ABSTRACT
Antidepressants, while effective in treating depression and anxiety disorders, also induce deficits in sensory (particularly auditory) processing, which in turn may exacerbate psychiatric symptoms. How antidepressants cause auditory signature deficits remains largely unknown. Here, we found that fluoxetine-treated adult female rats were significantly less accurate when performing a tone-frequency discrimination task compared with age-matched control rats. Their cortical neurons also responded less selectively to sound frequencies. The degraded behavioral and cortical processing was accompanied by decreased cortical perineuronal nets, particularly those wrapped around parvalbumin-expressing inhibitory interneurons. Furthermore, fluoxetine induced critical period-like plasticity in their already mature auditory cortices; therefore, a brief rearing of these drug-treated rats under an enriched acoustic environment renormalized auditory processing degraded by fluoxetine. The altered cortical expression of perineuronal nets was also reversed as a result of enriched sound exposure. These findings suggest that the adverse effects of antidepressants on auditory processing, possibly because of a reduction in intracortical inhibition, can be substantially alleviated by simply pairing drug treatment with passive, enriched sound exposure. They have important implications for understanding the neurobiological basis of antidepressant effects on hearing and for designing novel pharmacological treatment strategies for psychiatric disorders.SIGNIFICANCE STATEMENT Clinical experience suggests that antidepressants adversely affect sensory (particularly auditory) processing, which can exacerbate patients' psychiatric symptoms. Here, we show that the antidepressant fluoxetine reduces cortical inhibition in adult rats, leading to degraded behavioral and cortical spectral processing of sound. Importantly, fluoxetine induces a critical period-like state of plasticity in the mature cortex; therefore, a brief rearing under an enriched acoustic environment is sufficient to reverse the changes in auditory processing caused by the administration of fluoxetine. These results provide a putative neurobiological basis for the effects of antidepressants on hearing and indicate that antidepressant treatment combined with enriched sensory experiences could optimize clinical outcomes.
Subject(s)
Auditory Cortex , Fluoxetine , Rats , Female , Animals , Fluoxetine/pharmacology , Auditory Perception/physiology , Sound , Auditory Cortex/physiology , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Acoustic Stimulation/methodsABSTRACT
Objective:To investigate the longitudinal trajectory and influencing factors of cancer-related fatigue (CRF) in breast cancer patients during chemotherapy.Methods:From March 2019 to January 2020, breast cancer patients in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine and Peking Union Medical College Hospital were selected as the research objects to conduct follow-up investigation. The survey tools included general information questionnaire, Cancer-related Fatigue Assessment Scale, International Physical Activity Questionnaire, and the Pittsburgh Sleep Quality Index Scale.Results:A total of 91 patients were included in the study. The incidence of severe CRF at each time point before chemotherapy, 3 weeks after chemotherapy and 6 weeks after chemotherapy were 1.1% (1/91), 8.8% (5/57) and 2.1% (1/48), respectively. The results of the generalized estimation equation showed that the trajectory of the total score CRF firstly increased and then decreased, reaching a peak at 3 weeks after chemotherapy (35.45±13.07), and mild CRF change showed statistical difference ( P<0.05). In addition, BMI and sleep and daytime dysfunction were the influencing factors of the total score of CRF. Disease stage, sleep disturbance and daytime dysfunction were the influencing factors of CRF with different severity. Conclusions:CRF is a prominent problem in breast cancer patients during chemotherapy. Attention should be paid to high-risk individuals with abnormal BMI and daytime function by medical staff.
ABSTRACT
OBJECTIVE: To investigate the effect and safety of vitamin A supplementation in children with pneumonia through a systematic review. METHODS: Cochrane Library, EMbase, PubMed, China Biology Medicine disc, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) on vitamin A as an adjuvant therapy for pneumonia in children. Two reviewers independently screened the studies and evaluated their quality according to the inclusion and exclusion criteria. RevMan5.3 was used for the Meta analysis. RESULTS: A total of 15 RCTs with 3 021 patients were included. The Meta analysis showed that vitamin A supplementation did not reduce the mortality of children with pneumonia (P>0.05), but it increased the overall clinical response rate (P<0.05) and shortened the duration of pyrexia and cough, clearance time of signs and abnormal chest X-ray results, and length of hospital stay (P<0.05). As an adjuvant therapy, vitamin A did not increase the incidence rates of adverse reactions such as nausea, vomiting, diarrhea, allergy, and bregma bulging. CONCLUSIONS: Current evidence shows that in the treatment of pneumonia in children, vitamin A supplementation helps to relieve clinical symptoms and signs and shorten the length of hospital stay.The adjuvant therapy does not increase the incidence rates of adverse reactions.
Subject(s)
Pneumonia/drug therapy , Vitamin A/administration & dosage , Child , Dietary Supplements , Humans , Vitamin A/adverse effectsABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect and safety of vitamin A supplementation in children with pneumonia through a systematic review.</p><p><b>METHODS</b>Cochrane Library, EMbase, PubMed, China Biology Medicine disc, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) on vitamin A as an adjuvant therapy for pneumonia in children. Two reviewers independently screened the studies and evaluated their quality according to the inclusion and exclusion criteria. RevMan5.3 was used for the Meta analysis.</p><p><b>RESULTS</b>A total of 15 RCTs with 3 021 patients were included. The Meta analysis showed that vitamin A supplementation did not reduce the mortality of children with pneumonia (P>0.05), but it increased the overall clinical response rate (P<0.05) and shortened the duration of pyrexia and cough, clearance time of signs and abnormal chest X-ray results, and length of hospital stay (P<0.05). As an adjuvant therapy, vitamin A did not increase the incidence rates of adverse reactions such as nausea, vomiting, diarrhea, allergy, and bregma bulging.</p><p><b>CONCLUSIONS</b>Current evidence shows that in the treatment of pneumonia in children, vitamin A supplementation helps to relieve clinical symptoms and signs and shorten the length of hospital stay.The adjuvant therapy does not increase the incidence rates of adverse reactions.</p>
ABSTRACT
This research is to study the relationship between HPLC fingerprints of Moutan Cortex, Paeoniae Radix Rubra and Paeoniae Radix Alba and their activity on lipopolysaccharide-induced acute lung injury. HPLC fingerprints of each extract of Moutan Cortex,Paeoniae Radix Rubra and Paeoniae Radix Alba were established by an optimized HPLC-MS method. The activities of all samples against protein and tumor necrosis a factor were tested by the model of lipopolysaccharide-induced acute lung injury. The possible relationship between HPLC-MS fingerprints and the activitieswere deduced by the Partial least squares regression analysis method. Samples were analyzed by HPLC-MS/MS to identify the major peaks. The results showed that each sample had some effect on acute lung injury. Four components with a lager contribution rate of efficacy were calculated by the research of spectrum-effect relationship. Moutan Cortex exhibited good activity on acute lung injury, and gallic acid, paeoniflorin, galloylpaeoniflorin and paeonol were the main effective components.
Subject(s)
Animals , Male , Rats , Acetophenones , Chemistry , Pharmacology , Acute Lung Injury , Drug Therapy , Bridged Bicyclo Compounds, Heterocyclic , Chemistry , Pharmacology , Chromatography, High Pressure Liquid , Methods , Drugs, Chinese Herbal , Chemistry , Pharmacology , Gallic Acid , Chemistry , Pharmacology , Glucosides , Chemistry , Pharmacology , Lipopolysaccharides , Pharmacology , Monoterpenes , Chemistry , Pharmacology , Paeonia , Chemistry , Plant Roots , Chemistry , Rats, Wistar , Tandem Mass Spectrometry , MethodsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Ginsenoside Rg3 has shown multiple pharmacological activities and been considered as one of the most promising approaches for fatigue treatment. However, little is known about the cellular and molecular mechanisms of Rg3 on anti-fatigue and the effect of Rg3 on dopaminergic system has not been reported yet. The major aim of this study is to investigate the effect of Rg3 on TH expression and the related biochemical parameters, such as PKAα, ERK1/2, Akt and α-synuclein in brain of fatigue rats. MATERIALS AND METHODS: Weight-loaded forced swimming was performed to establish an animal model of fatigue. Rg3 (10mg/kg, 50mg/kg and 100mg/kg) was intragastrically administrated before swimming. The effect of Rg3 on the expression and phosphorylation of TH and TH-related proteins in fatigue rats or in SH-SY5Y cells was assessed with western blotting. HPLC was used to examine the level of DA and DOPAC in the fatigue rats tissues. RESULTS: TH and phosphorylated TH were decreased in different brain regions of which ventral midbrain were less affected in weight-loaded forced swimming rats. Pretreatment with Rg3 significantly suppressed fatigue-induced decrease expression of TH and TH phosphorylation. Also treatment with Rg3 reversed the decrease expression of PKAα as well as the phosphorylation of ERK1/2 and Akt which were induced by weight-loaded forced swimming. Moreover, weight-loaded swimming could induce the increase expression of α-synuclein in hippocampus and midbrain, while suppressed α-synuclein expression in striatum and prefrontal cortex. Furthermore, Rg3 could induce the increase of TH expression and phosphorylation which was accompanied with elevated expression and phosphorylation of related kinase proteins in vitro, while the inhibitors of kinase proteins could suppress these effects of Rg3. In addition, HPLC results showed that Rg3 could reverse the weight-loaded swimming-induced increase of DOPAC/DA ratio. CONCLUSION: Our data suggest that fatigue can induce the decrease of DA which might partially result from the change of TH expression and phosphorylation, and Rg3 can reverse these fatigue-induced changes. The underling mechanisms may include the activity changes of PKAα, ERK1/2, Akt and α-synuclein.