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1.
Eur Arch Psychiatry Clin Neurosci ; 271(8): 1445-1453, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32940786

RESUMEN

Movement slowness, linked to dysfunctional basal ganglia and cerebellum, is prevalent but lacks effective therapy in patients with schizophrenia spectrum disorders. This study was to examine immediate effects of rhythmic auditory stimulation (RAS) on upper-limb movement speed in patients. Thirty patients and 30 psychiatrically healthy people executed the right-hand task and the both-hand task of the Purdue Pegboard Test when listening to RAS with two tempi: normal (equal to the fastest movement tempo for each participant without RAS) and fast (120% of the normal tempo). The testing order of the RAS tempi for each participant was randomized. Patients had lower scores of right-hand and both-hand tasks than did psychiatrically healthy people. Scores of right-hand and both-hand tasks were higher in the fast-RAS condition than the normal-RAS condition in participants. This is the first study to explore the possibility of applying RAS to movement therapy for patients with schizophrenia spectrum disorders. The results demonstrated that faster RAS was effective in inducing faster upper-limb movements in patients and psychiatrically healthy people, suggesting that manipulating RAS may be a feasible therapeutic strategy utilized to regulate movement speed. The RAS may involve alternative neural pathways to modulate movement speed and thus to compensate for impaired function of basal ganglia and cerebellum in patients.


Asunto(s)
Estimulación Acústica , Movimiento , Esquizofrenia , Extremidad Superior , Humanos , Movimiento/fisiología , Esquizofrenia/fisiopatología , Esquizofrenia/terapia , Resultado del Tratamiento , Extremidad Superior/fisiología
2.
J Neurosci ; 36(19): 5193-9, 2016 05 11.
Artículo en Inglés | MEDLINE | ID: mdl-27170118

RESUMEN

UNLABELLED: Multiple sclerosis (MS) is a progressive autoimmune disease of the CNS with its underlying mechanisms not fully understood. In the present study, we tested the hypothesis that caveolin-1, a major membrane scaffolding protein, plays a critical role in the pathogenesis of experimental autoimmune encephalomyelitis, a laboratory murine model of MS. We found increased expression of caveolin-1 in serum and spinal cord tissues in association with disease incidence and severity in wild-type mice with active encephalomyelitis. After immunization, Cav-1 knock-out mice showed remarkable disease resistance with decreased incidence and clinical symptoms. Furthermore, Cav-1 knock-out mice had alleviated encephalitogenic T cells trafficking into the CNS with decreased expressions of adhesion molecules ICAM-1 and VCAM-1 within the lesions. In agreement with in vivo studies, in vitro knockdown of caveolin-1 compromised the upregulation of ICAM-1 in endothelial cells, leading to the amelioration of the transendothelial migration of pathogenic TH1 and TH17 cells. Together, those results indicate that caveolin-1 serves as an active modulator of CNS-directed lymphocyte trafficking and could be a therapeutic target for neuroinflammatory diseases, such as multiple sclerosis. SIGNIFICANCE STATEMENT: The hallmark feature of neuroinflammatory diseases is the massive infiltrations of encephalitogenic leukocytes into the CNS parenchyma, a process that remains largely unclear. Our study demonstrates the critical contribution of caveolin-1 to encephalomyelitis pathogenesis and CNS-directed lymphocyte trafficking by modulation of adhesion molecules ICAM-1 and VCAM-1, highlighting the pathological involvement of caveolin-1 in neuroinflammatory diseases.


Asunto(s)
Caveolina 1/metabolismo , Encefalomielitis Autoinmune Experimental/metabolismo , Médula Espinal/metabolismo , Linfocitos T/fisiología , Migración Transendotelial y Transepitelial , Animales , Caveolina 1/genética , Células Cultivadas , Encefalomielitis Autoinmune Experimental/genética , Femenino , Molécula 1 de Adhesión Intercelular/genética , Molécula 1 de Adhesión Intercelular/metabolismo , Ratones , Ratones Endogámicos C57BL , Molécula 1 de Adhesión Celular Vascular/genética , Molécula 1 de Adhesión Celular Vascular/metabolismo
3.
Int J Mol Sci ; 18(3)2017 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-28264437

RESUMEN

Injuries to peripheral nerves are frequent in serious traumas and spinal cord injuries. In addition to surgical approaches, other interventions, such as cell transplantation, should be considered to keep the muscles in good condition until the axons regenerate. In this study, E14.5 rat embryonic spinal cord fetal cells and cultured neural progenitor cells from different spinal cord segments were injected into transected musculocutaneous nerve of 200-300 g female Sprague Dawley (SD) rats, and atrophy in biceps brachii was assessed. Both kinds of cells were able to survive, extend their axons towards the muscle and form neuromuscular junctions that were functional in electromyographic studies. As a result, muscle endplates were preserved and atrophy was reduced. Furthermore, we observed that the fetal cells had a better effect in reducing the muscle atrophy compared to the pure neural progenitor cells, whereas lumbar cells were more beneficial compared to thoracic and cervical cells. In addition, fetal lumbar cells were used to supplement six weeks delayed surgical repair after the nerve transection. Cell transplantation helped to preserve the muscle endplates, which in turn lead to earlier functional recovery seen in behavioral test and electromyography. In conclusion, we were able to show that embryonic spinal cord derived cells, especially the lumbar fetal cells, are beneficial in the treatment of peripheral nerve injuries due to their ability to prevent the muscle atrophy.


Asunto(s)
Atrofia Muscular/etiología , Atrofia Muscular/patología , Células-Madre Neurales/citología , Traumatismos de los Nervios Periféricos/complicaciones , Médula Espinal/citología , Trasplante de Células Madre , Animales , Astrocitos/metabolismo , Axones/metabolismo , Biomarcadores , Diferenciación Celular , Proliferación Celular , Supervivencia Celular , Femenino , Neuronas Motoras/metabolismo , Atrofia Muscular/rehabilitación , Atrofia Muscular/terapia , Regeneración Nerviosa , Células-Madre Neurales/metabolismo , Unión Neuromuscular/citología , Oligodendroglía/metabolismo , Fenotipo , Ratas , Recuperación de la Función , Índice de Severidad de la Enfermedad
4.
Nanomedicine ; 11(3): 611-20, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-24907463

RESUMEN

There is no effective treatment for intracerebral hemorrhage (ICH). Intracerebral delivery of nanomaterials into the hemorrhagic lesion may be a new therapeutic strategy. In a rat model of ICH plus ultra-early hematoma aspiration, we found that locally delivered self-assembling peptide nanofiber scaffold (SAPNS) replaced the hematoma, reduced acute brain injury and brain cavity formation, and improved sensorimotor functional recovery. SAPNS serves as biocompatible material in the hemorrhagic brain cavity. Local delivery of this nanomaterial may facilitate the repair of ICH related brain injury and functional recovery. From the clinical editor: In a rat model of intracranial hemorrhage, these authors demonstrate that following ultra-early hematoma aspiration, local delivery of a self-assembling peptide nanofiber scaffold replaces the hematoma, reduces brain cavity formation, and improves sensorimotor functional recovery. Similar approaches would be welcome additions to the clinical treatment of this often devastating condition.


Asunto(s)
Lesiones Encefálicas/tratamiento farmacológico , Hemorragias Intracraneales/tratamiento farmacológico , Nanofibras/química , Péptidos , Recuperación de la Función/efectos de los fármacos , Enfermedad Aguda , Animales , Lesiones Encefálicas/patología , Lesiones Encefálicas/fisiopatología , Modelos Animales de Enfermedad , Hemorragias Intracraneales/patología , Hemorragias Intracraneales/fisiopatología , Masculino , Péptidos/química , Péptidos/farmacología , Ratas , Ratas Sprague-Dawley
5.
BMC Surg ; 13: 21, 2013 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-23799915

RESUMEN

BACKGROUND: Peripheral nerve (PN) transplantation and ventral root implantation are the two common types of recovery operations to restore the connection between motoneurons and their target muscles after brachial plexus injury. Despite experience accumulated over the past decade, fundamental knowledge is still lacking concerning the efficacy of the two microsurgical interventions. METHODS: Thirty-eight adult female Sprague-Dawley rats were divided into 5 groups. Immediately following root avulsion, animals in the first group (n = 8) and the second group (n = 8) received PN graft and ventral root implantation respectively. The third group (n = 8) and the fourth group (n = 8) received PN graft and ventral root implantation respectively at one week after root avulsion. The fifth group received root avulsion only as control (n = 6). The survival and axonal regeneration of severed motoneurons were investigated at 6 weeks post-implantation. RESULTS: Re-implantation of ventral roots, both immediately after root avulsion and in delay, significantly increased the survival and regeneration of motoneurons in the avulsed segment of the spinal cord as compared with PN graft transplantation. CONCLUSIONS: The ventral root re-implantation is a better surgical repairing procedure than PN graft transplantation for brachial plexus injury because of its easier manipulation for re-implanting avulsed ventral roots to the preferred site, less possibility of causing additional damage and better effects on motoneuron survival and axonal regeneration.


Asunto(s)
Plexo Braquial/cirugía , Microcirugia/métodos , Neuronas Motoras/fisiología , Regeneración Nerviosa , Nervios Periféricos/trasplante , Reimplantación , Raíces Nerviosas Espinales/cirugía , Animales , Axones/fisiología , Plexo Braquial/lesiones , Plexo Braquial/fisiología , Femenino , Ratas Sprague-Dawley , Raíces Nerviosas Espinales/lesiones , Raíces Nerviosas Espinales/fisiología
6.
BJPsych Open ; 9(3): e94, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37231817

RESUMEN

BACKGROUND: Early-life adverse experiences can elevate the magnitude of the risk of developmental psychopathology, but the potential synergistic effects of multiple factors have not been well studied. AIMS: To determine whether prenatal exposures to maternal stress (Superstorm Sandy) and maternal cannabis use synergistically alter the risk of developmental psychopathology. METHOD: The study included 163 children (53.4% girls), longitudinally tracked (ages 2-5 years) in relation to the effects of two early-life adverse exposures (Superstorm Sandy and maternal cannabis use). Offspring were grouped by exposure status (neither, only maternal cannabis use, only Superstorm Sandy or both). DSM-IV disorders for offspring were derived from structured clinical interviews; caregiver-reported ratings of family stress and social support were also assessed. RESULTS: A total of 40.5% had been exposed to Superstorm Sandy and 24.5% to maternal cannabis use. Offspring exposed to both (n = 13, 8.0%), relative to those exposed to neither, had a 31-fold increased risk of disruptive behavioural disorders (DBDs) and a seven-fold increased risk of anxiety disorders. The synergy index demonstrated that offspring with two exposures had synergistic elevation in risk of DBDs (synergy index, 2.06, P = 0.03) and anxiety disorders (synergy index, 2.60, P = 0.004), compared with the sum of single risks. Offspring with two exposures had the highest parenting stress and lowest social support. CONCLUSIONS: Our findings are consistent with the double-hit model suggesting that offspring with multiple early-life adverse exposures (Superstorm Sandy and maternal cannabis use) have synergistically increased risks of mental health problems. Given the increasing frequency of major natural disasters and cannabis use, especially among women under stress, these findings have significant public health implications.

7.
J Neuropathol Exp Neurol ; 68(1): 94-101, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19104442

RESUMEN

We previously showed that motor nerves are superior to sensory nerves in promoting axon regeneration after spinal root avulsion. It is, however, impractical to use motor nerves as grafts. One potential approach to enhancing axonal regeneration using sensory nerves is to deliver trophic factors to the graft. Here, we examined the regulation of receptors for brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor, and pleiotrophin after root avulsion in adult rats. We then tested their survival-promoting and neuroregenerative effects on spinal motoneurons. The results showed that receptors for brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor were upregulated and that these trophic factors promoted survival and axonal regeneration of motoneurons when they were injected into the sensory nerve graft before implantation. In contrast, receptors for ciliary neurotrophic factor and pleiotrophin were downregulated after avulsion. Ciliary neurotrophic factor did not promote survival and axonal regeneration, whereas pleiotrophin promoted axonal regeneration but not survival of injured spinal motoneurons. Our results suggest that infusion of trophic factors into sensory nerve grafts promote motoneuron survival and axonal regeneration. The technique is technically easy and is, therefore, potentially clinically applicable.


Asunto(s)
Neuronas Motoras/fisiología , Regeneración Nerviosa/fisiología , Nervios Periféricos/citología , Nervios Periféricos/trasplante , Radiculopatía/patología , Radiculopatía/cirugía , Animales , Supervivencia Celular/fisiología , Modelos Animales de Enfermedad , Masculino , Neuronas Motoras/efectos de los fármacos , Factores de Crecimiento Nervioso/farmacología , Factores de Crecimiento Nervioso/uso terapéutico , Regeneración Nerviosa/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Receptores de Factores de Crecimiento/metabolismo , Estilbamidinas , Factores de Tiempo
8.
J Neuropathol Exp Neurol ; 77(4): 325-343, 2018 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-29420729

RESUMEN

When spinal roots are torn off from the spinal cord, both the peripheral and central nervous system get damaged. As the motoneurons lose their axons, they start to die rapidly, whereas target muscles atrophy due to the denervation. In this kind of complicated injury, different processes need to be targeted in the search for the best treatment strategy. In this study, we tested glial cell-derived neurotrophic factor (GDNF) treatment and fetal lumbar cell transplantation for their effectiveness to prevent motoneuron death and muscle atrophy after the spinal root avulsion and delayed reimplantation. Application of exogenous GDNF to injured spinal cord greatly prevented the motoneuron death and enhanced the regeneration and axonal sprouting, whereas no effect was seen on the functional recovery. In contrast, cell transplantation into the distal nerve did not affect the host motoneurons but instead mitigated the muscle atrophy. The combination of GDNF and cell graft reunited the positive effects resulting in better functional recovery and could therefore be considered as a promising strategy for nerve and spinal cord injuries that involve the avulsion of spinal roots.


Asunto(s)
Células Madre Fetales/trasplante , Factor Neurotrófico Derivado de la Línea Celular Glial/uso terapéutico , Neuronas Motoras/fisiología , Recuperación de la Función/efectos de los fármacos , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/cirugía , Animales , Supervivencia Celular , Colina O-Acetiltransferasa/metabolismo , Embrión de Mamíferos , Femenino , Células Madre Fetales/fisiología , Aseo Animal/fisiología , Proteínas de Homeodominio/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Vaina de Mielina/metabolismo , Regeneración Nerviosa , Proteínas de Neurofilamentos/metabolismo , Ratas , Ratas Sprague-Dawley , Recuperación de la Función/fisiología , Reimplantación , Médula Espinal/citología , Tubulina (Proteína)/metabolismo
9.
Atherosclerosis ; 192(2): 266-74, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16945374

RESUMEN

Apolipoprotein A-IV (apoA-IV) inhibits lipid peroxidation, thus demonstrating potential anti-atherogenic properties. The aim of this study was to investigate how the inhibition of low density lipoprotein (LDL) oxidation was influenced by common apoA-IV isoforms. Recombinant wild type apoA-IV (100 microg/ml) significantly inhibited the oxidation of LDL (50 microg protein/ml) by 5 microM CuSO(4) (P<0.005), but not by 100 microM CuSO(4), suggesting that it may act by binding copper ions. ApoA-IV also inhibited the oxidation of LDL by the water-soluble free-radical generator 2,2'-azobis(amidinopropane) dihydrochloride (AAPH; 1 mM), as shown by the two-fold increase in the time for half maximal conjugated diene formation (T(1/2); P<0.05) suggesting it can also scavenge free radicals in the aqueous phase. Compared to wild type apoA-IV, apoA-IV-S347 decreased T(1/2) by 15% (P=0.036) and apoA-IV-H360 increased T(1/2) by 18% (P=0.046). All apoA-IV isoforms increased the relative electrophoretic mobility of native LDL, suggesting apoA-IV can bind to LDL and acts as a site-specific antioxidant. The reduced inhibition of LDL oxidation by apoA-IV-S347 compared to wild type apoA-IV may account for the previous association of the APOA4 S347 variant with increased CHD risk and oxidative stress.


Asunto(s)
Apolipoproteínas A/genética , Apolipoproteínas A/fisiología , Lipoproteínas LDL/metabolismo , Amidinas/química , Antioxidantes/farmacología , Apolipoproteína A-V , Sulfato de Cobre/química , Humanos , Peroxidación de Lípido/efectos de los fármacos , Mutagénesis Sitio-Dirigida , Oxidación-Reducción , Isoformas de Proteínas/fisiología
10.
Regen Biomater ; 4(1): 21-30, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28149526

RESUMEN

Peripheral nerves are fragile and easily damaged, usually resulting in nervous tissue loss, motor and sensory function loss. Advances in neuroscience and engineering have been significantly contributing to bridge the damage nerve and create permissive environment for axonal regrowth across lesions. We have successfully designed two self-assembling peptides by modifying RADA 16-I with two functional motifs IKVAV and RGD. Nanofiber hydrogel formed when combing the two neutral solutions together, defined as RADA 16-Mix that overcomes the main drawback of RADA16-I associated with low pH. In the present study, we transplanted the RADA 16-Mix hydrogel into the transected rat sciatic nerve gap and effect on axonal regeneration was examined and compared with the traditional RADA16-I hydrogel. The regenerated nerves were found to grow along the walls of the large cavities formed in the graft of RADA16-I hydrogel, while the nerves grew into the RADA 16-Mix hydrogel toward distal position. RADA 16-Mix hydrogel induced more axons regeneration and Schwann cells immigration than RADA16-I hydrogel, resulting in better functional recovery as determined by the gait-stance duration percentage and the formation of new neuromuscular junction structures. Therefore, our results indicated that the functional SAP RADA16-Mix nanofibrous hydrogel provided a better environment for peripheral nerve regeneration than RADA16-I hydrogel and could be potentially used in peripheral nerve injury repair.

11.
Circ Res ; 92(9): 969-75, 2003 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-12676816

RESUMEN

The impact of common variants in the apolipoprotein gene cluster (APOC3-A4-A5) on prospective coronary heart disease (CHD) risk was examined in healthy UK men. Of the 2808 men followed over 9 years, 187 had a clinically defined CHD event. Examination of 9 single nucleotide polymorphisms (SNPs) in this group revealed that homozygotes for APOA4 S347 had significantly increased risk of CHD [hazard ratio (HR) of 2.07 (95%CI 1.04 to 4.12)], whereas men homozygous for APOC3 1100T were protected [HR 0.28 (95%CI 0.09 to 0.87)]. In stepwise multiple regression analysis, after entering all the variants and adjusting for established risk factors APOA4 T347S alone remained in the model. Using all nine SNPs, the highest risk-estimate haplotypes carried APOA4 S347 and rare alleles of the two flanking intergenic markers. The protective effect of APOC3 1100T could be explained by negative linkage disequilibrium with these alleles. To determine the association of APOA4 T347S with apoAIV levels, the relationship was examined in 1600 healthy young European men and women. S347 homozygotes had significantly lower apoAIV plasma levels (13.64+/-0.59 mg/dL) compared with carriers of the T347 allele (14.90+/-0.12 mg/dL) (P=0.035). These results demonstrate that genetic variation in and around APOA4, independent of the effects of triglyceride, is associated with risk of CHD and apoAIV levels, supporting an antiatherogenic role for apoAIV.


Asunto(s)
Apolipoproteínas A/sangre , Apolipoproteínas A/genética , Enfermedad Coronaria/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Adolescente , Adulto , Antioxidantes/metabolismo , Apolipoproteínas A/metabolismo , Enfermedad Coronaria/epidemiología , Enfermedad Coronaria/mortalidad , Femenino , Haplotipos , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Familia de Multigenes , Estudios Prospectivos , Tasa de Supervivencia , Reino Unido/epidemiología
12.
J Consult Clin Psychol ; 74(5): 870-9, 2006 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-17032091

RESUMEN

In this study, the authors examined perceived benefits and costs of the outbreak of severe acute respiratory syndrome (SARS). Mixed accounts of benefits and costs, rather than exclusive accounts of only benefits or costs, were proposed to be characterized by nondefensiveness and enduring changes in psychosocial resources. Participants were 70 SARS recoverers, 59 family members of SARS recoverers, and 172 healthy adults residing in Hong Kong--a SARS-affected region. Results show that participants giving an exclusive account of benefits had higher levels of defensiveness than those giving a mixed account and those giving an exclusive account of costs. Only the perceived impact of benefits given in mixed accounts were related to future accruements in personal and social resources over an 18-month period.


Asunto(s)
Brotes de Enfermedades , Síndrome Respiratorio Agudo Grave/economía , Síndrome Respiratorio Agudo Grave/epidemiología , Adulto , Análisis Costo-Beneficio , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Estudios Prospectivos , Encuestas y Cuestionarios , Factores de Tiempo
13.
World J Gastroenterol ; 12(18): 2923-7, 2006 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-16718820

RESUMEN

AIM: The use of low-dose aspirin to prevent cardiovascular disease events is well established. However, the incidence and predictors of upper gastrointestinal bleeding (UGIB) with its use are unknown. We studied prospectively the incidence and outcome of peptic ulceration in low-dose aspirin users. METHODS: A total of 991 patients with coronary artery disease (CAD) on low-dose aspirin were prospectively followed-up for two years for the occurrence and clinical features of first hospitalized episode of UGIB. RESULTS: UGIB had a bimodal presentation with 45% occurring within four months of aspirin initiation and had an overall prevalence of 1.5% per year. There was no UGIB-related death. Hypertension (OR = 4.6, 95%CI 1.5-14.7, P = 0.009), history of peptic ulceration (OR = 3.1, 95%CI 1.1-9.0, P = 0.039), tertiary education (OR = 3.08, 95%CI 1.1-9.0, P = 0.039) and higher lean body mass (P = 0.016) were independent factors associated with UGIB. Use of nitrate did not reduce UGIB. CONCLUSION: The incidence of UGIB in patients with CAD on long-term low-dose aspirin is low, but is accompanied with significant morbidity. With prolonged use of aspirin, UGIB continues to be a problem for those with risk factors and especially in patients with a history of peptic ulcers, in which UGIB tends to occur early after aspirin therapy.


Asunto(s)
Aspirina/efectos adversos , Aspirina/uso terapéutico , Enfermedad de la Arteria Coronaria/prevención & control , Hemorragia Gastrointestinal/inducido químicamente , Anciano , Índice de Masa Corporal , Comorbilidad , Enfermedad de la Arteria Coronaria/epidemiología , Relación Dosis-Respuesta a Droga , Femenino , Hemorragia Gastrointestinal/epidemiología , Hemorragia Gastrointestinal/fisiopatología , Humanos , Hipertensión/complicaciones , Incidencia , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Úlcera Péptica/complicaciones , Valor Predictivo de las Pruebas , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Prevención Secundaria
14.
Cancer Res ; 63(13): 3819-25, 2003 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-12839979

RESUMEN

The adenoma:carcinoma sequence is well established. Understanding the molecular pathology of the adenoma is therefore important. There is great controversy within the field. The Vogelstein group champions the "top-down" theory (colorectal adenomas arise and grow across the mucosal surface and down into the crypts), whereas other studies, including our own, propose "bottom-up" spread. Serial sections of 40 small (<3 mm) sporadic colorectal adenomas were stained with H&E, MIB-1, and for beta-catenin. 10 early adenomas were Feulgen-stained and microdissected. We also examined the flat mucosa of three patients who had undergone colectomies for familial adenomatous polyposis (FAP) and specimens from a XO/XY individual with FAP, the latter using in situ hybridization for the Y chromosome. In the earliest sporadic adenomas, there were crypts entirely filled with adenomatous epithelium, which showed proliferative activity and nuclear localization of beta-catenin. There was a sharp cutoff between crypt epithelial cells showing nuclear beta-catenin and surface cells with membrane staining. In slightly larger lesions, adenomatous spread from above was seen. Microdissected adenomas showed multiple fission events, with proliferation distributed equally throughout. In FAP tissue, numerous isolated monocryptal adenomas, which were clonal in origin, were seen. Examination of adenomas in the XO/XY individual showed no instances of XY or XO adenomatous epithelium growing down into crypts of the other genotype. Both sporadic and FAP adenomas start as a unicryptal adenomas and grow initially by crypt fission--a bottom-up pattern. Later, in sporadic adenomas, there is evidence of growth down into adjacent crypts (top-down).


Asunto(s)
Adenoma/patología , Poliposis Adenomatosa del Colon/patología , Neoplasias del Colon/patología , Mucosa Intestinal/citología , Adenoma/cirugía , Colonoscopía , Disección/métodos , Humanos , Mucosa Intestinal/patología
15.
Neuroscience ; 329: 213-25, 2016 08 04.
Artículo en Inglés | MEDLINE | ID: mdl-27185485

RESUMEN

Brachial plexus injury (BPI) often involves the complete or partial avulsion of one or more of the cervical nerve roots, which leads to permanent paralysis of the innervated muscles. Reimplantation surgery has been attempted as a clinical treatment for brachial plexus root avulsion but has failed to achieve complete functional recovery. Lithium is a mood stabilizer drug that is used to treat bipolar disorder; however, its effects on spinal cord or peripheral nerve injuries have also been reported. The purpose of this study was to investigate whether lithium can improve functional motor recovery after ventral root avulsion and reimplantation in a rat model of BPI. The results showed that systemic treatment with a clinical dose of lithium promoted motor neuron outgrowth and increased the efficiency of motor unit regeneration through enhanced remyelination. An analysis of myelin-associated genes showed that the effects of lithium started during the early phase of remyelination and persisted through the late stage of the process. Efficient remyelination of the regenerated axons in the lithium-treated rats led to an earlier functional recovery. Therefore, we demonstrated that lithium might be a potential clinical treatment for BPI in combination with reimplantation surgery.


Asunto(s)
Axones/efectos de los fármacos , Compuestos de Litio/farmacología , Vaina de Mielina/efectos de los fármacos , Regeneración Nerviosa/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Raíces Nerviosas Espinales/efectos de los fármacos , Animales , Axones/patología , Axones/fisiología , Plexo Braquial/efectos de los fármacos , Plexo Braquial/lesiones , Plexo Braquial/fisiopatología , Plexo Braquial/cirugía , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Femenino , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/patología , Neuronas Motoras/fisiología , Vaina de Mielina/patología , Vaina de Mielina/fisiología , Regeneración Nerviosa/fisiología , Distribución Aleatoria , Ratas Sprague-Dawley , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Reimplantación , Raíces Nerviosas Espinales/lesiones , Raíces Nerviosas Espinales/fisiopatología , Raíces Nerviosas Espinales/cirugía
16.
World J Gastroenterol ; 11(18): 2726-32, 2005 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-15884111

RESUMEN

AIM: It is controversial whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H pylori) eradication treatment than those with peptic ulcer disease (PUD). To review the evidence for any difference in H pylori eradication rates between PUD and NUD patients. METHODS: A literature search for full articles and meeting abstracts to July 2004 was conducted. We included studies evaluating the efficacy of a proton pump inhibitor (P) or ranitidine bismuth citrate (RBC) plus two antibiotics of clarithromycin (C), amoxicillin (A), metronidazole (M), or P-based quadruple therapies for eradicating the infection. RESULTS: Twenty-two studies met the criteria. No significant difference in eradication rates was found between PUD and NUD patients when treated with 7-d RBCCA, 10-d PCA or P-based quadruple therapies. When the 7-d PCA was used, the pooled H pylori eradication rate was 82.1% (431/525) and 72.6% (448/617) for PUD and NUD patients, respectively, yielding a RR of 1.15 (95%CI 1.01-1.29). However, the statistically significant difference was seen only in meeting abstracts, but not in full publications. CONCLUSION: There is no convincing evidence to suggest that NUD patients respond to H pylori eradication treatments differently from those with PUD, although a trend exists with the 7-d PCA therapy.


Asunto(s)
Quimioterapia Combinada , Dispepsia/microbiología , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori , Úlcera Péptica/microbiología , Ranitidina/análogos & derivados , Antibacterianos , Antiulcerosos/uso terapéutico , Bismuto/uso terapéutico , Quimioterapia Combinada/uso terapéutico , Humanos , Inhibidores de la Bomba de Protones , Ranitidina/uso terapéutico , Resultado del Tratamiento
17.
World J Gastroenterol ; 11(26): 4067-77, 2005 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-15996033

RESUMEN

AIM: To systematically evaluate the efficacy of H(2)-receptor antagonists (H(2)RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H(2)RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H(2)RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H(2)RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H(2)RAs of all doses across all grades of esophagitis, including patients refractory to H(2)RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H(2)RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H(2)RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis.


Asunto(s)
Esofagitis/tratamiento farmacológico , Antagonistas de los Receptores H2 de la Histamina/uso terapéutico , Inhibidores de la Bomba de Protones , Humanos , Omeprazol/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Cicatrización de Heridas/efectos de los fármacos
18.
World J Gastroenterol ; 11(34): 5362-6, 2005 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-16149147

RESUMEN

AIM: To investigate coping mechanisms, constipation symptoms and anorectal physiology in 80 constipated subjects and 18 controls. METHODS: Constipation was diagnosed by Rome II criteria. Coping ability and anxiety/depression were assessed by validated questionnaires. Transit time and balloon distension test were performed. RESULTS: 34.5% patients were classified as slow transit type of constipation. The total colonic transit time (56 h vs 10 h, P<0.0001) and rectal sensation including urge sensation (79 mL vs 63 mL, P = 0.019) and maximum tolerable volume (110 mL vs 95 mL, P = 0.03) differed in patients and controls. Constipated subjects had significantly higher anxiety and depression scores and lower SF-36 scores in all categories. They also demonstrated higher scores of 'monitoring' coping strategy (14+/-6 vs 9+/-3, P = 0.001), which correlated with the rectal distension sensation (P = 0.005), urge sensation (P=0.002), and maximum tolerable volume (P = 0.035). The less use of blunting strategy predicted slow transit constipation in both univariate (P = 0.01) and multivariate analysis (P = 0.03). CONCLUSION: Defective or ineffective use of coping strategies may be an important etiology in functional constipation and subsequently reflected in abnormal anorectal physiology.


Asunto(s)
Adaptación Psicológica , Estreñimiento/fisiopatología , Estreñimiento/psicología , Estrés Psicológico/fisiopatología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Canal Anal/fisiopatología , Estreñimiento/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Recto/fisiopatología , Estrés Psicológico/epidemiología , Encuestas y Cuestionarios
19.
Psychosom Med ; 65(3): 443-9, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-12764218

RESUMEN

OBJECTIVE: This study sought to explore some psychosocial factors that distinguished individuals with noncardiac chest pain (NCCP) from those without NCCP, and whether these psychosocial factors were associated with anxiety and depression that are co-morbid factors of NCCP. METHODS: A matched case-control design was adopted to compare differences in psychosocial factors among a target group of patients with NCCP (N = 70), a pain control group of patients with rheumatism (N = 70), and a community control group of healthy individuals (N = 70). RESULTS: Compared with subjects from the two control groups, NCCP patients tended to monitor more, use more problem-focused coping, display a coping pattern with a poorer strategy-situation fit, and receive less emotional support in times of stress. Moreover, monitoring perceptual style and problem-focused coping were associated with higher levels of anxiety and depression. Coping pattern with a strategy-situation fit and emotional support were related to lower levels of anxiety and depression. CONCLUSIONS: The present new findings suggest that monitoring perceptual style and inflexible coping style are risk factors that enhance one's vulnerability to NCCP. Emotional support may be a resource factor that reduces one's susceptibility to NCCP.


Asunto(s)
Adaptación Psicológica , Dolor en el Pecho/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/epidemiología , Estudios de Casos y Controles , Dolor en el Pecho/etiología , Angiografía Coronaria , Depresión/epidemiología , Femenino , Hong Kong/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Enfermedades Reumáticas/complicaciones , Índice de Severidad de la Enfermedad , Método Simple Ciego , Apoyo Social , Factores Socioeconómicos , Estrés Psicológico/psicología
20.
Biomed Res Int ; 2014: 658753, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24967390

RESUMEN

Brachial plexus injury often involves traumatic root avulsion resulting in permanent paralysis of the innervated muscles. The lack of sufficient regeneration from spinal motoneurons to the peripheral nerve (PN) is considered to be one of the major causes of the unsatisfactory outcome of various surgical interventions for repair of the devastating injury. The present study was undertaken to investigate potential inhibitory signals which influence axonal regeneration after root avulsion injury. The results of the study showed that root avulsion triggered GSK-3ß activation in the injured motoneurons and remaining axons in the ventral funiculus. Systemic application of a clinical dose of lithium suppressed activated GSK-3ß in the lesioned spinal cord to the normal level and induced extensive axonal regeneration into replanted ventral roots. Our study suggests that GSK-3ß activity is involved in negative regulation for axonal elongation and regeneration and lithium, the specific GSK-3ß inhibitor, enhances motoneuron regeneration from CNS to PNS.


Asunto(s)
Axones/enzimología , Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Litio/farmacología , Neuronas Motoras/enzimología , Regeneración Nerviosa/efectos de los fármacos , Traumatismos de los Nervios Periféricos , Nervios Periféricos/enzimología , Animales , Axones/patología , Activación Enzimática , Femenino , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Neuronas Motoras/patología , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/enzimología , Traumatismos de los Nervios Periféricos/patología , Ratas , Ratas Sprague-Dawley , Raíces Nerviosas Espinales/enzimología , Raíces Nerviosas Espinales/lesiones
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