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1.
Eur J Pharm Sci ; 193: 106678, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38114052

RESUMEN

The advancement and practical use of small-molecule tyrosine kinase inhibitors (TKIs) that specifically target the BCR-ABL fusion protein have introduced a revolutionary era of precision medicine for the treatment of chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). This review offers a comprehensive exploration of the synthesis, mechanisms of action, and clinical implementation of clinically validated TKIs in the context of BCR-ABL, emphasizing the remarkable strides made in achieving therapeutic precision. We delve into the intricate design and synthesis of these small molecules, highlighting the synthetic strategies and modifications that have led to increased selectivity, enhanced binding affinities, and reduced off-target effects. Additionally, we discuss the structural biology of BCR-ABL inhibition and how it informs drug design. The success of these compounds in inhibiting aberrant kinase activity is a testament to the meticulous refinement of the synthetic process. Furthermore, this review provides a detailed analysis of the clinical applications of these TKIs, covering not only their efficacy in achieving deep molecular responses but also their impact on patient outcomes, safety profiles, and resistance mechanisms. We explore ongoing research efforts to overcome resistance and enhance the therapeutic potential of these agents. In conclusion, the synthesis and utilization of clinically validated small-molecule TKIs targeting BCR-ABL exemplify the transformative power of precision medicine in the treatment of hematological malignancies. This review highlights the evolving landscape of BCR-ABL inhibition and underscores the continuous commitment to refining and expanding the therapeutic repertoire for these devastating diseases.


Asunto(s)
Neoplasias Hematológicas , Humanos , Resistencia a Antineoplásicos , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas de Fusión bcr-abl/metabolismo , Neoplasias Hematológicas/tratamiento farmacológico
2.
Eur J Med Chem ; 261: 115847, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37801826

RESUMEN

Application of chemotherapeutic agents to inhibit the HIV replication process has brought about a significant metamorphosis in the landscape of AIDS. Substantial declines in morbidity and mortality rates have been attained, accompanied by notable decreases in healthcare resource utilization. However, treatment modalities do not uniformly inhibit HIV replication in every patient, while the emergence of drug-resistant viral strains poses a substantial obstacle to subsequent therapeutic interventions. Furthermore, chronic administration of therapy may lead to the manifestation of toxicities. These challenges necessitate the exploration of novel pharmacological agents and innovative therapeutic approaches aimed at effectively managing the persistent viral replication characteristic of chronic infection. This review examines the role of clinically approved small-molecule drugs in the treatment of HIV/AIDS, which provides an in-depth analysis of the major classes of small-molecule drugs, including nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors, entry inhibitors, and pharmacokinetic enhancers. The review mainly discusses the application, synthetic routes, and mechanisms of action of small-molecule drugs employed in the treatment of HIV, as well as their use in combination with antiretroviral therapy, presenting viewpoints on forthcoming avenues in the development of novel anti-HIV drugs.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Inhibidores de Fusión de VIH , Infecciones por VIH , Humanos , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/farmacología , Infecciones por VIH/tratamiento farmacológico
3.
J Laparoendosc Adv Surg Tech A ; 33(8): 738-742, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37074684

RESUMEN

Objective: This study aimed to investigate the feasibility, efficacy, and safety of laparoscopic transabdominal preperitoneal (TAPP) repair in the treatment of inguinal hernia in patients on peritoneal dialysis, and the optimal timing for initiating postoperative peritoneal dialysis. Methods: We conducted a retrospective analysis of the clinical data pertaining to patients on peritoneal dialysis with inguinal hernias treated with TAPP repair in the First Affiliated Hospital of Shandong First Medical University from July 15, 2020 to December 15, 2022. Follow-up observations of the treatment effect were also analyzed. Results: A total of 15 patients underwent TAPP repair with success. Contralateral occult hernias were found in 3 cases intraoperatively and were treated simultaneously. During the operation, it was found that the peritoneal dialysis tube was completely wrapped in the omentum majus in 1 case and incompletely wrapped in 5 cases and was separated smoothly under laparoscopy. Conclusion: For patients on peritoneal dialysis with inguinal hernia, TAPP repair has the advantages of less trauma, simultaneous treatment of contralateral occult hernias, adjustment and fixation of peritoneal dialysis tubes, lower incision complication rates, and lower recurrence rates, compared with open surgery. With the gradual resumption of peritoneal dialysis 7 days postoperatively, TAPP repair can be performed safely and effectively in this population group; thus it is a procedure worth promoting.


Asunto(s)
Hernia Inguinal , Laparoscopía , Diálisis Peritoneal , Humanos , Hernia Inguinal/cirugía , Hernia Inguinal/etiología , Estudios Retrospectivos , Herniorrafia/métodos , Laparoscopía/métodos , Mallas Quirúrgicas , Resultado del Tratamiento , Recurrencia
4.
Front Nutr ; 9: 960239, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35967806

RESUMEN

Numerous studies reported that betulinic acid (BA), a natural product extracted from birch bark, exhibited various beneficial effects in vitro. However, its pharmacological activities in aging are rarely understood. In this study, Caenorhabditis elegans was deployed as a whole animal model to investigate the impacts of BA on lifespan and stress resistance. Wild-type C. elegans were fed in the presence or absence of BA and tested for a series of phenotypes, including longevity, mobility, reproductive capacity, pharyngeal pumping, heat stress, and oxidative stress. BA at the optimal dose (50 µg/mL) extended the lifespan, improved the healthspan, and significantly evoked the increased oxidative stress resistance in C. elegans. Incorporating the genetic analysis with different types of longevity mutants, DAF-16, the downstream effector of the Insulin/IGF-1 receptor signaling, was revealed to mediate the protective effects of BA on lifespan and antioxidant activity. Together, these data showcased the potential of BA in promoting healthy aging, which shall facilitate its further development in the food and pharmaceutical industries.

5.
Artículo en Inglés | MEDLINE | ID: mdl-35954550

RESUMEN

The influence of national health level in the stability and sustainable development of national society is increasingly prominent. The purpose of this study is to examine whether, when, and how national fitness policies exert influence on national health. Panel data from 2008 to 2017 of 30 Chinese provinces (cities) (except the Tibet autonomous region) were used to systematically reveal the direct impact of national fitness policies on national health and its characteristics in different regions, as well as the interaction mechanisms of human capital and finance health expenditures in public sports. This study found that first, national fitness policies had a positive effect on adult health. Second, sports human capital weakens the health effect of national fitness policies, while public finance health expenditures strengthen this effect. Lastly, the health effect of national fitness policies varies significantly across regions due to uneven regional economic development, and the differences in the effects on different age groups (adults and children) are equally pronounced. This study suggests that national fitness public service system and diverse national fitness plans improving national health level are important for a new dynamic balance and high quality coordinated development in both Chinese economic growth and social welfare.


Asunto(s)
Desarrollo Económico , Desarrollo Sostenible , Adulto , Niño , China , Ejercicio Físico , Humanos , Bienestar Social
6.
Front Surg ; 9: 928743, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35983552

RESUMEN

Purpose: This study aimed to investigate the surgical treatment strategy of recurrent parastomal hernia (PH) and show its safety, feasibility, and outcomes at a mid-term follow-up. Methods: A total of 17 cases of recurrent PH treated at our hospital between January 2016 and October 2021 were included in this retrospective analysis. Patient characteristics were recorded, and the classification of PH, operative time, intraoperative blood loss, hernia repair techniques, follow-up times, complications, as well as recurrence were compared and analyzed. Results: Altogether, 17 patients with recurrent PH underwent successful hernia repair via surgical treatment at The First Affiliated Hospital of Shandong First Medical University and Shandong University Qilu Hospital. No recurrence or severe complications were noted during follow-ups (mean 32.8 ± 3.77 [range 3-68] months). Conclusions: For recurrent PH, selecting a suitable repair approach based on intraperitoneal conditions such as infection, abdominal adhesions, or the length of the bowel loop, can help in achieving better therapeutic results. The lap-redo + Sugarbaker technique is worth recommending when the appropriate conditions are met.

7.
World J Clin Cases ; 10(15): 4878-4885, 2022 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-35801023

RESUMEN

BACKGROUND: Familial gastrointestinal stromal tumors (GISTs) is a rare autosomal dominant disorder characterized by an array of clinical manifestations. Only 35 kindreds with germline KIT mutations and six with germline PDGFRA mutations have been reported so far. It is often characterized by a series of manifestations, such as multiple lesions and hyperpigmentation. However, the effect of imatinib treatment in these patients is still uncertain. CASE SUMMARY: Here, we report two patients (father and daughter) in a Chinese family (for the first time) with germline KIT mutation, and described their pathology, genetics and clinical manifestations. A 25-year-old Chinese woman went to hospital because of abdominal pain, and computed tomography showed multiple tumors in the small intestine. Small pigmented spots appeared on the skin within a few months after birth. Her father also had multiple pigmented spots and a history of multifocal GISTs. Multiple GISTs associated with diffuse interstitial Cajal cells (ICCs) hyperplasia were positive for CD117 and DOG-1. Gene sequencing revealed a germline mutation at codon 560 of exon 11 (p.V560G) of KIT gene in these two patients. Imatinib therapy showed the long-lasting disease stability after resection. Remarkably, the hypopigmentation of the skin could also be observed. Luckily germline KIT mutation has not been identified yet in the 3-year-old daughter of the female patient. CONCLUSION: Diagnosis of familial GISTs depends on combination of diffuse ICCs hyperplasia, germline KIT/PDGFRA mutation, hyperpigmentation and family history.

8.
Chinese Journal of Pediatrics ; (12): 413-420, 2022.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-935713

RESUMEN

Objective: To explore current vitamin D status and influential factors of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China. Methods: According to the "province-city-hospital" sampling technical route, a total of 1 531 healthy children under 7 years of age were sampled from 11 provinces, autonomous regions or municipalities in China by the cluster random sampling method from November 2020 to November 2021. The demographic information, family conditions, behavior and living habits and feeding behaviors were collected using unified questionnaire. Serum 25-hydroxyvitamin D(25(OH)D) levels were measured by liquid chromatography-tandem mass spectrometry. Serum 25(OH)D<30 nmol/L was considered deficient and 30-50 nmol/L was considered insufficient. With 25(OH)D≤50 nmol/L as the dependent variable, multivariate Logistic regression was applied to analyze the association between vitamin D deficiency and insufficiency and potential influential factors. Results: The prevalence of vitamin D deficiency and insufficiency among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China was 14.0% (215/1 531), 3.8% (25/664) and 21.9% (190/867) in 0-<3 and 3-<7 of age years, respectively. Compared to children aged 0-<3 years, children aged 3-<7 years had a 2.6-fold increased risk of vitamin D deficiency and insufficiency (OR=3.60, 95%CI 1.93-6.72, P<0.001). Frequent sunlight exposure (OR=0.46, 95%CI 0.29-0.73, P=0.001), vitamin D supplementation (sometimes, OR=0.33, 95%CI 0.21-0.51, P<0.001; daily, OR=0.20, 95%CI 0.11-0.36, P<0.001) and infant formula intake(4-7 times per weeks, OR=0.43, 95%CI 0.28-0.68, P<0.001) were protective factors for vitamin D deficiency and insufficiency. Conclusion: Vitamin D deficiency and insufficiency are common among children under 7 years of age in 11 provinces, autonomous regions or municipalities of China, which is affected by age, sunlight exposure, vitamin D supplementation and infant formula intake.


Asunto(s)
Niño , Humanos , Lactante , China/epidemiología , Estudios Transversales , Vitamina D , Deficiencia de Vitamina D/epidemiología , Vitaminas
9.
Front Surg ; 8: 706824, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34336921

RESUMEN

Background: We aimed to investigate the safety and effectiveness of laparoscopic repair for treating chronic traumatic diaphragmatic hernia (CTDH). Methods: In this retrospective analysis, we included 23 cases with CTDH underwent laparoscopy in our hospital between June 2015 and October 2019 was performed. The patient characteristics were recorded. We compared the diameter of hernia ring, surgery duration, intraoperative bleeding volume, means of repairing, as well as the follow-up data. Results: All the patients underwent laparoscopic diaphragmatic hernia repair, without conversion to laparotomy or thoracotomy. The operation time ranged from 60 min to 200 min (mean, 108.04 ± 42.93 min). The blood loss volume ranged from 10 to 300 ml (mean volume, 63.48 ± 71.69 ml). The postoperative hospital stayed ranged from 5 to 15 days (mean, 6.22 ± 2.11 days). The patients were followed up for 1-50 months (mean, 17.5 ± 10.90 months). No recurrence of diaphragmatic hernia was found. Conclusions: Laparoscopic repair of CTDH is featured by fast recovery, high security, and effectiveness. Reducing the hernia contents and close of the hernia ring are crucial for the surgery that is performed based on the size and location of the diaphragmatic hernia.

10.
Zookeys ; 977: 101-161, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33177944

RESUMEN

Multiple disciplines can help to discover cryptic species and resolve taxonomic confusions. The Asian horned toad genus Megophrys sensu lato as a diverse group was proposed to contain dozens of cryptic species. Based on molecular phylogenetics, morphology, osteology, and bioacoustics data, the species profiles of Megophrys toads in the eastern corner of Himalayas in Medog County, Tibet Autonomous Region, China was investigated. The results indicated that this small area harbored at least four Megophrys species, i.e., M. medogensis, M. pachyproctus, Megophrys zhoui sp. nov., and Megophrys yeae sp. nov., the latter two being described in this study. Additionally, the mitochondrial DNA trees nested the low-middle-elevation and high-elevation groups of M. medogensis into a monophyletic group, being in discordance with the paraphyletic relationship between them revealed in the nuclear DNA trees. The findings highlighted the underestimated biodiversity in Himalayas, and further indicated that the Megophrys toads here have been probably experienced complicated evolutionary history, for example, introgression between clades or incomplete lineage sorting and niche divergences in microhabitats. Anyway, it is urgent for us to explore the problems because these toads are suffering from increasing threats from human activities and climatic changes.

11.
Nitric Oxide ; 85: 1-9, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30659917

RESUMEN

Increasing evidence has demonstrated that dexmedetomidine (DEX) possesses multiple pharmacological actions. Herein, we explored the protective effect and potential molecular mechanism of DEX on lipopolysaccharide (LPS)-induced early acute kidney injury (AKI) from the perspective of antioxidant stress. We found that DEX (30 µg/kg, i.p.) ameliorated the renal dysfunction and histopathological damage (tubular necrosis, vacuolar degeneration, infiltration of inflammatory cells and cast formation) induced by LPS (10 mg/kg). DEX also attenuated renal oxidative stress remarkably in LPS-induced early AKI, as evidenced by reduction in production of reactive nitrogen species, decreasing malondialdehyde levels, as well as increasing superoxide dismutase activity and glutathione content. DEX prevented activator protein-1 translocation, inhibited phosphorylation of I-kappa B (IκB) and activation of nuclear factor kappa B (NF-κB) in LPS-induced early AKI, as assessed by real-time quantitative polymerase chain reaction and protein levels of c-Jun, c-Fos, IκB and NF-κB. Notably, DEX pretreatment had the same effect as intraperitoneal injection of an inhibitor of inducible nitric oxide synthase inhibitor (1400W; 15 mg/kg), and inhibited the activity of renal inducible nitric oxide synthase (iNOS) and decreased the expression of iNOS mRNA and NO production. However, the protective effect of DEX on LPS-induced early AKI was reversed by the alpha 2 adrenal receptor (α2-AR) inhibitor atipamezole, whereas the imidazoline receptor inhibitor idazoxan did not. Taken together, DEX protects against LPS-induced early AKI in rats by inhibiting the iNOS/NO signaling pathway, mainly by acting on α2-ARs instead of IRs.


Asunto(s)
Lesión Renal Aguda/prevención & control , Agonistas de Receptores Adrenérgicos alfa 2/farmacología , Dexmedetomidina/farmacología , Lipopolisacáridos/farmacología , Óxido Nítrico Sintasa de Tipo II/antagonistas & inhibidores , Óxido Nítrico/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Agonistas de Receptores Adrenérgicos alfa 2/química , Animales , Dexmedetomidina/química , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Sprague-Dawley
12.
Case Rep Gastrointest Med ; 2018: 3954260, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30425863

RESUMEN

Gastric cancer is a malignant tumor with a high degree of malignancy. Multiple liver metastases from gastric cancer (LMGCs) are common. However, the treatment of LMGCs is very difficult. It is rare to achieve complete remission (CR) and long-term survival after treatment. We present the case of a patient with gastric adenocarcinoma and multiple liver metastases who showed CR for more than 33 months after perioperative EOX (epirubicin, oxaliplatin, and capecitabine) combination chemotherapy with radical distal gastrectomy and resection of liver metastases. The patient is still in follow-up without tumor recurrence. These findings suggest that LMGC does not necessarily mean a poor prognosis; preoperative chemotherapy combined with surgery may be a good treatment option for LMGC in selected patients. Further studies are needed to support this treatment approach.

13.
Am J Obstet Gynecol ; 218(2): 249.e1-249.e12, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-29155142

RESUMEN

OBJECTIVE: Preeclampsia (PE) affects many women globally and remains a primary cause of neonatal and maternal morbidity and mortality. Aberrant placental microRNA (miRNA) expression might be associated with PE. Previously, 33 PE-related miRNAs, 11 up-regulated and 23 down-regulated, were detected in placentas of women with severe PE when compared with those of normal patients. One of the most up-regulated miRNAs in PE is miR-30a-3p. The predicted target of it is insulin-like growth factor 1 (IGF-1), which has been reported to have a relatively low expression level in PE patients. This study was conducted to determine the aberrant increased of miR-30a-3p in the placentas of women with preeclampsia and to elucidate the target and function of it in trophoblast cells. STUDY DESIGN: miR-30a-3p expression in placenta tissues was compared between women with preeclampsia (n = 25) and normal pregnant women (n = 20). The miRNA target was studied by in silico and functional assay. The effects of the miRNA were verified by apoptosis assay and invasion assay in the trophoblast cell line. RESULTS: miR-30a-3p was increased significantly in the placenta of women with preeclampsia when compared to those with normal pregnancies. Luciferase assay confirmed direct regulation of miR-30a-3p on the expression of IGF-1. Forced expression of miR-30a-3p suppressed IGF-1 protein expression in the HTR-8/SVneo cells. The functional assay suggests that the over-expression of miR-30a-3p alter the invasive capacity of JEG-3 cells and induce the apoptosis of HTR-8/SVneo cells (Figure). CONCLUSION: Expression of miR-30a-3p was significantly increased in the placentas of patients with preeclampsia. miR-30a-3p might be involved in the pathogenesis of preeclampsia by targeting IGF-1 and regulating the invasion and apoptosis of trophoblast cells.


Asunto(s)
Regulación del Desarrollo de la Expresión Génica , Factor I del Crecimiento Similar a la Insulina/metabolismo , MicroARNs/metabolismo , Placenta/metabolismo , Preeclampsia/genética , Trofoblastos/fisiología , Adulto , Apoptosis/genética , Biomarcadores/metabolismo , Western Blotting , Estudios de Casos y Controles , Células Cultivadas , Epigénesis Genética , Femenino , Humanos , Preeclampsia/metabolismo , Embarazo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba
14.
BMC Anesthesiol ; 17(1): 123, 2017 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-28870150

RESUMEN

BACKGROUND: Isoflurane-induced neuroapoptosis and cognitive impairment has been previously reported. Hydrogen sulfide (H2S) has been shown to be a neuromodulator that is thought to have anti-apoptotic, anti-inflammatory, and anti-oxidative benefits. However, it is not known if H2S is protective against anesthesia-induced apoptosis and cognitive defects. METHODS: In this study, postnatal day 7 (P7) Sprague-Dawley rats were randomly divided into four groups: control group (normal saline), H2S group (NaHS 28 µM/kg), isoflurane group (normal saline +0.75% isoflurane) and H2S preconditioning group (NaHS 28 µM/kg + 0.75% isoflurane). After exposure to isoflurane for 6 h, half the numbers of rats in each group were euthanized, and the hippocampus and cerebral cortex were dissected and examined for apoptosis by the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) technique and western blot. After 6 weeks, the remaining rats were subjected to a Morris water maze (MWM) test for behavioral assessment. RESULTS: The TUNEL assay and western blot showed that when rats were preconditioned with NaHS, neuroapoptosis decreased significantly both in hippocampus and cerebral cortex compering with the isofulrane group. The MWM showed that P7 rats administration of NaHS improved cognitive impairments induced by isoflurane. CONCLUSIONS: The current study demonstrates that H2S attenuates isoflurane-induced neuroapoptosis and improves cognitive impairments in the developing rat brain.


Asunto(s)
Apoptosis/efectos de los fármacos , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/prevención & control , Sulfuro de Hidrógeno/administración & dosificación , Isoflurano/toxicidad , Neuronas/efectos de los fármacos , Administración por Inhalación , Anestésicos por Inhalación/toxicidad , Animales , Animales Recién Nacidos , Apoptosis/fisiología , Disfunción Cognitiva/patología , Femenino , Masculino , Neuronas/patología , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
15.
PLoS One ; 12(4): e0175654, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28403230

RESUMEN

Isoflurane anesthesia has been shown to be responsible for cognitive impairment in Alzheimer's disease (AD) and development of AD in the older age groups. However, the pathogenesis of AD-related cognitive impairments induced by isoflurane anesthesia remains elusive. Thus, this study was designed to investigate the mechanism by which isoflurane anesthesia caused AD-related cognitive impairments. Aged Wistar rats were randomly divided into 6 groups (n = 12), 1 control group (CONT) and 5 isoflurane treated (ISO) groups (ISO 0, ISO 0.5D, ISO 1D, ISO 3D and ISO 7D). The CONT group inhaled 30% O2 for 2 h without any anesthesia. ISO groups were placed under anesthesia with 3% isoflurane and then exposed to 1.5% isoflurane delivered in 30% O2 for 2 h. Rats in each ISO group were then analyzed immediately (ISO 0) or at various time points (0.5, 1, 3 or 7 day) after this exposure. Cognitive function was assessed using the Morris water maze test. Protein levels of amyloid precursor protein (APP), ß-site APP cleavage enzyme-1 (BACE-1) and Aß42 peptide were analyzed in hippocampal samples by Western blot. ß-Amyloid (Abeta) plaques were detected in hippocampal sections by Congo red staining. Compared with controls, all ISO groups showed increased escape latency and impaired spatial memory. Isoflurane increased APP mRNA expression and APP protein depletion, promoting Aß42 overproduction, oligomerization and accumulation. However, isoflurane did not affect BACE-1 expression. Abeta plaques were observed only in those ISO groups sacrificed at 3 or 7 d. Our data indicate that aged rats exposed to isoflurane had increased APP mRNA expression and APP protein depletion, with Aß42 peptide overproduction and oligomerization, resulting in formation of Abeta plaques in the hippocampus. Such effects might have contributed to cognitive impairments, including in spatial memory, observed in these rats after isoflurane anesthesia.


Asunto(s)
Péptidos beta-Amiloides/metabolismo , Anestésicos por Inhalación/toxicidad , Disfunción Cognitiva/inducido químicamente , Hipocampo/metabolismo , Isoflurano/toxicidad , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Péptidos beta-Amiloides/genética , Anestesia por Inhalación/efectos adversos , Animales , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismo , Disfunción Cognitiva/metabolismo , Hipocampo/efectos de los fármacos , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Ratas Wistar , Memoria Espacial/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos
16.
Vet Anaesth Analg ; 44(1): 114-120, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27352003

RESUMEN

OBJECTIVE: To evaluate the behavior and some cardiopulmonary variables of dexmedetomidine-midazolam or dexmedetomidine-midazolam-butor-phanol in the silver fox (Vulpes vulpes). STUDY DESIGN: Blinded, randomized design. ANIMALS: Sixteen adult silver foxes, aged 7-9 months, weighting 6.0-9.2 kg. METHODS: Animals were randomly assigned to dexmedetomidine (50 µg kg-1) and midazolam (0.45 mg kg-1) (group DM) or to dexmedetomidine (30 µg kg-1), midazolam (0.45 mg kg-1) and butorphanol (0.25 mg kg-1) (group DMB), administered intramuscularly. Pulse rate (PR), respiratory rate (fR), noninvasive arterial pressures, oxygen saturation (SpO2), rectal temperature (T) and behavioral scores (posture, sedation, antinociception, jaw relaxation and auditory response) were measured at 5, 10, 20, 30, 40, 50 and 60 minutes after injection. Time from drug injection to recumbency with no response to stimuli (IT) and time from administration of atipamezole (0.2 mg kg-1) to standing with coordination (RT) were recorded. The occurrences of adverse events were recorded. Data were analyzed by two-tailed unpaired t-tests and Bonferroni post hoc tests. Significant differences were accepted at p<0.05. RESULTS: There were no statistically significant differences between the groups for IT or RT. Arterial pressures were higher in DMB at each time point except at 5 minutes. PR was lower in DM at each time point except at 10 and 60 minutes. No significant difference was found between the groups for fR, SpO2 and T. The behavioral scores were significantly lower (lower quality immobilization) in DMB at 5,10 and 60 minutes. CONCLUSIONS AND CLINICAL RELEVANCE: IT and RT were not different between the groups. Both protocols provided immobilization for 30-40 minutes with excellent muscle relaxation and analgesia adequate for clinical examinations and some simple surgical procedures.


Asunto(s)
Anestésicos Combinados/farmacología , Conducta Animal/efectos de los fármacos , Butorfanol/farmacología , Dexmedetomidina/farmacología , Zorros , Hipnóticos y Sedantes/farmacología , Midazolam/farmacología , Anestésicos Combinados/administración & dosificación , Animales , Presión Arterial/efectos de los fármacos , Temperatura Corporal/efectos de los fármacos , Butorfanol/administración & dosificación , Dexmedetomidina/administración & dosificación , Combinación de Medicamentos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hipnóticos y Sedantes/administración & dosificación , Masculino , Midazolam/administración & dosificación , Relajación Muscular/efectos de los fármacos , Oxígeno/sangre , Recto/fisiología , Frecuencia Respiratoria/efectos de los fármacos , Factores de Tiempo
17.
Chinese Journal of Urology ; (12): 848-851, 2017.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-668997

RESUMEN

Objective To compare the MRP8/14 level in Normal people,benign prostatic hyperplasia(BPH) patient and prostate cancer patient,and explore the relationgship between MRP8/14 and prostate cancer.Methods 150 cases of normal people,150 cases of BPH patients and 150 cases of prostate cancer patients were chose from December 2012 to December 2014 in our hospital.ELISA method was used to detect the MRP8/14 level in each group.ROC cure was used to analyse the prediction value of MRP8/14 for prostate cancer.According to the cut off value of MRP8/14,prostate cancer patients were divided into MRP8/14 low value group (MRP8/14 < cut off value) and MRP8/14 high value group (MRP8/14 ≥cut off value),and the difference of patient's clinical characteristics and survival function between high value group and low value group were explored.Results The MRP8/14 level of normal people was (966.7 ± 152.8) ng/ml,while the BPH patient was (1 207.0 ± 190.6) ng/ml,and the prostate cancer patient was (2 833.3 ± 1 101.5) ng/ml,the difference is statistically significant.ROC analysis result showed that the AUC for the prediction of prostate cancer was O.887 (95% CI 0.841-0.934),with a high statistical significance,indicating that MRP8/14 may possess high prediction value for prostate cancer.In addition,the cut off value was 2 845.682 ng/ml,with the specifity of 76.4% and sensitivity of 85.1%.According to the cut off value of MRP8/14,prostate cancer patients were divided into the low MRP8/14 group (< 2 845.682 ng/ml) and the high MRP8/14 group (≥2 845.682 ng/ml).Among the 150 prostate cancer patients,88 cases were in the low MRP8/14 group and 62 cases were in the high MRP8/14 group.Comparations of the baseline characteristics of the two groups showed that amount of patients belong to ECOG PS =1,Gleason score =8-10,organ involvement > 2 and tumour stage > Ⅲ were much more in MRP8/14 high value group.PSA level,LDH level,AKP level,CRP level and Alkaline Phosphatase level were also significantly increased in MRP8/14 high value group.Besides,prostate cancer patient with an average follow-up of 2 years,a total of 32 cases of patients died,12 cases in the MRP8/14 low value group with mortality of 13.6%,20 cases in MRP8/14 high value group with mortality of 32.3%.Kaplan Meier survival function curve shows 2 years survival rate of patients in high value group was significantly reduced.Cox regression analysis showed that MRP8/14 was possible risk factors associated with mortality,and the independent predictors for all-cause mortality during follow-up.Conclusion MRP8/14 was significantly increased in prostate cancer patients,and it was an independent predictor of 2-year mortality in prostate cancer patients.

18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-662068

RESUMEN

Objective To investigate the diagnostic performance of acoustic radiation force impulse (ARFI) imaging in assessing liver cirrhosis preoperatively in infants with biliary atresia (BA).Methods A total of 64 consecutive infants with BA who underwent ARFI imaging in 3 days before Kasai surgery were recruited.Virtual Touch Quantification mode was used to measure shear wave speed (SWS),All infants with BA underwent liver biopsy during the surgery.The mean SWS of infants with and without liver cirrhosis were compared and analyzed.The diagnostic efficacy of SWS was observed using ROC curves.Results Liver cirrhosis was found in 8 of 64 infants.The mean SWS in infants with cirrhosis was significant-ly higher than that in infants without cirrhosis ([2.51±0.50]m/s vs [1.74±0.31]m/s,t=6.039,P<0.001).The cutoff value of SWS for predicting liver cirrhosis was 2.16 m/s,the area under ROC curve was 0.930 (P<0.001),and the diagnostc sensitivity and specificity was 87.50% and 92.86%,respectively.Conclusion ARFI imaging is helpful to predic tion of liver cirrhosis in infants with BA preoperatively.It may be an effective method for clinical management and prognosis prediction in infants with BA.

19.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-659314

RESUMEN

Objective To investigate the diagnostic performance of acoustic radiation force impulse (ARFI) imaging in assessing liver cirrhosis preoperatively in infants with biliary atresia (BA).Methods A total of 64 consecutive infants with BA who underwent ARFI imaging in 3 days before Kasai surgery were recruited.Virtual Touch Quantification mode was used to measure shear wave speed (SWS),All infants with BA underwent liver biopsy during the surgery.The mean SWS of infants with and without liver cirrhosis were compared and analyzed.The diagnostic efficacy of SWS was observed using ROC curves.Results Liver cirrhosis was found in 8 of 64 infants.The mean SWS in infants with cirrhosis was significant-ly higher than that in infants without cirrhosis ([2.51±0.50]m/s vs [1.74±0.31]m/s,t=6.039,P<0.001).The cutoff value of SWS for predicting liver cirrhosis was 2.16 m/s,the area under ROC curve was 0.930 (P<0.001),and the diagnostc sensitivity and specificity was 87.50% and 92.86%,respectively.Conclusion ARFI imaging is helpful to predic tion of liver cirrhosis in infants with BA preoperatively.It may be an effective method for clinical management and prognosis prediction in infants with BA.

20.
Ying Yong Sheng Tai Xue Bao ; 27(2): 532-8, 2016 Feb.
Artículo en Chino | MEDLINE | ID: mdl-27396128

RESUMEN

Along the 368-591 mm precipitation gradient, 7 survey sites, i.e. a total 63 investigated plots were selected. At each sites, woodland, grassland, and cropland with similar restoration age were selected to investigate soil organic carbon distribution in surface soil (0-30 cm), and the influence of factors, e.g. climate, soil depth, and land uses, on soil organic carbon distribution were analyzed. The result showed that, along the precipitation gradient, the grassland (8.70 g . kg-1) > woodland (7.88 g . kg-1) > farmland (7.73 g . kg-1) in concentration and the grassland (20.28 kg . m-2) > farmland (19.34 kg . m-2) > woodland (17.14 kg . m-2) in density. The differences of soil organic carbon concentration of three land uses were not significant. Further analysis of pooled data of three land uses showed that the surface soil organic carbon concentration differed significantly at different precipitation levels (P<0.00 1). Significant positive relationship was detected between mean annual precipitation and soil organic carbon concentration (r=0.838, P<0.001) in the of pooled data. From south to north (start from northernmost Ordos), i.e. along the 368-591 mm precipitation gradient, the soil organic carbon increased with annual precipitation 0. 04 g . kg-1 . mm-1, density 0.08 kg . m-2 . mm-1. The soil organic carbon distribution was predicted with mean annual precipitation, soil clay content, plant litter in woodland, and root density in farmland.


Asunto(s)
Carbono/análisis , Bosques , Pradera , Suelo/química , Silicatos de Aluminio , Arcilla , Clima , Raíces de Plantas/crecimiento & desarrollo
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