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31.
Michael D. Weber Daniel B. McKim Anzela Niraula Kristina G. Witcher Wenyuan Yin Carly G. Sobol Yufen Wang Caroline M. Sawicki John F. Sheridan Jonathan P. Godbout 《Neuropsychopharmacology》2019,85(8):667-678
Background
Stress is associated with an increased prevalence of anxiety and depression. Repeated social defeat (RSD) stress in mice increases the release of monocytes from the bone marrow that are recruited to the brain by microglia. These monocytes enhance inflammatory signaling and augment anxiety. Moreover, RSD promotes stress sensitization, in which exposure to acute stress 24 days after cessation of RSD causes anxiety recurrence. The purpose of this study was to determine whether microglia were critical to stress sensitization and exhibited increased reactivity to subsequent acute stress or immune challenge.Methods
Mice were exposed to RSD, microglia were eliminated by colony-stimulating factor 1 receptor antagonism (PLX5622) and allowed to repopulate, and responses to acute stress or immune challenge (lipopolysaccharide) were determined 24 days after RSD sensitization.Results
Microglia maintained a unique messenger RNA signature 24 days after RSD. Moreover, elimination of RSD-sensitized microglia prevented monocyte accumulation in the brain and blocked anxiety recurrence following acute stress (24 days). When microglia were eliminated prior to RSD and repopulated and mice were subjected to acute stress, there was monocyte accumulation in the brain and anxiety in RSD-sensitized mice. These responses were unaffected by microglial elimination/repopulation. This may be related to neuronal sensitization that persisted 24 days after RSD. Following immune challenge, there was robust microglial reactivity in RSD-sensitized mice associated with prolonged sickness behavior. Here, microglial elimination/repopulation prevented the amplified immune reactivity ex vivo and in vivo in RSD-sensitized mice.Conclusions
Microglia and neurons remain sensitized weeks after RSD, and only the immune reactivity component of RSD-sensitized microglia was prevented by elimination/repopulation. 相似文献32.
S R Niraula D B Chhetry G K Singh S Nagesh P M Shyangwa 《Kathmandu University Medical Journal》2006,4(4):448-454
Objectives: This paper focuses to describe the role and activities of Drug Rehabilitation Centres (DRCs) in reducing the drug-abuse problem in Dharan. It also offers suggestions for increasing the effectiveness of prevention programs. Materials and methods: Records of three DRCs working in Dharan for the past 9 years were analyzed using appropriate statistical tools. Results: The yearly clean rate is significantly higher in these centres. Harm reduction program was currently available only in one centre. Pharmacotherapy along with short-term rehabilitation was available at de-addiction unit of B. P. Koirala Institute of Health Sciences whereas long-term rehabilitation was at others centres. Conclusion: Thus, there should be a strong coordination and network with each other to increase the effectiveness of the treatment program for drug abuse. The treatment centres should be increased in number as well as in quality. BPKIHS should take initiation to start long-term management with repeated booster programs. Key words: Role, rehabilitation, drug abuse, BPKIHS, Dharan, Nepal. 相似文献
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S Niraula RJ Dowling M Ennis MC Chang SJ Done N Hood J Escallon WL Leong DR McCready M Reedijk V Stambolic PJ Goodwin 《Breast cancer research and treatment》2012,133(3):821-830
Taxanes are a standard first-line option for metastatic breast cancer (MBC), but their utility may be limited by primary or acquired resistance. New microtubule-targeting agents have been developed to overcome taxane resistance and provide additional options for improving patient outcomes. This article reviews these alternative microtubule-targeting agents and their potential clinical benefits for MBC patients. Relevant clinical data were compiled through searches within PubMed and congress abstract databases. Ixabepilone, a novel microtubule-stabilizing drug approved by the US Food and Drug Administration (FDA), has proven efficacy across multiple lines of therapy, including patients with taxane-resistant/refractory disease. In phase III trials, ixabepilone plus capecitabine significantly improved progression-free survival compared with capecitabine alone in anthracycline/taxane-pretreated patients. Eribulin has recently been approved by the FDA and by the European Medicines Agency for the treatment of patients with MBC who have received at least two prior chemotherapy regimens for late-stage disease. In a phase III trial, eribulin extended overall survival compared with the physician's treatment choice in heavily pretreated MBC patients. In addition, several investigational microtubule-targeting agents may have therapeutic potential in MBC. The development of new microtubule-targeting agents helps to address the need for additional effective regimens for patients progressing after standard treatment with anthracycline- and taxane-containing regimens. 相似文献
35.
N Jha S Kumar B K Yadav G C P Singh S R Niraula 《Kathmandu University Medical Journal》2006,4(1):44-47
BACKGROUND: It is important to know the impact of health education on community. This may lead to improve the programs, commitment to students and staffs by taking feedback. These activities are aimed at producing changes in the community. OBJECTIVE: To assess the impact of health education as intervention program during Family Health Exercise (FHE) about the knowledge and practice of people related to health in a village of eastern Nepal. METHODS: During FHE, health education was given by the 3rd year medical students to the head of the 30 families. The neighbour 30 families were taken as control, where no health education was given. These two groups were compared after 6 months. RESULTS: Sanitary practice (Hand washing) before meal was known to both groups. But the material used for washing hand (soap and ash) was 53% in intervention as compared to 30% in control group. People were aware about the importance of care of the mother during pregnancy and lactation, but more in intervention group. The knowledge and practice for starting semisolid food other than breast milk for infants during weaning were higher in intervention (89%) than control (31%) group. CONCLUSION: There was significant change in the knowledge and practice of woman (mainly host) who received health education. The community also benefited in terms of their health knowledge and practices. Such programs are useful for the community at large. 相似文献