A Whiter Shade of Pale dei Procol Harum, incisa nel 1967 contiene numerosi elementi che potrebber... more 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?
La collana "Minima Storiografica" di Nuova Rivista storica pubblica un'interessantissima opera di... 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.
Protestanti, illuministi, alcuni marxisti e alcuni massoni (non tutti, per fortuna ...) hanno fat... 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.
Una "lettera aperta" agli storici circa la necessità di un dibattito sull'Unità d'Italia che coin... more Una "lettera aperta" agli storici circa la necessità di un dibattito sull'Unità d'Italia che coinvolga il grande pubblico
Pur non essendo risalente nel tempo quanto quello degli Argonauti o viepiù di Gilgamesh, il mito ... more Pur non essendo risalente nel tempo quanto quello degli Argonauti o viepiù di Gilgamesh, il mito di Odisseo/Ulisse è senza dubbio antichissimo: «Molti elementi indicano che Odisseo rappresenta un'antichissima figura della mitologia greca. Anzitutto il nome, che come quello di Achille, non si può spiegare con etimologie greche e rinvia a strati più antichi. Poi anche le molteplici esperienze e situazioni con le quali l'eroe appare strettamente collegato: i suoi incontri con streghe e giganti, con mostri e mangiatori d'uomini, il suo viaggio agli Inferi, i suoi contatti con esseri demoniaci, tutto ciò giustifica la supposizione che le sue radici vadano cercate nel mondo dell'antica favola, e addirittura nel mondo di primitive concezioni magiche e sciamaniche ». 1
Il Presidente dell'Associazione Culturale Neoborbonica Gennaro De Crescenzo ha recensito un libro... more Il Presidente dell'Associazione Culturale Neoborbonica Gennaro De Crescenzo ha recensito un libro di Eugenio Di Rienzo con una "stroncatura" che val la pena riportare per intero.
This essay compares two different historiographic interpretations of the concepts of State, Natio... more This essay compares two different historiographic interpretations of the concepts of State, Nation, Ethnic groups.
Nell'epoca della Rete, con il libero accesso alla diffusione delle proprie idee, soprattutto attr... 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;
A margine del "vademecum" dell'Istituto regionale per la storia della Resistenza e dell’Età cont... more 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"?
Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain.... 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.
In clinical glaucoma, as well as in experimental models, the loss of retinal ganglion cells occur... 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.
Glaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a numbe... 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.
Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain.... 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...
The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticep... 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.
Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorde... 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.
Cardiac valve calcifications are present in dialysis patients and regarded as dependent on a dera... 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.
A Whiter Shade of Pale dei Procol Harum, incisa nel 1967 contiene numerosi elementi che potrebber... more 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?
La collana "Minima Storiografica" di Nuova Rivista storica pubblica un'interessantissima opera di... 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.
Protestanti, illuministi, alcuni marxisti e alcuni massoni (non tutti, per fortuna ...) hanno fat... 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.
Una "lettera aperta" agli storici circa la necessità di un dibattito sull'Unità d'Italia che coin... more Una "lettera aperta" agli storici circa la necessità di un dibattito sull'Unità d'Italia che coinvolga il grande pubblico
Pur non essendo risalente nel tempo quanto quello degli Argonauti o viepiù di Gilgamesh, il mito ... more Pur non essendo risalente nel tempo quanto quello degli Argonauti o viepiù di Gilgamesh, il mito di Odisseo/Ulisse è senza dubbio antichissimo: «Molti elementi indicano che Odisseo rappresenta un'antichissima figura della mitologia greca. Anzitutto il nome, che come quello di Achille, non si può spiegare con etimologie greche e rinvia a strati più antichi. Poi anche le molteplici esperienze e situazioni con le quali l'eroe appare strettamente collegato: i suoi incontri con streghe e giganti, con mostri e mangiatori d'uomini, il suo viaggio agli Inferi, i suoi contatti con esseri demoniaci, tutto ciò giustifica la supposizione che le sue radici vadano cercate nel mondo dell'antica favola, e addirittura nel mondo di primitive concezioni magiche e sciamaniche ». 1
Il Presidente dell'Associazione Culturale Neoborbonica Gennaro De Crescenzo ha recensito un libro... more Il Presidente dell'Associazione Culturale Neoborbonica Gennaro De Crescenzo ha recensito un libro di Eugenio Di Rienzo con una "stroncatura" che val la pena riportare per intero.
This essay compares two different historiographic interpretations of the concepts of State, Natio... more This essay compares two different historiographic interpretations of the concepts of State, Nation, Ethnic groups.
Nell'epoca della Rete, con il libero accesso alla diffusione delle proprie idee, soprattutto attr... 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;
A margine del "vademecum" dell'Istituto regionale per la storia della Resistenza e dell’Età cont... more 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"?
Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain.... 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.
In clinical glaucoma, as well as in experimental models, the loss of retinal ganglion cells occur... 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.
Glaucoma is a disease where retinal ganglion cells (RGC) are specifically affected though a numbe... 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.
Ischemic stroke is a devastating condition primarily caused by reduced blood supply to the brain.... 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...
The epileptogenic and neurodegenerative effects of gamma-dendrotoxin, from Dendroaspis angusticep... 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.
Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorde... 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.
Cardiac valve calcifications are present in dialysis patients and regarded as dependent on a dera... 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; th... 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, ...
Glaucoma is the leading cause of irreversible blindness worldwide. Although the intraocular press... 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.
Glaucoma is a neurodegenerative disease caused by the progressive apoptotic death of retinal gang... 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.
Glaucoma, the second leading cause of blindness in the world, is a chronic optic neuropathy often... 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.
The lateral geniculate nucleus (LGN) is the thalamic relay of retinal inputs to the visual cortex... 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...
1. The antidepressant trazodone and its main metabolite m-chlorophenylpiperazine (mCPP) were inve... 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.
Patients with chronic kidney disease (CKD) have markedly higher rates of severe vitamin D deficie... more Patients with chronic kidney disease (CKD) have markedly higher rates of severe vitamin D deficiency and reduced ability to convert 25-(OH)vitamin D into the active form, 1,25-dihydroxyvitamin D . In the setting of CKD, secondary hyperparathyroidism develops as a consequence of reduced renal production of active vitamin D and phosphate retention resulting in hypocalcaemia and hyperphosphataemia. This is a process that is dangerously linked with metabolic bone disease, arterial calcifications and cardiovascular mortality . Therefore, the conventional rationale for vitamin D treatment in CKD is to slow the progression of secondary hyperparathyroidism.
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