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1.
J Phys Ther Sci ; 36(8): 457-470, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39092409

RESUMEN

[Purpose] Virtual reality has been increasingly used to improve the balance performance of older adults; however, the effect remains inconclusive. This study aimed to examine the effects of virtual reality on the balance performance of older adults through a systematic review and meta-analysis. [Methods] The PubMed, MEDLINE, CINAHL, Cochrane Library, and PEDro electronic databases were searched. Only randomized clinical trials published in English from January 1st, 1980, to September 30, 2022, were included and reviewed. Outcome measures included the Berg Balance Scale, Timed Up and Go Test and Activity-specific Balance Confidence scale. [Results] The results showed that virtual reality training for older adults led to significant improvements in Berg Balance Scale scores and Timed Up and Go Test times compared with non-virtual reality training. However, such an outcome was not observed with regard to the Activity-specific Balance Confidence scale. [Conclusion] Virtual reality training is effective in improving both static and dynamic balance among older adults. However, its effect on their self-confidence regarding balance is not significant.

2.
Brain Res ; 1836: 148938, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38615924

RESUMEN

Prepulse inhibition (PPI) of the auditory startle response, a key measure of sensorimotor gating, diminishes with age and is impaired in various neurological conditions. While PPI deficits are often associated with cognitive impairments, their reversal is routinely used in experimental systems for antipsychotic drug screening. Yet, the cellular and circuit-level mechanisms of PPI remain unclear, even under non-pathological conditions. We recently showed that brainstem neurons located in the caudal pontine reticular nucleus (PnC) expressing the glycine transporter type 2 (GlyT2±) receive inputs from the central nucleus of the amygdala (CeA) and contribute to PPI but via an uncharted pathway. Here, using tract-tracing, immunohistochemistry and in vitro optogenetic manipulations coupled to field electrophysiological recordings, we reveal the neuroanatomical distribution of GlyT2± PnC neurons and PnC-projecting CeA glutamatergic neurons and we provide mechanistic insights on how these glutamatergic inputs suppress auditory neurotransmission in PnC sections. Additionally, in vivo experiments using GlyT2-Cre mice confirm that optogenetic activation of GlyT2± PnC neurons enhances PPI and is sufficient to induce PPI in young mice, emphasizing their role. However, in older mice, PPI decline is not further influenced by inhibiting GlyT2± neurons. This study highlights the importance of GlyT2± PnC neurons in PPI and underscores their diminished activity in age-related PPI decline.


Asunto(s)
Tronco Encefálico , Proteínas de Transporte de Glicina en la Membrana Plasmática , Glicina , Neuronas , Inhibición Prepulso , Reflejo de Sobresalto , Animales , Inhibición Prepulso/fisiología , Neuronas/fisiología , Neuronas/metabolismo , Reflejo de Sobresalto/fisiología , Ratones , Tronco Encefálico/fisiología , Tronco Encefálico/metabolismo , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Masculino , Glicina/metabolismo , Optogenética , Ratones Transgénicos , Ratones Endogámicos C57BL , Transmisión Sináptica/fisiología , Núcleo Amigdalino Central/fisiología , Núcleo Amigdalino Central/metabolismo
3.
Ying Yong Sheng Tai Xue Bao ; 35(3): 739-748, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38646762

RESUMEN

Biological soil crust (biocrust) is widely distributed on the Loess Plateau and plays multiple roles in regulating ecosystem stability and multifunctionality. Few reports are available on the distribution characteristics of biocrust in this region, which limits the assessment of its ecological functions. Based on 388 sampling points in different precipitation zones on the Loess Plateau from 2009 to 2020, we analyzed the coverage, composition, and influencing factors of biocrust across different durations since land abandonment, precipitation levels, topography (slope aspect and position), and utilization of abandoned slopelands (shrubland, forest, and grassland). On this base, with the assistance of machine learning and spatial modeling methods, we generated a distribution map of biocrust and its composition at a resolution of 250 m × 250 m, and analyzed the spatial distribution of biocrust on the Loess Plateau. The results showed that the average biocrust coverage in the woodlands and grasslands was 47.3%, of which cyanobacterial crust accounted for 25.5%, moss crust 19.7%, and lichen crust 2.1%. There were significant temporal and spatial variations. Temporally, the coverage of biocrust in specific regions fluctuated with the extension of the abandoned durations and coverage of cyanobacterial crust, while moss crust showed a reverse pattern. In addition, the coverage of biocrust in the wet season was slightly higher than that in the dry season within a year. Spatially, the coverage of biocrusts on the sandy lands area on the Loess Plateau was higher and dominated by cyanobacterial crusts, while the coverage was lower in the hilly and gully area. Precipitation and utilization of abandoned land were the major factors driving biocrust coverage and composition, while slope direction and position did not show obvious effect. In addition, soil organic carbon content, pH, and texture were related to the distribution of biocrust. This study uncovered the spatial and temporal variability of biocrust distribution, which might provide important data support for the research and management of biocrust in the Loess Plateau region.


Asunto(s)
Ecosistema , Bosques , Líquenes , Suelo , Análisis Espacio-Temporal , China , Suelo/química , Líquenes/crecimiento & desarrollo , Pradera , Cianobacterias/crecimiento & desarrollo , Microbiología del Suelo , Altitud , Monitoreo del Ambiente , Briófitas/crecimiento & desarrollo , Árboles/crecimiento & desarrollo
4.
Org Lett ; 26(2): 519-524, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38190623

RESUMEN

Herein, we described a copper(I)-catalyzed dearomatization of benzofurans with 2-(chloromethyl)anilines to prepare various tetrahydrobenzofuro[3,2-b]quinolines and 2-(quinolin-2-yl)phenols in good to excellent yields through radical addition and an intramolecular cyclization process. Mechanistic studies revealed that 2-(chloromethyl)anilines served as radical precursors. The present method features broad substrate scope, good functional group tolerance, quinoline scaffold diversity, and radical addition dearomatization of benzofurans.

5.
Eur J Med Res ; 28(1): 457, 2023 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-37876003

RESUMEN

BACKGROUND: Migraine is one of four major chronic diseases that cause disability. Decreases in regional cerebral blood flow (rCBF) occur during migraine attacks. Laser therapy is extensively employed in treating other vascular diseases; nevertheless, its effectiveness in migraine management remains largely unknown. Therefore, we evaluated the effect of low-level intravascular laser irradiation of blood (ILIB) therapy in patients with migraine. METHODS: We performed an observational case-control study in 24 patients suffering from migraine. Patients were divided into an ILIB treatment group and a traditional rehabilitation group. This study performed clinical assessments and single-photon emission computed tomography (SPECT) prior to and after the treatment and 1 month later. Changes in rCBF-SPECT between groups and between timepoints were compared to clinical outcomes. RESULTS: Nine patients undergoing rehabilitation and fifteen patients undergoing ILIB were studied from baseline to 1 month follow-up. The ILIB group, visual analog scale for pain (P = 0.001), Montreal Cognitive Assessment (P = 0.003), and Athens Insomnia Scale (P < 0.001) symptom scores significantly improved after treatment. SPECT imaging showed a 1.27 ± 0.27 fold increase in rCBF after ILIB treatment, and no significant differences in the rehabilitation group. CONCLUSIONS: Low-level ILIB therapy is associated with better clinical and vascular outcomes, and may be a feasible treatment option for migraine. Although our sample size was small, our data provide a starting point for migraine laser therapy research.


Asunto(s)
Terapia por Láser , Terapia por Luz de Baja Intensidad , Trastornos Migrañosos , Humanos , Estudios de Casos y Controles , Trastornos Migrañosos/radioterapia , Enfermedad Crónica , Terapia por Luz de Baja Intensidad/métodos , Tomografía Computarizada de Emisión de Fotón Único , Circulación Cerebrovascular
6.
Analyst ; 148(7): 1437-1441, 2023 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-36919562

RESUMEN

Formaldehyde (FA) and viscosity play multiple roles in human health and diseases, and viscosity has great regional differences due to the diversity of subcellular organelles. However, it is challenging to achieve dual detection of viscosity and FA in subcellular organelles. Herein, we developed a near infrared (NIR) fluorescent probe FA-Cy, which can simultaneously monitor the viscosity and FA concentration of mitochondria in living cells. The probe could detect mitochondrial viscosity and exogenous and endogenous FA in living cells and zebrafish.


Asunto(s)
Colorantes Fluorescentes , Pez Cebra , Animales , Humanos , Colorantes Fluorescentes/toxicidad , Células HeLa , Viscosidad , Imagen Óptica/métodos , Mitocondrias , Formaldehído
7.
Mater Today Bio ; 16: 100379, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36042850

RESUMEN

Recognizing multidrug-resistant (MDR) bacteria with high accuracy and precision from clinical samples has long been a difficulty. For reliable detection of MDR bacteria, we investigated a programmable molecular circuit called the Background-free isothermal circuital kit (BRICK). The BRICK method provides a near-zero background signal by integrating four inherent modules equivalent to the conversion, amplification, separation, and reading modules. Interference elimination is largely owing to a molybdenum disulfide nanosheets-based fluorescence nanoswitch and non-specific suppression mediated by molecular inhibitors. In less than 70 â€‹min, an accurate distinction of various MDR bacteria was achieved without bacterial lysis. The BRICK technique detected 6.73 â€‹CFU/mL of methicillin-resistant Staphylococcus aureus in clinical samples in a proof-of-concept trial. By simply reprogramming the sequence panel, such a high signal-to-noise characteristic has been proven in the four other superbugs. The proposed BRICK method can provide a universal platform for infection surveillance and environmental management thanks to its superior programmability.

8.
J Back Musculoskelet Rehabil ; 35(5): 963-969, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35068439

RESUMEN

BACKGROUND: Sudden onset of acute torticollis in children is rare and is usually diagnosed as atlantoaxial rotatory subluxation (AARS). The common treatment for acute AARS without neurological symptoms is halter traction in conjunction with muscle relaxant and sedative agents, followed by cervicothoracic orthotic immobilization. To the best of our knowledge, a case of acute AARS treatment with high-intensity laser therapy (HILT) has not yet been reported so far. OBJECTIVE: We aimed to report a case of acute AARS treatment with HILT successfully and to discuss about the clinical effect of HILT in AARS. METHODS: We reported a 9-year-old girl with acute onset of torticollis visiting the rehabilitation outpatient department. RESULS: The physical examination revealed a typical cock robin position without neurological symptoms. A series of evaluations, including open-mouth odontoid radiograph and soft tissue sonography, confirmed the diagnosis of acute AARS. The patient received HILT over the left suboccipital and upper back muscle groups, which started on the day of the first rehabilitation clinic visit, once a week, for four weeks. Torticollis and neck pain improved gradually with each session of HILT, and the symptoms resolved completely after the fourth session. Dynamic computed tomography (CT) of the cervical spine showed no evidence of obvious AARS after the treatment. CONCLUSIONS: The patient had no complaints after HILT in a case of acute AARS resulting from a mechanical factor. Due to its pain-relief and muscle-release characteristics, HILT indicates the probable benefit of relaxation of spastic muscles for patients with AARS.


Asunto(s)
Articulación Atlantoaxoidea , Luxaciones Articulares , Terapia por Láser , Tortícolis , Articulación Atlantoaxoidea/diagnóstico por imagen , Vértebras Cervicales , Niño , Femenino , Humanos , Luxaciones Articulares/cirugía , Tortícolis/terapia
9.
Geriatr Nurs ; 44: 24-29, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35007867

RESUMEN

Surveys based on western populations have identified many risk factors for dysphagia in older people, but the potential risk factors consistent with the demographic characteristics of older, hospitalized Chinese patients require further study. This single-center prospective study aimed to determine the incidence of dysphagia in western China, and to develop and validate a model to predict the risk of dysphagia among older patients. A total of 343 inpatients (aged ≥ 65 years without dysphagia and cognitive impairment) were included. A score ≥ 2 on the Eating Assessment Tool-10 was defined as dysphagia. After a six-month follow-up, 70 (20.4%) patients were found to have dysphagia. The final model included age, wearing dentures, activities of daily living, cerebral vascular disease, coronary heart disease, and malignancy. The developed model has high predictive accuracy and can be easily implemented in daily practice.


Asunto(s)
Disfunción Cognitiva , Trastornos de Deglución , Actividades Cotidianas , Anciano , China/epidemiología , Disfunción Cognitiva/complicaciones , Trastornos de Deglución/epidemiología , Humanos , Estudios Prospectivos
10.
J Formos Med Assoc ; 121(3): 592-603, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34247893

RESUMEN

BACKGROUND/PURPOSE: Task-oriented functional walking is important in stroke patients. We aimed to investigate effects of a quad-cane with auxiliary laser illuminator (laser-cane) among stroke patients. METHODS: This was a randomized-prospective study. Patients in the experimental group (EG) received 15-min of walking training with laser-cane and 15-min of traditional physical therapy. Patients in the control group (CG) received the same rehabilitation without laser-cane. The rehabilitation lasted for 4 weeks, twice per week. Primary outcome were gait parameters. Secondary outcomes were Berg Balance Scale (BBS), Timed Up and Go Test (TUG), and Barthel index (BI). Outcomes were measured at baseline, at the end of the rehabilitation (visit-1), and 4 weeks later (visit-2). RESULTS: Both the groups (both n = 15) showed improvement of cadence, relative stance and swing phase duration of non-paretic side, BBS, and TUG at both visits. In the intragroup comparison, the EG additionally improved at stride length, relative stance and swing phase duration of paretic side, and gait speed at both visits; temporal swing symmetry, and toe-off angle of non-paretic side at the visit-2. Intergroup comparing for changing of outcomes with the CG, stride length and gait speed increased, relative stance phase duration of the non-paretic site decreased, and the temporal swing symmetry improved at the visit-1; relative stance phase duration of the paretic side decreased and the temporal stance symmetry improved at the visit-2 in the EG. CONCLUSION: Rehabilitation with laser-cane improved the balance, activity of daily living, gait symmetry and gait parameters of stroke patients.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Marcha , Humanos , Rayos Láser , Equilibrio Postural , Estudios Prospectivos , Estudios de Tiempo y Movimiento , Caminata
11.
BMC Biol ; 19(1): 116, 2021 06 03.
Artículo en Inglés | MEDLINE | ID: mdl-34082731

RESUMEN

BACKGROUND: Sensorimotor gating is a fundamental pre-attentive process that is defined as the inhibition of a motor response by a sensory event. Sensorimotor gating, commonly measured using the prepulse inhibition (PPI) of the auditory startle reflex task, is impaired in patients suffering from various neurological and psychiatric disorders. PPI deficits are a hallmark of schizophrenia, and they are often associated with attention and other cognitive impairments. Although the reversal of PPI deficits in animal models is widely used in pre-clinical research for antipsychotic drug screening, the neurotransmitter systems and synaptic mechanisms underlying PPI are still not resolved, even under physiological conditions. Recent evidence ruled out the longstanding hypothesis that PPI is mediated by midbrain cholinergic inputs to the caudal pontine reticular nucleus (PnC). Instead, glutamatergic, glycinergic, and GABAergic inhibitory mechanisms are now suggested to be crucial for PPI, at the PnC level. Since amygdalar dysfunctions alter PPI and are common to pathologies displaying sensorimotor gating deficits, the present study was designed to test that direct projections to the PnC originating from the amygdala contribute to PPI. RESULTS: Using wild type and transgenic mice expressing eGFP under the control of the glycine transporter type 2 promoter (GlyT2-eGFP mice), we first employed tract-tracing, morphological reconstructions, and immunohistochemical analyses to demonstrate that the central nucleus of the amygdala (CeA) sends glutamatergic inputs lateroventrally to PnC neurons, including GlyT2+ cells. Then, we showed the contribution of the CeA-PnC excitatory synapses to PPI in vivo by demonstrating that optogenetic inhibition of this connection decreases PPI, and optogenetic activation induces partial PPI. Finally, in GlyT2-Cre mice, whole-cell recordings of GlyT2+ PnC neurons in vitro paired with optogenetic stimulation of CeA fibers, as well as photo-inhibition of GlyT2+ PnC neurons in vivo, allowed us to implicate GlyT2+ neurons in the PPI pathway. CONCLUSIONS: Our results uncover a feedforward inhibitory mechanism within the brainstem startle circuit by which amygdalar glutamatergic inputs and GlyT2+ PnC neurons contribute to PPI. We are providing new insights to the clinically relevant theoretical construct of PPI, which is disrupted in various neuropsychiatric and neurological diseases.


Asunto(s)
Inhibición Prepulso , Reflejo de Sobresalto , Estimulación Acústica , Amígdala del Cerebelo , Animales , Antígeno Carcinoembrionario , Humanos , Ratones
12.
PLoS One ; 16(5): e0251843, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34019557

RESUMEN

Studies on physiotherapists are generally focused on clinical professionalism, with very few examining job performance from a management standpoint. To address this gap, this study sought to investigate the relationship between impression management and organizational citizenship behavior and job performance. This study targeted medical institutions offering rehabilitation and physiotherapy services and conducted a questionnaire survey based on scales developed by domestic and foreign scholars. A total of 600 questionnaires were distributed and 523 valid ones collected. The data was tested and verified using regression analysis and hierarchical linear modeling (HLM). In the survey, the Impression Management Scale, Organizational Citizenship Behavior Scale, and Job Performance Scale indicated that at the individual level, the impression management of physiotherapists is significantly related to their organizational citizenship behaviors and job performance. The organizational citizenship behaviors were also found to have a mediating effect between impression management and job performance. At the group level, impression management had a conditioning effect on organizational citizenship behaviors and job performance. In terms of statistical methods, group-level variables act as moderators, which affects the power of individual-level explanatory variables on outcome variables, i.e., the influence of the slope. The job behaviors of physiotherapists entail direct service and their performance is closely related to organizational development. Impression management gives people certain purposes and behaviors while organizational citizenship behaviors are a type of non-self-seeking, selfless dedication behaviors. Therefore, the motivation of physiotherapists who demonstrate organizational citizenship behaviors should be further explored.


Asunto(s)
Actitud del Personal de Salud , Cultura Organizacional , Fisioterapeutas/psicología , Rendimiento Laboral/estadística & datos numéricos , Adulto , Altruismo , Femenino , Humanos , Satisfacción en el Trabajo , Masculino , Persona de Mediana Edad , Motivación , Lealtad del Personal , Conformidad Social , Encuestas y Cuestionarios , Taiwán , Rendimiento Laboral/ética
13.
Gait Posture ; 88: 10-15, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33946024

RESUMEN

BACKGROUND: Patients with chronic stroke have reduced capacity for performing activities of daily living (ADLs) and are at increased risk for falls during walking due to long-term changes to muscle tone and force, as well as movement control. RESEARCH QUESTION: To investigate the efficacy of lateral stair walking training on muscle strength of affected lower extremities, balance, ADLs, and gait ability in patients with chronic stroke. METHODS: The experimental group received 15 min of lateral stair walking exercise along with 15 min of traditional physiotherapy, whereas the control group received only traditional physiotherapy for 30 min. Both groups received the intervention once a week for 12 weeks. Outcome measurements included muscle strength, postural assessment scale for stroke patients (PASS), Fugal-Meyer assessment for lower extremity (FMA-LE), Barthel index (BI), timed up and go test (TUG), and the gait parameters which were determined by the Reha-Watch system. RESULTS: A total of 24 participants completed the study. The experimental group showed significant improvements in hip extensor, flexor, and abductor strength of the affected limb, FMA-LE, BI, TUG, and gait parameters of stride length, velocity, and cadence. Significant differences in affected limb ankle plantar strength (p = 0.024), PASS (p = 0.017), BI (p = 0.039), TUG (p = 0.049), and gait velocity (p < 0.001) were observed between the 2 groups. SIGNIFICANCE: Lateral stair walking training alongside physical therapy resulted in significant improvements in hip muscle strength and gait parameters in patients with chronic stroke. Our results support the incorporation of lateral stair walking training into clinical rehabilitation programs. Lateral stair walking training in patients with chronic stroke can be used as an effective treatment to improve gait, balance performance, and ADLs.


Asunto(s)
Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Actividades Cotidianas , Terapia por Ejercicio , Marcha , Humanos , Proyectos Piloto , Equilibrio Postural , Estudios de Tiempo y Movimiento , Resultado del Tratamiento , Caminata
14.
Ann Palliat Med ; 9(4): 2037-2044, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32762225

RESUMEN

BACKGROUND: Intravenous chemotherapy is one of the most common treatments for hematological tumors, a major threat to human health and life. Due to its safety, comfort, and convenience, a peripherally inserted central catheter (PICC) is the preferred route of administration of intravenous chemotherapy. However, some PICC-related complications are drawing increasing attention. In this study, we investigated the use and role of sterile chitosan-based dressing in PICC-related complications in patients with hematological tumors. METHODS: We retrospectively analyzed the clinical data of 205 patients with hematological tumors who had a PICC placed. The patients were divided into two groups, the observation group (sterile chitosan-based dressing, n=105) and the control group (sterile gauze dressing; n=100). The incidences of bleeding, infection, poor healing, and phlebitis, as well as the risk of bleeding, infection, and poor healing at the puncture site within a week of PICC placement, were analyzed. RESULTS: The overall incidences of bleeding, infection, and poor healing were, respectively, 42.9%, 6.7%, and 6.7% in the observation group and 63.0%, 22.0%, and 34% in the control group (all P<0.05). The risk of local bleeding was significantly lower in the observation group than in the control group [odds ratio (OR) 0.366; 95% confidence interval (CI): 0.211-0.634; P<0.001]. The risk of local bleeding was significantly higher in the platelets <50×109/L group than in the platelets >100×109/L group (OR 3.068; 95% CI: 1.397-6.740; P=0.005), while no significant difference was observed in the risk of bleeding between the platelets 50×109-100×109/L group and the platelets >100×109/L group (OR 0.839; 95% CI: 0.404-1.742; P=0.638). The risk of infection (OR 0.214; 95% CI: 0.088-0.522; P<0.001) and the risk of poor healing (OR 0.139; 95% CI: 0.058-0.331; P<0.001) were significantly lower in the observation group than in the control group. CONCLUSIONS: For patients with hematological tumors, sterile chitosan-based dressing after PICC placement reduces the risk of bleeding and infection and promotes healing at the puncture site.


Asunto(s)
Vendajes , Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Cateterismo Periférico , Quitosano , Infecciones Relacionadas con Catéteres/prevención & control , Cateterismo Venoso Central/efectos adversos , Cateterismo Periférico/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Quitosano/uso terapéutico , Neoplasias Hematológicas/tratamiento farmacológico , Humanos , Estudios Retrospectivos
15.
Bioorg Chem ; 99: 103814, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32278208

RESUMEN

A new anticancer N-containing heterocyclic scaffold was designed and 30 pyridazino[1,6-b]quinazolinone derivatives were synthesized and characterized. Antiproliferation evaluation in vitro against four human cancer cell lines including SK-OV-3(ovarian cell), CNE-2(nasopharyngeal cell), MGC-803(gastric cell) and NCI-H460(lung cell) indicated that most of them exhibited potent anticancer activity and the IC50 value of the most potent compound lowered to sub-µM. DNA interaction assay indicated that compounds 4e, 4g, 6o, 6p, 8o can intercalate into DNA. Compounds 6 and 8 also demonstrated potent topoisomerase I (topo I) activity. Annexin V- FITC/propidium iodide dual staining assay and cell cycle analysis indicated that 2-(4-bromophenyl)-4-((3-(diethylamino)propyl)amino) -10H-pyridazino [1,6-b]quinazolin- 10-one (8p) could induce arrest cell cycle at G2 phase and apoptosis in MGC-803 cells in a dose-dependent manner. The in vivo antitumor efficiency of compound 8p was also evaluated on MGC-803 xenograft nude mice, and the relative tumor growth inhibition was up to 55.9% at a dose of 20 mg/kg per two days. The results suggested that pyridazino[1,6-b]-quinazolinones might serve as a promising novel scaffold for the development of new antitumor agents.


Asunto(s)
Antineoplásicos/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , ADN/química , Quinazolinonas/farmacología , Inhibidores de Topoisomerasa I/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Bovinos , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Simulación del Acoplamiento Molecular , Estructura Molecular , Quinazolinonas/síntesis química , Quinazolinonas/química , Relación Estructura-Actividad , Inhibidores de Topoisomerasa I/síntesis química , Inhibidores de Topoisomerasa I/química , Células Tumorales Cultivadas
16.
Chemistry ; 26(41): 8951-8957, 2020 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-32196786

RESUMEN

Chiral ß-aminoalkylzinc halides were prepared starting from optically pure commercial ß-amino-alcohols. These amino-alcohols were converted to the corresponding N-pyrrolyl-protected alkyl iodides which undergo a zinc insertion in the presence of LiCl (THF, 25 °C, 10-90 min). Subsequent Negishi cross-coupling or acylation reactions with acid chlorides produced amino-derivatives with retention of chirality. Diastereoselective CBS-reductions of some prepared N-pyrrolyl-ketones provided 1,3-subsituted N-pyrrolyl-alcohols with high diastereoselectivity. Additionally, a deprotection procedure involving an ozonolysis allowed the conversion of the pyrrole-ring into a formamide without loss of optical purity.

17.
Eur J Med Chem ; 186: 111851, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31761381

RESUMEN

Forty-eight analogues of CP-31398, an antitumor agent modulated the mutant p53 gene were synthesized and their cytotoxicities against four cancer cell lines with different p-53 status including bladder cell T24 (w-p53), gastric cell MGC-803 (m-p53), prostate cell DU145 (m-p53), prostate cell PC-3 (null-p53), lung cell A549 (w-p53) and normal liver cell line HL-7702 (w-p53) were examined. (E)-2-(4-Nitrostyryl)-4-(3-dimethylaminopropyl)-aminoquinazoline (10ah) was identified as the most potent compound in anti-proliferation against MGC-803 cells, with IC50 lowed to 1.73 µM, far potency than that of CP-31398. Molecular mechanism study revealed that 10ah and CP-31398 differ greatly in mechanism to exert their antitumor properties. 10ah could intercalate into DNA and resulted in significant DNA double-strand break. 10ah-treatment in MGC-803 cells increased the expression of p53, phosphorylated p53 (p-p53), CDK4, p21 to cause cell cycle arrest at G2/M phase, significantly up-regulated the levels of pro-apoptosis proteins Bak, Bax, Bim while down-regulated the anti-apoptosis proteins Bcl-2, Bcl-xL and the levels of cyclin B1, fluctuated the intracellular reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential, activated Caspase-9 and Caspase-3 to induce apoptosis. 10ah also displayed potent anticancer efficiency against MGC-803 xenograft tumors models, with tumor growth inhibition (TGI) up to 61.8% at 20 mg/kg without obvious toxicity.


Asunto(s)
Antineoplásicos/farmacología , Quinazolinas/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Apoptosis/efectos de los fármacos , Línea Celular , Proliferación Celular/efectos de los fármacos , División del ADN/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Estructura Molecular , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/metabolismo , Neoplasias Experimentales/patología , Quinazolinas/síntesis química , Quinazolinas/química , Relación Estructura-Actividad , Proteína p53 Supresora de Tumor/genética
18.
Haemophilia ; 25(5): 876-884, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31282066

RESUMEN

AIM: Low bone mineral density occurs more commonly in patients with haemophilia (PWH) than the general population. However, the risk of haemophilia-related osteoporotic fractures has not been well established. We aim to explore the relationship between haemophilia and the development of osteoporotic fractures following haemophilia. METHODS: This was a nationwide population-based cohort study based on the data in the Taiwan National Health Insurance Research Database (TNHIRD). Patients who were diagnosed with haemophilia were selected. A comparison cohort was formed of patients without haemophilia who were matched according to age and sex. The incidence rate and the hazard ratios (HRs) of new-onset osteoporotic fractures were calculated for both cohorts. RESULTS: The haemophilia cohort consisted of 75 patients, and the comparison cohort comprised 300 matched control patients without haemophilia. The risk of osteoporotic fractures was higher in the haemophilia cohort than in the comparison cohort (HR = 5.41, 95% confidence interval [CI] = 2.42-12.1, P < 0.001). After adjustments for age, sex, comorbidities, urbanizations and socio-economic status, PWH were 4.37 times more likely to develop osteoporotic fractures (95% CI = 1.88-10.17, P = 0.001) as compared to matched cohort. In addition, the incidence of newly diagnosed osteoporotic fractures was significantly increased after 5-year follow-up durations. CONCLUSION: Though our study by TNHIRD presented methodologic flaws by its design nature, we observed that haemophilia may increase the risk of osteoporotic fractures and the cumulative incidence was significantly higher for PWH diagnosed more than 5 years. Clinicians should pay particular attention to osteoporotic fractures following haemophilia in PWH as they age.


Asunto(s)
Hemofilia A/complicaciones , Fracturas Osteoporóticas/etiología , Anciano , Estudios de Cohortes , Femenino , Humanos , Masculino , Factores de Riesgo
19.
Int J Stroke ; 14(3): 306-309, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30777811

RESUMEN

BACKGROUND: Early neurological deterioration occurs in approximately 10% acute ischemic stroke patients after thrombolysis. Over half of the early neurological deterioration occurred without known causes and is called unexplained early neurological deterioration. AIMS: We aimed to explore the development of early neurological deterioration at 24 h after thrombolysis, and whether it could be predicted by the presence of baseline hypoperfusion in lenticulostriate arteries territory in acute ischemic stroke patients. METHODS: We retrospectively reviewed our prospectively collected database of acute ischemic stroke patients in the unilateral middle cerebral artery territory who had baseline perfusion image and received thrombolysis. Unexplained early neurological deterioration was defined as ≥ 2 points increase of National Institutes of Health Stroke Scale (NIHSS) from baseline to 24 h, without known causes. Hypoperfusion lesions in different territories were identified on perfusion maps. RESULTS: A total of 306 patients were included in analysis. Patients with pure lenticulostriate arteries hypoperfusion (defined as the presence of hypoperfusion in lenticulostriate artery territory, but not in middle cerebral artery terminal branch territory) were more likely to have unexplained early neurological deterioration than others (27.6% vs. 6.1%; OR, 5.974; p = 0.001), after adjusting for age, baseline NIHSS and onset to treatment time. CONCLUSIONS: Patients presenting hypoperfusion in pure lenticulostriate arteries territory were easier to experience unexplained early neurological deterioration.


Asunto(s)
Isquemia Encefálica/tratamiento farmacológico , Arterias Cerebrales/patología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Enfermedades del Sistema Nervioso/epidemiología , Accidente Cerebrovascular/tratamiento farmacológico , Terapia Trombolítica/efectos adversos , Administración Intravenosa , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/epidemiología , Arterias Cerebrales/efectos de los fármacos , China/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/etiología , Perfusión , Estudios Retrospectivos , Accidente Cerebrovascular/epidemiología
20.
Hong Kong Physiother J ; 39(2): 115-124, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31889762

RESUMEN

BACKGROUND: Many patients after acute stage of stroke are present with abnormal gait pattern due to weakness or hypertonicity of the affected limbs. Facilitation of normal gait is a primary goal of rehabilitation on these patients. OBJECTIVE: We aimed to investigate whether walking assist device with auxiliary illuminator (quad-cane with laser) providing visual feedback during ambulation could improve parameters of gait cycle immediately among patients with subacute and chronic stroke. METHODS: This was a cross-sectional study and 30 participants (male 23, female 7, group 1) with mean age 60 . 20 ± 11 . 12 years were recruited. Among them, 22 used ankle-foot orthosis [(AFO), group 2] and 8 did not use AFO (group 3) at usual walking. All the participants walked along a strait corridor with even surface for 20 m without and with using a quad-cane with laser, respectively. A gait analyzer (Reha-Watch1 system) was used to measure the changes of the parameters of gait cycle, including stride length, cadence, gait speed, stance phase, swing phase, duration of single support and double support, the angle between toes and the ground at the time of toe-off (the toe-off angle) and the angle between calcaneus and the ground at the time of heel-strike (the heel-strike angle), before and with the use of a quad-cane with laser. RESULTS: The increase in the heel-strike angle reached a significant difference in groups 1 2, and 3 ( p = 0 . 02 ,< 0 . 01 , and = 0 . 05 , respectively). However, the stride length, the gait speed, the cadence, percentage of the stance phase, swing phase, single-support phase, and double-support phase in a gait cycle, and the toe-off angle showed no significant change with the use of quad-cane with laser. CONCLUSION: Patients after acute stroke had an immediate and significant increase in the heel-stroke angle by using a quad-cane with laser during ambulation, which might help the patients to reduce knee hyperextension moment and lessen the pressure of heel at loading phase.

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