RESUMEN
The early stages of ageing are a critical time window in which the ability to detect and identify precocious molecular and cognitive markers can make the difference in determining a healthy vs unhealthy course of ageing. Using the 6-different object task (6-DOT), a highly demanding hippocampal-dependent recognition memory task, we classified a population of middle-aged (12-month-old) CD1 male mice in Impaired and Unimpaired based on their short-term memory. This approach led us to identify a different microRNAs expression profile in the hippocampus of Impaired mice compared to Unimpaired ones. Among the dysregulated microRNAs, miR-153-3p was upregulated in the hippocampus of Impaired mice and appeared of high interest for its putative target genes and their possible implication in memory-related synaptic plasticity. We showed that intra-hippocampal injection of the miR-153-3p mimic in adult (3-month-old) mice is sufficient to induce a short-term memory deficit similar to that observed in middle-aged Impaired mice. Overall, these findings unravel a novel role for hippocampal miR-153-3p in modulating short-term memory that could be exploited to prevent early cognitive deficits in ageing.
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Hippocampus erectus inhabiting the shallow coastal waters of the southern Gulf of Mexico are naturally exposed to marked temperature variations occurring in different temporal scales. Under such heterogeneous conditions, a series of physiological and biochemical adjustments take place to restore and maintain homeostasis. This study investigated the molecular mechanisms involved in the response of H. erectus to increased temperature using transcriptome analysis based on RNA-Seq technology. Data was obtained from seahorses after 0.5-h exposure to combinations of different target temperatures (26 °C: control, and increased to 30 and 33 °C) and rates of thermal increase (abrupt: < 5 min; gradual: 1-1.5 °C every 3 h). The transcriptome of seahorses was assembled de novo using Trinity software to obtain 29,211 genes and 30,479 transcripts comprising 27,520,965 assembled bases. Seahorse exposure to both 30 and 33 °C triggered characteristic processes of the cellular stress response, regardless of the rate of thermal change. The transcriptomic profiles of H. erectus suggest an arrest of muscle development processes, the activation of heat shock proteins, and a switch to anaerobic metabolism within the first 0.5 h of exposure to target temperatures to ensure energy supply. Interestingly, apoptotic processes involving caspase were activated principally in gradual treatments, suggesting that prolonged exposure to even sublethal temperatures results in the accumulation of deleterious effects that may eventually terminate in cellular death. Results herein validate 30 °C and 33 °C as potential upper limits of thermal tolerance for H. erectus at the southernmost boundary of its geographic distribution.
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Smegmamorpha , Animales , Perfilación de la Expresión Génica , Calor , Smegmamorpha/genética , Smegmamorpha/metabolismo , Temperatura , TranscriptomaRESUMEN
PURPOSE: COVID-19 pandemics and cardiometabolic health are mutually interconnected. Chronic metabolic diseases are known risk factors for increased mortality after SARS-CoV-2 infection. In turn, COVID pandemics imposed sudden changes in lifestyle and social isolation with consequent potential cardiometabolic sequelae. The present study aimed at investigating the impact of changes in lifestyle and social life on metabolic profile in hyperprolactinemic or osteoporotic patients without pre-existing cardiometabolic diseases at the time of COVID-19. METHODS: The primary study outcome measurement was the prevalence of obesity, arterial hypertension, impaired glucose tolerance (IGT) or diabetes mellitus (DM), dyslipidemia and metabolic syndrome after COVID-19 outbreak. Seventy-four patients (21 men and 53 women, aged 51.8 ± 17.8 years) were admitted to the outpatient clinic of the Neuroendocrine Disease Unit at University "Federico II" of Naples, Italy, as per their routine clinical practice because of tumoral and non-tumoral hyperprolactinemia in 52 patients (70.3%), and osteoporosis/osteopenia in 22 (29.7%). Among female patients, 25 (47.2%) were at menopausal age. RESULTS: At the end of lockdown, prevalence of obesity (from 37.8% to 51.3%, p < 0.0001), dyslipidemia (from 28.4 to 48.6%, p = 0.003) and metabolic syndrome (from 14.9 to 27%, p < 0.0001) significantly increased compared to pre-COVID evaluation. No significant change was found in the prevalence of arterial hypertension and IGT/DM. CONCLUSION: SARS-CoV-2 outbreak has led to a rapid increase in the prevalence of metabolic syndrome, potentially contributing to the increased COVID-19 related mortality.
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COVID-19 , Factores de Riesgo Cardiometabólico , Síndrome Metabólico/epidemiología , Pandemias , Cuarentena , Adulto , Anciano , Anciano de 80 o más Años , Dislipidemias/epidemiología , Femenino , Estado de Salud , Humanos , Hiperprolactinemia/complicaciones , Italia/epidemiología , Estilo de Vida , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Osteoporosis/complicaciones , Prevalencia , Medio SocialRESUMEN
Indiscriminate activation of opioid receptors provides pain relief but also severe central and intestinal side effects. We hypothesized that exploiting pathological (rather than physiological) conformation dynamics of opioid receptor-ligand interactions might yield ligands without adverse actions. By computer simulations at low pH, a hallmark of injured tissue, we designed an agonist that, because of its low acid dissociation constant, selectively activates peripheral µ-opioid receptors at the source of pain generation. Unlike the conventional opioid fentanyl, this agonist showed pH-sensitive binding, heterotrimeric guanine nucleotide-binding protein (G protein) subunit dissociation by fluorescence resonance energy transfer, and adenosine 3',5'-monophosphate inhibition in vitro. It produced injury-restricted analgesia in rats with different types of inflammatory pain without exhibiting respiratory depression, sedation, constipation, or addiction potential.
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Dolor Agudo/tratamiento farmacológico , Analgésicos Opioides/química , Analgésicos Opioides/farmacología , Diseño de Fármacos , Fentanilo/análogos & derivados , Piperidinas/química , Piperidinas/farmacología , Receptores Opioides mu/agonistas , Receptores Opioides mu/química , Adenosina Monofosfato/antagonistas & inhibidores , Analgesia , Analgésicos Opioides/efectos adversos , Animales , Simulación por Computador , Estreñimiento/inducido químicamente , Fentanilo/efectos adversos , Transferencia Resonante de Energía de Fluorescencia , Subunidades alfa de la Proteína de Unión al GTP/metabolismo , Células HEK293 , Humanos , Concentración de Iones de Hidrógeno , Ligandos , Modelos Moleculares , Manejo del Dolor , Piperidinas/efectos adversos , Unión Proteica , Conformación Proteica , Ratas , Receptores Opioides mu/genética , Insuficiencia Respiratoria/inducido químicamente , TransfecciónRESUMEN
MicroRNAs are endogenous, noncoding RNAs crucial for the post-transcriptional regulation of gene expression. In this study, we investigated the role of miR-335-5p in spatial learning and synaptic plasticity. To this end we first showed spatial learning induced down-regulation of miR-335-5p. Next we found impairment in long-term memory and reduction in hippocampal long-term potentiation by exogenous administration of the miRNA. These findings demonstrate that miR-335-5p is a key coordinator of the intracellular pathways that mediate experience-dependent changes in the brain.
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Hipocampo/metabolismo , MicroARNs/metabolismo , Plasticidad Neuronal/genética , Aprendizaje Espacial/fisiología , Memoria Espacial/fisiología , Animales , Hipocampo/efectos de los fármacos , Masculino , Memoria a Largo Plazo/efectos de los fármacos , Memoria a Largo Plazo/fisiología , Ratones , MicroARNs/genética , MicroARNs/farmacología , Plasticidad Neuronal/efectos de los fármacos , Aprendizaje Espacial/efectos de los fármacos , Memoria Espacial/efectos de los fármacosRESUMEN
Claudin-5 is a tight junction (TJ) protein which limits the diffusion of small hydrophilic molecules. Thus, it represents a potential pharmacological target to improve drug delivery to the tissues protected by claudin-5-dependent barriers. Sodium caprate is known as an absorption enhancer which opens the paracellular space acting on TJ proteins and actin cytoskeleton. Its action on claudin-5 is not understood so far. Epithelial and endothelial systems were used to evaluate the effect of caprate on claudin-5 in TJ-free cells and on claudin-5 fully integrated in TJ. To this aim, confocal microscopy on live and fixed cells and isolated mouse brain capillaries, Western blotting and permeability assays were employed. Caprate reversibly reduced claudin-5 trans-interactions in TJ-free human embryonic kidney-293 cells expressing claudin-5-YFP. It decreased the membranous claudin-5 and the F-actin content in Madin-Darby canine kidney-II cells expressing Flag-claudin-5, thereby increasing the permeability to the small molecule lucifer yellow. Interestingly, zonula occludens protein 1 (ZO-1), which links transmembranous TJ proteins to the actin cytoskeleton, was not affected by caprate treatment. Similarly, endogenous claudin-5 in the membrane of brain endothelia was displaced together with F-actin, whereas ZO-1 remained unaffected. Caprate transiently opens the paracellular space, reducing the intercellular claudin-5/claudin-5 interactions and the polymerized actin at the perijunctional region of endothelial and epithelial cells. In conclusion, the study further elucidates the cellular effects of caprate at the tight junctions.
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Claudina-5/metabolismo , Ácidos Decanoicos/farmacología , Células Endoteliales/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Proteínas de la Membrana/metabolismo , Uniones Estrechas/efectos de los fármacos , Citoesqueleto de Actina/efectos de los fármacos , Citoesqueleto de Actina/metabolismo , Actinas/efectos de los fármacos , Actinas/metabolismo , Animales , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Capilares/efectos de los fármacos , Capilares/metabolismo , Línea Celular , Perros , Células Endoteliales/metabolismo , Células Epiteliales/metabolismo , Células HEK293 , Humanos , Isoquinolinas/metabolismo , Células de Riñón Canino Madin Darby , Ratones , Ratones Endogámicos C57BL , Permeabilidad/efectos de los fármacos , Uniones Estrechas/metabolismo , Proteína de la Zonula Occludens-1/metabolismoRESUMEN
The establishment of rat embryonic stem cells constitutes a precious tool since rat has been extensively used in biomedical research, in particular for the generation of human neurodisease animal models. Up to now only a few studies have described the isolation of rat embryonic stem-like cells. One out of 9 isolated rat embryonic stem-like cell lines (B1-RESC) obtained from a 4.5-day post-coitum blastocyst were extensively characterized and kept in culture for up to 80 passages on feeders with LIF. The stable growth of these cells and the expression of pluripotent markers were confirmed up to a high number of passages in culture, also in the absence of feeders and LIF. B1-RESC expresses the three germ layers markers both in vitro, within differentiating embryoid bodies, and in vivo through teratoma formation. Collectively, the B1-RESC line with a stable near-diploid karyotype can be used as a highly sensitive tool for testing anti-proliferative molecules.
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Descubrimiento de Drogas/métodos , Células Madre Embrionarias/citología , Investigación con Células Madre , Animales , Diferenciación Celular/genética , Diferenciación Celular/fisiología , Separación Celular/métodos , Células Cultivadas , Células Madre Embrionarias/metabolismo , Femenino , Regulación del Desarrollo de la Expresión Génica , Ratones , Modelos Biológicos , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
Remyelination failure is a key landmark in chronic progression of multiple sclerosis (MS), the most diffuse demyelinating disease in human, but the reasons for this are still unknown. It has been shown that thyroid hormone administration in the rodent models of acute and chronic demyelinating diseases improved their clinical course, pathology and remyelination. In the present study, we translated this therapeutic attempt to experimental allergic encephalomyelitis (EAE) in the non-human primate Callithrix Jacchus (marmoset). We report that short protocols of triiodothyronine treatment shifts the demyelination/remyelination balance toward remyelination, as assessed by morphology, immunohistochemistry and molecular biology, and improves the clinical course of the disease. We also found that severely ill animals display hypothyroidism and severe alteration of deiodinase and thyroid hormone receptor mRNAs expression in the spinal cord, which was completely corrected by thyroid hormone treatment. We therefore suggest that thyroid hormone treatment improves myelin sheath morphology in marmoset EAE, by correcting the dysfunction of thyroid hormone cellular effectors.
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Enfermedades Desmielinizantes/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental , Hipotiroidismo/tratamiento farmacológico , Esclerosis Múltiple , Regeneración Nerviosa/efectos de los fármacos , Triyodotironina/uso terapéutico , Animales , Biomarcadores/metabolismo , Callithrix , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/fisiopatología , Femenino , Humanos , Hipotiroidismo/patología , Hipotiroidismo/fisiopatología , Masculino , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/patología , Esclerosis Múltiple/fisiopatología , Vaina de Mielina/patología , Vaina de Mielina/fisiología , Vaina de Mielina/ultraestructura , Regeneración Nerviosa/fisiología , Oligodendroglía/citología , Oligodendroglía/fisiología , Células Madre/citología , Células Madre/fisiología , Hormonas Tiroideas/metabolismoRESUMEN
BACKGROUND: Thromboembolism is a complication of acute lymphoblastic leukemia therapy in children. The majority of thromboembolic events are cerebral thromboses and deep venous thromboses; many asymptomatic deep venous thromboses are detected in children with acute lymphoblastic leukemia by instrumental screening. The aim of this study was to assess the incidence of asymptomatic cerebral thromboembolic events in children with acute lymphoblastic leukemia (ALL) screened by magnetic resonance imaging and magnetic resonance venography. METHODS: 46 children with acute lymphoblastic leukemia, during the induction phase of the AIEOP ALL 2000 protocol, were stratified into 2 groups. In group "A" cerebral thromboembolic events were suspected following the appearance of suggestive signs and symptoms and confirmed by cerebral magnetic resonance imaging and magnetic resonance venography; in group "B" children underwent a screening by cerebral magnetic resonance imaging and magnetic resonance venography, at set times, in absence of symptoms. RESULTS: We observed one cerebral thromboembolic event in both groups; we found no differences between early detecting asymptomatic cerebral thromboembolic events among monitored and not monitored patients. CONCLUSIONS: Our study does not seem to suggest a screening for asymptomatic cerebral thromboembolic events in children with ALL during the induction phase.
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Trombosis Intracraneal/diagnóstico , Trombosis Intracraneal/etiología , Imagen por Resonancia Magnética/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Angiografía por Resonancia Magnética , Masculino , Tamizaje Masivo/métodos , Proyectos Piloto , Estudios ProspectivosRESUMEN
Most cases of Meckel's diverticulum (MD) are asymptomatic and discovered by chance. Management of MD is controversial. The authors describe an exceptional case of intestinal obstruction caused by a giant MD in a patient who had previously undergone appendectomy. A review of the contradictory literature on this subject leads to the conclusion that careful consideration of clinical and morphological data (patient's age, ASA score, the surgical procedure to be performed, morphology and position of the MD, any fibrotic bands) is required before deciding whether or not to resect an asymptomatic MD.
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Enfermedades del Íleon/etiología , Obstrucción Intestinal/etiología , Divertículo Ileal/complicaciones , Dolor Abdominal/etiología , Apendicectomía , Humanos , Enfermedades del Íleon/prevención & control , Enfermedades del Íleon/cirugía , Obstrucción Intestinal/cirugía , Masculino , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirugía , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/cirugía , Adherencias Tisulares/cirugía , Adulto JovenRESUMEN
Polychlorinated dibenzo-dioxins, furans and dioxin-like polychlorinated biphenyls are ubiquitous in foodstuffs of animal origin and accumulate in the fatty tissues of animals and humans. The most toxic congener is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a lipophilic endocrine-disrupting molecule that accumulates in adipose tissue, placenta and milk. polychlorinated biphenyls and TCDD are known to interfere with thyroid hormone metabolism and signaling in the developing brain. As thyroid hormone is critical in the myelination process during development, we investigated the effect of a single dose of TCDD prenatal exposure (gestational day 18) on the myelination process. A semi-quantitative analysis of oligodendrocyte markers at different stages of maturation was performed in the offspring's medulla oblongata, cerebellum, diencephalon and telenchephalon at different postnatal days (2/3, 14, 30 and 135). The most significant alterations observed were: (i) cerebellum and medulla oblongata: altered expression of oligodendroglial lineage and platelet-derived growth factor alpha receptor, myelin basic protein (MBP) mRNAs (P2/3, P135) and MBP protein (P135); (ii) diencephalon: increase in platelet- derived growth factor alpha receptor mRNA level (P2/3); (iii) telenchephalon: decrease in MBP mRNA expression. The oligodendroglial generation capability of adult neural stem/precursor cells obtained ex vivo from TCDD and vehicle-treated dams was then explored. TCDD impairs neurosphere proliferation and retards CNPase-positive cell generation from adult neurospheres.
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Encéfalo/efectos de los fármacos , Encéfalo/crecimiento & desarrollo , Disruptores Endocrinos/administración & dosificación , Inhibidores de Crecimiento/administración & dosificación , Fibras Nerviosas Mielínicas/efectos de los fármacos , Dibenzodioxinas Policloradas/administración & dosificación , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Animales , Animales Recién Nacidos , Encéfalo/patología , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Disruptores Endocrinos/toxicidad , Femenino , Inhibidores de Crecimiento/toxicidad , Masculino , Fibras Nerviosas Mielínicas/patología , Oligodendroglía/efectos de los fármacos , Oligodendroglía/patología , Dibenzodioxinas Policloradas/toxicidad , Embarazo , Efectos Tardíos de la Exposición Prenatal/patología , RatasRESUMEN
AIMS: Neurogenesis in adult humans occurs in at least two areas of the brain, the subventricular zone of the telencephalon and the subgranular layer of the dentate gyrus in the hippocampal formation. We studied dentate gyrus subgranular layer neurogenesis in patients subjected to tailored antero-mesial temporal resection including amygdalohippocampectomy due to pharmacoresistant temporal lobe epilepsy (TLE) using the in vitro neurosphere assay. METHODS: Sixteen patients were enrolled in the study; mesial temporal sclerosis (MTS) was present in eight patients. Neurogenesis was investigated by ex vivo neurosphere expansion in the presence of mitogens (epidermal growth factor + basic fibroblast growth factor) and spontaneous differentiation after mitogen withdrawal. Growth factor synthesis was investigated by qRT-PCR in neurospheres. RESULTS: We demonstrate that in vitro proliferation of cells derived from dentate gyrus of TLE patients is dependent on disease duration. Moreover, the presence of MTS impairs proliferation. As long as in vitro proliferation occurs, neurogenesis is maintained, and cells expressing a mature neurone phenotype (TuJ1, MAP2, GAD) are spontaneously formed after mitogen withdrawal. Finally, formed neurospheres express mRNAs encoding for growth (vascular endothelial growth factor) as well as neurotrophic factors (brain-derived neurotrophic factor, ciliary neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor). CONCLUSION: We demonstrated that residual neurogenesis in the subgranular layer of the dentate gyrus in TLE is dependent on diseases duration and absent in MTS.
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Giro Dentado/fisiopatología , Epilepsia del Lóbulo Temporal/fisiopatología , Neurogénesis/fisiología , Neuronas/citología , Adolescente , Adulto , Proliferación Celular , Giro Dentado/patología , Epilepsia del Lóbulo Temporal/patología , Femenino , Humanos , Inmunohistoquímica , Masculino , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Esclerosis/patologíaRESUMEN
The authors describe a case of giant appendiceal mucocele, secondary to a mucinous neoplasm of the appendix, diagnosed during laparotomy for acute abdomen. By a review of the literature they stress the rarity of this lesion, the particular onset in their case as acute complication of appendiceal neoplasm with rupture of the intestinal wall, the difficulties of diagnosis and management in emergency.
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Abdomen Agudo/cirugía , Neoplasias del Apéndice/diagnóstico , Apéndice , Cistoadenoma Mucinoso/diagnóstico , Laparotomía , Mucocele/patología , Mucocele/cirugía , Abdomen Agudo/etiología , Anciano , Neoplasias del Apéndice/complicaciones , Neoplasias del Apéndice/cirugía , Apéndice/patología , Apéndice/cirugía , Índice de Masa Corporal , Cistoadenoma Mucinoso/complicaciones , Cistoadenoma Mucinoso/cirugía , Diagnóstico Diferencial , Femenino , Humanos , Hallazgos Incidentales , Mucocele/complicaciones , Mucocele/etiología , Obesidad/complicaciones , Factores de Riesgo , Resultado del TratamientoRESUMEN
The neuropeptide galanin is a modulator of cholinergic function and may play a role in A beta peptide-induced degeneration of cholinergic forebrain neurons. We have studied the effect of galanin and its galanin receptor subtype 2/3 agonist Gal2-11on toxicity induced by freshly-prepared beta-amyloid(25-35) in the cholinergic cell line SN56. Both nuclear fragmentation and caspase-3 expression were analysed. beta-amyloid(25-35)-exposure induced a significant increase in caspase-3 mRNA expression after 30, 60, 90 or 150 min of beta-amyloid(25-35) exposure. These effects were abolished in the presence of Gal2-11 (10 nM). Similarly, beta-amyloid(25-35)-induced nuclear fragmentation was prevented by the galanin agonist at all time points studied. These findings indicate that the galanin 2/3 agonist Gal2-11 protects SN56 cholinergic cells from beta-amyloid(25-35)-induced cell death and that this action is mediated by an early reduction of caspase-3 expression.
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Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/antagonistas & inhibidores , Galanina/farmacología , Neuronas/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/antagonistas & inhibidores , Fragmentos de Péptidos/farmacología , Receptor de Galanina Tipo 2/agonistas , Acetilcolina/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/toxicidad , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Núcleo Basal de Meynert/efectos de los fármacos , Núcleo Basal de Meynert/metabolismo , Núcleo Basal de Meynert/fisiopatología , Caspasa 3/genética , Línea Celular Transformada , Fibras Colinérgicas/efectos de los fármacos , Fibras Colinérgicas/metabolismo , Fibras Colinérgicas/patología , Fragmentación del ADN/efectos de los fármacos , Galanina/metabolismo , Galanina/uso terapéutico , Ratones , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/metabolismo , Degeneración Nerviosa/fisiopatología , Neuronas/metabolismo , Fármacos Neuroprotectores/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/uso terapéutico , Fragmentos de Péptidos/toxicidad , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Receptor de Galanina Tipo 2/metabolismo , Factores de TiempoRESUMEN
Thyroid hormone exerts a critical role in developmental myelination, acting on the production and maturation of oligodendrocyte, and on the expression of genes encoding for myelin protein. Since remyelination is considered a recapitulation of cellular and molecular events occurring during development, we tested the possibility of stimulating the oligodendroglial lineage and maturation in neurospheres derived from the subventricular zone of adult rats using 3,5,3'-L-triiodothyronine (T3). Both non-pathological and pathological brains derived from rats affected by the inflammatory-demyelinating disease experimental allergic encephalomyelitis (EAE) were included in the study. We investigated the effect of in vitro T3 exposure on: (i) the expression of nuclear thyroid hormone receptors; (ii) proliferation rate; (iii) differentiation into neurons, astrocytes and oligodendrocytes, focusing our attention on oligodendrocyte maturation. T3 reduced the proliferation rate of neurospheres when cultured in the presence of mitogens, shifting towards oligodendroglial lineage as indicated by increased expression of olig-1, and also favoring oligodendrocyte maturation, as indicated by the expression of antigens associated with different maturation stages. Neurospheres derived from EAE rats show a strong limitation in oligodendrocyte generation, which is completely restored by T3 treatment. These results indicate that T3 is a key factor in regulating neurosphere biology, when derived either from non-pathological or pathological adult brains, suggesting that T3 might be an important factor in favoring remyelination in demyelinating disorders.
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Proteínas de la Mielina/metabolismo , Regeneración Nerviosa/efectos de los fármacos , Neuroglía/fisiología , Triyodotironina/farmacología , Animales , Encéfalo/citología , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Linaje de la Célula , Células Cultivadas , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/metabolismo , Enfermedades Desmielinizantes/patología , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Femenino , Humanos , Regeneración Nerviosa/fisiología , Neuroglía/citología , Ratas , Ratas Endogámicas Lew , Triyodotironina/metabolismo , Triyodotironina/uso terapéuticoRESUMEN
Acute ischaemic brain damages, including both strokes and local ischaemia, are powerful stimulators of neurogenesis in the dentate gyrus of the hippocampus in adult rats and mice. As no data are available in chronic cerebral hypoperfusion, we investigated neurogenesis in rats after bilateral chronic occlusion of the carotid arteries (2VO). 2VO was performed in 3- and 12-month-old rats. Proliferation was investigated by bromodeoxyuridine uptake and MCM2 nuclear immunoreactivity, neurogenesis by counting doublecortin-IR cells in the subgranular area of the dentate gyrus of the hippocampus. We found increased proliferation and neurogenesis in the subgranular area of the dentate gyrus of the hippocampus in adult (3-month-old) rats 8 days after 2VO. This capability is lost in middle-aged (12-month-old) rats. Our data suggest that 2VO ligation can be a useful model for studying neurogenesis in experimental conditions mimicking long-lasting human pathologies, and also in the exploration of the uncertain relation between chronic brain hypoperfusion and age-related changes of cognitive function.
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Envejecimiento/fisiología , Isquemia Encefálica/fisiopatología , Diferenciación Celular , Hipocampo/citología , Neuronas/citología , Animales , Arterias Carótidas/cirugía , Proliferación Celular , Modelos Animales de Enfermedad , Proteína Doblecortina , Hipocampo/irrigación sanguínea , Procesamiento de Imagen Asistido por Computador , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-Dawley , Células Madre/citologíaRESUMEN
Hereditary hemorrhagic telangiectasia (HHT) or the Rendu-Osler-Weber disease is a systemic fibrovascular autosomal dominant dysplasia, recognised when three of the following four clinical manifestations are present, according to the proposal of Shovlin.: recurrent nosebleeds, lelangiectasias of the skin, visceral lesions, and positive family history. HHT is often difficult to diagnose on the basis of history and physical examination alone, especially in infants and children. The signs and symptoms of HHT are nonspecific and are extremely variable within families. Given the frequent occurrence of clinically silent lesions in lung and brain arteriovenous malformations which can result in morbidity or death, much consideration should be given to screening patients with HHT for asymptomatic fistulae and to their treating once they are discovered. Presymptomatic interventions in such cases may substantially affect the outcome. It may be possible to state that lesions of HHT arise early in life, but do not reach sufficient size to cause symptoms until the second decade. Furthermore, as clinical manifestations often occur later in life, the development and the implementation of a molecular diagnosis will allow the identification of subjects with no evident signs of the disease but carrying the familial mutation. This is fundamental in order to establish reliable screening protocols for the prevention and cure of the disease and, to determine the presence of family members with no disease-associated mutation, who do not require further clinical screening.
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Telangiectasia Hemorrágica Hereditaria/diagnóstico , Envejecimiento/fisiología , Niño , Pruebas Genéticas , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/genética , Telangiectasia Hemorrágica Hereditaria/patologíaRESUMEN
Liver disease is the second cause of mortality in thalassemia major. We present a review on the hepatic damage in thalassemic patients aimed at a knowledge of current preventive, diagnostic and therapeutic approaches, useful to guide in clinical judgment and treatment decisions. Transfusion related iron overload and hepatitis are the causes of liver damage in thalassemic patients. We examined means of primary prevention, anti-hepatitis vaccinations, blood donors screening; diagnostic tests for secondary prevention (computed tomography, magnetic resonance imaging, super conducting quantum interference device and biopsy) were also discussed about. A survey of treatment methods and strategies ( chelation therapy, antiviral treatments and liver and bone marrow transplantation) follows.
Asunto(s)
Hepatitis Viral Humana/tratamiento farmacológico , Sobrecarga de Hierro/tratamiento farmacológico , Talasemia/complicaciones , Antivirales/uso terapéutico , Hepatitis Viral Humana/prevención & control , Hepatitis Viral Humana/virología , Humanos , Quelantes del Hierro/uso terapéutico , Sobrecarga de Hierro/etiología , Trasplante de Hígado , Talasemia/terapia , Reacción a la Transfusión , Vacunas contra Hepatitis Viral/uso terapéuticoRESUMEN
The life expectancy of patients with thalassemia major has significantly increased in recent years, as reported by several groups in different countries. However, complications are still frequent and affect the patients' quality of life. In a recent study from the United Kingdom, it was found that 50% of the patients had died before age 35. At that age, 65% of the patients from an Italian long-term study were still alive. Heart disease is responsible for more than half of the deaths. The prevalence of complications in Italian patients born after 1970 includes heart failure in 7%, hypogonadism in 55%, hypothyroidism in 11%, and diabetes in 6%. Similar data were reported in patients from the United States. In the Italian study, lower ferritin levels were associated with a lower probability of experiencing heart failure and with prolonged survival. Osteoporosis and osteopenia are common and affect virtually all patients. Hepatitis C virus antibodies are present in 85% of multitransfused Italian patients, 23% of patients in the United Kingdom, 35% in the United States, 34% in France, and 21% in India. Hepatocellular carcinoma can complicate the course of hepatitis. A survey of Italian centers has identified 23 such cases in patients with a thalassemia syndrome. In conclusion, rates of survival and complication-free survival continue to improve, due to better treatment strategies. New complications are appearing in long-term survivors. Iron overload of the heart remains the main cause of morbidity and mortality.
Asunto(s)
Talasemia beta/mortalidad , Adolescente , Adulto , Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/etiología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Cardiomiopatías/etiología , Cardiomiopatías/mortalidad , Causas de Muerte , Terapia por Quelación , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus/epidemiología , Supervivencia sin Enfermedad , Femenino , Ferritinas/análisis , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Humanos , Hipogonadismo/epidemiología , Hipogonadismo/etiología , Lactante , Recién Nacido , Sobrecarga de Hierro/etiología , Sobrecarga de Hierro/mortalidad , Italia/epidemiología , Esperanza de Vida , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Masculino , Mortalidad/tendencias , Estudios Multicéntricos como Asunto , Osteoporosis/epidemiología , Osteoporosis/etiología , Embarazo , Complicaciones Hematológicas del Embarazo , Prevalencia , Reacción a la Transfusión , Talasemia beta/complicaciones , Talasemia beta/terapiaRESUMEN
AIM: To evaluate plasma protein Z (PZ) levels in healthy and high-risk newborn infants. METHODS: A longitudinal observational study was conducted. Inclusion criteria were: healthy term and preterm newborns normal for gestational age and newborns belonging to one of the following groups: newborns small for gestational age (SGA), newborns affected by respiratory distress syndrome (RDS), newborns from mothers with pre-eclampsia. Newborns with sepsis, congenital malformation or haemorrhagic disorders were excluded. Plasma PZ levels, protein C (PC) concentration, PC activity and protein-induced vitamin K absence levels were measured. RESULTS: 53 newborns were enrolled into the study. PZ and PC antigen levels varied significantly among analysed subgroups on day 1 (p < 0.01): lower levels of these inhibitors were found in RDS newborns (group C), newborns from mothers affected by pre-eclampsia (group D) and SGA newborns (group E) than in healthy term and preterm newborns (groups A and B). CONCLUSION: PZ deficiency occurs in newborns affected by severe RDS, in newborns from pre-eclamptic mothers and in SGA newborns, probably owing to activated coagulation in the first two conditions and to reduced PZ synthesis in the last condition.