Terpyridine Functionalized Cyclodextrin Nanoparticles as Carriers for Doxorubicin: Analysis of In Vitro Antiproliferative Activity.

BACKGROUND/AIM: We have recently described the development of cyclodextrin-based nanoparticles (NPs) functionalized with terpyridine and decorated with biotin-terpyridine ligands via Cu(II) and Fe(II) coordination. In the present study, we report the performance of these novel NPs as a delivery system for anticancer drugs. In particular, we analyzed the feasibility of loading these new NPs with the topoisomerase II inhibitor Doxorubicin (Doxo), still administered to patients to treat different forms of cancers. We developed Doxo-encapsulated polymeric NPS to generate nanoformulations with higher efficacy than free Doxo. MATERIALS AND METHODS: We investigated the inhibition of cell proliferation in A2780, A549, SKHep1, and MDA-MB-453 cancer cell lines using the MTT assay. RESULTS: NPs loaded with Doxo displayed higher antiproliferative activity than free Doxo. CONCLUSION: The NPs generated in this study inhibited the proliferation of cancer cells and were able to entrap the classic anticancer drug Doxo. The Doxo-loaded NP showed increased cytotoxicity in comparison to free Doxo.

Terpyridine Glycoconjugates and Their Metal Complexes: Antiproliferative Activity and Proteasome Inhibition.

Metal terpyridine complexes have gained substantial interest in many application fields, such as catalysis and supramolecular chemistry. In recent years, the biological activity of terpyridine and its metal complexes has aroused considerable regard. On this basis, we synthesised new terpyridine derivatives of trehalose and glucose to improve the water solubility of terpyridine ligands and target them in cancer cells through glucose transporters. Glucose derivative and its copper(II) and iron(II) complexes showed antiproliferative activity. Interestingly, trehalose residue reduced the cytotoxicity of terpyridine. Moreover, we tested the ability of parent terpyridine ligands and their copper complexes to inhibit proteasome activity as an antineoplastic mechanism.

Childhood-Onset Leber Hereditary Optic Neuropathy-Clinical and Prognostic Insights.

PURPOSE: To investigate the clinical and molecular genetic features of childhood-onset Leber hereditary optic neuropathy (LHON) to gain a better understanding of the factors influencing the visual outcome in this atypical form of the disease. DESIGN: Retrospective cohort study. METHODS: We retrospectively included 2 cohorts of patients with LHON with onset of visual loss before the age of 12 years from Italy and the United Kingdom. Ophthalmologic evaluation, including best-corrected visual acuity, orthoptic evaluation, slit-lamp biomicroscopy, visual field testing, and optical coherence tomography, was considered. Patients were classified based on both the age of onset and the pattern of visual loss. RESULTS: A total of 68 patients were stratified based on the age of onset of visual loss: group 1 (<3 years): 14 patients (20.6%); group 2 (≥3 to <9 years): 27 patients (39.7%); and group 3 (≥9 to ≤12 years): 27 patients (39.7%). Patients in group 2 achieved a better visual outcome than those in group 3. Patients in groups 1 and 2 had better mean deviation on visual field testing than those in group 3. The mean ganglion cell layer thickness on optical coherence tomography in group 2 was higher than those in groups 1 and 3. Patients were also categorized based on the pattern of visual loss as follows: Subacute Bilateral: 54 patients (66.7%); Insidious Bilateral: 14 patients (17.3%); Unilateral: 9 patients (11.1%); and Subclinical Bilateral: 4 patients (4.9%). CONCLUSIONS: Children who lose vision from LHON before the age of 9 years have a better visual prognosis than those who become affected in later years, likely representing a "form frustre" of the disease.

Factors affecting yawning frequencies in preterm neonates.

Yawning is a long neglected behavioral pattern, but it has recently gained an increasing interdisciplinary attention for its theoretical implications as well as for its potential use as a clinical marker, with particular regard to perinatal neurobehavioral assessment. The present study investigated the factors affecting yawning frequencies in hospitalized preterm neonates (N = 58), in order to distinguish the effects of hunger and sleep-related modulations and to examine the possible impact of demographic and clinical variables on yawning frequencies. Results showed that preterm neonates yawned more often before than after feeding, and this modulation was not explained by the amount of time spent in quiet sleep in the two conditions. Moreover, second born twins, known to be more prone to neonatal mortality and morbidity, showed increased yawning rates compared to first born twins. Overall, our results are consistent with the hypothesis that yawning frequencies in preterm neonates are modulated by separate mechanisms, related e.g. to hunger, vigilance and stress. These findings, although preliminary and based only on behavioral data, might indicate that several distinct neuropharmacological pathways that have been found to be involved in yawn modulation in adults are already observable in preterm neonates.

The Pattern of Retinal Ganglion Cell Loss in Wolfram Syndrome is Distinct From Mitochondrial Optic Neuropathies.

PURPOSE: To describe the clinical phenotype of a cohort of patients with Wolfram syndrome (WS), focusing on the pattern of optic atrophy correlated with brain magnetic resonance imaging (MRI) measurements, as compared with patients with OPA1-related dominant optic atrophy (DOA). DESIGN: Retrospective, comparative cohort study. METHODS: We reviewed 25 patients with WS and 33 age-matched patients affected by OPA1-related DOA. Ophthalmologic, neurologic, endocrinologic, and MRI data from patients with WS were retrospectively retrieved. Ophthalmologic data were compared with data from patients with OPA1-related DOA and further analyzed for age dependency dividing patients in age quartiles. In a subgroup of patients with WS, we correlated the structural damage assessed by optical coherence tomography (OCT) with brain MRI morphologic measurements. Visual acuity (VA), visual field mean defect (MD), retinal nerve fiber layer (RNFL), and ganglion cell layer (GCL) thickness were assessed by OCT and MRI morphologic measurements of anterior and posterior visual pathways. RESULTS: Optic atrophy was present in 100% of patients with WS. VA, MD, and RNFL thickness loss were worse in patients with WS with a faster decline since early age as compared with patients with DOA, who displayed a more stable visual function over the years. Conversely, GCL sectors were overall thinner in patients with DOA since early age compared to patients with WS, in which GCL thickness started to decline later in life. The neuroradiologic subanalysis on 11 patients with WS exhibited bilateral thinning of the anterior optic pathway, especially the prechiasmatic optic nerves and optic tracts. Optic tract thinning was significantly correlated with GCL thickness but not with RNFL parameters. CONCLUSIONS: Our results showed a generally more severe and diffuse degeneration of both anterior and posterior visual pathways in patients with WS, with fast deterioration of visual function and structural OCT parameters since early age. The pattern observed with OCT suggests that retinal ganglion cell axonal degeneration (ie, RNFL) precedes cellular body atrophy (ie, GCL) by about a decade. This differs substantially from DOA, in which a more stable visual function is evident with predominant early loss of GCL, indirectly supporting the lack of a primary mitochondrial dysfunction in patients with WS.

Terpyridine functionalized cyclodextrin nanoparticles: metal coordination for tuning anticancer activity.

Multi-metal and multi-cavity systems based on the coordination properties of terpyridine functionalized cyclodextrin polymers were synthesized and characterized. Nanoparticles decorated with terpyridine derivatives via metal coordination showed high antiproliferative activity in tumor cells.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY EVALUATION OF PERIPAPILLARY MICROVASCULAR CHANGES AFTER RHEGMATOGENOUS RETINAL DETACHMENT REPAIR.

PURPOSE: To evaluate the radial peripapillary capillary plexus (RPCP) vessel density (VD) and the retinal nerve fiber layer (RNFL) thickness in eyes successfully treated with pars plana vitrectomy for primary rhegmatogenous retinal detachment. METHODS: In this cross-sectional multicenter clinical study, eyes with a minimum 12-month follow-up were reexamined. The RPCP VD and RNFL thickness in the rhegmatogenous retinal detachment subfields of the affected eye (study group) were compared with the corresponding areas of the healthy fellow eyes (control group). RESULTS: Fifty-three eyes were included in the study. A significantly lower RPCP VD and RNFL thickness were observed in those subfields affected by rhegmatogenous retinal detachment compared with those of the control group (P < 0.001). No statistically significant differences were observed between undetached subfields in the study group and their corresponding images in the control group. In the study group, a significant correlation was found between RPCP VD and RNFL thickness in subfields with detached retina (r = 0.393, P < 0.001) and undetached retina (r = 0.321, P < 0.001). CONCLUSION: Radial peripapillary capillary plexus VD changes were found in the subfields of detached retina successfully treated with pars plana vitrectomy and they correlated with RNFL thinning. These data suggest a coexistence of neuronal and microvascular damage in patients affected by rhegmatogenous retinal detachment.