2,017 research outputs found
Pediatric glaucoma: current perspectives
Giorgio Marchini, Marco Toscani, Francesca Chemello Eye Clinic, Department of Neurological and Movement Sciences, University of Verona, Verona, Italy Abstract: "Childhood glaucoma" is a heterogeneous group of severe pediatric conditions often associated with significant visual loss and characterized by elevated intraocular pressure (IOP) and optic-disk cupping. Successful IOP control is crucial but challenging and most often achieved surgically, with medical therapy playing a supportive role. There are many classifications of childhood glaucoma, but they can simply be divided into primary, in which a developmental abnormality of the anterior chamber angle only exists, and secondary, in which aqueous outflow is reduced due to independent mechanisms that secondarily impair the function of the filtration angle. The worldwide prevalence of childhood blindness ranges from 0.03% in high-income countries to 0.12% in undeveloped countries. The majority of cases do not have an identified genetic mutation and, where the mutation is known, the genes often account for only a small proportion of cases. Several pathogenetic mechanisms are known to contribute to the development of childhood glaucoma. Whatever the cause, it results in a reduced aqueous outflow at the level of the trabecular meshwork. Age of onset and magnitude of the elevated IOP largely determine the clinical manifestation the high variability of clinical manifestations. Glaucoma from any cause in a neonate and infant is characterized by the classic triad of epiphora, photophobia, and blepharospasm, and could be associated with eye enlargement (buphthalmos) and Haab striae. The eye examination, usually performed under general anesthesia, includes: tonometry, anterior-segment examination, gonioscopy, corneal diameter and axial length measurement, dilated fundoscopy with optic-nerve-head evaluation. Medical therapy, considering the high frequency of side effects, is generally used as temporizing IOP-lowering treatment before surgery or as adjuvant treatment postoperatively in case of partially successful procedures for refractory glaucomas. Surgery is the nodal point of the management of refractory childhood glaucoma, so it is crucial to opt for a forward-looking strategy to reach the target IOP and minimize the visual loss. Keywords: childhood glaucoma, congenital glaucoma, glaucoma surgical therapy, childhood visual los
Ectopic mineralization in heart valves: New insights from in vivo and in vitro procalcific models and promising perspectives on noncalcifiable bioengineered valves
Ectopic calcification of native and bioprosthetic heart valves represents a major public health
problem causing severe morbidity and mortality worldwide. Valve procalcific degeneration is known to be
caused mainly by calcium salt precipitation onto membranes of suffering non-scavenged cells and dead-cellderived
products acting as major hydroxyapatite nucleators. Although etiopathogenesis of calcification in
native valves is still far from being exhaustively elucidated, it is well known that bioprosthesis mineralization
may be primed by glutaraldehyde-mediated toxicity for xenografts, cryopreservation-related damage for
allografts and graft immune rejection for both. Instead, mechanical valves, which are free from calcification,
are extremely thrombogenic, requiring chronic anticoagulation therapies for transplanted patients. Since
surgical substitution of failed valves is still the leading therapeutic option, progressive improvements in tissue
engineering techniques are crucial to attain readily available valve implants with good biocompatibility,
proper functionality and long-term durability in order to meet the considerable clinical demand for valve
substitutes. Bioengineered valves obtained from acellular non-valvular scaffolds or decellularized native
valves are proving to be a compelling alternative to mechanical and bioprosthetic valve implants, as they
appear to permit repopulation by the host\u2019s own cells with associated tissue remodelling, growth and repair,
besides showing less propensity to calcification and adequate hemodynamic performances. In this review,
insights into valve calcification onset as revealed by in vivo and in vitro procalcific models are updated as well
as advances in the field of valve bioengineering
Biochar impact on the estimation of the colorimetric-based enzymatic assays of soil
This study was carried out in order to assess the influence of biochar applications on
the estimation of colorimetric-based
enzymatic assays and to verify the effectiveness
of the most common methods. Since most methods used to determine enzymatic
activities in the soil are based on colorimetry, biochar may absorb substrates and/
or coloured products thereby distorting the analytical result. Biochar was added to
two soils, with different textures and cation exchangeable capacities, at a rate of
2% (w/w), and seven enzyme activities were determined following standard methods.
The biochar amendment lowered the spectrophotometer reading of the activity
of FDAase and dehydrogenase in the sandy soil. In the three enzymatic activities
based on p-nitrophenol
production (β-glucosidase,
phosphatase and arylsulphatase),
the addition of biochar did not change the enzyme assays. The biochar led to an
overestimation in terms of the protease and urease activities in the sandy soil. In the
clay loamy soil, biochar did not change the response of any of the enzyme activities
tested. A biochar dose of up to 2% only guarantees the effectiveness of the most common
spectrophotometric methods for not excessively sandy soils
Cholesterol dependent macropinocytosis and endosomal escape control the transfection efficiency of lipoplexes in CHO Living Cells
Here we investigate the cellular uptake mechanism and final intracellular fate of two cationic liposome formulations characterized by similar physicochemical properties but very different lipid composition and efficiency for intracellular delivery of DNA. The first formulation is made of cationic lipid 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and the zwitterionic helper dioleoylphosphocholine (DOPC), while the second one is made of the cationic 3 beta-[N-(N,N-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and the zwitterionic lipid dioleoylphosphatidylethanolamine (DOPE). Combining pharmacological and imaging approaches we show that both DOTAP-DOPC/DNA and DC-Chol-DOPE/DNA lipoplexes are taken up in Chinese hamster ovary (CHO) living cells mainly through fluid-phase macropinocytosis. Our results also indicate that lipoplex macropinocytosis is a cholesterol-sensitive uptake mechanism. On the other side, both clathrin-mediated and caveolae-mediated endocytosis play a minor role, if any, in the cell uptake. Colocalization of fluorescently tagged lipoplexes and Lysosensor, a primary lysosome marker, reveals that poorly efficient DOTAP-DOPC/DNA lipoplexes are largely degraded in the lysosomes, while efficient DC-Chol-DOPE/DNA systems can efficiently escape from endosomal compartments
The picture of the Bianchi I model via gauge fixing in Loop Quantum Gravity
The implications of the SU(2) gauge fixing associated with the choice of
invariant triads in Loop Quantum Cosmology are discussed for a Bianchi I model.
In particular, via the analysis of Dirac brackets, it is outlined how the
holonomy-flux algebra coincides with the one of Loop Quantum Gravity if paths
are parallel to fiducial vectors only. This way the quantization procedure for
the Bianchi I model is performed by applying the techniques developed in Loop
Quantum Gravity but restricting the admissible paths. Furthermore, the local
character retained by the reduced variables provides a relic diffeomorphisms
constraint, whose imposition implies homogeneity on a quantum level. The
resulting picture for the fundamental spatial manifold is that of a cubical
knot with attached SU(2) irreducible representations. The discretization of
geometric operators is outlined and a new perspective for the super-Hamiltonian
regularization in Loop Quantum Cosmology is proposed.Comment: 6 page
The non-indigenous Paranthura japonica Richardson, 1909 in the Mediterranean Sea: travelling with shellfish?
An anthurid isopod new to the Mediterranean Sea has recently been observed in samples from three localities of the Italian coast: the Lagoon of Venice (North Adriatic Sea), La Spezia (Ligurian Sea) and Olbia (Sardinia, Tyrrhenian Sea). The specimens collected showed strong affinity to a species originally described from the NW Pacific Ocean: Paranthura japonica Richardson, 1909. The comparison with specimens collected from the Bay of Arcachon (Atlantic coast of France), where P. japonica had been recently reported as non-indigenous, confirmed the identity of the species. This paper reports the most relevant morphological details of the Italian specimens, data on the current distribution of the species and a discussion on the pathways responsible for its introduction. The available data suggest that the presence of this Pacific isopod in several regions of coastal Europe might be due to a series of aquaculture-mediated introduction events that occurred during the last decades of the 1900s. Since then, established populations of P. japonica, probably misidentified, remained unnoticed for a long time
Short-term use of dexamethasone/netilmicin fixed combination in controlling ocular inflammation after uncomplicated cataract surgery
Purpose: To evaluate the short-term anti-inflammatory effect of dexamethasone/netilmicin fixed combination in the management of ocular inflammation after cataract surgery. Patients and Methods: Open-label, randomized, active-controlled, clinical study con-ducted in 6 sites in Italy; 238 patients were randomized 2:1 to dexamethasone/netilmicin (dexa/net, n=158) or betamethasone/chloramphenicol (beta/chl, n=80). Treatment started the day of surgery and continued 4 times daily for 7 days. The primary efficacy parameter was the anterior chamber (AC) flare. The percentage of patients displaying none or mild (ie, only barely detectable) AC flare was defined as “efficacy rate”, whereas the percentage of patients showing a decrease of AC flare score from baseline was defined as “percentage of responders”. Additional parameters evaluated were AC cells, conjunctival hyperaemia, corneal and lid oedema, symptoms of ocular discomfort, visual acuity, and intraocular pressure. Dexa/net was considered effective if the efficacy rate was not inferior (by means of 97.5% confidence interval) to that of beta/chl. Results: After 7 days of treatment, no AC flare was observed in 92.8% (dexa/net) and 92.3% (beta/chl) of patients, whereas no AC cells were observed in 91.5% (dexa/net) and 93.6% (beta/chl) of patients, respectively. The “efficacy rate” was 100% in both groups, whereas the “percentage of responders” was 94.1% in the dexa/net and 93.6% in the beta/chl group. The p-value to reject the null hypothesis of inferiority was <0.001. Other efficacy parameters confirmed both treatments as highly effective, despite their difference in steroid content (2 mg/mL for beta/chl vs 1 mg/mL for dexa/net). IOP and visual acuity at the end of the study were comparable. Two cases of allergic conjunctivitis were considered adverse events and were both related to dexa/net. Conclusion: Short-term use of dexa/net fixed combination is safe and effective in the control of post-operative inflammation following uncomplicated cataract surgery
Biomimetic Electrospun Self-Assembling Peptide Scaffolds for Neural Stem Cell Transplantation in Neural Tissue Engineering
Spinal cord regeneration using stem cell transplantation is a promising strategy for regenerative therapy. Stem cells transplanted onto scaffolds that can mimic natural extracellular matrix (ECM) have the potential to significantly improve outcomes. In this study, we strived to develop a cell carrier by culturing neural stem cells (NSCs) onto electrospun 2D and 3D constructs made up of specific crosslinked functionalized self-assembling peptides (SAPs) featuring enhanced biomimetic and biomechanical properties. Morphology, architecture, and secondary structures of electrospun scaffolds in the solid-state and electrospinning solution were studied step by step. Morphological studies showed the benefit of mixed peptides and surfactants as additives to form thinner, uniform, and defect-free fibers. It has been observed that β-sheet conformation as evidence of self-assembling has been predominant throughout the process except for the electrospinning solution. In vitro NSCs seeded on electrospun SAP scaffolds in 2D and 3D conditions displayed desirable proliferation, viability, and differentiation in comparison to the gold standard. In vivo biocompatibility assay confirmed the permissibility of implanted fibrous channels by foreign body reaction. The results of this study demonstrated that fibrous 2D/3D electrospun SAP scaffolds, when shaped as micro-channels, can be suitable to support NSC transplantation for regeneration following spinal cord injury
Critical involvement of calcium-dependent cytosolic phospholipase A2\u3b1 in aortic valve interstitial cell calcification
The involvement of calcium-dependent cytosolic phospholipase A2\u3b1 (cPLA2\u3b1) in aortic valve calcification is not exhaustively elucidated. Here, cPLA2\u3b1 expression in aortic valve interstitial cell (AVIC) pro-calcific cultures simulating either metastatic or dystrophic calcification was estimated by qPCR, Western blotting, and counting of cPLA2\u3b1-immunoreactive cells, with parallel ultrastructural examination of AVIC calcific degeneration. These evaluations also involved pro-calcific AVIC cultures treated with cPLA2\u3b1 inhibitor dexamethasone. cPLA2\u3b1 over-expression resulted for both types of pro-calcific AVIC cultures. Compared to controls, enzyme content was found to increase by up to 300% and 186% in metastatic and dystrophic calcification-like cultures, respectively. Increases in mRNA amounts were also observed, although they were not as striking as those in enzyme content. Moreover, cPLA2\u3b1 increases were time-dependent and strictly associated with mineralization progression. Conversely, drastically lower levels of enzyme content resulted for the pro-calcific AVIC cultures supplemented with dexamethasone. In particular, cPLA2\u3b1 amounts were found to decrease by almost 88% and 48% in metastatic and dystrophic calcification-like cultures, respectively, with mRNA amounts showing a similar trend. Interestingly, these drastic decreases in cPLA2\u3b1 amounts were paralleled by drastic decreases in mineralization degrees, as revealed ultrastructurally. In conclusion, cPLA2\u3b1 may be regarded as a crucial co-factor contributing to AVIC mineralization in vitro, thus being an attractive potential target for designing novel therapeutic strategies aimed to counteract onset or progression of calcific aortic valve diseases
Transfection efficiency boost of cholesterol-containing lipoplexes
Most lipid formulations require cholesterol for successful transfection, but the precise reason remains to be more clearly understood. Here, we have studied the effect of cholesterol on the transfection efficiency (TE) of lipoplexes in vitro. Addition of cholesterol to highly effective DC-Chol-DOPE/DNA lipoplexes increases TE, with 40mol% cholesterol yielding about 10-fold improvement. The transfection mechanisms of cholesterol-containing lipoplexes have been investigated by combining dynamic light scattering, synchrotron small angle X-ray scattering, laser scanning confocal microscopy and transfection efficiency measurements. Our results revealed that cholesterol-containing lipoplexes enter the cells partially by membrane fusion and this mechanism accounts for efficient endosomal escape. We also found evidence that formulations with high cholesterol content are not specifically targeted to metabolic degradation. These studies will contribute to rationally design novel delivery systems with superior transfection efficiency
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