- Luigi Morrone - avvocato - appassionato di storia e letteratura classicaedit
A Whiter Shade of Pale dei Procol Harum, incisa nel 1967 contiene numerosi elementi che potrebbero essere interpretati come richiami a simboli esoterici o a testi letterari. L'autore del testo smentisce. Qual è la verità?
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La collana "Minima Storiografica" di Nuova Rivista storica pubblica un'interessantissima opera di Gioacchino Volpe, curata dal direttore Eugenio Di Rienzo e da Fabrizio Rudi. Volpe aveva concepito un grande affresco sulla storia d'Italia... more
La collana "Minima Storiografica" di Nuova Rivista storica pubblica un'interessantissima opera di Gioacchino Volpe, curata dal direttore Eugenio Di Rienzo e da Fabrizio Rudi. Volpe aveva concepito un grande affresco sulla storia d'Italia a cavallo della Grande Guerra, di cui aveva pubblicato nel 1940 il primo volume, "Il popolo italiano fra la pace e la guerra", ma le vicende belliche ed il successivo buen retiro a Sant'Arcangelo di Romagna, gli impedirono di portarlo a termine. In forma dattiloscritta, era rimasto solo il secondo volume dell'opera come concepita da Volpe: "Il popolo italiano nel primo anno della Grande Guerra", limitato al periodo 23 maggio 1915-17 agosto 1916.
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Protestanti, illuministi, alcuni marxisti e alcuni massoni (non tutti, per fortuna ...) hanno fatto a gara per costruire la leggenda di un medioevo epoca oscura, sentina di ogni inciviltà. Raffaello Morghen annotava: "È universalmente... more
Protestanti, illuministi, alcuni marxisti e alcuni massoni (non tutti, per fortuna ...) hanno fatto a gara per costruire la leggenda di un medioevo epoca oscura, sentina di ogni inciviltà. Raffaello Morghen annotava: "È universalmente noto che il Medioevo non ha mai goduto di quella che comunemente si chiama buona stampa". Da questo fuoco concentrico i cattolici hanno sviluppato una sorta di complesso di inferiorità onde si sono autoconvinti di essere responsabili di una serie indeterminata di misfatti e di essere stati per secoli nemici del progresso. Anche i "colti" hanno recepito questa immagine negativa del medioevo: nella sua scopiazzata Storia d'Italia, Montanelli titola "L'Italia dei secoli bui" la parte dedicata al medioevo; le vestali della politically correctness inneggiarono al "coraggio" della Fallaci che alla fine di un'intervista a Khomeini disse: " Me lo tolgo immediatamente questo stupido cencio da medioevo", utilizzando il termine nel senso di "inciviltà", così dimostrando ignoranza e maleducazione al tempo stesso. E nell'immaginario collettivo si sono radicati convincimenti a volte assurdi, ma comunque così penetrati a fondo, da essere patrimonio del "pensare comune". Meritoria l'opera di Chiara Frugoni nello scrivere libri di taglio divulgativo per smentire tanti luoghi comuni. Io, più modestamente, utilizzerò le mie letture per sfatare alcune "leggende metropolitane" fiorite sul medioevo.
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Una "lettera aperta" agli storici circa la necessità di un dibattito sull'Unità d'Italia che coinvolga il grande pubblico
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Improbabili parallelismi tra l'unificazione italiana e quella tedesca
This essay compares two different historiographic interpretations of the concepts of State, Nation, Ethnic groups.
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Nell'epoca della Rete, con il libero accesso alla diffusione delle proprie idee, soprattutto attraverso le comunità virtuali (che gli anglomani chiamano "social network"), si assiste ad attacchi quotidiani verso questo "eccesso di... more
Nell'epoca della Rete, con il libero accesso alla diffusione delle proprie idee, soprattutto attraverso le comunità virtuali (che gli anglomani chiamano "social network"), si assiste ad attacchi quotidiani verso questo "eccesso di libertà". Uno dei temi ricorrenti è quello delle "fake news", che-secondo i detrattori della Rete-troverebbero nei "social network" una sorta di "terreno di coltura" ideale. Non è assolutamente così. I falsi circolano da sempre. E si incistano diventando verità recepita dalla massa, anche quando la menzogna viene smascherata. L'esempio paradigmatico è la Donazione di Costantino (Constitutum Constantini), un documento secondo cui l'imperatore Costantino avrebbe donato a Papa Silvestro la parte Occidentale dell'Impero. Un falso smaccato, quello che i giuristi definiscono "falso grossolano". La sua falsità venne svelata già all'inizio della sua diffusione, dall'imperatore Ottone III, che fece tagliare le mani al diacono Giovanni, presunto autore del falso 1. Eppure, per secoli e secoli, non si ebbero dubbi sulla sua autenticità, tanto che «Ai tempi di Dante nessuno riteneva falsa la Donazione; anzi era salda una tradizione di autenticità che risaliva al XII sec., quando il documento era stato inserito nel Decretum Gratiani, il testo ufficiale per l'insegnamento del diritto canonico. Ma era del pari viva una secolare polemica tra canonisti e civilisti, cercando questi ultimi d'infirmare il valore giuridico della Donazione con argomenti che avevano il loro sostegno nelle leggi romane» 2 Lo stesso Dante, senza dubitare della sua autenticità, ne negava la rilevanza: « ... sua probatio nulla est, quia Constantinus alienare non poterat Imperii dignitatem, nec Ecclesia recipere» 3 Curiosamente, gli umanisti, che con Niccolò da Cusa 4 e Lorenzo Valla 5 contribuirono a svelare la falsità della presunta donazione, furono una vera e propria fabbrica di falsi. Ad Omero e Virgilio, i due massimi poeti dell'antichità, continuarono ad essere attribuite una serie di opere chiaramente altrui 6 A volte, addirittura, fabbricavano di sana pianta opere in latino attribuendole ai poeti romani Celeberrimo l'aneddoto, totalmente inventato, di Virgilio che, risentito per l'usurpazione di alcune sue opere da parte di terzi, avrebbe scritto i versi Hos ego versiculos feci, tulit alter honores: Sic vos non vobis nidificatis aves;
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A margine del "vademecum" dell'Istituto regionale per la storia della Resistenza e dell’Età contemporanea nel Friuli Venezia Giulia: quella dei titini ai danni dei nostri connazionali del confine orientale, fu "pulizia etnica"?
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Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain. Interleukin... more
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. Although previous studies have suggested that caspase-1 is the main enzyme implicated in the cleavage of pro-IL-1β into the biologically active cytokine, recent work has demonstrated that, under ischemia-reperfusion conditions, other mechanisms may be involved in cytokine maturation. Indeed, we have shown that in rats subjected to transient middle cerebral artery occlusion (MCAo), elevation of IL-1β levels is paralleled by an elevation of gelatinolytic, but not caspase-1 activity in the injured hemisphere and pharmacological inhibition of gelatinases, i.e. matrix metalloproteases (MMP)-2 and MMP-9 prevents cytokine maturation. These findings further support the hypothesis that, under ischemia-reperfusion injury, cerebral elevation of IL-1β occurs via mechanisms other than caspase-1, likely involving gelatinases.
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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... more
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.
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Glaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible... more
Glaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a number of evidences endorse the hypothesis that glaucoma is a neuro-degenerative disorder of the central nervous system and suggest a possible connection between glaucomatous damage and cerebrovascular alterations. The mechanisms underlying RGC loss are not yet fully known but alterations of the autophagy machinery have been recently proposed as a potential contributing factor as for Alzheimer's disease. Here we review the current literature on new strategies for neuroprotection in glaucoma, focusing on pharmacologic strategies to minimize RGC damage.
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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... more
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. Although previous studies have suggested that caspase-1 is the main enzyme implicated in the cleavage of pro-IL-1β into the biologically active cytokine, recent work has demonstrated that, under ischemia-reperfusion conditions, other mechanisms may be involved in cytokine maturation. Indeed, we have shown that in rats subjected to transient middle cerebral artery occlusion (MCAo), elevation of IL-1β levels is paralleled by an elevation of gelatinolytic, but not caspase-1 activity in the injured hemisphere and pharmacological inhibition of gelatinases, i.e. matrix metalloproteases (MMP)-2 and MMP-9...
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The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in... more
The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticeps, a specific blocker of a non-inactivating, voltage-sensitive K+ channel, were studied after focal injection into one dorsal hippocampus in rats pretreated with CGP040116, a N-methyl-D-aspartate (NMDA) receptor antagonist, and in rats bearing a monolateral surgical lesion of the Schaffer collaterals whose terminals originate from CA3 pyramids and release glutamate in the CA1 hippocampal area. Administration of 35 pmol gamma-dendrotoxin elicited in all of the treated animals (n=8) bilateral EEG discharges and damage to the hippocampal formation. Quantitation of the damage revealed significant bilateral neuronal cell loss in the CA1, CA3 and CA4 pyramidal cell layers. The lowest dose (0.35 pmol; n=4) of the toxin used did not affect EEG activity and failed to cause significant hippocampal cell loss whereas the 3.5 pmol (n=6) dose caused EEG seizures and hippocampal cell loss limited to the CA1 area. Systematic intraperitoneal administration of CGP040116 (5mg/kg given 30 min. previously) delayed the onset of EEG seizures and reduced the number of epileptogenic discharges typically observed in rats receiving an injection of gamma-dendrotoxin (35 pmol) alone. Similarly, this treatment prevented the damage inflicted to the hippocampus by the toxin and in no instance was significant neuronal loss observed. Protection against seizures and hippocampal damage was also observed by a monolateral surgical lesion to the Schaffer collaterals. In conclusion, the present data suggest that an excitotoxic, glutamate-mediated, type of mechanism underlies seizures and hippocampal damage induced by gamma-dendrotoxin in rats.
Research Interests: Electroencephalography, Hippocampus, Animals, Male, Peptides, and 5 moreNeurons, Rats, Wistar Rats, Seizures, and Glutamic Acid
ABSTRACT no abstract.
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Research Interests: Health Care, Kidney diseases, Adolescent, Biopsy, Italy, and 15 moreAcute renal failure, Humans, Clinical research, Kidney, Female, Clinical Sciences, Aged, Chronic Renal Failure, Adult, Kidney Disease, Clinical Presentation, IgA nephropathy, Epidemiologic Studies, Internet, and Focal Segmental Glomerulosclerosis
Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of lipoprotein metabolism, resulting from loss of function of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), a key enzyme in... more
Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of lipoprotein metabolism, resulting from loss of function of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), a key enzyme in extracellular cholesterol metabolism and reverse cholesterol transport (RCT). The human LCAT gene has been mapped to chromosome band 16q22, and consists of 6 exons encoding for a mature protein of 416 amino acids. In the present study, we describe the molecular phenotype of a patient with classical LCAT deficiency and progressive renal failure. Sequence analysis of the LCAT gene showed 2 homozygous missense mutations: the common variant p.S208T, described as a homozygous change for the first time, and a missense mutation characterized by the substitution of Leu372 to Arg. Clinical, biochemical and renal histological studies were also performed to elucidate the functional effects of these variations. In the proband and his brother, LCAT activity and plasma cholesterol esterification rate (CER) were absent, while plasma LCAT concentrations were slightly reduced. By light microscopy, silver-stained renal biopsy specimens of the proband showed focal segmental glomerulosclerosis, while electron microscopy detected lipid deposits with both vacuolar lucent appearance and electron-dense lamellar structures within the mesangial matrix and glomerular basement membrane. This study describes for the first time the occurrence of two homozygous missense mutations as the common variant p.S208T and the mutation p.L372R in familial LCAT deficiency.
Research Interests: Nephrology, Kidney diseases, Italy, Lipids, Humans, and 6 moreFemale, Male, Pedigree, Phenotype, Clinical Sciences, and Adult
Cardiac valve calcifications are present in dialysis patients and regarded as dependent on a deranged mineral metabolism. Few data are available for patients with chronic kidney disease (CKD) not on dialysis. This study evaluates the... more
Cardiac valve calcifications are present in dialysis patients and regarded as dependent on a deranged mineral metabolism. Few data are available for patients with chronic kidney disease (CKD) not on dialysis. This study evaluates the potential association between the extent of cardiac valve calcification and levels of intact parathyroid hormone (i-PTH), phosphorus, calcium, 25-OH vitamin D, fibroblast growth factor 23 (FGF-23), Klotho and C-reactive protein (CRP) simultaneously measured in patients with mild to moderate CKD. Consecutive non-hospitalized patients referring to five nephrology units were evaluated. Inclusion criteria were age >18 years, CKD Stages 3-4, and the presence of aortic and/or mitral valve calcification assessed by echocardiography as routinely clinical evaluation. Patients underwent clinical examination and routine biochemistry. Baseline i-PTH, phosphorus, calcium, 25-OH vitamin D, FGF-23, Klotho and CRP were simultaneously ascertained. Extent of aortic valve calcification (n = 100 patients) was moderate in 68 patients and mild in the remaining patients. Mitral valve calcification (n = 96 patients) score was 1, 2 and 3 in 61, 34 and 1 patients, respectively. In univariate analysis, no association was found between extent of mitral valve calcification and markers of mineral metabolism and CRP; aortic valve extent of calcification was positively associated with i-PTH (r(2) = 0.212; P = 0.03) and FGF-23 (r(2) = 0.272; P = 0.01), and negatively with Klotho (r(2) = -0.208; P = 0.04). In multivariable analysis, extent of aortic valve calcification was associated with FGF-23 (P = 0.01) and PTH (P = 0.01) levels. Extent of aortic valve calcification is associated to FGF-23 and PTH in naïve CKD patients with mild to moderate CKD. Further studies should examine whether FGF-23 assay should be included in routine clinical evaluation of CKD as part of cardiovascular risk stratification.
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... more
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. Homotaurine is a natural aminosulfonate compound endowed with neuromodulatory effects, while the dipeptide L-carnosine is known for its antioxidant properties. Retinal ischemia was induced in the right eye of adult male Wistar rats by acutely increasing the IOP. Forskolin, ...
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Glaucoma is the leading cause of irreversible blindness worldwide. Although the intraocular pressure (IOP) has been considered for long time the key point and the only treatable risk factor of the disease, there are cases in which... more
Glaucoma is the leading cause of irreversible blindness worldwide. Although the intraocular pressure (IOP) has been considered for long time the key point and the only treatable risk factor of the disease, there are cases in which glaucoma continues to progress despite normal IOP values. Vision loss in glaucoma is related to a selective decrease in the number of retinal ganglion cells by apoptosis that is associated to alterations of the central visual pathways. Interestingly, similar events have been also described in disorders of the central nervous system (CNS), such as Alzheimer's disease, Parkinson's disease, Leber's hereditary optic neuropathy, and cerebrovascular diseases. In this review, we discuss recent evidence supporting pathological links between glaucoma and disorders of the CNS.
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Glaucoma is a neurodegenerative disease caused by the progressive apoptotic death of retinal ganglion cells (RGCs). The mechanisms leading to the RGC loss are still unknown but it is now clear that, besides elevated intraocular pressure... more
Glaucoma is a neurodegenerative disease caused by the progressive apoptotic death of retinal ganglion cells (RGCs). The mechanisms leading to the RGC loss are still unknown but it is now clear that, besides elevated intraocular pressure (IOP), which is considered the main risk factor, other IOP-independent determinants are responsible for the development of the optic neuropathy. Autophagy is a highly conserved catabolic pathway by which cellular components are degraded through the lysosomes. Dysfunctional autophagic pathway has been associated with several neuropathological conditions and a considerable number of studies have proved autophagy as a potential target for pharmacological modulation to achieve neuroprotection. Here, we review the current literature bridging the degeneration of RGCs to alterations of the autophagic pathway; we also discuss the possible role of autophagy in the pathogenesis and progression of glaucoma in view of the future application of autophagy modulators for glaucoma therapy.
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Glaucoma, the second leading cause of blindness in the world, is a chronic optic neuropathy often associated with increased intraocular pressure and characterized by progressive retinal ganglion cell (RGC) axons degeneration and death... more
Glaucoma, the second leading cause of blindness in the world, is a chronic optic neuropathy often associated with increased intraocular pressure and characterized by progressive retinal ganglion cell (RGC) axons degeneration and death leading to typical optic nerve head damage and distinctive visual field defects. Although the pathogenesis of glaucoma is still largely unknown, it is hypothesized that RCGs become damaged through various insults/mechanisms, including ischemia, oxidative stress, excitotoxicity, defective axonal transport, trophic factor withdrawal, and neuroinflammation. In this review, we summarize the potential benefits of several natural compounds for RGCs neuroprotection.
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The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex. It contains a rich array of brain terminals, which modulate the visual signals to the cortex. Several data have documented that beside... more
The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex. It contains a rich array of brain terminals, which modulate the visual signals to the cortex. Several data have documented that beside cholinergic, GABA-nergic, istaminergic, serotoninergic, and glutamatergic signals, the LGN contains also fibers and interneurons expressing the enzyme that produces nitric oxide (NO). Here, we review the documented physiological roles of NO in the transmission of visual inputs to the cortex and in the processes of activity-dependent refinement of LGN connections. Moreover we focus on the recently suggested role of NO in processes of neurotoxicity in the LGN. Particular relevance is given to studies documenting that, through an excitotoxic cascade, NO triggers apoptosis in the LGN of new-born rats deprived of vision in one eye. Data are also discussed on a possible role of NO in the mechanisms of LGN neuronal loss induced by glaucoma. We believe that a b...
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1. The antidepressant trazodone and its main metabolite m-chlorophenylpiperazine (mCPP) were investigated for their analgesic properties and their sensitivity to a threshold dose of morphine in acetic acid abdominal constriction and hot... more
1. The antidepressant trazodone and its main metabolite m-chlorophenylpiperazine (mCPP) were investigated for their analgesic properties and their sensitivity to a threshold dose of morphine in acetic acid abdominal constriction and hot plate tests. 2. The drugs elicited hypoalgesic effects at about the same doses in the two analgesic assays. 3. Naloxone (2 mg/kg i.p.) prevented the hypoalgesia of trazodone but not of mCPP in the hot plate test. The opiate antagonist did not affect the responses of both drugs to the writhing test. 4. Subanalgesic doses of the two drugs increased the sensitivity to morphine in both assays. The results further support the suggested role played by opioid and 5-HT systems on depression.
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In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against... more
In addition to its effects in the hypothalamus to control body weight, leptin is involved in the regulation of neuronal function, development and survival. Recent findings have highlighted the neuroprotective effects of leptin against ischemic brain injury; however, to date, little is known about the role performed by the signal transducer and activator of transcription (STAT)-3, a major mediator of leptin receptor transduction pathway in the brain, in the beneficial effects of the hormone. Our data demonstrate that systemic acute administration of leptin produces neuroprotection in rats subjected to permanent middle cerebral artery occlusion (MCAo), as revealed by a significant reduction of the brain infarct volume and neurological deficit up to 7 days after the induction of ischemia. By combining a subcellular fractionation approach with immunohistofluorescence, we observe that neuroprotection is associated with a cell type-specific modulation of STAT3 phosphorylation in the ische...
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Autophagy is the major intracellular degradation pathway that regulates long-lived proteins and organelles turnover. This process occurs at basal levels in all cells but it is rapidly upregulated in response to starvation and cellular... more
Autophagy is the major intracellular degradation pathway that regulates long-lived proteins and organelles turnover. This process occurs at basal levels in all cells but it is rapidly upregulated in response to starvation and cellular stress. Although being recently implicated in neurodegeneration, it remains still unclear whether autophagy has a detrimental or protective role. In this study, we investigated the dynamics of the autophagic process in retinal tissue that has undergone transient ischemia, an experimental model that recapitulates features of ocular pathologies, including glaucoma, anterior ischemic optic neuropathy and retinal vessels occlusion. Retinal ischemia, induced in adult rats by increasing the intraocular pressure, was characterized by a reduction in the phosphatidylethanolamine-modified form of LC3 (LC3II) and by a significant decrease in Beclin-1. The latter event was associated with a proteolytic cleavage of Beclin-1, leading to the accumulation of a 50-kDa ...
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Bergamot (Citrus bergamia Risso et Poiteau) is a citrus fruit growing almost exclusively in the South of Italy. Its essential oil is obtained by cold pressing of the epicarp and, partly, of the mesocarp of the fresh fruit. Although this... more
Bergamot (Citrus bergamia Risso et Poiteau) is a citrus fruit growing almost exclusively in the South of Italy. Its essential oil is obtained by cold pressing of the epicarp and, partly, of the mesocarp of the fresh fruit. Although this phytocomplex has been used for centuries, reputedly effectively, as a traditional medicine, there is very little verified scientific evidence to support this use. This paper reports original data on the systemic effects of the essential oil of bergamot (BEO) on gross behaviour and EEG activity recorded from the hippocampus and cerebral cortex of the rat. The Fast Fourier Transformation (FFT) was used to analyse and quantify the energy in single frequency bands of the EEG spectrum. The results obtained indicate that systemic administration of increasing volumes of BEO produces dose-dependent increases in locomotor and exploratory activity that correlate with a predominant increase in the energy in the faster frequency bands of the EEG spectrum. These ...
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Recent studies support a role for excitotoxicity in the development of retinal ganglion cell (RGC) damage in subjects suffering from glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported... more
Recent studies support a role for excitotoxicity in the development of retinal ganglion cell (RGC) damage in subjects suffering from glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection, preventing the formation of the mitochondrial permeability transition pore. Using an established animal model of retinal ischemia/reperfusion here, we show that synaptic glutamate increases at 130min from beginning of reperfusion and delayed apoptosis in the RGC layer is seen at 24h. Intraocular administration of CoQ10 minimizes glutamate increase and affords neuroprotection, suggesting that oxidative stress and energy failure might be implicated in the mechanisms of RGC death.
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Because of a marked increase in the number of requests for antinuclear antibodies, anti-extractable nuclear antigen antibodies, and anti-double-stranded DNA antibodies for the diagnosis of autoimmune rheumatic disease, guidelines have... more
Because of a marked increase in the number of requests for antinuclear antibodies, anti-extractable nuclear antigen antibodies, and anti-double-stranded DNA antibodies for the diagnosis of autoimmune rheumatic disease, guidelines have been proposed for their appropriate use. To evaluate in terms of clinical efficacy and cost-benefit ratio the outcome of applying a protocol for the diagnosis of autoimmune rheumatic disease. A diagnostic protocol for the rational utilization of second-level tests (anti-extractable nuclear antigen antibodies and anti-double-stranded DNA antibodies) was applied at Hospital Polyclinic beginning January 2004. The appropriateness of 685 consecutive requests received at the clinical pathology laboratory from January to June 2004 was assessed. Patients who underwent these laboratory tests were followed up for 12 months after blood sample drawing. Introduction of the protocol led to a significant reduction in the number of second-level tests prescribed (27.9%...
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There is clear clinical evidence that a drastic lowering of plasma LDL-Cholesterol (LDL) concentrations significantly reduces the rate of total and coronary mortality as well as the incidence of cardiovascular events in high risk... more
There is clear clinical evidence that a drastic lowering of plasma LDL-Cholesterol (LDL) concentrations significantly reduces the rate of total and coronary mortality as well as the incidence of cardiovascular events in high risk hypercholesterolemic patients. We describe the case of a 51-year-old woman with coronary heart disease (CHD) who presented with increasing angina on exertion in 1995, at the age of 45. She suffered from a heterozygous familial hypercholesterolemia and in 1985 her total cholesterol (TCHO) was 328 +/- 62 mg/dl (mean value of ten analysis). After ten years of statins her mean values (20 analysis, 2 per year) were: TCHO 259 +/- 71, LDL 209 +/- 47, HDL 35 +/- 7 mg/dl. Coronary angiography (CA) performed in 1995 disclosed three vessel coronary heart disease with significant stenoses of the distal right coronary artery, multiple calcifications of the interventricularis artery and multiple plaques with significant stenoses in the ramus circumflexus. The woman under...
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Brown tumors are unusual but serious complications of renal osteodystrophy, and can be successfully treated by parathyroidectomy or by pharmacological treatment of hyperparathyroidism. Brown tumors in patients with severe... more
Brown tumors are unusual but serious complications of renal osteodystrophy, and can be successfully treated by parathyroidectomy or by pharmacological treatment of hyperparathyroidism. Brown tumors in patients with severe hyperparathyroidism (HPT) secondary to renal failure have been increasingly reported. We describe an unusual case of brown tumors at the maxillary bone and the seventh right rib, in a 57-year old man with a long history of hemodialysis. The maxillary lesion caused serious local discomfort due to its rapid growth. In this setting, surgical total parathyroidectomy was chosen as the most adequate therapeutic approach, given the previous unsatisfactory response to calcitriol. After successful parathyroidectomy, rapid healing was achieved with sclerosis of both brown tumors, as documented by serial computerized tomograms. In conclusion, although vitamin D therapy has been beneficial in several cases of secondary hyperparathyroidism complicated by brown tumors, we propos...
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In vivo studies have suggested that the kappa opioid system can partially inhibit the development of physical dependence to mu agonists. Vice versa, activation of mu receptors may inhibit the expression of physical dependence to kappa... more
In vivo studies have suggested that the kappa opioid system can partially inhibit the development of physical dependence to mu agonists. Vice versa, activation of mu receptors may inhibit the expression of physical dependence to kappa agonists. We studied mu-kappa interactions in the isolated guinea-pig ileum (GPI). In the isolated GPI briefly exposed to mu or kappa agonists the addition of the respective antagonists precipitated a withdrawal contracture. After a first withdrawal response, however, some tissues failed to exhibit subsequent mu or kappa withdrawal contractures. A withdrawal contracture to the selective mu antagonist, cyprodime, after repeated exposures to a selective mu agonist, dermorphin, was restored by nor-binaltorphimine (BNI), a selective kappa antagonist. Vice versa, after repeated exposures to the kappa agonist, U-50,488H, cyprodime restored tissue responsiveness to BNI. Tissues repeatedly exposed to dermorphin and washed after each exposure contracted to the ...
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We present the case of a 55-year-old patient who underwent total parathyroidectomy for severe hyperparathyroidism unresponsive to medical therapy, 4 years after having started hemodialysis treatment. It was decided to perform total... more
We present the case of a 55-year-old patient who underwent total parathyroidectomy for severe hyperparathyroidism unresponsive to medical therapy, 4 years after having started hemodialysis treatment. It was decided to perform total parathyroidectomy because at macroscopic evaluation the parathyroid glands appeared completely compromised. After surgery, the patient developed hungry bone disease, characterized by severe hypocalcemia and hypophosphatemia. After parathyroidectomy, serial measurements were made for the long-term monitoring of the calcemia, phosphatemia and the serum levels of intact parathormone and bone alkaline phosphatase, a marker of bone turnover that mainly expresses bone formation. There was initially a slight decrease in the circulating levels of bone alkaline phosphatase as the calcemia dropped dramatically, then a new increase that anticipated the subsequent calcemia increase and finally, 6 months later, a decrease to very low values. We believe that the calcem...
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Many studies have shown how gene mutations and genetic polymorphisms could influence secondary uremic hyperparathyroidism (HPTH), modulating parathyroid (PT) function and hyperplasia. Parathyroid hormone (PTH) gene expression and hormone... more
Many studies have shown how gene mutations and genetic polymorphisms could influence secondary uremic hyperparathyroidism (HPTH), modulating parathyroid (PT) function and hyperplasia. Parathyroid hormone (PTH) gene expression and hormone secretion is regulated mainly by serum calcium, with a post-transcriptional effect, and by vitamin D with a transcriptional effect. PT cells retain the ability to proliferate and to apoptose. Hyperphosphatemia, hypocalcemia and vitamin D deficiency all stimulate PT cell proliferation. In the early stage of chronic uremia, PT proliferation is polyclonal, as in diffuse hyperplasia, whereas nodular hyperplasia growth is monoclonal with an increasingly recognized genetic background. HPTH has been associated with a number of familial diseases, such as multiple endocrine neoplasia-type 1 (MEN1), multiple endocrine neoplasia-type2A (MEN2A), neurofibromatosis type1 (NF1) and HPTH with multiple ossifying jaw fibromas (HPT-JT Syndrome). The genes involved in ...
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Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of lipoprotein metabolism, resulting from loss of function of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), a key enzyme in... more
Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder of lipoprotein metabolism, resulting from loss of function of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), a key enzyme in extracellular cholesterol metabolism and reverse cholesterol transport (RCT). The human LCAT gene has been mapped to chromosome band 16q22, and consists of 6 exons encoding for a mature protein of 416 amino acids. In the present study, we describe the molecular phenotype of a patient with classical LCAT deficiency and progressive renal failure. Sequence analysis of the LCAT gene showed 2 homozygous missense mutations: the common variant p.S208T, described as a homozygous change for the first time, and a missense mutation characterized by the substitution of Leu372 to Arg. Clinical, biochemical and renal histological studies were also performed to elucidate the functional effects of these variations. In the proband and his brother, LCAT activity and pla...
Research Interests: Nephrology, Kidney diseases, Italy, Lipids, Humans, and 6 moreFemale, Male, Pedigree, Phenotype, Clinical Sciences, and Adult
Essential oils are complex mixtures of several components endowed with a wide range of biological activities, including antiseptic, anti-inflammatory, spasmolytic, sedative, analgesic, and anesthetic properties. A growing body of... more
Essential oils are complex mixtures of several components endowed with a wide range of biological activities, including antiseptic, anti-inflammatory, spasmolytic, sedative, analgesic, and anesthetic properties. A growing body of scientific reports has recently focused on the potential of essential oils as anticancer treatment in the attempt to overcome the development of multidrug resistance and important side effects associated with the antitumor drugs currently used. In this review we discuss the literature on the effects of essential oils in in vitroandin vivomodels of cancer, focusing on the studies performed with the whole phytocomplex rather than single constituents.
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Neuroprotection exerted by 17beta-estradiol (17beta-E(2)) has been widely investigated in animal models of acute cerebral ischemia. Estrogens interact with intracellular receptors (ERalpha and ERbeta) to modulate the transcription of... more
Neuroprotection exerted by 17beta-estradiol (17beta-E(2)) has been widely investigated in animal models of acute cerebral ischemia. Estrogens interact with intracellular receptors (ERalpha and ERbeta) to modulate the transcription of target genes, including those implicated in neuronal survival. Neuroprotection may also occur via interaction with ER-like membrane receptors mediating rapid, non-genomic, actions or via receptor-independent mechanisms. There is also evidence that blockade of inflammatory factors may represent an important mechanism involved in estrogenic neuroprotection. Here we investigate whether reduced brain damage by acute pharmacological treatment with 17beta-E(2) in male rats subjected to transient (2h) middle cerebral artery occlusion (tMCAo) involves modulation of interleukin-1beta (IL-1beta), a proinflammatory cytokine strongly implicated in the pathophysiology of ischemic stroke. Administration of 17beta-E(2) (0.2mg/kg, i.p., 1h before tMCAo) results in significant reduction of brain infarct volume, and this is reverted by the ER antagonist ICI 182,780 (0.25mg/kg, i.p.) administered 1h before 17beta-E(2). Two hours MCAo followed by 2-h reperfusion results in a significant, threefold increase of IL-1beta levels in the cortical tissue ipsilateral to the ischemic damage. Interestingly, a pretreatment with a neuroprotective dose of 17beta-E(2) attenuates the cytokine elevation and this appears to occur through ER activation. In addition, neuroprotection by 17beta-E(2) is accompanied by reduced cytochrome c translocation both in the striatum and in the cortex as revealed by Western blotting 3h after reperfusion. In conclusion, we report the original observation that neuroprotection exerted by 17beta-E(2) in a rat model of transient focal brain ischemia is accompanied by reduced cytochrome c translocation to the cytosol and involves early modulation of IL-1beta production.
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Glaucoma, is a progressive optic neuropathy often associated with increased intraocular pressure (IOP) and characterized by progressive death of retinal ganglion cells (RGCs). High acute rise of IOP is a model for retinal ischemia and may... more
Glaucoma, is a progressive optic neuropathy often associated with increased intraocular pressure (IOP) and characterized by progressive death of retinal ganglion cells (RGCs). High acute rise of IOP is a model for retinal ischemia and may represent a model of acute angle closure glaucoma. Here we have used this experimental model in combination with a neurochemical and neuropathological approach to gain more insight in the neuroprotective profile of 17beta-estradiol (E2), a steroid hormone, which has been shown to increase the viability, survival, and differentiation of primary neuronal cultures from different brain areas including amygdala, hypothalamus, and neocortex. Our data demonstrate that systemic administration of E2 significantly reduces RGC loss induced by high IOP in rat. In addition, pretreatment with E2, 30 min before ischemia, minimizes the elevation of glutamate observed during the reperfusion period. These effects seem to be in part mediated by the activation of the estrogen receptor, since a pretreatment with ICI 182-780, a specific estrogen receptor antagonist, partially counteracts the neuroprotection afforded by the estrogen.
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Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers... more
Glaucoma is a worldwide leading cause of irreversible vision loss characterized by progressive death of retinal ganglion cells (RGCs). In the course of glaucoma, RGC death may be the consequence of energy impairment that triggers secondary excitotoxicity and free radical generation. There is substantial evidence also that a number of free radical scavengers and/or agents that improve mitochondrial function may be useful as therapies to ameliorate cell death in various neurological disorders including glaucoma. Coenzyme Q10 (CoQ10), an essential cofactor of the electron transport chain, has been reported to afford neuroprotection in neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases, and its protective effect has been attributed in part to its free radical scavenger ability and to a specific regulation of the mitochondrial permeability transition pore. Using an established animal model of transient retinal ischemia, we have conclusively identified a role for abnormal elevation of extracellular glutamate in the mechanisms underlying RGC death that occurs, at least in part, via activation of the apoptotic program. Under these experimental conditions, N-methyl-D-aspartate (NMDA) and non-NMDA subtype of glutamate receptor antagonists, nitric oxide synthase inhibitors, and CoQ10 afford retinal protection supporting an important role for excitotoxicity in the mechanisms underlying RGC death.
Research Interests: Cognitive Science, Oxidative Stress, Free Radical, Glutamate, Humans, and 15 moreGlaucoma, Animals, Cell Death, Intraocular Pressure, Animal Model, Electron Transport, Calpain, Rats, Nitric Oxide Synthase, Neurodegenerative Disease, Mitochondrial Permeability Transition Pore, Neurosciences, Glutamic Acid, Neuroprotective Agents, and Glutamate Receptor
The link between serum parathyroid hormone (iPTH) and cardiovascular (CVS) mortality has not been fully elucidated. The EVOLVE Study was designed to test whether a drug such as cinacalcet, aimed at lowering iPTH, could reduce the... more
The link between serum parathyroid hormone (iPTH) and cardiovascular (CVS) mortality has not been fully elucidated. The EVOLVE Study was designed to test whether a drug such as cinacalcet, aimed at lowering iPTH, could reduce the astonishingly high cardiovascular risk in patients on maintenance dialysis (CKD-5D). Accordingly, the primary outcome of the study was the combined endpoint of time to death or hospitalization due to CVS factors or from any cause. Time to bone fracture and parathyroidectomy were regarded as secondary endpoints. At study completion, the Intention-To-Treat analysis documented a non- significant 7% (Hazard Ratio: 0.93; 95% Confidence interval: 0.85-1.02; P = 0.11) reduction of the primary composite endpoint. However, the intention to treat analysis does not take into account adherence to drug regimens or control for factors that may potentially jeopardize the conduction of the study. In particular, in spite of a careful pre-planned study sample calculation, th...
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KDIGO (Kidney Disease: Improving Global Outcomes) is an international nonprofit organization devoted to “improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration, and integration of... more
KDIGO (Kidney Disease: Improving Global Outcomes) is an international nonprofit organization devoted to “improve the care and outcomes of kidney disease patients worldwide through promoting coordination, collaboration, and integration of initiatives to develop and implement clinical practice guidelines.” The mineral and bone disorder (MBD) in patients with chronic kidney disease (CKD) has been the first area of interest of KDIGO international initiative. KDIGO guidelines on CKD-MBD were published in 2009 with the intent to modify the previous KDOQI guidelines that had failed to consistently change the global outcome of CKD patients. After the publication of KDOQI guidelines for bone metabolism and disease in 2003, a large number of observational data emerged in literature linking disordered mineral metabolism with adverse clinical outcomes. Notwithstanding this large body of observational data, a paucity of evidence from high-quality clinical trials was available for the development...
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Elevated uric acid levels are a common finding in patients with metabolic syndrome and in those with cardiovascular and renal disease, but the meaning of this elevation is still unclear. In patients with chronic kidney diseases, it could... more
Elevated uric acid levels are a common finding in patients with metabolic syndrome and in those with cardiovascular and renal disease, but the meaning of this elevation is still unclear. In patients with chronic kidney diseases, it could merely reflect the reduction in glomerular filtration rate: but uric acid levels are known to be elevated in people, also in younger ones, prior to the development of hypertension or renal disease, independently of several risk factors. Multiple potential mechanisms suggest a causative role for uric acid in vascular disease. Uric acid has been shown to be involved in metabolic pathways that lead to oxidative stress, endothelial disfunction, and to a vascular and systemic inflammatory response. Moreover, the elevation in uric acid levels observed after fructose ingestion, with a consequent reduction in nitric oxide, may lead to a reduced glucose uptake in the skeletal muscle, hyperinsulinemia, and insulin resistance. Besides these bench research data, also clinical studies showed the beneficial effects of lowering uric acid therapies on several markers of cardiovascular and renal disease. To date, however, there is no evidence indicating that such therapies, that are not free of risk, may reduce cardiovascular events; so that to manage our prescriptions, we need larger, prospective, interventional data.
Research Interests: Chronic kidney disease, Metabolic syndrome, Inflammatory Immune Response, Humans, Nitric oxide, and 15 moreFemale, Male, Hyperuricemia, Peripheral Vascular Disease, Prognosis, Clinical Study, Cardiovascular Diseases, Biological markers, Risk Factors, Metabolic pathway, Glucose Uptake, Renal disease, Glomerular Filtration Rate, Inflammatory response, and Metabolic Syndrome X
Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the... more
Recent evidence shows that the endocannabinoid system is involved in the pathogenesis of numerous neurodegenerative diseases of the central nervous system. Pharmacologic modulation of cannabinoid receptors or the enzymes involved in the synthesis, transport, or breakdown of endogenous cannabinoids has proved to be a valid alternative to conventional treatment of these diseases. In this review, we will examine recent findings that demonstrate the involvement of the endocannabinoid system in glaucoma, a major neurodegenerative disease of the eye that is a frequent cause of blindness. Experimental findings indicate that the endocannabinoid system contributes to the control of intraocular pressure (IOP), by modulating both production and drainage of aqueous humor. There is also a growing body of evidence of the involvement of this system in mechanisms leading to the death of retinal ganglion cells, which is the end result of glaucoma. Molecules capable of interfering with the ocular endocannabinoid system could offer valid alternatives to the treatment of this disease, based not only on the reduction of IOP but also on neuroprotection.
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Research Interests:
Antiphospholipid syndrome (APS) is a rare autoimmune disorder. It can be secondary to systemic lupus erythematosus (SLE) or occur in the absence of autoimmune disease. The hallmark of this so-called primary APS is the presence of... more
Antiphospholipid syndrome (APS) is a rare autoimmune disorder. It can be secondary to systemic lupus erythematosus (SLE) or occur in the absence of autoimmune disease. The hallmark of this so-called primary APS is the presence of circulating antiphospholipid antibodies. Renal involvement in primary APS is caused by thrombosis within the renal vasculature. Recently, nonthrombotic glomerulonephritic renal lesions have been described in primary APS as a new histological entity. We here report a patient with primary APS in whom both lesion types were present. A 58-year-old Caucasian man with no significant past medical history presented to our nephrology unit with diffuse edema. Urinalysis showed proteinuria exceeding 400 mg/dL. The autoantibody panel (p-ANCA, c- ANCA, anti-nucleus, anti-DS-DNA) was negative except for anticardiolipin antibodies, which tested positive in two different samples. The diagnostic workup included a kidney biopsy that revealed thrombotic lesions compatible wit...
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ABSTRACT no abstract.
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Despite the increasing use of aromatherapy oils, there have not been many studies exploring the biological activities of bergamot (Citrus bergamia, Risso) essential oil (BEO). Recently, we have investigated the effects of BEO injected... more
Despite the increasing use of aromatherapy oils, there have not been many studies exploring the biological activities of bergamot (Citrus bergamia, Risso) essential oil (BEO). Recently, we have investigated the effects of BEO injected into the plantar surface of the hindpaw in the capsaicin test in mice. The intraplantar injection of capsaicin produced an intense and short-lived licking/biting response toward the injected hindpaw. The capsaicin-induced nociceptive response was reduced significantly by intraplantar injection of BEO. The essential oils of Clary Sage (Salvia sclarea), Thyme ct. linalool (linalool chemotype of Thymus vulgaris), Lavender Reydovan (Lavandula hybrida reydovan), and True Lavender (Lavandula angustifolia), had similar antinociceptive effects on the capsaicin-induced nociceptive response, while Orange Sweet (Citrus sinensis) essential oil was without effect. In contrast to a small number of pharmacological studies of BEO, there is ample evidence regarding isolated components of BEO which are also found in other essential oils. The most abundant compounds found in the volatile fraction are the monoterpene hydrocarbons, such as limonene, gamma-terpinene, beta-pinene, and oxygenated derivatives, linalool and linalyl acetate. Of these monoterpenes, the pharmacological activities of linalool have been examined. Following intraperitoneal (i.p.) administration in mice, linalool produces antinociceptive and antihyperalgesic effects in different animal models in addition to anti-inflammatory properties. Linalool also possesses anticonvulsant activity in experimental models of epilepsy. We address the importance of linalool or linalyl acetate in BEO-or the other essential oil-induced antinociception.
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In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the... more
In rodents, CsA has been shown to affect T-cell development, giving rise to an abnormal production of mature T cells and the absence of many T-cell subsets as well as to autoimmunity. Surprisingly, only a few studies investigated the effect of the immunosuppressive drug on the immune system of the human fetus. We examined six infants born to female kidney transplant recipients who had received cyclosporine and methylprednisolone throughout their pregnancies. Peripheral blood was obtained 1 day and 2, 4, 6, and 12 months after birth, and two-color flow cytometric immunophenotyping of lymphocytes was performed. Total T cells, as well as CD4+ and CD8+ T cells, were low at birth, but normalized thereafter. Among T-cell activation markers, the expression of CD25, the alpha chain of the interleukin-2 receptor, was below the normal range or low range throughout the study period, and HLA-DR expression was extremely low at birth and failed to increase up to 12 months. The number of total B cells was lower than normal at birth, but steeply increased over time. In contrast, B-cell subset bearing CD5 antigen was severely depleted throughout the first year of life. Total IgG concentration was significantly lower than in controls at 2 months, mainly because of subnormal levels of IgG1 and IgG3 subclasses, which remained in the low range up to 6 months. Finally, infants showed normal numbers of true natural killer (NK) cells (CD3-CD16+CD56+), whereas the expression of CD57 antigen, defining non-MHC-restricted cytotoxic lymphocytes, was barely detectable at birth and failed to increase over time, in both CD8+ and CD8- subsets. Of note, none of the infants had clinical evidence of an immunodeficient state. continuous exposure to CsA in utero seemingly impairs T-, B-, and NK-cell development and/or maturation, and most of its effects are still apparent at 1 year, which might suggest that conventional vaccinations should be delayed in these infants.
Research Interests: Kidney transplantation, Birth Weight, Pregnancy, Humans, Female, and 15 moreInfant, Cyclosporine, Longitudinal Studies, Kidney Transplant, First Year, Immunophenotyping, B Lymphocytes, Gestational Age, Reference Values, Immunoglobulin, immunoglobulin G, Methylprednisolone, Immunoglobulin A, Immunosuppressive Agents, and immunoglobulin M
Second messenger cAMP and cGMP represent a key step in the action of dopamine that modulates directly or indirectly their synthesis. We aimed to verify whether levodopa-induced dyskinesias are associated with changes of the time course of... more
Second messenger cAMP and cGMP represent a key step in the action of dopamine that modulates directly or indirectly their synthesis. We aimed to verify whether levodopa-induced dyskinesias are associated with changes of the time course of levodopa/dopamine stimulated cAMP and cGMP levels, and/or with changes of their catabolism by phosphodiesterase activity in rats with experimental hemiparkinsonism. Microdialysis and tissue homogenates of the striatal tissues demonstrated that extracellular and intracellular cAMP/cGMP levels were lower in dyskinetic animals during the increasing phase of dyskinesias compared to eukinetic animals, but cAMP/cGMP levels increased in dyskinetic animals during the phase of decreasing and extinction of dyskinesias. Dyskinesias and the abnormal lowering of striatal cGMP and cAMP after levodopa were prevented by pretreatment with the multipotent drug amantadine, outlining the inverse relationship of cAMP/cGMP to dyskinesias. Moreover, dyskinetic animals showed higher striatal hydrolyzing cGMP-phosphodiesterase but not hydrolyzing cAMP-phosphodiesterase activity, suggesting that low cGMP but not cAMP levels could be due to increased catabolism. However, expressions of isozyme phosphodiesterase-1B and -10A highly and specifically located in the basal ganglia were not changed after levodopa in dyskinetic and eukinetic animals: accordingly, selective inhibitors of phosphodiesterase-1B and -10A were ineffective on levodopa dyskinesias. Therefore, the isozyme(s) expressing higher cGMP-phosphodiesterase activity in the striatum of dyskinetic animal should be determined. These observations suggest that dopamine-mediated processes of synthesis and/or degradation of cAMP/cGMP could be acutely impaired in levodopa dyskinesias, opening new ways to understanding physiopathology and treatment.
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Excitotoxic neuronal death is a common feature of neurodegenerative and ischemic diseases of the central nervous system (CNS) and of a variety of ocular diseases, including glaucoma. Glaucoma, one of the leading causes of blindness in the... more
Excitotoxic neuronal death is a common feature of neurodegenerative and ischemic diseases of the central nervous system (CNS) and of a variety of ocular diseases, including glaucoma. Glaucoma, one of the leading causes of blindness in the world, is characterized by a progressive degeneration of retinal ganglion cells (RGCs) and their axons and is often associated with elevated intraocular pressure (IOP). Retinal ischemia/reperfusion induced by experimental elevation of IOP leads to damage and loss of RGCs. Under these conditions, structural, functional, and biochemical changes implicate the accumulation of extracellular glutamate and activation of the excitotoxic cascade. Beside the activation of associated pathways, death of RGCs is accompanied by impaired endogenous defenses, such as the PI3K/Akt prosurvival pathway. Original neurochemical and pharmacological evidence are discussed here to strengthen the role for excitotoxicity in RGCs death occurring in experimental, angle closure, glaucoma in conjunction with the discovery of novel molecular targets to potentiate endogenous prosurvival defenses in the glaucomatous retina.
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Recent data indicate that factors other than erythropoietin (EPO), such as insulin-like growth factor 1 (IGF-1), can promote erythropoiesis in vitro and correct the anemia of chronic renal failure in vivo. IGF-1 is produced by the liver... more
Recent data indicate that factors other than erythropoietin (EPO), such as insulin-like growth factor 1 (IGF-1), can promote erythropoiesis in vitro and correct the anemia of chronic renal failure in vivo. IGF-1 is produced by the liver under growth hormone control, as well as by other sources, including the kidney. The erythropoietic role of growth factors and cytokines and their possible modulation by angiotensin-converting enzyme inhibitors (ACEI) has never been explored. This study evaluated the serum levels of EPO, IGF-1, interleukin (IL)-2, IL-3, and granulocyte macrophage-colony-stimulating factor in 40 kidney transplanted patients with or without posttransplant erythrocytosis (PTE) and in 10 living kidney donors. Then, the effect of ACEI therapy on the above pattern was examined in patients with PTE. EPO and IGF-1 serum levels were significantly higher in patients with PTE than in patients without PTE and in living kidney donor subjects. ACEI therapy significantly reduced hematocrit (Hct) as well as circulating IGF-1 and EPO levels. Of note, the decrease in IGF-1 was prominent mainly in those patients whose EPO levels were not significantly modified by ACEI therapy. In all of the patients Hct levels displayed a direct relationship with circulating IGF-1 levels, but not with EPO concentration. Growth hormone did not significantly differ among the groups examined, whereas it steeply increased under ACEI. Finally, no significant difference in IL-2, IL-3, and granulocyte macrophage-colony-stimulating factor serum levels was detected. IGF-1 seems to play a role in the ACEI-related decrease of Hct in patients with PTE, chiefly in patients without any modification of EPO serum levels.
Research Interests: Treatment, Kidney transplantation, Transplantation, Erythropoietin, Humans, and 15 moreFemale, Male, Regression Analysis, Kidney Transplant, Polycythemia, Adult, Erythropoiesis, Analysis of Variance, Growth Factor, Angiotensin Converting Enzyme Inhibitors, Hematocrit, Platelet Count, Hemoglobins, Creatinine, and Interleukin
Endogenous levels of the endocannabinoid anandamide, and the activities of the synthesizing and hydrolyzing enzymes, i.e. N-acylphosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, respectively, were... more
Endogenous levels of the endocannabinoid anandamide, and the activities of the synthesizing and hydrolyzing enzymes, i.e. N-acylphosphatidylethanolamine-hydrolyzing phospholipase D and fatty acid amide hydrolase, respectively, were determined in the cortex and the striatum of rats subjected to transient middle cerebral artery occlusion. Anandamide content was markedly increased ( approximately 3-fold over controls; P < 0.01) in the ischemic striatum after 2 h of middle cerebral artery occlusion, but not in the cortex, and this elevation was paralleled by increased activity of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D ( approximately 1.7-fold; P < 0.01), and reduced activity ( approximately 0.6-fold; P < 0.01) and expression ( approximately 0.7-fold; P < 0.05) of fatty acid amide hydrolase. These effects of middle cerebral artery occlusion were further potentiated by 1 h of reperfusion, whereas anandamide binding to type 1 cannabinoid and type 1 vanilloid receptors was not affected significantly by the ischemic insult. Additionally, the cannabinoid type 1 receptor antagonist SR141716, but not the receptor agonist R-(+)-WIN55,212-2, significantly reduced (33%; P < 0.05) cerebral infarct volume detected 22 h after the beginning of reperfusion. A neuroprotective intraperitoneal dose of 17beta-estradiol (0.20 mg x kg(-1)) that reduced infarct size by 43% also minimized the effect of brain ischemia on the endocannabinoid system, in an estrogen receptor-dependent manner. In conclusion, we show that the endocannabinoid system is implicated in the pathophysiology of transient middle cerebral artery occlusion-induced brain damage, and that neuroprotection afforded by estrogen is coincident with a re-establishment of anandamide levels in the ischemic striatum through a mechanism that needs to be investigated further.