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1.
Aging Cell ; 22(12): e14007, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37997569

ABSTRACT

The age-related decline in immunity reduces the effectiveness of vaccines in older adults. Immunosenescence is associated with chronic, low-grade inflammation, and the accumulation of senescent cells. The latter express Bcl-2 family members (providing resistance to cell death) and exhibit a pro-inflammatory, senescence-associated secretory phenotype (SASP). Preexisting senescent cells cause many aging-related disorders and therapeutic means of eliminating these cells have recently gained attention. The potential consequences of senescent cell removal on vaccine efficacy in older individuals are still ignored. We used the Bcl-2 family inhibitor ABT-263 to investigate the effects of pre-vaccination senolysis on immune responses in old mice. Two different ovalbumin (OVA)-containing vaccines (containing a saponin-based or a CpG oligodeoxynucleotide adjuvant) were tested. ABT-263 depleted senescent cells (apoptosis) and ablated the basal and lipopolysaccharide-induced production of SASP-related factors in old mice. Depletion of senescent cells prior to vaccination (prime/boost) had little effect on OVA-specific antibody and T-cell responses (slightly reduced and augmented, respectively). We then used a preclinical melanoma model to test the antitumor potential of senolysis before vaccination (prime with the vaccine and OVA boost by tumor cells). Surprisingly, ABT-263 treatment abrogated the vaccine's ability to protect against B16 melanoma growth in old animals, an effect associated with reduced antigen-specific T-cell responses. Some, but not all, of the effects were age-specific, which suggests that preexisting senescent cells were partly involved. Hence, depletion of senescent cells modifies immune responses to vaccines in some settings and caution should be taken when incorporating senolytics into vaccine-based cancer therapies.


Subject(s)
Cancer Vaccines , Vaccination , Animals , Mice , Cancer Vaccines/pharmacology , Cellular Senescence , Immunity , Proto-Oncogene Proteins c-bcl-2
2.
Biomed Opt Express ; 14(8): 3988-4002, 2023 Aug 01.
Article in English | MEDLINE | ID: mdl-37799688

ABSTRACT

Fixation methods such as formalin are commonly used for the preservation of tissue with the aim of keeping their structure as close as possible to the native condition. However, fixatives chemically interact with tissue molecules, such as collagen in the extracellular matrix (ECM) or myosin, and may thus modify their structure. Taking advantage of the second- and third-harmonic generation (SHG and THG) emission capabilities of such components, we used nonlinear two-photon microscopy (NL2PM) to evaluate the effect that preservation methods, such as chemical fixatives, have on the nonlinear capabilities of protein components within mouse tissues. Our results show that depending on the preservation technique used, the nonlinear capabilities of collagen, lipid droplets and myosin microarchitecture are strongly affected. Parameters of collagen fibers, such as density and branch points, especially in collagen-sparse regions, e.g., in kidneys, were found to be altered upon formalin fixation. Moreover, cryo-freezing drastically reduced SHG signals from myosin. Our findings provide valuable information to select the best tissue fixation method for visualization and quantification of structural proteins, such as collagen and myosin by advanced NL2PM imaging techniques. This may advance the interpretation of the role these proteins play in disease.

3.
J Neurol ; 269(7): 3597-3604, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35184210

ABSTRACT

BACKGROUND: Lafora disease (LD) is a neurodegenerative disorder featuring action and stimulus-sensitive myoclonus, epilepsy, and cognitive deterioration. Mutations in the EPM2A/EPM2B genes classically prove causative for the disease in most cases. Since full-field electroretinogram (ffERG) may reveal early-stage changes in a wide spectrum of diseases, we aimed to evaluate retinal cones and rods dysfunction in a cohort of Italian LD patients. METHODS: Patients with genetically confirmed LD were recruited and subjected to ffERG analysis following the International Society for Clinical Electrophysiology of Vision (ISCEV) protocol. RESULTS: Six patients aged between 13 and 26 years (mean 19.5 years) were included. The mean age at disease onset was 12.5 years with a mean disease duration of 7 years. The ffERG analysis revealed a global mild to severe generalized cones dysfunction in all patients. Linear correlation was identified between disease stage and the degree of cones and rods dysfunction, as well as between the type of mutation and the cones and rods dysfunction. CONCLUSIONS: This study brings further evidence of early retinal alterations in LD patients. The cones and rods dysfunction grade is related to disease duration. The ffERG is an important tool to determine the disease stage, allowing to evaluate either natural or treatment-related disease progression in a minimally invasive way.


Subject(s)
Lafora Disease , Myoclonic Epilepsies, Progressive , Humans , Lafora Disease/genetics , Mutation/genetics , Myoclonic Epilepsies, Progressive/genetics , Phenotype , Protein Tyrosine Phosphatases, Non-Receptor/genetics , Ubiquitin-Protein Ligases/genetics
4.
Children (Basel) ; 9(2)2022 Jan 24.
Article in English | MEDLINE | ID: mdl-35204869

ABSTRACT

(1) Background: Congenital pseudoarthrosis of the clavicle is a rare condition due to the failure of the union process of the ossification nuclei of the clavicle. The aim of this study was to conduct a systematic review of relevant case series about the argument to find an up-to-date base of evidence for treatment choice. (2) Methods: an electronic literature research of Ovid, MEDLINE and the Cochrane Library databases was conducted, and articles were selected based on inclusion criteria. Demographic data, clinical features, treatment options, outcomes and complications were analyzed. (3) Results: 21 articles met the inclusion criteria, showing a poor overall study quality; 231 pediatric patients (240 clavicles) were analyzed. The condition was typically right sided, showed no sex predominance and no clear predisposing factors. 156 patients underwent surgical treatment, mainly open debridement and refresh of bony ends, fixation with pin or plate and bone graft, with a successful union rate of 87.4%. The nonunion rate was significantly higher in the allograft group (44.4%, p = 0.019). (4) Conclusions: this paper presents an updated systematic review about treatment of congenital pseudoarthrosis of the clavicle. We confirm the generally satisfactory results of surgery, demonstrating that successful union is achievable in 87.4% of cases with a prevalence of 15.7% of major complications. Nonetheless our results should be interpreted with caution due to several limitations.

5.
Ann Jt ; 7: 38, 2022.
Article in English | MEDLINE | ID: mdl-38529145

ABSTRACT

Background and Objective: The discoid lateral meniscus (DLM) is a congenital abnormality of the meniscal shape, characterized by a typical central hypertrophy and a diameter larger than a regular meniscus, potentially leading to knee pain and symptoms, especially in children. The present study provides an update and a general review of this uncommon meniscal pathology. The incidence of discoid meniscus is about 0.4-17% for the lateral and 0.1-0.3% for the medial, although, being often asymptomatic, the true prevalence is unknown. We aim to enhance awareness on this subject to medical care provider. Methods: A literature search was performed on PubMed, including articles written in English until October 2021. Key Content and Findings: The articles regarding etiology, diagnosis and management of DLM in children or in patients younger than 18 years were reviewed using the narrative approach. Conclusions: Recent literature has shown that DLM is one of the most frequent congenital anomalies of the knee encountered during childhood. While asymptomatic children with incidental finding can be managed nonoperatively, symptomatic painful DLM should be addressed surgically, restoring typical anatomy using saucerization, tear repair, and stable fixation of the meniscus. The risk of osteoarthritis progression seems to be higher in children with operated DLM, imposing prolonged follow-up and cartilage preserving strategies for these patients.

6.
Children (Basel) ; 8(12)2021 Dec 06.
Article in English | MEDLINE | ID: mdl-34943340

ABSTRACT

(1) Background: Sprengel's deformity (SD) is a rare congenital anomaly caused by failure in the descent of the scapula. We aimed to systematically review the current literature reporting data from children undergoing surgery for SD, in order to explore the rate of success and complications of the different surgical techniques, possibly providing recommendations about the management of SD in children. (2) Methods: we electronically searched the literature from Ovid, MEDLINE and the Cochrane Library databases. Demographic data, surgical procedures, outcomes and complications were analyzed. We categorized surgical procedures into five groups. (3) Results: 41 articles met the inclusion criteria, showing a poor overall study quality; 674 patients (711 shoulders) were analyzed. Green's and Woodward's procedures, both aiming the scapular relocation in a more anatomical position, were the most commonly used techniques. We counted 168 adverse events (18 major complications). The best clinical and cosmetic results seem to be achieved when surgery is performed in children aged less than eight years. (4) Conclusions: this paper represents the first systematic review reporting qualitative and quantitative data about the surgical treatment of SD. Surgery for SD seems to be effective in increasing the shoulder's range of motion and improving the cosmetic appearance in almost all cases, with a low rate of major complications.

7.
Children (Basel) ; 8(10)2021 Sep 27.
Article in English | MEDLINE | ID: mdl-34682123

ABSTRACT

Background: total hip replacement (THR) is a rare surgical option in children and adolescents with disabling hip diseases. The aim of this study is to report results from a retrospective cohort of patients aged 18 years or less who underwent cementless Ceramic-on-Ceramic (CoC) THR at a single institution, investigating clinical and radiographic outcomes, survival rates, and reasons for revision of the implants. Materials and methods: we queried the Registry of Prosthetic Orthopedic Implants (RIPO) to identify all children and adolescents undergoing THR between 2000 and 2019 at a single Institution. Inclusion criteria were patients undergoing cementless CoC THR, aged less than 18 years at surgery, followed for at least 2 years. Sixty-eight patients (74 hips) matched all the inclusion criteria and were enrolled in the study. We assessed the clinical and radiographic outcomes, the rate of complications, the survival rate, and reasons for revision of the implants. Results: The mean follow-up was 6.6 ± 4.4 years (range 2-20). The most frequent reason for THR was post-traumatic or chemotherapy-induced avascular necrosis (38%). The overall survival rate of the cohort was 97.6% (95% CI: 84.9-99.7%) at 5 years of follow-up, 94.4% (95% CI: 79.8-98.6%) at 10 years and 15 years of follow-up. Two THR in two patients (2.7%) required revision. With the numbers available, Cox regression analysis could not detect any significant interaction between preoperative or intraoperative variables and implant survivorship (p-value 0.242 to 0.989)." The average HOOS was 85 ± 14.3 (range 30.6-100). Overall, 23 patients (48%) reported excellent HOOS scores (>90 points), 21 patients (44%) reported acceptable HOOS scores (60-90 points) while 4 patients (8%) reported poor outcomes (<60 points). Twenty-one patients (43%) were regularly involved into moderate- to high-intensity sport activities (UCLA ≥ 6). Conclusions: Cementless CoC THR is a successful procedure in children and teenagers, having demonstrated high implant survivorship and low rates of complications and failure. A meticulous preoperative planning and implant selection is mandatory, to avoid implant malposition, which is the main reason of failure and revision in these cases. Further studies are needed to assess the impact of the THR on the psychosocial wellbeing of teenagers, as well as risks and benefits and cost-effectiveness in comparison to the hip preserving surgical procedures.

8.
Brain Res Bull ; 176: 142-150, 2021 11.
Article in English | MEDLINE | ID: mdl-34500037

ABSTRACT

Psychological stress and occlusal alterations are contributing etiologic factors for temporomandibular and muscular disorders in the orofacial area. The neural modulation recruited for this relationship, however, is not elucidated. The aim of this study was to investigate potential central mechanisms involved in the exodontia-induced occlusal instability associated with unpredictable chronic stress (UCS). Male adult Wistar rats were submitted to occlusal instability (unilateral molar teeth extraction) and/or to a UCS protocol and treated with diazepam or vehicle. The anxiety-like behavior was evaluated by elevated plus maze (EPM) and open field (OF) tests. Limbic structures such as the central nucleus of the amygdala (CeA), paraventricular nucleus of the hypothalamus (PVN), dorsal periaqueductal gray matter (dPAG) and nucleus accumbens core (NAc) were analyzed for expression of FosB/ΔFosB (immediate early genes) by immunohistochemistry. Exodontia and/or UCS decreased the time spent in the open arms at the EPM and the distance travelled at the OF, and increased the immobility time at the OF, suggesting anxiety-like behavior. In addition, exodontia induction resulted in an upregulation of FosB/ΔFosB in the CeA, PVN and dPAG, while UCS and exodontia + UCS upregulate FosB/ΔFosB immunoreactivity in the CeA, PVN, dPAG and NAc. Treatment with diazepam decreased the expression of FosB/ΔFosB in all analyzed structures of animals subject to UCS and exodontia + UCS, while promoted a reduction in the FosB/ΔFosB expression in the CeA, PVN and dPAG in animals subject to exodontia. Our findings showed an anxiogenic effect of exodontia and UCS, which is correlated with intranuclear neuron activation of limbic structures in a spatially dependent manner and that is prevented by the administration of diazepam.


Subject(s)
Limbic System/metabolism , Neurons/metabolism , Proto-Oncogene Proteins c-fos/metabolism , Stress, Psychological/metabolism , Tooth Extraction , Animals , Anti-Anxiety Agents/pharmacology , Diazepam/pharmacology , Immunohistochemistry , Limbic System/drug effects , Male , Neurons/drug effects , Rats , Rats, Wistar , Up-Regulation
9.
Soc Neurosci ; 16(5): 534-548, 2021 10.
Article in English | MEDLINE | ID: mdl-34253155

ABSTRACT

Cohabitation with a partner undergoing chronic pain induces pain hypersensitivity. Among a lot of other neurochemical pathways, the serotonin (5-HT) role, specifically the 5-HT3 receptor (5-HT3R), in the amygdala has never been evaluated in this model. Here we studied the effects of the amygdala's chemical inhibition, its neuronal activation pattern, and 5-HT, 5-HIAA, and 5-HT turnover within the amygdala. Furthermore, the systemic and intra-amygdala 5-HT3R activation and blockade in mice that cohabited with a conspecific subjected to chronic constriction injury were investigated. Male Swiss mice were housed in partners for 28 days. The dyads were divided into two groups on the 14th day: cagemate nerve constriction (CNC) and cagemate sham (CS). On the 24th day, cagemates underwent a stereotaxic surgery (when necessary) and, on the 28th day, they were evaluated on the writhing test. The amygdala inactivation promotes pain-hypersensitivity behaviors in groups and dyads; cohabitation with a partner with chronic pain did not change FosB-labeled cells in the amygdala's nucleus and increases 5-HT turnover in cagemates. Systemic and intra-amygdala 5-HT3R activation attenuated and enhanced the number of writhes, respectively. In contrast, 5-HT3R blockade reduced hypersensitivity pain response. Results suggest the involvement of amygdala serotonergic signaling via 5-HT3R in empathy-like behavior.


Subject(s)
Chronic Pain , Serotonin , Amygdala , Animals , Chronic Pain/metabolism , Empathy , Humans , Male , Mice , Serotonin/metabolism , Serotonin/pharmacology
10.
Acta Diabetol ; 57(6): 645-650, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31912329

ABSTRACT

PURPOSE: To report on the prevalence of diabetes, diabetic macula oedema (DME) and retinopathy and their respective grading in a large cohort of patients undergoing cataract surgery. METHODS: Data on previous diagnosis of diabetes, fasting glucose, glycated haemoglobin, presence and type of retinopathy and other maculopathy of 3657 patients over 55 years of age undergoing cataract surgery in 13 centres scattered throughout Italy were analysed. RESULTS: A total of 20.4% of patients were known diabetics and 27.9% of diabetics showed signs of retinopathy. Haemoglobin A1C was higher than 48 mmol/L (6.5%) in 32% of diabetics and 2.4% non-diabetics. Fasting blood glucose level was higher than 120 mg/dL in 4.3% non-diabetics and 50% diabetics. Duration of diabetes did not significantly correlate with either fasting glucose or glycated haemoglobin, while higher grades of diabetic retinopathy were significantly more prevalent as duration of disease increased. DME was present in almost 40% of diabetics and 22% of patients showed non-diabetic maculopathy. DISCUSSION: Diabetic retinopathy and DME worsen after cataract extraction thus complicating long-term prognosis and requiring expensive injective therapy. Since unknown diabetics represent 2-4% of the many million cataract candidates and even known diabetics show poor metabolic control and high rates of DME, preoperative medical testing and accurate retinopathy screening may prove both ethically necessary and cost-effective.


Subject(s)
Cataract Extraction/statistics & numerical data , Cataract/epidemiology , Diabetes Mellitus/epidemiology , Diabetic Retinopathy/epidemiology , Macular Edema/epidemiology , Aged , Aged, 80 and over , Cataract/complications , Cataract/diagnosis , Cohort Studies , Diabetes Mellitus/diagnosis , Diabetes Mellitus/surgery , Diabetic Retinopathy/complications , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/surgery , Female , Humans , Italy/epidemiology , Macular Edema/diagnosis , Macular Edema/etiology , Macular Edema/surgery , Male , Middle Aged , Prevalence , Prognosis , Treatment Outcome
11.
Neuropharmacology ; 163: 107808, 2020 02.
Article in English | MEDLINE | ID: mdl-31706993

ABSTRACT

Medications that improve pain threshold can be useful in the pharmacotherapy of Parkinson's disease (PD). Pain is a prevalent PD's non-motor symptom with a higher prevalence of analgesic drugs prescription for patients. However, specific therapy for PD-related pain are not available. Since the endocannabinoid system is expressed extensively in different levels of pain pathway, drugs designed to target this system have promising therapeutic potential in the modulation of pain. Thus, we examined the effects of the 6-hydroxydopamine- induced PD on nociceptive responses of mice and the influence of cannabidiol (CBD) on 6-hydroxydopamine-induced nociception. Further, we investigated the pathway involved in the analgesic effect of the CBD through the co-administration with a fatty acid amide hydrolase (FAAH) inhibitor, increasing the endogenous anandamide levels, and possible targets from anandamide, i.e., the cannabinoid receptors subtype 1 and 2 (CB1 and CB2) and the transient receptor potential vanilloid type 1 (TRPV1). We report that 6-hydroxydopamine- induced parkinsonism decreases the thermal and mechanical nociceptive threshold, whereas CBD (acute and chronic treatment) reduces this hyperalgesia and allodynia evoked by 6-hydroxydopamine. Moreover, ineffective doses of either FAAH inhibitor or TRPV1 receptor antagonist potentialized the CBD-evoked antinociception while an inverse agonist of the CB1 and CB2 receptor prevented the antinociceptive effect of the CBD. Altogether, these results indicate that CBD can be a useful drug to prevent the parkinsonism-induced nociceptive threshold reduction. They also suggest that CB1 and TRPV1 receptors are important for CBD-induced analgesia and that CBD could produce these analgesic effects increasing endogenous anandamide levels.


Subject(s)
Cannabidiol/pharmacology , Nociception/drug effects , Parkinson Disease/physiopathology , Amidohydrolases/antagonists & inhibitors , Analgesics/pharmacology , Animals , Benzamides/pharmacology , Brain/pathology , Capsaicin/analogs & derivatives , Capsaicin/pharmacology , Carbamates/pharmacology , Celecoxib/pharmacology , Hyperalgesia/chemically induced , Hyperalgesia/drug therapy , Hyperalgesia/pathology , Male , Mice , Mice, Inbred C57BL , Morphine/pharmacology , Oxidopamine , Pain/drug therapy , Piperidines/pharmacology , Pyrazoles/pharmacology , Thienamycins/pharmacology
12.
Nitric Oxide ; 93: 90-101, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31604145

ABSTRACT

The mechanisms underlying temporomandibular disorders following orofacial pain remain unclear. Hydrogen sulfide (H2S), a newly identified gasotransmitter, has been reported to modulate inflammation. Cystathionine γ-lyase (CSE) is responsible for the systemical production of H2S, which exerts both pro- and antinociceptive effects through inflammation. In the current study, we investigated whether the endogenous H2S production pathway contributes to arousal and maintenance of orofacial inflammatory pain, through the investigation of the effects of a CSE inhibitor, propargyglycine (PAG), in a rat CFA (Complete Freund Adjuvant)-induced temporomandibular inflammation model to mimic persistent pain in the orofacial region. For this, rats received either CFA or saline in the temporomandibular joints (TMJs), and after 3 or 14 days, they received a single injection of PAG or saline and were evaluated for nociception with the von Frey and formalin test. Also, pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß) were analyzed in TMJs and trigeminal ganglion (TG). In this last one, glial cells reactivity was also verified. Endogenous H2S production rate were measured in both, TMJ and TG. Our results indicated decreased allodynia and hyperalgesic responses in rats submitted to CFA after injection of PAG. Moreover, PAG inhibited leucocyte migration to temporomandibular synovial fluid after 3 and 14 days of inflammation. PAG was able to reduce levels of CBS, CSE, TNF-α, and IL-1ß in the TMJ and TG, after 13 days of CFA injection. The observed increased activation of glial cells in the trigeminal ganglia on the 14th day of inflammation can be prevented by the highest dose of PAG. Finally, CBS and CSE expression, and endogenous H2S production rate in the TMJ and TG was found higher in rats with persistent temporomandibular inflammation compared to rats injected with saline and PAG was able to prevent this elevation. Our results elucidated the molecular mechanisms by which H2S exerts its pro-inflammatory and pro-nociceptive role in the orofacial region by alterations in both local tissue and TG.


Subject(s)
Alkynes/therapeutic use , Glycine/analogs & derivatives , Hydrogen Sulfide/metabolism , Hyperalgesia/drug therapy , Inflammation/metabolism , Pain/drug therapy , Temporomandibular Joint/metabolism , Animals , Cystathionine gamma-Lyase/antagonists & inhibitors , Enzyme Inhibitors/therapeutic use , Glycine/therapeutic use , Interleukin-1beta/metabolism , Male , Neuroglia/drug effects , Rats, Wistar , Trigeminal Ganglion/cytology , Trigeminal Ganglion/metabolism , Tumor Necrosis Factor-alpha/metabolism
13.
Graefes Arch Clin Exp Ophthalmol ; 257(11): 2367-2373, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31418105

ABSTRACT

PURPOSE: The purpose of the present paper is to describe a surgical technique aimed at creating multiple layers of Internal Limiting Membrane (ILM) using Perfluorocarbon Liquid (PFCL) in order to favour the closure of large, chronic and myopic Macular Holes (MH). METHODS: Thirty patients belonging to 3 subgroups: large (> 500 µm), chronic (> 12 months) and myopic (> - 9 diopters), MHs, underwent surgery and completed 6 months follow-up. The ILM was engaged and peeled 360° around the MH, hinged to the rim and folded over the hole. A PFCL bubble spanning the vascular arcades was then injected and the ILM is grasped repeatedly to fold the distal edge towards the MH centre, creating multiple ILM layers over the MH. RESULTS: MH closed in 26/30 cases (86.6%) with no significant difference among subgroups. Vision improved 2.57 ± 1.56 Snellen lines from LogMAR 1.50 ± 1.19 to 1.19 ± 1.32 (p < 0.01). Ellipsoid Zone (EZ) interruption width reduced from 1129 ± 439 µm to 258 ± 507 µm (p < 0.001) and correlated to pattern of MH closure, post-BCVA and line improvement (p < 0.001 in all cases). DISCUSSION: The use PFCL allows multiple ILM layers and resulted in a high closure rate. Pattern of MH closure differs from those previously described leaving a plug of ILM tissue that interrupts retinal architecture often only in the inner layers. PFCL gravity and hydrophobicity displace aqueous while the intensely polar opposite faces of the ILM attract each other. The folded ILM plugs MH and bridges the gap and may help glial cell proliferation and migration.


Subject(s)
Basement Membrane/transplantation , Endotamponade/methods , Fluorocarbons/pharmacology , Myopia/complications , Refraction, Ocular/physiology , Retinal Perforations/surgery , Surgical Flaps , Aged , Chronic Disease , Female , Follow-Up Studies , Humans , Macula Lutea/pathology , Male , Middle Aged , Myopia/diagnosis , Myopia/physiopathology , Retinal Perforations/diagnosis , Retinal Perforations/etiology , Retrospective Studies , Tomography, Optical Coherence , Treatment Outcome , Visual Acuity , Vitrectomy/methods
14.
Nutrients ; 11(2)2019 Jan 22.
Article in English | MEDLINE | ID: mdl-30678262

ABSTRACT

Glaucoma is a multifactorial disease in which pro-apoptotic signals are directed to retinal ganglion cells. During this disease the conventional outflow pathway becomes malfunctioning. Aqueous humour builds up in the anterior chamber, leading to increased intraocular pressure. Both of these events are related to functional impairment. The knowledge of molecular mechanisms allows us to better understand the usefulness of substances that can support anti-glaucoma therapy. The goal of glaucoma therapy is not simply to lower intraocular pressure; it should also be to facilitate the survival of retinal ganglion cells, as these constitute the real target tissue in this disease, in which the visual pathway is progressively compromised. Indeed, an endothelial dysfunction syndrome affecting the endothelial cells of the trabecular meshwork occurs in both normal-tension glaucoma and high-tension glaucoma. Some substances, such as polyunsaturated fatty acids, can counteract the damage due to the molecular mechanisms - whether ischemic, oxidative, inflammatory or other - that underlie the pathogenesis of glaucoma. In this review, we consider some molecules, such as polyphenols, that can contribute, not only theoretically, to neuroprotection but which are also able to counteract the metabolic pathways that lead to glaucomatous damage. Ginkgo biloba extract, for instance, improves the blood supply to peripheral districts, including the optic nerve and retina and exerts a neuro-protective action by inhibiting apoptosis. Polyunsaturated fatty acids can protect the endothelium and polyphenols exert an anti-inflammatory action through the down-regulation of cytokines such as TNF-α and IL-6. All these substances can aid anti-glaucoma therapy by providing metabolic support for the cells involved in glaucomatous injury. Indeed, it is known that the food we eat is able to change our gene expression.


Subject(s)
Glaucoma/drug therapy , Glaucoma/pathology , Fatty Acids, Unsaturated/therapeutic use , Food , Glaucoma/diet therapy , Humans , Polyphenols/therapeutic use
15.
Nutrients ; 10(6)2018 May 24.
Article in English | MEDLINE | ID: mdl-29795004

ABSTRACT

Polyunsaturated fatty acids (PUFA) are known to have numerous beneficial effects, owing to their anti-inflammatory and antioxidant properties. From a metabolic standpoint, the mitochondria play a fundamental role in cellular homeostasis, and oxidative stress can affect their functioning. Indeed, the mitochondria are the main source of ROS, and an imbalance between ROS and antioxidant defenses leads to oxidative stress. In addition, aging, the decline of cellular functions, and continual exposure to light underlie many diseases, particularly those of the eye. Long-term exposure to insults, such as UV light, visible light, ionizing radiation, chemotherapeutics, and environmental toxins, contribute to oxidative damage in ocular tissues and expose the aging eye to considerable risk of pathological consequences of oxidative stress. Ample antioxidant defenses responsible for scavenging free radicals are essential for redox homeostasis in the eye, indeed, eye tissues, starting from the tear film, which normally are exposed to high oxygen levels, have strong antioxidant defenses that are efficient for protecting against ROS-related injuries. On the contrary, instead, the trabecular meshwork is not directly exposed to light and its endothelial cells are poorly equipped with antioxidant defenses. All this makes the eye a target organ of oxidative damage. This review focuses on the role of the polyunsaturated fatty acids in the human eye, particularly in such pathologies as dry eye, glaucoma, and macular degeneration, in which dietary PUFA supplementation can be a valid therapeutic aid.


Subject(s)
Dietary Supplements , Eye Diseases/prevention & control , Eye/metabolism , Fatty Acids, Unsaturated/administration & dosage , Oxidative Stress , Animals , Antioxidants/metabolism , Eye/pathology , Eye Diseases/epidemiology , Eye Diseases/metabolism , Eye Diseases/pathology , Fatty Acids, Unsaturated/metabolism , Humans , Protective Factors , Reactive Oxygen Species/metabolism , Risk Factors
16.
J Rheumatol ; 45(8): 1167-1172, 2018 08.
Article in English | MEDLINE | ID: mdl-29657140

ABSTRACT

OBJECTIVE: Anti-TNF-α agents have significantly changed the management of juvenile idiopathic arthritis (JIA). We evaluated the safety and efficacy of adalimumab (ADA) and infliximab (IFX) for the treatment of JIA-associated uveitis in patients treated for ≥ 2 years. METHODS: Patients with JIA-associated uveitis treated with IFX and ADA were managed by a standardized protocol and data were entered in the ORCHIDEA registry. At baseline, all patients were refractory to standard immunosuppressive treatment or were corticosteroid-dependent. Data recorded every 3 months were uveitis course, number/type of ocular flares and complications, drug-related adverse events (AE), and treatment switch or withdrawal. Data of patients treated for ≥ 2 years were analyzed by descriptive statistics. RESULTS: Up to December 2014, 154 patients with ≥ 24 months followup were included in the study. Fifty-nine patients were treated with IFX and 95 with ADA. Clinical remission, defined as the absence of flares for > 6 months on treatment, was achieved in 69 patients (44.8%), with a better remission rate for ADA (60.0%) as compared to IFX (20.3%; p < 0.001). A significant reduction of flares was observed in all patients without difference between the 2 treatment modalities. The number of new ocular complications decreased in both groups but was lower for ADA (p = 0.015). No serious AE were recorded; 16.4% of patients experienced 35 minor AE and the incidence rate was lower with ADA than with IFX. CONCLUSION: At the 2-year followup, ADA showed a better efficacy and safety profile than IFX for the treatment of refractory JIA-associated uveitis.


Subject(s)
Adalimumab/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Juvenile/drug therapy , Immunosuppressive Agents/therapeutic use , Infliximab/therapeutic use , Uveitis/drug therapy , Adalimumab/adverse effects , Adolescent , Antirheumatic Agents/adverse effects , Arthritis, Juvenile/complications , Child , Child, Preschool , Female , Humans , Immunosuppressive Agents/adverse effects , Infliximab/adverse effects , Male , Treatment Outcome , Uveitis/etiology
17.
Am J Ophthalmol ; 170: 128-132, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27521606

ABSTRACT

PURPOSE: To analyze changes in tear osmolarity and the Ocular Surface Disease Index (OSDI) in patients after cataract surgery. DESIGN: Prospective, observational cohort study. METHODS: setting: Institutional. PATIENT POPULATION: Fifty-two patients with a unilateral cataract (study eye) scheduled for surgery and good visual function in the fellow (control eye). Patients were excluded who were receiving chronic topical therapy, such as glaucoma medications, or had a history of previous ocular surgery. INTERVENTION: Examinations were performed preoperatively and 1 and 3 months postoperatively. At each visit, complete anterior and posterior segment examinations were performed. MAIN OUTCOME MEASURES: Best-corrected and uncorrected visual acuities, tear osmolarity, and OSDI scores. RESULTS: The mean tear osmolarity values were, respectively, 305.63 ± 15.07, 305.70 ± 16.48, and 303.88 ± 11.75 mOsm/L at baseline and 1 and 3 months postoperatively (P = .067), compared with 309.74 ± 15.92, 306.74 ± 13.22, and 303.19 ± 11.02 mOsm/L at the same times in the unoperated control eyes (P = .064). Patients with normal osmolarity (<312 mOsm/L) and hyperosmolarity values (≥312 mOsm/L) had respective OSDI scores of 22.77 ± 15.73 and 36.02 ± 12.20 at baseline (P = .01), 12.44 ± 12.44 and 14.45 ± 13.45 at 1 month (P = .7), and 10.37 ± 11.11 and 16.48 ± 8.08 at 3 months postoperatively (P = .01). CONCLUSIONS: We did not find differences in tear film osmolarity between the operated eyes and the fellow unoperated control eyes at any time period during the study. Patients with tear osmolarity values of 312 mOsm/L or higher are more likely to have more ocular discomfort postoperatively. Ophthalmologists should consider evaluating tear osmolarity preoperatively, especially in highly demanding patients.


Subject(s)
Dry Eye Syndromes/physiopathology , Lens Implantation, Intraocular , Phacoemulsification , Tears/chemistry , Aged , Dry Eye Syndromes/etiology , Female , Humans , Intraocular Pressure/physiology , Male , Osmolar Concentration , Postoperative Complications , Prospective Studies , Surveys and Questionnaires , Visual Acuity/physiology
18.
Environ Monit Assess ; 187(9): 586, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26307688

ABSTRACT

The cultivation of rice, one of the most important staple crops worldwide, has very high water requirements. A variety of irrigation practices are applied, whose pros and cons, both in terms of water productivity and of their effects on the environment, are not completely understood yet. The continuous monitoring of irrigation and rainfall inputs, as well as of soil water dynamics, is a very important factor in the analysis of these practices. At the same time, however, it represents a challenging and costly task because of the complexity of the processes involved, of the difference in nature and magnitude of the driving variables and of the high variety of field conditions. In this paper, we present the prototype of an integrated, multisensor system for the continuous monitoring of water dynamics in rice fields under different irrigation regimes. The system consists of the following: (1) flow measurement devices for the monitoring of irrigation supply and tailwater drainage; (2) piezometers for groundwater level monitoring; (3) level gauges for monitoring the flooding depth; (4) multilevel tensiometers and moisture sensor clusters to monitor soil water status; (5) eddy covariance station for the estimation of evapotranspiration fluxes and (6) wireless transmission devices and software interface for data transfer, storage and control from remote computer. The system is modular and it is replicable in different field conditions. It was successfully applied over a 2-year period in three experimental plots in Northern Italy, each one with a different water management strategy. In the paper, we present information concerning the different instruments selected, their interconnections and their integration in a common remote control scheme. We also provide considerations and figures on the material and labour costs of the installation and management of the system.


Subject(s)
Agriculture/methods , Oryza , Water , Floods , Groundwater , Italy , Software , Soil/chemistry , Wireless Technology
19.
In Vivo ; 29(1): 45-50, 2015.
Article in English | MEDLINE | ID: mdl-25600529

ABSTRACT

BACKGROUND/AIM: Standard stapled transanal rectal resection (STARR) with two PPH-01™ poses some questions regarding the completeness of prolapse resection in patients with obstructed defecation syndrome (ODS) since 20% to 30% of patients have persistent rectocele or rectal intussusception that may impair the physiological recovery of rectal sensitivity. New high-volume (HV) devices, such as CPH34 HV™ and CPH36 SMS™, allow for wider prolapsectomy to be performed and we herein assessed the possibility and safety of a STARR mono-stapler. MATERIALS AND METHODS: On May 30th-31st 2011, 13 pigs were selected to undergo standard STARR with two PPH-01™ (n=2) or STARR mono-stapler with one CPH34 HV™ (n=11) at the Experimental Center of Vila do Conde (Portugal); another set of 13 pigs was selected on January 14th-17th 2014 to undergo standard STARR (n=2) or STARR mono-stapler by means of one CPH36 SMS™ (n=11). The length, height, square surface, and volume of resected specimens were intra-operatively assessed. Pigs were monitored for three days before undergoing transrectal sonography and autopsy to check for locoregional complications. RESULTS: CPH36 SMS™ STARR mono-stapler achieved 57% higher volume of prolapsectomy compared to Standard STARR (p=0.008); moreover, surface measures of the specimens of CPH36 SMS™ STARR mono-stapler were significantly higher (length, p=0.003; height, p=0.004; square surface, p=0.002) compared to CPH34 HV™ STARR mono-stapler, with a 97.8% increase of prolapsectomy (p<0.001). No intra- or early postoperative complications occurred. Transrectal sonography and autopsy detected: two (50%) small intra-parietal and two (50%) extra-rectal haematomata after Standard STARR; five small intraparietal (45.5%) and one (9%) extra-rectal haematoma after CPH34 HV™ STARR mono-stapler; three (27.2%) small intraparietal and (27.2%) extra-rectal haematomata after CPH36 SMS™ STARR mono-stapler. CONCLUSION: CPH36 SMS™ STARR mono-stapler is quite feasible both from the technological and safety standpoint; most importantly, the higher volume of prolapsectomy achievable with CPH36 SMS™ compared to standard STARR with two PPH-01™ might reduce the risk of residual/recurrent prolapse and further improve the clinical efficacy of the STARR procedure.


Subject(s)
Rectal Diseases/etiology , Rectal Diseases/surgery , Animals , Postoperative Complications , Rectal Diseases/pathology , Surgical Procedures, Operative/adverse effects , Surgical Procedures, Operative/methods , Surgical Staplers , Surgical Stapling , Swine , Treatment Outcome
20.
Hip Int ; 21(6): 653-6, 2011.
Article in English | MEDLINE | ID: mdl-22183446

ABSTRACT

The authors report a series of 11 patients treated surgically by trochanteroplasty for septic arthritis of the hip at our institution from 1974 to 2010. Trochanteroplasty was indicated due to the absence of a valid alternative, and because it does not rule out the option of total hip arthroplasty at a later stage.


Subject(s)
Arthritis, Infectious/surgery , Arthroplasty/methods , Bone Malalignment/surgery , Femur/surgery , Hip Dislocation/surgery , Hip Joint/surgery , Arthritis, Infectious/complications , Bone Malalignment/etiology , Child , Child, Preschool , Female , Hip Dislocation/etiology , Hip Dislocation, Congenital/complications , Hip Dislocation, Congenital/surgery , Hip Joint/pathology , Humans , Male , Osteotomy , Treatment Outcome
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