Ru(ii)–N-heterocyclic carbene complexes: synthesis,characterization, transfer hydrogenation reactions and biological determination

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions. All new compounds were characterized by spectroscopic and analytical methods. These ruthenium(ii)–NHC complexes were found to be efficient precatalysts for the transfer hydrogenation of ketones by using 2-propanol as the hydrogen source in the presence of KOH as a co-catalyst. The antibacterial activity of ruthenium N-heterocyclic carbene complexes 3a–f was measured by disc diffusion method against Gram positive and Gram-negative bacteria. Compounds 3d exhibited potential antibacterial activity against five bacterial species among the six used as indicator cells. The product 3e inhibits the growth of all the six tested microorganisms. Moreover, the antioxidant activity determination of these complexes 3a–f, using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS) as reagent, showed that compounds 3b and 3d possess DPPH and ABTS antiradical activities. From a concentration of 1 mg ml⁻¹, these two complexes presented a similar scavenging activity to that of the two used controls gallic acid (GA) and butylated hydroxytoluene (BHT). From a concentration of 10 mg ml⁻¹, the percentage inhibition of complexes 3b and 3d was respectively 70% and 90%. In addition, these two Ru–NHC complexes exhibited antifungal activity against Candida albicans. Investigation of the anti-acetylcholinesterase activity of the studied complexes showed that compounds 3a, 3b, 3d and 3e exhibited good activity at 100 μg ml⁻¹ and product 3d is the most active. In a cytotoxicity study the complexes 3 were evaluated against two human cancer cell lines MDA-MB-231 and MCF-7. Both 3d and 3e complexes were found to be active against the tested cell lines showing comparable activity with examples in the literature.

A series of ruthenium(ii) complexes with N-heterocyclic carbene ligands were successfully synthesized by transmetalation reactions between silver(i) N-heterocyclic carbene complexes and [RuCl₂(p-cymene)]₂ in dichloromethane under Ar conditions.     

Remote loading of curcumin-in-modified β-cyclodextrins into liposomes using a transmembrane pH gradient

Curcumin (CRM) is a natural polyphenol with antioxidative, anti-inflammatory, and anticancer therapeutic properties. However, CRM therapeutic potential is limited by low water solubility and bioavailability. Intraliposomal remote loading describes the retention of drugs in liposome cores in response to transmembrane pH gradient. The current study describes for the first time the remote loading of CRM into liposomes using secondary (E-βCD) and tertiary (D-βCD) amino-modified β-cyclodextrins (βCDs) as carriers and solubilizers. βCDs were chemically modified to prepare the ionizable weak base functional group followed by forming a guest-host complex of CRM in the modified βCDs hydrophobic cavities via a solvent evaporation encapsulation technique. These complexes were then actively loaded into preformed liposomes, composed of DPPC/cholesterol (65/35 molar ratio) via pH gradient. The formation of CRM-βCDs inclusion complexes was characterized using UV-Vis spectroscopy, thermal analysis, and NMR spectroscopy. The complex stoichiometric ratio was determined to be 1 : 1 of CRM-βCDs based on Job''s plot which was also confirmed by the modified Benesi–Hildebrand equation with increasing probability of forming the 1 : 2 ratio of CRM-βCDs. The apparent formation constants (K_f) of 51.6, 100.9 and 55.4 mM⁻² were determined for CRM-βCD, CRM-E-βCD, and CRM-D-βCD complexes, respectively. Liposome size, charge and polydispersity index indicate the presence of a homogeneous population before and after active loading. The encapsulation efficiencies of CRM-βCD complexes into pH gradient preformed liposomes were 16.5, 51.1, and 41.7 for CRM-βCD, CRM-E-βCD, and CRM-D-βCD, respectively, showing more than 5 fold increase compared to normal liposomes. The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.

The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.     

Structural study and large magnetocaloric entropy change at room temperature of La1−x□xMnO3 compounds

In this study, our central focus is to investigate the magnetocaloric characteristics of a La_1−x□_xMnO₃ (x = 0.1, 0.2 and 0.3) series prepared by a sol–gel technique published in Prog. Mater. Sci., 93, 2018, 112–232. The crystallographic study revealed that our compounds crystallize in a rhombohedral structure with R$\bar{3}$c. Ferromagnetic (FM) and paramagnetic (PM) characters were detected from the variation in magnetization as a function of magnetic fields at different temperatures. The second order transition was verified from the Arrott plots (M²vs. (μ₀H/M)), where the slopes have a positive value. In order to verify the second order, we traced the variation of magnetization vs. temperature at different magnetic fields for x = 0.2. This revealed a ferromagnetic (FM)–paramagnetic (PM) transition when temperature increases. Relying on the indirect method while using the Maxwell formula, we determined the variation in the entropy (−ΔS_M) as a function of temperature for different magnetic fields for the three samples. We note that all the studied systems stand as good candidates for magnetic refrigeration with relative cooling power (RCP) values of around 131.4, 83.38 and 57.26 J kg⁻¹ with magnetic fields below 2 T, respectively. Subsequently, the magnetocaloric effect was investigated by a phenomenological model for x = 0.2. The extracted data confirm that this phenomenological model is appropriate for the prediction of magnetocaloric properties. The study also demonstrated that this La_0.8□_0.2MnO₃ system exhibits a universal behaviour.

In this study, our central focus is to investigate the magnetocaloric characteristics of a La_1−x□_xMnO₃ (x = 0.1, 0.2 and 0.3) series prepared by a sol–gel technique.     

In vitro evaluation of novel low-pressure spark plasma sintered HA–BG composite scaffolds for bone tissue engineering

The low-pressure spark plasma sintering (SPS) technique is adopted to fabricate hydroxyapatite–bioglass (HA–BG) scaffolds while maintaining the physical properties of both components, including their bulk and relative density and hardness. However, prior to their orthopaedic and dental applications, these scaffolds must be validated via pre-clinical assessments. In the present study, scaffolds with different ratios of HA : BG, namely, 100 : 0 (HB 0 S), 90 : 10 (HB 10 S), 80 : 20 (HB 20 S) and 70 : 30 (HB 30 S) were fabricated. These scaffolds were characterized by investigating their physicochemical properties (X-ray diffraction (XRD) and surface wettability), bioactivity in a simulated body fluid (SBF) (field emission scanning electron microscopy (FESEM), Fourier-transform infrared spectroscopy (FTIR) and calcium dissolution), antimicrobial properties, biocompatibility and osteoinduction of human bone marrow-derived mesenchymal stromal cells (hBMSCs) and human monocyte immune cell response. The XRD and surface wettability results confirmed no formation of undesirable phases and the enhanced surface hydrophilicity of the scaffolds, respectively. The bioactivity in SBF indicated the formation of bone-like apatite on the surface of the scaffolds, corresponding to an increase in BG%, which was confirmed through FTIR spectra and the increasing trend of calcium release in SBF. The scaffolds showed inhibition properties against Staphylococcus aureus and Staphylococcus epidermidis. The scanning electron microscopy (SEM) micrographs and Alamar Blue proliferation assay indicated the good attachment and significant proliferation, respectively, of hBMSCs on the scaffolds. Alizarin Red S staining confirmed that the scaffolds supported the mineralisation of hBMSCs. The osteogenic protein secretion (bone morphogenetic protein-2 (BMP2), type-I collagen (COL1) and osterix (OSX)) was significant on the HB 30 S-seeded hBMSCs when compared with that of HB 0 S. The monocyte migration was significantly halted in response to HA–BG-conditioned media when compared with the positive control (monocyte chemoattractant protein-1: MCP-1). In conclusion, the HB 30 S composite scaffold has a greater potential to substitute bone grafts in orthopaedic and dental applications.

HB 30 S composite scaffold inhibits Staphylococcus spp., supports the biocompatibility and osteogenic differentiation of hBMSCs and resists monocyte migration.     

The Prevalence and the Characteristics of Tuberculosis Patients Undergoing Chronic Dialysis Treatment: Experience of a Dialysis Center in Southeast Turkey

Tuberculosis remains a significant health problem for patients receiving chronic dialysis. The purpose of this study was to evaluate the prevalence, clinical characteristics, and outcomes of tuberculosis among patients with end-stage renal failure (ESRF) undergoing chronic hemodialysis and continuous ambulatory peritoneal dialysis. Between 1999 and 2006, we diagnosed 21 active tuberculosis patients among a total of 674-dialysis patient in our dialysis center (582 patients on hemodialysis and 92 patients on continuous ambulatory peritoneal dialysis program). Fourteen patients developed extrapulmonary tuberculosis (generally tuberculous lymphadenitis, n = 8) and seven patients developed pulmonary tuberculosis. All patients who developed tuberculosis after starting dialysis had low creatinine clearances and, in general, anemia and hypoalbuminemia. Three of patients greater than 40 years died. In conclusion, tuberculous lymphadenitis was the most frequent form of extrapulmonary tuberculosis in our dialysis population. If no cause is found despite extensive investigations in an end stage renal failure case with fever, loss of weight, and/or atypical lymphadenopathy, the physician should consider the possibility of tuberculosis. Finally, it was considered that ESRF is associated with depressed immune system and elevated risk of tuberculosis; thus, in this population, clinicians must evaluate patients carefully.     

The Comparison in Terms of Early Complications of a New Technique and Percutaneous Method for the Placement of CAPD Catheters

Background. Starting continuous ambulatory peritoneal dialysis (CAPD) immediately after insertion of a peritoneal dialysis catheter is essential in end-stage renal disease (ESRD). In relation to the insertion methods, various mechanical and infectious complications may arise. In this study, we aimed to compare early complications of the laparoscopic tunneling method of CAPD placement that we developed recently in order to minimize the complications, with those of the conventional percutaneous method. Subjects and method. Included in this study were 12 consecutive patients with ESRD to whom we introduced catheters for CAPD by way of laparoscopic tunneling between April 2003 and July 2003 and followed up for at least 6 months, and 30 patients to whom the catheters were placed percutaneously in the same time period with the same follow-up time. The complications seen during the first 6 months after catheter placement with these two different methods were compared. Results. In all of the subjects, dialysis was started soon after catheter placement. No per-operative morbidity was seen in any of the patients. While with laparoscopic tunneling method no mechanical problem was seen, the percutaneous method resulted in early leakage in 10%, pericatheter bleeding in 3.3%, and hernia in 3.3% of the patients. As infectious complications, peritonitis occurred as one episode/36 patient-months in laparoscopic tunneling and one episode/22.5 patient-months in percutaneous method; catheter insertion site infection was seen in none in the laparoscopic method, while one episode/90patient-months was seen with the percutaneous method. Tunnel infection did not arise in any of the subjects. Conclusion. The authors of this study think that the peritoneal tunneling method for introducing CAPD, which has been recently developed and began to be routinely used by them, is rather safe in terms of early complications.     

β-Glucan treatment prevents progressive burn ischaemia in the zone of stasis and improves burn healing: An experimental study in rats

Saving the zone of stasis is one of the major goals of burn specialists. Increasing the tissue tolerance to ischaemia and inhibiting inflammation have been proposed to enable salvage of this zone. After a burn, excessive inflammation, including increased vascular permeability, local tissue oedema and neutrophil activation, causes local tissue damage by triggering vascular thrombosis and blocking capillaries, resulting in tissue ischaemia and necrosis. Oxygen radicals also contribute to tissue damage after a burn. However, macrophages play a pivotal role in the response to burn. We studied β-glucan because of its many positive systemic effects that are beneficial to burn healing, including immunomodulatory effects, antioxidant effects (free-radical scavenging activity) and effects associated with the reduction of the inflammatory response.     

Assessment of atherosclerosis risk due to the homocysteine–asymmetric dimethylarginine–nitric oxide cascade in children taking antiepileptic drugs

PurposeThe aim of this study was to assess the atherogenicity risk of antiepileptics in children by investigating the cascade, “hyperhomocysteinemia (HHcy) → asymmetric dimethylarginine (ADMA) increase → nitric oxide (NO) decrease”, which is thought to contribute to the developmental process of atherosclerosis.MethodsThe participants included 53 epilepsy patients who received either valproic acid (VPA, n = 26) or oxcarbazepine (OXC, n = 27). Twenty-four healthy sex- and age-matched children served as controls. Fasting plasma total homocysteine (tHcy), ADMA and NO levels were measured.ResultsThe differences in Hcy, ADMA, NO, vitamin B₁₂ and folate levels between VPA, OXC and control groups were all insignificant (p > 0.05 for all). In the patient group (VPA and OXC groups), 22.6% of the children (12/53) had tHcy levels above the normal cutoff (13.1 μmol/l) for children and 17% of the children (9/53) had tHcy levels of greater than 15 μmol/l which is accepted as the critical value for an increased atherosclerosis risk (p < 0.05 for both). The difference in rate of HHcy between VPA and OXC groups was statistically insignificant (p > 0.05, for both cut off levels of HHCy). There was a positive correlation of tHcy levels and antiepileptic drug treatment duration in the patient group (r = +0.276, p < 0.05).ConclusionHHcy may develop in patients using OXC. Contrary to some previous publications, our data do not suggest that OXC is safer than VPA in terms of HHcy risk. Further prospective, large scale and longer term studies investigating all suggested pathways responsible for development of atherosclerosis due to HHcy should be conducted to define the exact mechanism responsible for AEDs related atherosclerosis.     

Psychiatric disorders and characteristics of abuse in sexually abused children and adolescents with and without intellectual disabilities

The purpose of this study was to compare sexually abused children and adolescents, with and without intellectual disabilities (ID), in terms of post-abuse psychiatric disorders, features of the sexual abuse, and sociodemographic characteristics. The study included sexually abused children aged 6–16 years, who were sent to three different child mental health units for forensic evaluation; there were 102 cases (69 girls and 33 boys) with ID and 154 cases (126 girls and 28 boys) without ID. Researchers retrospectively examined the files, social examination reports, and the judicial reports of the cases. It was determined that in the group with ID, sexual abuse types including penetration and contact had higher rates, they were exposed to more frequent repeated abuses, the abuses were revealed with their own reports at a later period and lower rates, and post-abuse pregnancies were more frequent. It was also determined that the abuser was a familiar person and a family member at lower rates and more than one abuser was encountered more frequently, compared to the group without ID. While no difference was determined between the two groups in terms of the frequency of post-abuse post-traumatic stress disorder (PTSD) and major depressive disorder (MDD), conduct disorder (CD) was observed more frequently in the group with ID. This study emphasizes that sexual abuse, which is an important problem in individuals with ID, has different features and effects.