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1.
J Orthop Traumatol ; 18(4): 343-348, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28707122

RESUMEN

BACKGROUND: Segond's fracture is a well-recognised radiological sign of an anterior cruciate ligament (ACL) tear. While previous studies evaluated the role of the anterolateral ligament (ALL) and complex injuries on rotational stability of the knee, there are no studies on the biomechanical effect of Segond's fracture in an ACL deficient knee. The aim of this study was to evaluate the effect of a Segond's fracture on knee rotation stability as evaluated by a navigation system in an ACL deficient knee. MATERIALS AND METHODS: Three different conditions were tested on seven knee specimens: intact knee, ACL deficient knee and ACL deficient knee with Segond's fracture. Static and dynamic measurements of anterior tibial translation (ATT) and axial tibial rotation (ATR) were recorded by the navigation system (2.2 OrthoPilot ACL navigation system B. Braun Aesculap, Tuttlingen, Germany). RESULTS: Static measurements at 30° showed that the mean ATT at 30° of knee flexion was 5.1 ± 2.7 mm in the ACL intact condition, 14.3 ± 3.1 mm after ACL cut (P = 0.005), and 15.2 ± 3.6 mm after Segond's fracture (P = 0.08). The mean ATR at 30° of knee flexion was 20.7° ± 4.8° in the ACL intact condition, 26.9° ± 4.1° in the ACL deficient knee (P > 0.05) and 30.9° ± 3.8° after Segond's fracture (P = 0.005). Dynamic measurements during the pivot-shift showed that the mean ATT was 7.2 ± 2.7 mm in the intact knee, 9.1 ± 3.3 mm in the ACL deficient knee(P = 0.04) and 9.7 ± 4.3 mm in the ACL deficient knee with Segond's fracture (P = 0.07). The mean ATR was 9.6° ± 1.8° in the intact knee, 12.3° ± 2.3° in the ACL deficient knee (P > 0.05) and 19.1° ± 3.1° in the ACL deficient knee with Segond's lesion (P = 0.016). CONCLUSION: An isolated lesion of the ACL only affects ATT during static and dynamic measurements, while the addition of Segond's fracture has a significant effect on ATR in both static and dynamic execution of the pivot-shift test, as evaluated with the aid of navigation.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/fisiopatología , Inestabilidad de la Articulación/fisiopatología , Articulación de la Rodilla/fisiopatología , Fracturas de la Tibia/fisiopatología , Anciano , Fenómenos Biomecánicos , Cadáver , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronavegación , Examen Físico , Rango del Movimiento Articular , Rotación , Tibia/lesiones , Tibia/fisiopatología
2.
Brain Lang ; 244: 105312, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37579516

RESUMEN

Theories of embodied cognition postulate that language processing activates similar sensory-motor structures as when interacting with the environment. Only little is known about the neural substrate of embodiment in a foreign language (L2) as compared to the mother tongue (L1). In this fMRI study, we investigated embodiment of motor and non-motor action verbs in L1 and L2 including 31 late bilinguals. Half had German as L1 and French as L2, and the other half vice-versa. We collapsed across languages to avoid the confound between language and order of language acquisition. Region of interest analyses showed stronger activation in motor regions during L2 than during L1 processing, independently of the motor-relatedness of the verbs. Moreover, a stronger involvement of motor regions for motor-related as compared to non-motor-related verbs, similarly for L1 and L2, was found. Overall, the similarity between L1 and L2 embodiment seems to depend on individual and contextual factors.


Asunto(s)
Multilingüismo , Humanos , Imagen por Resonancia Magnética , Lenguaje , Desarrollo del Lenguaje , Cognición
3.
Knee Surg Sports Traumatol Arthrosc ; 20(5): 870-7, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21877296

RESUMEN

PURPOSE: The purpose of this study is to evaluate the kinematics changes of the knee after cutting of the ACL with or without injury of the anterolateral structures. METHODS: In this study, the role of the ACL and one of the secondary restraints in controlling knee stability using a navigation system was evaluated. The kinematics of the knee was evaluated in different conditions of instability: ACL intact, after dissection of the posterolateral (PL) bundle, after dissection of the anteromedial (AM) bundle, and after lesion of the lateral capsular ligament (LCL). Anterior tibial translation and rotation were measured with a computer navigation system in 10 fresh-frozen cadaveric knees by use of a manual maximum load. Anterior translation was evaluated at 30°, 60°, and 90° of flexion; rotation at 0°, 15°, 30°, 45°, 60°, and 90°. RESULTS: Cutting the PL bundle does not increase anterior translation and rotation of the knee. Cutting the AM bundle significantly increased the anteroposterior (AP) translation at 30° and 60° (P = 0.01), but does not increase rotation of the knee. Cutting the LCL increased anterior translation at 60° (P = 0.04) and rotation at 30°, 45°, and 60° (P = 0.03). CONCLUSIONS: Within the testing conditions of this study, the PL bundle does not affect anterior translation and rotation of the knee; the AM bundle is the primary restraint of the anterior translation but does not affect rotation of the knee while the lesion of the LCL increases tibial rotation and could be related to the pivot shift phenomenon, so it is more correct and biomechanical valid to assess and repair the associated lesion of the antero-lateral structure of the knee at the time of ACL surgery.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior , Inestabilidad de la Articulación/fisiopatología , Traumatismos de la Rodilla/fisiopatología , Ligamentos Articulares/lesiones , Anciano , Anciano de 80 o más Años , Ligamento Cruzado Anterior/cirugía , Fenómenos Biomecánicos , Cadáver , Femenino , Humanos , Traumatismos de la Rodilla/cirugía , Ligamentos Articulares/cirugía , Masculino , Persona de Mediana Edad , Rango del Movimiento Articular
4.
Front Endocrinol (Lausanne) ; 13: 839300, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35769080

RESUMEN

Background and aims: There is still limited knowledge regarding the clinical profile and appropriateness of treatment in patients with hypothyroidism hospitalized in Internal Medicine (IM) Departments in Italy. The aim of this study is to evaluate: 1) the characteristics of patients and possible deviations from national and international clinical practice recommendations (CPRs) in evidence-based guidelines (EBGs); 2) the improvement of patient management by means of a standardized educational programme (EP). Methods: A nationwide multicentre study, comprising two replications of a retrospective survey (phases 1 and 3) with an intervening EP (phase 2) in half of the centres and no EP in the other half, was conducted. The EP was based on outreach visits. Centres were assigned to the two arms of the study, labelled the training group (TG) and control group (CG) respectively, by cluster randomization. Four EBGs and 39 CPRs provided the basis on which 22 treatment management indicators were identified (7 referring to the time of hospital admission, 15 to post-admission). Results: The 21 participating centres recruited 587 hospitalized patients with hypothyroidism, 421 of which were females (71.7%, mean age 74.1 + 14.4 yrs): 318 in phase 1 and 269 in phase 3. The cause of hypothyroidism was unknown in 282 patients (48%). Evaluation at the time of admission identified satisfactory adherence to CPRs (>50%) for 63.6% of the indicators. In the phase 3, TG centres showed significant improvement vs CG in 4 of the 15 post-admission indicators, while 1 out of 15 was significantly worse. Conclusions: The EP based on outreach visits significantly improved some indicators in the management of patients with hypothyroidism, with specific reference to appropriateness of TSH dosage and levothyroxine (LT4) treatment modality. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05314790.


Asunto(s)
Hipotiroidismo , Anciano , Anciano de 80 o más Años , Femenino , Hospitalización , Humanos , Hipotiroidismo/tratamiento farmacológico , Italia , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tiroxina/uso terapéutico
5.
J Orthop Sci ; 15(1): 125-31, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20151262

RESUMEN

BACKGROUND: A number of anterior cruciate ligament (ACL) fixation techniques are currently in use. Slippage or failure of the graft by excessive loading or aggressive rehabilitation may result in an unstable knee. Load and slippage of the ACL graft varies according to the fixation technique used. METHODS: Graft slippage, load to failure, and stiffness were evaluated using an animal model. Six soft tissue ACL fixation techniques and bone cement as a fixation device were tested: group A, Endo Button CL-Bio RCI; group B, Swing Bridge-Evolgate; group C, Rigidfix-Intrafix; group D, Bone Mulch-Washer Lock; group E, Transfix-Retroscrew; group F, Transfix-Deltascrew; group G, Kryptonite bone cement. Maximum failure load, stiffness, and slippage at the 1st and 1000th cycles and mode of failure were evaluated. RESULTS: The maximum failure load was significantly higher in group B (1030 N) and significantly lower in group E (483 N) than in the others. The stiffness of group B (270 N/mm) was significantly higher than the others. As for the mode of failure, group C showed failure in the femoral side in all tests (four device ruptures and two tendon ruptures on the femoral side). All failures of the other groups occurred on the tibial side except one test in group A. All failures in group G were due to slippage of the tendons. CONCLUSION: Load to failure and stiffness was significantly different between the ACL fixation techniques. All but one of the fixation techniques showed sufficient properties for adequate postoperative rehabilitation. Bone cement used as a fixation device in soft tissue grafts did not seem to provide adequate initial fixation suitable for early rehabilitation after ACL reconstruction.


Asunto(s)
Ligamento Cruzado Anterior/cirugía , Tornillos Óseos , Análisis de Falla de Equipo , Procedimientos Ortopédicos/efectos adversos , Anclas para Sutura , Tendones/trasplante , Animales , Lesiones del Ligamento Cruzado Anterior , Modelos Animales de Enfermedad , Sus scrofa
6.
Case Rep Dent ; 2020: 8856206, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32832166

RESUMEN

The study presents two monozygotic twins (MZ) with multiple impacted teeth, affecting the upper canines and lower second molars, as well as congenital aniridia. The clinical aspect of the upper canines is peculiar because of the different positions-palatal in one and buccal in the other twin. Studies reporting different scenarios of impaction in monozygotic twins can contribute more data to the debate on tooth eruption aetiology and more so in this case because of the association with a genetic panocular disease. Patients' Concerns. The patients were referred by a general dentist, who diagnosed the presence of multiple inclusions. Diagnostic Study. Both patients showed severe malocclusion, classified as grade 5 of the Index of Orthodontic Treatment Need (IOTN). The MZ showed class I malocclusion, upper and lower crowding, and impacted lower right and left second molars. A Dentascan was prescribed for the canine impaction. The impaction of the upper canine was palatal of 2.3 in one of the MZ and buccal of 1.3 in the other one. The same altered pattern of eruption of the lower second molars was identified in both twins. The proposed treatment plan contemplated orthodontic surgical recovery of the impacted elements, followed by orthodontic treatment with multibracket appliance after the extraction of the first four premolars, given the crowding entity. The use of a retraction spring action was chosen for the recovery of the lower second molars. Many aspects of the possible genetic aetiology of tooth impaction are still under discussion. The study of diseases in twins offers decisive information. Finally, the possibility that alterations in the eruptive pattern of the dental elements may be associated with other congenital problems broadens the range of investigations related to the possible aetiological causes of the inclusions in humans.

7.
Clin Ter ; 171(6): e509-e516, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33151249

RESUMEN

OBJECTIVE: The aim of this cross-sectional research was to analyze the association between the disc position of the temporomandibular joint (TMJ) evaluated by magnetic resonance imaging (MRI) and the mandibular deviation evaluated by posteroanterior cephalometric (PA) in adolescents. MATERIALS AND METHODS: The sample was 53 adolescents aged 11-18 years. This cross-sectional study was based on the analysis of PA and bilateral TMJ MRI images retrospectively selected. The mandibular deviation was evaluated by PA and defined by the amount of menton (Me) deviation from the midsagittal reference line. The temporomandibular disc position was evaluated by MRI: normal (N), disc displacement with reduction (DDR) and disc displacement without reduction (DDNR). The DDNR was considered more severe than the DDR. The patients were classified into three groups based on the bilateral disc position: group I, the same bilateral disc position; group II, disc displacement more severe on the ipsilateral side of the menton deviation; group III, disc displacement more severe on the contralateral side of the menton deviation. ANOVA followed by post hoc Tukey's test was used to evaluate the interaction between the menton deviation and the bilateral disc position. RESULTS: There was an association statistically significant between the bilateral disc position and the Me deviation (p<0.05). There were significant differences in the mean of the menton deviation between group II (4,40 ±2,26), and group I (2,17±1,93) and III (2,10±1,70). CONCLUSIONS: The menton deviation was significantly correlated with the disc position in the TMJ exhibit more deflection to the side more affected.


Asunto(s)
Imagen por Resonancia Magnética , Disco de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Adolescente , Cefalometría/métodos , Niño , Estudios Transversales , Asimetría Facial/patología , Femenino , Humanos , Masculino , Radiografía , Estudios Retrospectivos , Disco de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/patología
8.
Theriogenology ; 71(3): 450-7, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18835636

RESUMEN

Fertility-related phosphoprotein osteopontin (OPN) is present in the bovine oviduct epithelium and fluid. The objectives were to determine the effects of OPN on percentages of cleavage and embryo development in vitro in cattle, and to assess the ability of OPN to induce in vitro capacitation of bovine sperm. In vitro-matured bovine oocytes were fertilized in the presence of 0, 10, 20, or 40 microg/mL OPN. There were greater percentages (P<0.01) of cleavage and compact morulae-blastocysts (79.7 and 43.3%, respectively) with 10 microg/mL OPN than in the control group (without OPN; 71.2 and 32.1%, respectively). Furthermore, percentages of advanced blastocysts were greater in the group receiving 40 microg/mL OPN versus control (56.4% vs. 42.0%, P<0.05). Capacitation was assessed by the ability of sperm to undergo the acrosome reaction after incubation with lysophosphatidylcholine. Semen from three bulls was incubated for 2h in either TALP medium alone (control) or with TALP medium containing 0.01 mM heparin, or with TALP medium containing 10 or 20 microg/mL OPN. Incubation with 10 and 20 microg/mL OPN produced more (P<0.01) capacitated sperm (14.4 and 13.6%, respectively) than the untreated control group (8.3%), but both untreated sperm and those treated with OPN had significantly fewer capacitated sperm than those treated with 0.01 mM of heparin (30.5%). In conclusion, OPN improved the efficiency of bovine in vitro embryo production and influenced sperm capacitation.


Asunto(s)
Bovinos/embriología , Embrión de Mamíferos/efectos de los fármacos , Osteopontina/farmacología , Animales , Medios de Cultivo/química , Relación Dosis-Respuesta a Droga , Femenino , Fertilización In Vitro/veterinaria , Masculino , Ovario , Capacitación Espermática/efectos de los fármacos , Espermatozoides/efectos de los fármacos
9.
Sci Total Environ ; 624: 294-308, 2018 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-29253777

RESUMEN

Climate change (CC) directly influences agricultural sectors, presenting the need to identify both adaptation and mitigation actions that can make local farming communities and crop production more resilient. In this context, the viticultural sector is one of those most challenged by CC due to the need to combine grape quality, grapevine cultivar adaptation and therefore farmers' future incomes. Thus, understanding how suitability for viticulture is changing under CC is of primary interest in the development of adaptation strategies in traditional wine-growing regions. Considering that climate is an essential part of the terroir system, the expected variability in climate change could have a marked influence on terroir resilience with important effects on local farming communities in viticultural regions. From this perspective, the aim of this paper is to define a new dynamic viticultural zoning procedure that is able to integrate the effects of CC on grape quality responses and evaluate terroir resilience, providing a support tool for stakeholders involved in viticultural planning (winegrowers, winegrower consortiums, policy makers etc.). To achieve these aims, a Hybrid Land Evaluation System, combining qualitative (standard Land Evaluation) and quantitative (simulation model) approaches, was applied within a traditional region devoted to high quality wine production in Southern Italy (Valle Telesina, BN), for a specific grapevine cultivar (Aglianico). The work employed high resolution climate projections that were derived under two different IPCC scenarios, namely RCP 4.5 and RCP 8.5. The results obtained indicate that: (i) only 2% of the suitable area of Valle Telesina expresses the concept of terroir resilience orientated towards Aglianico ultra quality grape production; (ii) within 2010-2040, it is expected that 41% of the area suitable for Aglianico cultivation will need irrigation to achieve quality grape production; (iii) by 2100, climate change benefits for the cultivation of Aglianico will decrease, as well as the suitable areas.

10.
Clin Biomech (Bristol, Avon) ; 44: 99-103, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28384527

RESUMEN

BACKGROUND: To evaluate the reliability of the Iliotibial band compared to gracilis tendon as a graft to be used in anterolateral ligament reconstruction. METHODS: Gracilis tendon and a strip of Iliotibial band compared were harvested from 8 fresh human cadaveric knees. The gracilis tendon was prepared to obtain a graft of 10cm in length (Group 1). Iliotibial band compared was prepared to obtain a graft of 10cm in length and 0.5cm in width from the middle portion (Group 2). All the specimens were fixed on a servo hydraulic tensile machine with dedicated cryo-clamp. The loading protocol, used to compare the previously published results of ultimate failure load and Stiffness of the anterolateral ligament (Group 3), included a cyclic preconditioning between 10 and 25N at 0.1Hz for 10cycles and then a load to failure test at 20mm/min. FINDINGS: Gracilis tendon showed higher Ultimante Failure Load and stiffness when compared to a strip of Iliotibial band. Gracilis tendon and a strip of Iliotibial band compared showed higher Ultimante Failure Load and stiffness when compared with native anterolateral ligament as reported by Kennedy. INTERPRETATION: Both grafts tested in the present studies are suitable for an anatomical anterolateral ligament reconstruction.


Asunto(s)
Ligamento Cruzado Anterior/cirugía , Ligamentos Articulares/cirugía , Tendones/trasplante , Anciano , Fenómenos Biomecánicos , Femenino , Humanos , Masculino , Procedimientos de Cirugía Plástica , Reproducibilidad de los Resultados , Estrés Mecánico , Trasplante Autólogo
11.
Knee ; 23(5): 837-41, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27338510

RESUMEN

BACKGROUND: The aim of this study was to compare bone femoral tunnel enlargement in patients who underwent anterior cruciate ligament (ACL) transtibial reconstruction using an adjustable-loop length suspensory fixation device and a fixed-loop length suspensory fixation device. METHODS: All patients treated for ACL reconstruction with an ipsilateral hamstring between March 2013 and March 2014 were evaluated. Subjects were assigned to Group A (TightRope™ (TR) femoral fixation) or Group B (EndoButton® (EB) femoral fixation). All patients were evaluated with the Lachman test, pivot-shift test, 2000 International Knee Documentation Committee (IKDC) knee examination and KT1000 arthrometer. The subjective evaluation was performed using the 2000 IKDC Subjective Knee score, the Lysholm knee score, and the Tegner activity scale. CT examination was performed to evaluate femoral tunnel enlargement at four different levels. All patients were assessed at a 12month follow-up visit. Power analysis was performed a priori in accordance with the femoral tunnel enlargement values from the CT scans. Differences with P-values of ≤0.05 were considered to be statistically significant. RESULTS: The groups were homogenous at baseline with regard to age, gender, BMI, dominance and disease duration. At the final follow-up, no statistically significant differences (P>0.05) were found according to subjective and objective clinical outcome measures. According to the femoral tunnel enlargement, no statistically significant difference was found between the two groups (P>0.05). CONCLUSION: In transtibial ACL reconstruction, the use of a fixed or adjustable-loop length device products, on the femoral side, led to similar clinical and radiological results.


Asunto(s)
Lesiones del Ligamento Cruzado Anterior/cirugía , Reconstrucción del Ligamento Cruzado Anterior/instrumentación , Fémur/cirugía , Adulto , Reconstrucción del Ligamento Cruzado Anterior/métodos , Femenino , Fémur/diagnóstico por imagen , Humanos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Masculino , Dispositivos de Fijación Ortopédica , Estudios Prospectivos , Tendones/trasplante , Tibia/cirugía , Tomografía Computarizada por Rayos X , Adulto Joven
12.
Oncogene ; 19(45): 5153-62, 2000 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-11064452

RESUMEN

There are two IL-15 isoforms and eight isoforms for the IL-15Ralpha chain whose biological role is poorly understood. Here, we have analysed the intracellular trafficking of IL-15 and IL-15Ralpha and tried to shed some light on their function(s). In IL-15/GFP CHO transfectants both IL-15 isoforms show nuclear localization. Two melanoma cell lines (MELP and MELREO) spontaneously expressing the IL-15 isoforms, display different intracellular trafficking of the IL-15/IL-15Ralpha complex. In MELP cells only IL-15Ralpha is detected inside the nucleus, whereas IL-15 and IL-15Ralpha assemble at the cell surface and are internalized. Moreover, the transducing molecule TRAF2 co-immunoprecipitates with IL-15Ralpha and may be deflected to TNFRI using anti-IL-15 blocking mAbs and TNF-alpha. By contrast, MELREO cells display IL-15Ralpha and IL-15 nuclear localization but only a partial co-localization of these molecules on the cell surface. In these cells, TRAF2 is strongly associated with IL-15Ralpha and cannot be deflected by any treatment. Since TRAF2 activates the transcription factor NF-kappaB, IL-15 through IL-15Ralpha, could have a role in the control of this pathway. Indeed, anti-IL-15 MaB inhibit the constitutive nuclear localization of NFkappaB and the phosphorylation of its inhibitor Ikappa-Balpha. Thus, IL-15Ralpha controls NF-kappaB activation, however differences in the intracellular trafficking of the IL-15 and/or IL-15Ralpha suggest a different biological role for this complex in MELP versus MELREO cells.


Asunto(s)
Interleucina-15/metabolismo , Melanoma/metabolismo , Receptores de Interleucina-2/metabolismo , Animales , Células CHO , Compartimento Celular , Núcleo Celular , Cricetinae , Proteínas Fluorescentes Verdes , Humanos , Interleucina-15/genética , Interleucina-15/aislamiento & purificación , Proteínas Luminiscentes/genética , Proteínas Luminiscentes/aislamiento & purificación , Microscopía Confocal , FN-kappa B/metabolismo , Unión Proteica , Señales de Clasificación de Proteína , Subunidades de Proteína , Transporte de Proteínas , Proteínas/aislamiento & purificación , Receptores de Interleucina-15 , Receptores de Interleucina-2/genética , Receptores de Interleucina-2/aislamiento & purificación , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal , Factor 2 Asociado a Receptor de TNF
13.
Curr Med Chem ; 10(5): 367-79, 2003 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-12570697

RESUMEN

The development of small molecule kinase inhibitors as potential cancer therapeutics is an area of intense interest, and a subset of these agents target cyclin-dependent kinase (CDK) activity. Ten distinct CDKs (1-9, 11), when paired with their cyclin activators, are integral to such diverse processes as cell cycle control, neuronal development, and transcriptional regulation. Mutation and/or aberrant expression of certain CDKs and their regulatory counterparts are associated with uncontrolled proliferation and tumorigenesis. As such, CDK selective inhibitors (CDKIs) that attenuate or prevent tumor growth have been developed. Recently, interest in the therapeutic potential of CDKIs has expanded to include neurodegenerative diseases, where dysregulated CDK activity has been linked to the pathogenesis of Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), and stroke. Specifically, aberrant activation of cell cycle CDKs or CDK5 is associated with apoptosis and neuronal dysfunction in response to various neuronal stressors. To date, CDKIs have shown promise as neuroprotective agents in the research laboratory and, in the future, may prove useful in the neurology clinic.


Asunto(s)
Antineoplásicos/farmacología , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Inhibidores Enzimáticos/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Antineoplásicos/uso terapéutico , Quinasas Ciclina-Dependientes/fisiología , Inhibidores Enzimáticos/uso terapéutico , Humanos , Fármacos Neuroprotectores/uso terapéutico
15.
Ann N Y Acad Sci ; 876: 164-79, 1999 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-10415607

RESUMEN

Glucocorticoid hormones (GCH) induce apoptosis in PHA-primed peripheral blood T lymphocytes (PBL) and down-regulate membrane-bound proteins involved in the immune response. We have analyzed whether GCH are able to affect the expression of the TCR-associated molecules CD3, CD4, and CD8 on PBL-PHA, and whether the modulation of those receptors is related to the GCH-driven apoptosis of the PBL-PHA. Lymphocytes were cultured with PHA or with PHA plus prednisone (PDN) 10(-3), 10(-6), and 10(-9) M. Then expression of CD2, CD3, CD4, CD8, and CD56 antigens was studied by cytofluorimetric assay using propidium iodide (PI) staining and annexin procedure, and by gel electrophoresis of low molecular weight DNA. PDN, at a pharmacological concentration (10(-6) M), was able to inhibit the CD3 expression on T cells. The kinetics of CD3 decrement and of apoptosis show that the down-regulation of CD3 molecules precedes DNA fragmentation and that the cells lacking CD3 are those prone to PDN-induced apoptosis. The inhibition of CD3 is not related to a transcriptional or posttranscriptional phenomenon, because both PBL-PHA and PBL-PHA-PDN expressed the same amount of intracytoplasmic CD3 molecule. PDN also induced a down-regulation of the CD4 and CD8 molecules that resulted sooner in more intense CD8. In vitro PDN is able to induce apoptosis in PBL-PHA through a down-regulation of CD3 molecules.


Asunto(s)
Corticoesteroides/fisiología , Apoptosis/fisiología , Complejo CD3/análisis , Glucocorticoides/farmacología , Sistema Inmunológico/fisiología , Prednisona/farmacología , Linfocitos T/efectos de los fármacos , Antígenos CD4/análisis , Antígenos CD8/análisis , Humanos , Fenotipo , Fitohemaglutininas/farmacología , Linfocitos T/inmunología , Linfocitos T/fisiología
16.
Ann N Y Acad Sci ; 876: 193-7, 1999 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-10415609

RESUMEN

Different glucocorticoid hormones (GCH) show differences in the intensity and in the kinetics of their immunomodulating activity. The mechanism(s) of action of GCH is under investigation, but is has been noted that they exert immune activity via the genomic pathway. We have studied the effects of prednisone (PDN), deflazacort (DFC), and dexamethasone (DXM) on the production of cytokines (IL-2, IL-6, TNF-alpha, IL-10) by peripheral T lymphocytes, and the effects on the inhibition of NF-kB DNA binding activity by activated Jurkat cell line. The data obtained show that the three GCH molecules exert an immunosuppression on cytokine production by T lymphocytes and a strong decrease in the nuclear translocation of NF-kB in Jurkat cells; moreover, (a) not all the cytokines investigated were affected, and not with the same intensity, by the three GCH and (b) DXM inhibited the binding activity of NF-kB less than that of DFC and PDN. These data are in agreement with the concept that different GCH compounds might differ in their binding and affinity properties, tissue-specific metabolism, and interaction with transcription factor.


Asunto(s)
Dexametasona/farmacología , Glucocorticoides/farmacología , Inmunosupresores/farmacología , Prednisona/farmacología , Pregnenodionas/farmacología , Adulto , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , ADN/metabolismo , Expresión Génica/efectos de los fármacos , Humanos , FN-kappa B/antagonistas & inhibidores , FN-kappa B/genética , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo
17.
Curr Alzheimer Res ; 1(1): 33-8, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15975083

RESUMEN

Based on a growing literature, cyclin-dependent kinase 5 (Cdk5) has been implicated in the pathological processes that contribute to neurodegeneration in Alzheimer's disease (AD). Cdk5 is ubiquitously expressed, but its activity is largely localized to post-mitotic neurons due to neuron-specific expression of its activators p35 and p39. Sufficient Cdk5 activity is critical to normal central nervous system development, as in its absence, neuronal migration and axonal path finding are deranged. Conversely, excessive and mislocalized Cdk5 activity appears to be detrimental to neuronal function. In fact, the pathological hallmarks of AD, beta-amyloid aggregates and neurofibrillary tangles, have been linked to Cdk5-mediated neuronal death. In this model, beta-amyloid is the toxic stimulus that disrupts intracellular calcium homeostasis, leading to activation of calpains, a family of calcium-dependent proteases. Calpain-mediated cleavage of p35, yields a truncated p25 fragment that possesses a longer half-life, lacks the necessary sequence targeting it to membranes, but retains the capacity to activate Cdk5. The resulting excessive and mislocalized Cdk5 activity targets tau as a substrate for hyperphosphorylation, which is a prerequisite of paired helical filament (PHF) formation. A number of recent reports, utilizing diverse methods, lend further support to this model of AD neurodegeneration, and several strategies for combating Cdk5 dysregulation have even been devised. However, the study of Cdk5 in AD is not without controversy, and questions remain regarding its role in the pathology. Herein, the most recent findings regarding this model are reviewed.


Asunto(s)
Enfermedad de Alzheimer/enzimología , Quinasas Ciclina-Dependientes/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Animales , Encéfalo/enzimología , Cadáver , Quinasa 5 Dependiente de la Ciclina , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/uso terapéutico , Humanos
18.
J Neurosci Methods ; 58(1-2): 39-48, 1995 May.
Artículo en Inglés | MEDLINE | ID: mdl-7475232

RESUMEN

A tilting apparatus has been designed and constructed to produce fore-aft whole head-and-body tilt (WHBT) alone, or in combination with ankle dorsiflexion of standing subjects, about an axis colinear with the ankle joint. The apparatus is composed of a vertical tilting structure attached to a supporting base. Mechanical rotation of the vertical tilting structure is achieved by a spring activating system mounted on its base. Subjects are secured to the vertical structure by a body harness system with the head fixed, and the feet secured to the standing platform. Simultaneous dynamic WHBT and ankle joint displacement are induced by rotating the vertical support; whereas WHBT alone is achieved by concurrent rotation of both the vertical support and standing platform. Tilts are triggered manually, and data acquisition precedes head acceleration onset by 50-100 ms to provide suitable baseline values. This tilting apparatus has been successfully used to apply forward WHBT in 34 subjects with height ranging from 1.55 to 1.87 m and weights from 42 to 95 kg, and at magnitudes of peak head acceleration varying from 0.4 to 2.2 g as measured by a linear accelerometer mounted on a dental bite. These acceleration rates can be reproduced with minor variation in the same subjects. Moreover, the area under the head acceleration traces was reproducible within 15% between subjects. Tilts can be delivered with concomitant ankle dorsiflexion. These features make the low-cost tilting apparatus a very useful tool for the study of human tilting reactions in both laboratories and clinical settings.


Asunto(s)
Neurofisiología/instrumentación , Equilibrio Postural/fisiología , Aceleración , Adulto , Tobillo/fisiología , Cabeza/fisiología , Humanos , Movimiento/fisiología , Músculo Esquelético/inervación , Músculo Esquelético/fisiología , Propiocepción/fisiología , Vestíbulo del Laberinto/fisiología
19.
Eur J Neurol ; 5(5): 459-462, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10210874

RESUMEN

Objective: to determine possible risk factors of a stroke after percutaneous transluminal coronary angioplasty (PTCA). Design: this is a retrospective evaluation of a consecutive group of 4088 patients undergoing PTCA between 1988 and 1995. We have studied the incidence, clinical characteristics, risk factors, and outcome. Results: seven patients, six males and one female (0.17%) developed a stroke after this procedure. In comparison with the control group, the stroke group did not differ regarding age or gender. The existence of a stroke (six located in the brain, and one in the spinal cord), represented 1.24% of all complications (P < 0.001), and 5% of all deaths (P < 0.01) of PTCA. Three patients developed TIA, two patients developed hemorrhagic strokes (in which they received previous thrombolytic therapy), and the other two patients suffered from an ischemic stroke. The statistically significant risk factors of a stroke after PTCA included: intracoronary thrombolytic therapy (P < 0.01), hypercholesterolemia (P < 0.001) and a prior PTCA (P < 0.05). Conclusions: although these procedural complications are infrequent, they are usually serious and important risk factors which could be identified prior to the procedure. These risk factors would allow identification of patients who are prone to a stroke after PTCA. Intracranial hemorrhage occurred only after thrombolytic therapy, and the factors related to hemorrhagic strokes were probably different from those predisposed to ischemic strokes and TIA. Copyright 1998 Lippincott Williams & Wilkins

20.
Clin Chim Acta ; 110(2-3): 327-34, 1981 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-7194750

RESUMEN

This paper describes a direct method for determining sex hormone binding globulin (SHBG)-bound sex hormones in human plasma after separation of SHBG-bound and unbound hormone fractions by selective precipitation with ammonium sulphate. In normal women variations in SHBG-bound and -free hormone generally paralleled fluctuations in total hormone. Changes in SHBG-free estradiol did not have any marked effect on plasma SHBG and sHBG-free testosterone. Our results suggest a buffer role for SHBG through which the biological response to sudden changes in sex hormone concentration is moderated.


Asunto(s)
Estradiol/sangre , Globulina de Unión a Hormona Sexual/análisis , Testosterona/sangre , Adulto , Sulfato de Amonio , Precipitación Química , Femenino , Humanos , Menstruación , Unión Proteica , Albúmina Sérica/análisis
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