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1.
Behav Brain Res ; 471: 115122, 2024 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-38942086

RESUMO

Stressful life event is closely associated with depression, thus strategies that blunt or prevent the negative effect stress on the brain might benefits for the treatment of depression. Although previous study showed the role of protein kinase R (PKR)-like ER kinase (PERK) in inflammation related depression, its involvement in the neuropathology of chronic stress induced depression is still unknown. We tried to explore whether block the PERK pathway would alleviate the animals' depression-like behavior induced by chronic restraint stress (CRS) and investigate the underlying mechanism. The CRS-exposed mice exhibited depression-like behavior, including anhedonia in the sucrose preference test (SPT), and increased immobility time in tail suspension test (TST) and forced swim test (FST). ISRIB administration for 2 weeks significantly improved the depression-like behavior in male mice exposed to CRS, which was manifested by markedly increasing the sucrose preference and reducing the immobility time in the FST and TST. However, we observed that exposure to the same dose of ISRIB in CRS female mice only showed improved anhedonia-like deficits,leaving unaltered improvement in the FST and TST. Mechanically, we found that ISRIB reversed the hypothalamic-pituitary-adrenal (HPA) axis hyperactivity, indicating decreased levels of serum corticosterone, reduced hippocampal glucocorticoidreceptor (GR) expression and expression of FosB in hypothalamic paraventricularnucleus (PVN), which was accompanied by preserved hippocampal neurogenesis. The present findings further expand the potential role of ER stress in depression and provide important details for a therapeutic path forward for PERK inhibitors in mood disorders.


Assuntos
Anedonia , Depressão , Sistema Hipotálamo-Hipofisário , Sistema Hipófise-Suprarrenal , Restrição Física , Estresse Psicológico , Animais , Masculino , Depressão/etiologia , Depressão/tratamento farmacológico , Depressão/metabolismo , Estresse Psicológico/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Camundongos , Sistema Hipófise-Suprarrenal/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Anedonia/efeitos dos fármacos , Anedonia/fisiologia , Feminino , eIF-2 Quinase/metabolismo , eIF-2 Quinase/antagonistas & inibidores , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Pirimidinas/farmacologia , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Corticosterona/sangue , Aminoacetonitrila/análogos & derivados , Aminoacetonitrila/farmacologia , Antidepressivos/farmacologia
2.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-803585

RESUMO

Objective@#To explore the nursing experience of growth hormone provocative test in pediatric clinic.@*Methods@#Five thousand and thirty-six children with short stature or slowing growth received combined simultaneous Levodopa Pyridostigmine stimulation test from June 2008 to October 2018 in the Child Growth Center of the First Affiliated Hospital of SUN Yat-sen University. Comprehensive nursing intervention was conducted to ensure the test carry through successfully before, during and after the test.@*Results@#All children completed the five collections in the 120-minute growth hormone provocative test without cannula obstruction and blurt out. Some (986 out of 5 036 children, 19.58%) had different degrees of adverse reactions including nausea, vomiting, abdominal pain, sweating, salivation, dizziness, pallor, etc., most of which disappeared or alleviated after nursing, except 11 patients (0.22%) needed atropine muscular injection and 3 of whom needed intravenous fluids to release the marked symptoms.@*Conclusion@#Combined simultaneous Levodopa Pyridostigmine stimulation test is safe and practicable in pediatric clinics with nursing experience.

3.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-823761

RESUMO

Objective To explore the nursing experience of growth hormone provocative test in pediatric clinic. Methods Five thousand and thirty-six children with short stature or slowing growth received combined simultaneous Levodopa Pyridostigmine stimulation test from June 2008 to October 2018 in the Child Growth Center of the First Affiliated Hospital of SUN Yat- sen University. Comprehensive nursing intervention was conducted to ensure the test carry through successfully before, during and after the test. Results All children completed the five collections in the 120-minute growth hormone provocative test without cannula obstruction and blurt out. Some (986 out of 5 036 children, 19.58% ) had different degrees of adverse reactions including nausea,vomiting,abdominal pain, sweating,salivation,dizziness,pallor,etc.,most of which disappeared or alleviated after nursing, except 11 patients (0.22%) needed atropine muscular injection and 3 of whom needed intravenous fluids to release the marked symptoms. Conclusion Combined simultaneous Levodopa Pyridostigmine stimulation test is safe and practicable in pediatric clinics with nursing experience.

4.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-669841

RESUMO

To improve the effect of teaching practice of blood cell morphology,typical cases of peripheral blood erythrocyte,granulocyte and platelet were chosen,case show and problem-based teaching way were applied to encourage students to find information of autonomous learning.Then teacher organized the class discussion,and the information was analyzed and summarized.In the implementation of the case teaching,we should pay attention to improving students' learning initiative.At the same time,teachers need to have knowledge,comprehensive ability and ability in organization and leadership,to promote students' active participation in discussion in the teaching,pay attention to the information feedback,and improve the teaching details

5.
Protein & Cell ; (12): 631-642, 2014.
Artigo em Inglês | WPRIM (Pacífico Ocidental) | ID: wpr-757476

RESUMO

A major barrier to the use of antimicrobial peptides as antibiotics is the toxicity or ability to lyse eukaryotic cells. In this study, a 26-residue amphipathic α-helical antimicrobial peptide A12L/A20L (Ac-KWKSFLKTFKSLKKTVLHTLLKAISS-amide) was used as the framework to design a series of D- and L-diastereomeric peptides and study the relationships of helicity and biological activities of α-helical antimicrobial peptides. Peptide helicity was measured by circular dichroism spectroscopy and demonstrated to correlate with the hydrophobicity of peptides and the numbers of D-amino acid substitutions. Therapeutic index was used to evaluate the selectivity of peptides against prokaryotic cells. By introducing D-amino acids to replace the original L-amino acids on the non-polar face or the polar face of the helix, the hemolytic activity of peptide analogs have been significantly reduced. Compared to the parent peptide, the therapeutic indices were improved of 44-fold and 22-fold against Gram-negative and Gram-positive bacteria, respectively. In addition, D- and L-diastereomeric peptides exhibited lower interaction with zwitterionic eukaryotic membrane and showed the significant membrane damaging effect to bacterial cells. Helicity was proved to play a crucial role on peptide specificity and biological activities. By simply replacing the hydrophobic or the hydrophilic amino acid residues on the non-polar or the polar face of these amphipathic derivatives of the parent peptide with D-amino acids, we demonstrated that this method could have excellent potential for the rational design of antimicrobial peptides with enhanced specificity.


Assuntos
Humanos , Anti-Infecciosos , Química , Farmacologia , Dicroísmo Circular , Desenho de Fármacos , Eritrócitos , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Hemólise , Fragmentos de Peptídeos , Química , Farmacologia , Estrutura Secundária de Proteína , Relação Estrutura-Atividade , Especificidade por Substrato
6.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-529002

RESUMO

OBJECTIVE To investigate the radiological findings of labyrinthitis and evaluate the diagnosis value of HRCT and MRI. METHODS The HRCT and MR images of 27 cases ( 31 ears) with labyrinthitis,suggested by clinical examinations and abnormal changes on images coexisting,were studied. RESULTS In the 22 ears which underwent HRCT examinations,6 ears showed increase of the density of one or more structures of inner ear,8 ears showed increase of the density of structure as well as change of the shape of the inner ear,1 ear showed change of the shape only. Labyrinth inner cavity appeared local or total sclerosis and disappearance in 7 ears. Among the 22 ears,there was bony incompleteness in 4 besides the changes mentioned above. In the 9 ears which accepted HRCT and MR scanning,7 ears showed abnormal changes of different degree in the inner ear on HRCT images and the other 2 appeared normal. On MR images,all 9 ears showed decrease or disappearance of the signal of T2WI in one or more structures of membranous labyrinth. Among the 6 ears which performed contrast scanning,markedly enhancement was seen in 4 and no enhancement in 2 ears. Of all the 31 ears,cochlea was involved in 30,of which only basal turn involved in 5,upper and second turns in 2 and all turns in 23,semicircular canal involved in 26,vestibule in 20,oval window in 18 and round window in 19. CONCLUSION HRCT can demonstrate the abnormal changes of bony labyrinth,and MRI is helpful to detect the changes of labyrinth inner cavity. They have important value in the detection and diagnosis of labyrinthitis.

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