The Antidepressant Drug Amitriptyline Affects Human SH-SY5Y Neuroblastoma Cell Proliferation and Modulates Autophagy.

Amitriptyline is a tricyclic antidepressant commonly used for depressive disorders and is prescribed off-label for several neurological conditions like neuropathic pain, migraines and anxiety. Besides their action on the reuptake of monoaminergic neurotransmitters, tricyclic antidepressants interact with several additional targets that may contribute to either therapeutic or adverse effects. Here, we investigated the effects of amitriptyline on proliferation and autophagy (i.

Neuroprotective Effect of a Nutritional Supplement Containing Spearmint Extract, Forskolin, Homotaurine and Group B Vitamins in a Mouse Model of Transient Ocular Hypertension.

Glaucoma is one of the most common sight-threatening eye disorders and one of the main causes of irreversible blindness worldwide. The current therapies focusing on reducing intraocular pressure (IOP) are often insufficient to prevent the progression of the disease, so the therapeutic management of glaucoma remains a challenge. The aim of this study was to evaluate the neuroprotective, IOP-lowering independent effects of a nutritional supplement containing forskolin, homotaurine, spearmint extract and vitamins of the B group in a model of acute glaucoma developed in mice.

Autophagy: A Novel Pharmacological Target in Diabetic Retinopathy.

Autophagy is the major catabolic pathway involved in removing and recycling damaged macromolecules and organelles and several evidences suggest that dysfunctions of this pathway contribute to the onset and progression of central and peripheral neurodegenerative diseases. Diabetic retinopathy (DR) is a serious complication of diabetes mellitus representing the main preventable cause of acquired blindness worldwide. DR has traditionally been considered as a microvascular disease, however this concept has evolved and neurodegeneration and neuroinflammation have emerged as important determinants in the pathogenesis and evolution of the retinal pathology.

The promise of neuroprotection by dietary restriction in glaucoma.

Glaucoma, a progressive age-related optic neuropathy characterized by the death of retinal ganglion cells, is the most common neurodegenerative cause of irreversible blindness worldwide. The therapeutic management of glaucoma, which is limited to lowering intraocular pressure, is still a challenge since visual loss progresses in a significant percentage of treated patients. Restricted dietary regimens have received considerable attention as adjuvant strategy for attenuating or delaying the progression of neurodegenerative diseases.

Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia.

Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia.

Natural Products: Evidence for Neuroprotection to Be Exploited in Glaucoma.

Glaucoma, a leading cause of irreversible blindness worldwide, is an optic neuropathy characterized by the progressive death of retinal ganglion cells (RGCs). Elevated intraocular pressure (IOP) is recognized as the main risk factor. Despite effective IOP-lowering therapies, the disease progresses in a significant number of patients.

The Role of Autophagy in Glaucomatous Optic Neuropathy.

Autophagy is a conserved lysosomal-dependent pathway responsible for the degradation of cytoplasmic macromolecules. Based on the mechanism of cargo delivery to lysosomes, mammalian cells can undergo micro, macro, and chaperone-mediated autophagy. Other than physiological turnover of proteins and organelles, autophagy regulates cellular adaptation to different metabolic states and stressful conditions by allowing cellular survival or, when overactivated, participating to cell death.

Pattern of triptans use: a retrospective prescription study in Calabria, Italy.

Triptans are 5-hydroxytryptamine 1B/1D receptor agonists used in moderate to severe migraine attacks as first line when non-specific, symptomatic, nonsteroidal anti-inflammatory drugs are not effective. To gain insight in the treatment of migraine in the regional context, this retrospective (from January to August of the years 2017 and 2018) study aimed at monitoring the use of triptans approved by the regional health authority in Calabria. The data demonstrate that the overall treatment of migraine with triptans in the different provinces of Calabria falls in the average regional prescription/dispensation.

Medical Equipment Replacement Prioritisation: A Comparison Between Linear and Fuzzy System Models.

In hospital management, health technology assessment techniques are being increasingly developed. This paper presents a comparison of the results obtained using two models for replacement priority value calculation applied to the Galliera hospital in Genoa (Italy). One the models was developed at the Galliera Hospital along the lines of the model by Fennigkoh and addresses four primary replacement issues: equipment service and support, equipment function, cost benefits and clinical efficacy, by a "yes-no" scheme.

The tricyclic antidepressant clomipramine inhibits neuronal autophagic flux.

Antidepressants are commonly prescribed psychotropic substances for the symptomatic treatment of mood disorders. Their primary mechanism of action is the modulation of neurotransmission and the consequent accumulation of monoamines, such as serotonin and noradrenaline. However, antidepressants have additional molecular targets that, through multiple signaling cascades, may ultimately alter essential cellular processes.

Neuroinflammation as a target for glaucoma therapy.

The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation - involving the activation and proliferation of resident glial cells (astrocytes, Muller cells and microglia) and the release of a plethora of anti- and pro-inflammatory cytokines, chemokines and reactive oxygen species - has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome.

Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival.

Autophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal-lysosomal pathway, is fundamental for neuronal homeostasis and its deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic-ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process.

Dibutyryl cAMP- or Interleukin-6-induced astrocytic differentiation enhances mannose binding lectin (MBL)-associated serine protease (MASP)-1/3 expression in C6 glioma cells.

Mannose-binding lectin (MBL)-Associated Serine Proteases (MASP)-1 and 3, key enzymes in the lectin complement pathway of innate immune response, are also expressed in glioma cell lines. We investigated MASP-1 and MASP-3 expression during dibutyryl cyclic AMP (dbcAMP)- or Interleukin-6 (rIL-6)-induced astrocytic differentiation of C6 glioma cells. Our results demonstrate that C6 cells express basal levels of MASP-1 and MASP-3 and following exposure to dbcAMP or IL-6, a consistent MASP-1 and MASP-3 mRNA up-regulation was found, with a behavior similar to that showed by the fibrillary acidic protein (GFAP).

Early LC3 lipidation induced by d-limonene does not rely on mTOR inhibition, ERK activation and ROS production and it is associated with reduced clonogenic capacity of SH-SY5Y neuroblastoma cells.

Background: d-Limonene is a natural monoterpene abundant in Citrus essential oils. It is endowed with several biological activities, including inhibition of carcinogenesis and promotion of tumour regression. Recently, d-limonene has been shown to modulate autophagic markers in vitro at concentrations found in vivo, in clinical pharmacokinetic studies.

Post-ischemic treatment with azithromycin protects ganglion cells against retinal ischemia/reperfusion injury in the rat.

Purpose: Retinal ischemic phenomena occur in several ocular diseases that share the degeneration and death of retinal ganglion cells (RGCs) as the final event. We tested the neuroprotective effect of azithromycin, a widely used semisynthetic macrolide antibiotic endowed with anti-inflammatory and immunomodulatory properties, in a model of retinal ischemic injury induced by transient elevation of intraocular pressure in the rat.

Methods: Retinal ischemia was induced in adult rats with transient elevation of intraocular pressure.

Rational Basis for Nutraceuticals in the Treatment of Glaucoma.

Background: Glaucoma, the second leading cause of blindness worldwide, is a chronic optic neuropathy characterized by progressive retinal ganglion cell (RGC) axons degeneration and death. Primary open-angle glaucoma (OAG), the most common type, is often associated with increased intraocular pressure (IOP), however other factors have been recognized to partecipate to the patogenesis of the optic neuropathy. IOP-independent mechanisms that contribute to the glaucoma-related neurodegeneration include oxidative stress, excitotoxicity, neuroinflammation, and impaired ocular blood flow.

Retinal ganglion cell death in glaucoma: Exploring the role of neuroinflammation.

In clinical glaucoma, as well as in experimental models, the loss of retinal ganglion cells occurs by apoptosis. This final event is preceded by inflammatory responses involving the activation of innate and adaptive immunity, with retinal and optic nerve resident glial cells acting as major players. Here we review the current literature on the role of neuroinflammation in neurodegeneration, focusing on the inflammatory molecular mechanisms involved in the pathogenesis and progression of the optic neuropathy.

Caspase-1-independent Maturation of IL-1β in Ischemic Brain Injury: is there a Role for Gelatinases?

Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain. Interleukin (IL)-1β is a pro-inflammatory cytokine that plays a pivotal role in the detrimental inflammatory processes that participate to cerebral ischemic damage. After injury, it is produced by distinct cells of the neurovascular unit as an inactive precursor, pro-IL-1β.

Rational Basis for the Use of Bergamot Essential Oil in Complementary Medicine to Treat Chronic Pain.

In complementary medicine, aromatherapy uses essential oils to improve agitation and aggression observed in dementia, mood, depression, anxiety and chronic pain. Preclinical research studies have reported that the essential oil obtained from bergamot (BEO) fruit (Citrus bergamia, Risso) modifies normal and pathological synaptic plasticity implicated, for instance, in nociceptive and neuropathic pain. Interestingly, recent results indicated that BEO modulates sensitive perception of pain in different models of nociceptive, inflammatory and neuropathic pain modulating endogenous systems.

Intravitreal injection of forskolin, homotaurine, and L-carnosine affords neuroprotection to retinal ganglion cells following retinal ischemic injury.

Purpose: Retinal ganglion cell (RGC) death is the final event leading to visual impairment in glaucoma; therefore, identification of neuroprotective strategies able to slow down or prevent the process is one of the main challenges for glaucoma research. The purpose of this study was to evaluate the neuroprotective potential of RGC death induced by the in vivo transient increase in intraocular pressure (IOP) of a combined treatment with forskolin, homotaurine, and L-carnosine. Forskolin (7beta-acetoxy-8, 13-epoxy-1a, 6β, 9a-trihydroxy-labd-14-en-11-one) is an activator of adenylate cyclase that decreases IOP by reducing aqueous humor production and functions as a neuroprotector due to its neurotrophin-stimulating activity.

Role of D-Limonene in autophagy induced by bergamot essential oil in SH-SY5Y neuroblastoma cells.

Bergamot (Citrus bergamia, Risso et Poiteau) essential oil (BEO) is a well characterized, widely used plant extract. BEO exerts anxiolytic, analgesic and neuroprotective activities in rodents through mechanisms that are only partly known and need to be further investigated. To gain more insight into the biological effects of this essential oil, we tested the ability of BEO (0.