11,632 research outputs found
Chronic treatment with SCH 23390 increases the production rate of dopamine D1 receptors in the nigro-striatal system of the rat
No full textSensibilità allo stress e memoria spaziale nei figli dei ratti sottoposti a stress cronico
No full textImpatto clinico della metodica del counting dei carboidrati sul management di pazienti affetti da diabete tipo 1 in terapia multiniettiva e con microinfusore
No full textOGGETTO Il counting dei carboidrati rappresenta l’approccio nutrizionale più efficace nel DM1 nell’ottimizzare la terapia insulinica sulla base dell’intake dei carboidrati. La finalità di questo metodo educativo è il miglioramento della qualità di vita del paziente in trattamento insulinico intensivo che si realizza attraverso il raggiungimento di un’aumentata flessibilità alimentare. Lo scopo di questo studio è stato quello di valutare l’impatto della metodica del counting su variabili cliniche, biochimiche e antropometriche e sulla variabilità glicemica in una popolazione di soggetti con DM1 in un follow-up di 3 mesi.
DISEGNO DELLO STUDIO E METODI In questo studio osservazionale prospettico della durata di 3 mesi sono stati arruolati consecutivamente 30 pazienti affetti da DMT1, afferenti alla U.O.D. di Diabetologia del Policlinico Umberto I di Roma tra Marzo e Maggio 2018. I pazienti hanno seguito il corso di counting dei carboidrati, articolato in 4 incontri pomeridiani della durata di 2 ore ciascuno, per un arco temporale totale di 1 mese. Ai pazienti è stato applicato per una settimana all’inizio del corso (T0) e a 3 mesi (T3) un sensore glicemico (CGM) retrospettivo modello Medtronic Enlite. Di tutti i soggetti sono stati raccolti dati clinici, antropometrici e glicemici al basale (T0) e a 3 mesi (T3).
RISULTATI Si evidenza un miglioramento significativo del valore del BMI medio (24,67±3,60 vs 23,55±3,32 kg/m2 – p<.001) e della circonferenza della vita (87,42±9,57 vs 82,72±8,12 cm – p<.001). Il valore medio dell’HbA1c è passato da un valore di 8,52±1,20 a 7,40±0,61 % (p<.001), mentre il fabbisogno insulinico giornaliero si è significativamente ridotto (39,59±11,80 vs 32,20±8,90 UI/die – p<.001). La popolazione al T3 è caratterizzata da una riduzione significativa del valore di glicemia media (198,23±55,57 vs 143,50±27,16 mg/dl- p<.001) ed il valore medio dell’area sotto la curva (AUC) della glicemia sopra il limite è passato da un valore di 73,21±42,42 a 24,49±16,74 mg/dL x min (p<.001), mentre quello dell’area sotto la curva (AUC) della glicemia sotto il limite ha avuto una riduzione significativa (0,42±0,53 vs 0,21±0,57 mg/dL x min- p<.001).
A T3 la media della percentuale delle glicemie in target è significativamente aumentata (27,36±17,87 vs 49,06±20,59 % - p<.001), contestualmente il valore medio delle glicemie sopra il target si è significativamente ridotto (70,16±16,48 vs 44,63±20,21 % - p<.001), così come quello delle glicemie sotto il target (2,86±2,96 vs 2,20±4,13 % - p=0.046).
CONCLUSIONI In questo studio il counting si è dimostrato efficace nel raggiungimento di un migliore controllo glicometabolico, confermando quindi l’importanza di questa metodica sia come strumento per gestire in modo più consapevole la terapia insulinica sia come percorso educativo che porta a scelte nutrizionali più corrette
Thyroid hormone receptor ligands induce regression of rat preneoplastic liver lesions causing their reversion to a differentiated phenotype
No full textHepatology. 2009 Apr;49(4):1287-96.
Thyroid hormone receptor ligands induce regression of rat preneoplastic liver lesions causing their reversion to a differentiated phenotype.
Perra A, Kowalik MA, Pibiri M, Ledda-Columbano GM, Columbano A.
SourceDepartment of Toxicology, Oncology and Molecular Pathology Unit, University of Cagliari, Cagliari, Italy.
Abstract
Triiodothyronine (T3), through interaction with its intracellular thyroid hormone receptors (TRs), influences various physiological functions, including metabolism, development, and growth. We investigated the effect of T3 and the selective TR-beta agonist GC-1 in two models of hepatocarcinogenesis. Preneoplastic lesions were induced in F-344 rats via a single dose of diethylnitrosamine, followed by a choline-deficient (CD) diet for 10 weeks. Rat subgroups were then fed the CD diet or a CD diet containing either 4 mg/kg T3 or 5 mg/kg GC-1 for another week. Rats fed a CD diet alone showed a large number (65/cm(2)) of preneoplastic lesions positive for the placental form of glutathione S-transferase (GSTP). Coadministration of T3 for the last week caused an almost complete disappearance of the foci (3/cm(2)). A reduction of GSTP-positive foci was also observed in rats fed a CD + GC-1 diet (28/cm(2) versus 75/cm(2) of rats fed a CD diet alone) in the absence of significant differences in labeling or apoptotic index of preneoplastic hepatocytes between the two groups. An antitumoral effect of GC-1 was also observed with the resistant hepatocyte model of hepatocarcinogenesis. Nodule regression was associated with a return to a fully differentiated phenotype, indicated by the loss of the fetal markers GSTP and gamma glutamyl transpeptidase, and reacquisition of the activity of glucose 6-phosphatase and adenosine triphosphatase, two enzymes expressed in normal hepatocytes. CONCLUSION: Our results indicate that activated TRs negatively influence the carcinogenic process through induction of a differentiation program of preneoplastic hepatocytes. The results also suggest that TRs could be a meaningful target in liver cancer therapy.
PMID:19115221[PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, SubstancesPublication TypesResearch Support, Non-U.S. Gov'tMeSH TermsAnimalsApoptosis/drug effectsCell Differentiation/drug effects*Choline Deficiency/complicationsDiethylnitrosamineGlutathione Transferase/metabolismHepatocytes/metabolismLiver Neoplasms, Experimental/drug therapy*MalePrecancerous Conditions/drug therapy*Precancerous Conditions/etiologyRatsRats, Inbred F344Receptors, Thyroid Hormone/metabolismTriiodothyronine/analogs & derivativesTriiodothyronine/pharmacologyTriiodothyronine/therapeutic use*SubstancesReceptors, Thyroid HormoneDiethylnitrosamineTriiodothyronineGlutathione Transferase
LinkOut - more resourcesFull Text SourcesJohn Wiley & Sons, Inc.EBSCOOhioLINK Electronic Journal CenterSwets Information ServicesMolecular Biology DatabasesN-NITROSODIETHYLAMINE - HSDBLIOTHYRONINE - HSD
Down-regulation of hippocampal BDNF and Arc associated with improvement in aversive spatial memory performance in socially isolated rats
No full textRats deprived of social contact with other rats at a young age experience a form of prolonged stress that leads to long-lasting changes in behavioral profile. Such isolation is thought to be anxiogenic for these normally gregarious animals, and the abnormal reactivity of isolated rats to environmental stimuli is thought to be a product of prolonged stress. We now show that isolation of rats at weaning reduced immobility time in the forced swim test, decreased sucrose intake and preference, and down-regulated both brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeletal associated protein (Arc) in the hippocampus. In the Morris water maze, isolated rats showed a reduced latency to reach the hidden platform during training, indicative of an improved learning performance, compared with group-housed rats. The cumulative search error during place training trials indicated a reliable difference between isolated and group-housed rats on days 4 and 5. The probe trial revealed a significant decrease of the average proximity to the target location in the isolated rats suggesting an improvement in spatial memory. Isolated rats also showed an increase in the plasma level of corticosterone on the 5th day of training and increased expression of BDNF and Arc in the hippocampus on both days 1 and 5. These results show that social isolation from weaning in rats results in development of depressive-like behavior but has a positive effect on spatial learning, supporting the existence of a facilitating effect of stress on cognitive functio
Social enrichment affects and reverses changes of emotional state and HPA sensitivity induced by early postweaning social isolation
No full textAdverse stress events during the adolescence period may have long-term effects on developing and emotional/behavioral state inducing deep, and sometimes irreversible, changes in the adulthood. It is well known that environmental enrichment has an heavy impact in the development brain networks as well as neuroendocrine system in the lifespan. Long-lasting stress experiences such as social isolation lead to profound neuronal and behavioral changes, increasing anxiety state, reduction in neurogenesis and dendritic arborization as well as an alteration of HPA axis function related to an abnormal hormones pattern fluctuation. We used a mild chronic stress model in rats in order to study the long-lasting effect of environmental enrichment in the future outcomes in the offspring previously socially isolated (SI). We evaluated the potential role of environmental conditions in rats deprived of social contact experience for long time (4-8 weeks) starting from weaning (21PND). Socially isolated rats usually show biochemical and behavioral alterations that persist into adult life if they live in this condition. Moreover, this kind of stress condition changes both hormones pattern and also the responsiveness to novel acute stress stimuli suggesting a greater HPA axis sensitivity. Environmental enrichment is able to revert some neuronal and behavior deficits switching the rearing social isolation. Here, we focused our attention on the effects of rat reintegration in group after 4 weeks of social isolation on different stress-related parameters such as anxiety, HPA hormones pattern and responsiveness to acute stress. We found that eight weeks of social isolation induced a decrease of plasmatic corticosterone and allopregnanolone content that in socially isolated-joined group (SI-J) were subsequently restored to levels observed in group housed animals. Similar effect was found in foot-shock-induced changes in corticosterone content and in several behavioral test such as Vogel, elevated plus maze and motility test. Our results further support that, in rats, the positive impact of environmental conditions reverts the plastic neuronal and behavioral responses to long-lasting stress
La separazione materna riduce gli effetti indotti sulla sensibilità dell’asse iis dall’isolamento sociale durante l’adolescenza
No full textLe cure materne che i neonati ricevono dopo la nascita stanno alla base del loro equilibrio
emotivo, interpersonale e sociale. Nella prima infanzia, infatti, uno degli eventi più stressanti può essere
rappresentato dalla ripetuta e protratta separazione materna (MS) la quale innesca una serie di
modificazioni molecolari, comportamentali e ormonali. Un altra importante tappa, della crescita nella vita
dei mammiferi, è il periodo post-svezzamento, infatti, quando si verificano eventi stressanti come
l'isolamento sociale (IS), questo provoca diversi cambiamenti nello sviluppo del cervello e del
comportamento. La nostra ipotesi è che gli effetti indotti da un ambiente sfavorevole come l’isolamento
sociale possano essere influenzati da precedenti stress come quello post-natale con un effetto risultante
diverso da quello osservato nei singoli eventi stressori. Tre ore di separazione materna (3°-15° giorno post
natale) riduce gli effetti indotti dall’isolamento sociale sui livelli allopregnanolone e corticosterone e
modifica inoltre la risposta al foot-shock stress, suggerendo che il protocollo separazione materna potrebbe
aiutare gli animali in età adulta ad essere meno sensibili agli stimoli stressanti. Questo effetto è mostrato
anche nella misurazione del fattore neurotrofico BDNF, infatti la le variazione di espressione di BDNF
osservata negli animali sottoposti a separazione materna e successivamente a isolamento sociale è simile a
quello misurato nel gruppo sottoposto a sola separazione materna ma significativamente più alto degli
animali socialmente isolati. I nostri risultati suggeriscono che nei ratti una breve separazione giornaliera
dalla madre durante la prima settimana di vita, che di per sé non altera sostanzialmente la funzionalità e
reattività dell'asse HPA nell’età adulta, aumenta la resilienza a protratte esperienze stressanti come
l’isolamento sociale
Picotamide: prevention and therapy of diabetic vasculopathies. A double-blind clinical study].
No full textPicotamide is the most interesting compound of 4-OH isophthalic acid. It is effective in vitro and in vivo. Picotamide induces inhibition of platelet aggregation: it is a thromboxane synthetase inhibitor and a thromboxane receptor antagonist. Picotamide causes cyclic endoperoxide accumulation and diverts their metabolism toward PgI2 synthesis in endothelial cells. PGI2 stimulates the adenylate cyclase with cAMP synthesis which makes platelets less sensitive to aggregatory stimulation. Picotamide induces enhancement of fibrinolytic activity, with significant reduction in the level of circulating plasminogen but in the same time it does not affect antithrombin III and FDP levels. In the present study picotamide or placebo were administered in a double blind trial at 600 mg daily for six months to 51 patients effected by diabetic macro and/or microangiopathy. The patients were 38 men and 13 women, the age was between 20 and 80 years (mean age 62.34). Twenty-seven patients were affected by type I diabetes and 24 by type II diabetes. Twenty-three of these patients presented macro-angiopathic lesions, 9 only microangiopathic lesions and 13 both. Twenty-five patients received picotamide and the other 25 an identical placebo for six months. One patient manifested myocardial infarction during the wash-out period and failed to enter the study. The following determinations were carried out: at T0 clinical examination, Doppler ultrasonography, Winsor Index, laboratory parameters; after 90 days (T90) clinical examination and Winsor Index and after 180 days (T180) were repeated photoplethysmography and clinical parameters too. Patients were not only evaluated for the vascular disease of lower extremities, but also for the other complications of diabetes, as retinopathy, nephropathy, cardiac and cerebrovascular disease
Study on the Mg-Li-Zn ternary alloy system with improved mechanical properties, good degradation performance and different responses to cells
No full textNovel Mg-(3.5, 6.5wt%)Li-(0.5, 2, 4wt%)Zn ternary alloys were developed as new kinds of biodegradable metallic materials with potential for stent application. Their mechanical properties, degradation behavior, cytocompatibility and hemocompatibility were studied. These potential biomaterials showed higher ultimate tensile strength than previously reported binary Mg-Li alloys and ternary Mg-Li-X (X=Al, Y, Ce, Sc, Mn and Ag) alloys. Among the alloys studied, the Mg-3.5Li-2Zn and Mg-6.5Li-2Zn alloys exhibited comparable corrosion resistance in Hank's solution to pure magnesium and better corrosion resistance in a cell culture medium than pure magnesium. Corrosion products observed on the corroded surface were composed of Mg(OH)2, MgCO3 and Ca-free Mg/P inorganics and Ca/P inorganics. In vitro cytotoxicity assay revealed different behaviors of Human Umbilical Vein Endothelial Cells (HUVECs) and Human Aorta Vascular Smooth Muscle Cells (VSMCs) to material extracts. HUVECs showed increasing nitric oxide (NO) release and tolerable toxicity, whereas VSMCs exhibited limited decreasing viability with time. Platelet adhesion, hemolysis and coagulation tests of these Mg-Li-Zn alloys showed different degrees of activation behavior, in which the hemolysis of the Mg-3.5Li-2Zn alloy was lower than 5%. These results indicated the potential of the Mg-Li-Zn alloys as good candidate materials for cardiovascular stent applications. Statement of significance: Mg-Li alloys are promising as absorbable metallic biomaterials, which however have not received significant attention since the low strength, controversial corrosion performance and the doubts in Li toxicity. The Mg-Li-Zn alloy in the present study revealed much improved mechanical properties higher than most reported binary Mg-Li and ternary Mg-Li-X alloys, with superior corrosion resistance in cell culture media. Surprisingly, the addition of Li and Zn showed increased nitric oxide release. The present study indicates good potential of Mg-Li-Zn alloy as absorbable cardiovascular stent material.Accepted Author ManuscriptBiomaterials & Tissue Biomechanic
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