rats (n = 64) weighing 200 ± 20 g. By dietary and pharmacological treatment, all animals were divided into 8 groups: 1. CTRL group; 2. CTRL + OLZ group; 3. CTRL + FA group; 4. CTRL + OLZ + FA group; 5. PD group; 6. PD + OLZ group; 7. PD + FA group; 8. PD + OLZ + FA group. After 6 weeks of pharmacological/diet treatment, all animals were sacrificed to collect blood samples and determine the biomarkers of oxidative stress. The following oxidative stress markers were measured spectrophotometrically: superoxide anion radical (O2-), hydrogen peroxide (H2O2), nitric oxide (NO-), index of lipid peroxidation measured as TBARS, reduced glutathione, catalase and superoxide dismutase. The study has shown that Olanzapine treatment was associated with increased release of pro-oxidants and diminished activity of anti-oxidant markers. Additional supplementation with PD and FA succeeded in abolishing the negative influence in most of the measured parameters. However, these beneficial impacts were stronger in the case of their separate application, which could be the practical and clinical importance of these results.

The importance of the blood levels of homocysteine, folate and vitamin B12 in patients with primary malignant brain tumors.

PURPOSE: Glioblastoma multiforme and anaplastic astrocytoma represent one of the most frequently occurring primary brain tumors with dismal survival rates. The aim of our study was to investigate whether values of homocysteine, folates and vitamin B12 can be prognostic markers in relapse diagnosis, treatment and monitoring of adult patients with malignant brain tumors. METHODS: Twenty-seven patients from the Neurosurgical Clinic, Clinical Center of Serbia with diagnosed malignant brain tumors (anaplastic astrocytoma GR III and glioblastoma multiforme GR IV), were included in the study. The patients were divided in two groups according to the progression of disease, 15 with and 12 without progression. RESULTS: Mean values of homocysteine were significantly higher in the group with progression compared to the group without malignant tumor progression, at the baseline point and after six months. Mean values of folate were similar across groups in all measurements, except in the 3rd month after surgery. Results regarding vitamin B12 were similar to folate, without any significance in group comparisons in the examined time points, as well as in vitamin B12 values change. CONCLUSIONS: Our results pointed out that total homocysteine in blood circulation appears to be a tumor marker for monitoring primary malignant brain tumor patients before and after surgery. The association of hyperhomocysteinemia with folate deficiency, also provides strong support for viewing hyperhomocysteinemia as a predictive marker for carcinogenesis. It is hoped that future research will continue to explore the clinical relevance of homocysteine as a tumor marker and a risk factor for astrocytoma and glioblastoma.

Assessment of hemostatic disturbances in women with established rheumatoid arthritis.

OBJECTIVES: This study was aimed to assess hemostatic disturbances in female patients with established rheumatoid arthritis (RA) in relation to menopausal status and disease activity. METHOD: Ninety women were included in the study, 42 patients and 48 age-matched healthy controls. There were no differences between the investigated groups regarding the presence of traditional cardiovascular risk factors. Two global hemostatic assays were employed, namely endogenous thrombin potential (ETP) and overall hemostasis potential (OHP). The parameters of the ETP assay (ETP, C-max, t-lag, t-max) and OHP assay (overall coagulation potential (OCP) and overall fibrinolytic potential (OFP)) were assessed. Moreover, the parameters of the fibrin clot (lag time, Max Abs, and slope) were measured by clot turbidity and scanning electron microscopy (SEM). Both patients and controls were divided into four subgroups according to menopause status. RESULTS: The premenopausal controls differed significantly from all other subgroups in terms of diminished levels of ETP (p = 0.02), C-max (p = 0.01), OCP (p = 0.02), OHP (p = 0.001), and Max Abs (p = 0.008), while OFP (p = 0.0001) was increased. This tendency was not seen in the premenopausal RA patients compared with the postmenopausal RA patients. SEM images showed denser clots composed of thinner fibers in samples from RA patients. The disease activity measured by DAS28 correlated with OCP and OHP (r = 0.54; p = 0.001 and r = 0.44; p = 0.003, respectively) indicating persistent hypercoagulable condition in the whole group of RA patients. CONCLUSIONS: Our results point towards coagulation activation in premenopausal women with established RA. The patients were well characterized, which enabled assessment in a real-life setting. Key Points • Extensive assessment points towards persistent coagulation activation in premenopausal women with established rheumatoid arthritis. • Impaired thrombin generation and fibrin formation are associated with menopause in healthy women, while rheumatoid arthritis closes the gap within patients regarding menopause. • Fibrin morphology is unfavorably altered and fibrinolysis is decreased in patients with established rheumatoid arthritis. • Increased activity of thrombin activatable fibrinolysis inhibitor (TAFI) may contribute to impaired fibrinolysis in patients with rheumatoid arthritis.

Chronic effects of platinum(IV) complex and its diamine ligand on rat heart function: comparison with cisplatin.

The aim of the present study was to compare the cardiodynamic parameters in the isolated rat heart in animals chronically treated with cisplatin, platinum(IV) complex and its diamine ligand. Sixty Wistar albino rats (8 weeks old) were divided into five groups: three experimental and two control groups. Animals in all groups were treated with a dose of 4 mg/kg body weight once a week for 4 weeks with different substances; experimental groups received cisplatin, ligand and octahedral platinum(IV) complex, and control groups received saline and dimethyl sulfoxide. After sacrificing the animals, hearts were isolated and perfused according to the Langendorff technique at gradually increased coronary perfusion pressures (40-120 cmH2O). The following parameters of cardiac function were continuously recorded: maximum and minimum rate of change of pressure in the left ventricle, systolic and diastolic left ventricular pressure, heart rate and coronary flow. The results showed statistically significant differences between all experimental groups in maximum and minimum rate of pressure development as well as in systolic pressure of the left ventricle, whereas cisplatin, ligand and the platinum(IV) complex had effects on heart contractility without significant influences on coronary circulation. The findings of the present study could be important for a better understanding of anticancer drug cardiac side effects. Our results indicate that compared to cisplatin as a "gold standard", novel platinum complexes and ligands do not possess fewer negative effects on the heart, indicating insufficient safety for their usage in terms of affecting cardiac function, a result that can be of great interest for further investigations.

The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats.

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 µmol/L of spironolactone, diabetic rats treated with 0.1 µmol/L of spironolactone, healthy rats treated with 3 µmol/L of spironolactone, and diabetic rats treated with 3 µmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

Interleukin-6 as possible early marker of stress response after femoral fracture.

Bone fracture healing is a complex process which at best results in full recovery of function and structure of injured bone tissue, but all the mechanisms involved in this process, and their mutual interaction, are not fully understood. Despite advancement of surgical procedures, this type of fractures is still a major public health concern. In the last few decades, a lot of attention is focused on the oxygen-free radicals and inflammatory response markers as important factors of skeletal injury. Thus, the aim of the present study was to follow the changes in redox balance and inflammatory response in elderly patients with femoral fractures during the earliest stages of fracture healing, by measuring the values of the observed markers immediately after fracture, as well as the first, third, and seventh postoperative day. Present study was performed on a group of 65 elderly patients with femoral neck fractures, recruited from the Orthopedic Clinic, Clinical Centre Kragujevac in the period from February to May 2015. Redox status was measured spectrophotometrically and evaluated by measuring the levels of index of lipid peroxidation (measured as TBARS), nitrite (NO2-), superoxide anion radical (O2-), and hydrogen peroxide (H2O2) in plasma, while activities of corresponding antioxidative enzymes, catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) were measured in erythrocytes. The cytokine concentrations of interleukin (IL)-6 and tumor necrosis factor (TNF)-α were determined in plasma, using ELISA assays specific for human cytokines. Our study showed that redox status and TNF-α in elderly patients with femoral fractures did not show statistically significant changes during the early phase of fracture healing. On the other hand, IL-6 increased statistically in first day after intervention. This preliminary study has shown our observations, and we hope that these results may help in better understanding mechanisms which are included at fracture healing. More importantly, this study attempted to create a platform for further research.

Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin.

Evidences have suggested that flavanol compound (-)-epicatechin is associated with reduced risk of cardiovascular diseases. One of the mechanisms of its cardioprotective effect is vasodilation. However, the exact mechanisms by which (-)-epicatechin causes vasodilation are not yet clearly defined. The aims of the present study were to investigate relaxant effect of flavanol (-)-epicatechin on the isolated human internal mammary artery (HIMA) and to determine the mechanisms underlying its vasorelaxation. Our results showed that (-)-epicatechin induced a concentration-dependent relaxation of HIMA rings pre-contracted by phenylephrine. Among the K(+) channel blockers, 4-aminopyridine (4-AP) and margatoxin, blockers of voltage-gated K(+) (KV) channels, and glibenclamide, a selective ATP-sensitive K(+) (KATP) channels blocker, partly inhibited the (-)-epicatechin-induced relaxation of HIMA, while iberiotoxin, a most selective blocker of large conductance Ca(2+)-activated K(+) channels (BKCa), almost completely inhibited the relaxation. In rings pre-contracted by 80mM K(+), (-)-epicatechin induced partial relaxation of HIMA, whereas in Ca(2+)-free medium, (-)-epicatechin completely relaxed HIMA rings pre-contracted by phenylephrine and caffeine. Finally, thapsigargin, a sarcoplasmic reticulum Ca(2+)-ATPase inhibitor, slightly antagonized (-)-epicatechin-induced relaxation of HIMA pre-contracted by phenylephrine. These results suggest that (-)-epicatechin induces strong endothelium-independent relaxation of HIMA pre-contracted by phenylephrine whilst 4-AP- and margatoxin-sensitive KV channels, as well as BKCa and KATP channels, located in vascular smooth muscle, mediate this relaxation. In addition, it seems that (-)-epicatechin could inhibit influx of extracellular Ca(2+), interfere with intracellular Ca(2+) release and re-uptake by the sarcoplasmic reticulum.