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ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo-pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.
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<p><b>PURPOSE</b>To investigate effects of neuro-immuno-modulation on wound healing by observing changes of cytokines and hypothalamic-pituitary-adrenal (HPA) axis hormones in acute stress reaction in rats with wound and combined local radiation injury.</p><p><b>METHODS</b>Sixty female Wistar rats (weighting 200 ± 20 g) were randomly divided into normal control group, wound group and combined wound-local radiation (CWR) group (25 Gy local radiation post wound), 20 rats in each group. Contents of IL-1β, IL-6 and IFN-γ and IL-4 in serum were measured and changes of adrenocorticotropic hormone (ACTH) and glucocorticoid (GC) in serum were analyzed by using enzyme-linked immunosorbent assay and radioimmunologic assay, respectively at different time points post wound and radiation.</p><p><b>RESULTS</b>(1) The level of IFN-γ, one of the Th1 cell cytokines increased significantly at 14 d post CWR, which was markedly higher than that in control group and wound group. However, the level of IL-4, IL-1β and IL-6, one of the Th2 cell cytokines, did not show obvious change. (2) Ratio of Th1/Th2 (IFN-γ/IL-4) in wound group and CWR group increased significantly at 7 d after wound and radiation, which suggested that Th1/Th2 balance drifted to Th1 immune response. The ratio of Th1/Th2 in wound group returned to the normal level up to 14 d after the wound and radiation, while the Th1/Th2 ratio in CWR group increased persistently and was much higher than that in control and wound groups. (3) Level of serous ACTH and GC in CWR group increased at 3 d post wound and radiation, and among them, level of GC showed statistically significant increase, which was much higher than that in control and wound groups.</p><p><b>CONCLUSION</b>Level of serous neurohormone GC in rats increased significantly immediately after wound and radiation; while the level of IFN-γ showed significant increase only up to 14 d after wound and radiation, and the Th1/Th2 imbalance sustained till 28 d post wound and radiation. In order to reduce acute damage caused by CWR, organic immune system and nerve system showed up a marked regulate effects simultaneously and mutually. Nonetheless, the excessive stress induced by CWR causes disturbance of immunoregulation, which is one of the key reasons for delayed wound healing in CWR.</p>
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Objective: To study the effect of melatonin (Mel) , a potent antioxidant, on the oxidative stress and the activity of hypothalamo-pituitary-adrenal axis in diabetic rats. Methods: Male SD rats were assigned to the following 4 groups: normal control (treated with 2% ethyl alcohol lavage[ NC, n=6 ]), diabetes mellitus control (treated with 2% ethyl alcohol lavage [DM, n=7]), diabetes mellitus model group 1 (treated with Mel lavage [10 mg · kg-1 d-1, DM+Mell, n=61), diabetes mellitus model group 2 (treated with Mel lavage [0. 2 mg · kg-1 · d-1 , DM+Me2, n=61). Diabetes in DM group, DM+Mell group and DM+Mel2 group was induced by intraperitoneal injection of streptozotacin (65mg/kg). Blood glucose, body weight and adrenal gland weight/body weight(AW/BW) were determined in the 4 groups 12 weeks later; malondialdehyde (MDA) was examined with visible spectrophotometry; blood total cholesterol (TC) and triglyceride (TG) were examined with enzymology method; blood corticotrophin-releasing hormone (CRH), adreno-corticotrophic hormone(ACTH) and corticosterone(CORT) were examined with radioimmune method. Results: Blood glucose, MDA , TC, TG, CRH, ACTH, CORT and AW/BW in DM group were significantly higher than those in NC group (P<0.01); and the body weight of rats in DM group were significantly lower those of NC group(P<0.01). Compared with DM group, DM+Mel1 and DM+Mel2 group had a significantly lower blood glucose, MDA TC, TG and AW/BW (P<0.01 or P
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AIM: To observe the different changes of neuroendocrine systems between the state of sport fatigue and poverty of movement. METHODS: 60 male Wistar rats were randomly divided into three groups: normal control group, sport fatigue model group and poverty of movement model group (20 rats in each group). The sport fatigue model was established by the method of combining basal diet and loaded swimming during 2 weeks, whereas the method of restricted activities was used to establish the poverty of movement model with total experimental time of 10 weeks. By the end of experiment, the climbing pole time was determined. The contents of hypothalamus thyrotropin releasing hormone (TRH), and serum norepinephrine (NE) and epinephrine (E) in rats with different treatments were determined by ELISA. In addition, the changes of hypothalamus corticotropin release hormone (CRH), pituitary adrenocorticotropic hormone (ACTH) and thyroid stimulating hormone (TSH), and serum corticosterone (CORT), triiodothyronine (T_3), tetraiodothyronine (T_4) were determined by radioimmunoassay to evaluate the functions of adrenergic nerve-adrenomedullin system, hypothalamo-pituitary-adrenal (HPA) axis and hypothalamo-pituitary-thyroid (HPT) axis. RESULTS: Compared to control group, the climbing pole time of the animals was obviously decreased in two model group. The adrenergic nerve-adrenomedullin system and HPA axis were inhibited in sport fatigue model rats, but HPT axis was unchanged. Interestingly, the HPA axis was hyperfunctional and HPT axis was inhibited in poverty of movement model rats. However, no change in the adrenergic nerve-adrenomedullin system was observed. CONCLUSION: Sport fatigue and poverty of movement all affect neuroendocrine system and lead to the adjustment mechanism imbalance, but the target and tendency are different.
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Objective To observe the effect of Shenkang-Ⅱ on hypothalamus-pituitary-adrenal axis (HPA axis) in nephrotic syndrome rats during high-dose glucocorticoids withdrawal, and provide a theoretical basis for clinical application of Shenkang-Ⅱ during the withdrawing and maintaining stages of glucocorticoids in the treatment of nephrotic syndrome. Methods The models of nephrotic syndrome in rats were established with adriamycin, and treated with high-dose glucocorticoid which can cause HPA axis suppression. After the HPA axis was suppressed, the hormone was reduced gradually. At the same time, the rats were treated by intragastric administration with different doses of Shenkang-Ⅱ. The changes of serum ACTH, cortisol and adrenal morphological in large dose of Shenkang-Ⅱ group, small dose of Shenkang-Ⅱ group, hormone control group, nephrotic syndrome model group and normal group were observed after two weeks. Results In the stage of withdrawing glucocorticoids, there were some amelioration in the changes of serum ACTH, cortisol in every group. After 2 weeks, those changes didn’t return to normal level. However, compared with the level of hormone control group, there were obvious increases in the levels of serum ACTH and cortisol in the large and small dose of Shenkang-Ⅱ group (P
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Lymphopenia, or decreased NK cell counts or activity after exercise are often referred to as immunosuppression. But unlike lymphopenia of HIV infection, which is an absolute loss of CD4 T cells, exercise or stress induces transient redistribution of lymphocytes which eventually will be recovered. Similarly NK cells may leave and come into the circulation in response to physical exercise and various stressors, both good and bad. Redistribution of CD4 T cells is mediated mainly by glucocorticoid in the blood stream, while NK cells are regulated by sympathetic outflow. The clinical significance of these fluctuation remains to be elucidated, but unlikely to lead to increased susceptibility to infection or cancer. They may rather be considered as a practical marker to know the activities of HPA axis or sympathetic activity.
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Serum cortisol and plasma ACTH were determined in 10 patients with severe sepsis and 12 with septic shock on day 1,3,5 after diagnosis were made,and the data were compared with 12 control patients. To evaluate the hypothalamic-pituitary-adrenal(HPA)axis function in patients with severe sepsis and septic shock,1?g ACTH stimulation test was applied after hormone concentrations were obtained on day 1.Compared with the control patients,ACTH level was significantly higher in patients with severe sepsis and lower in septic shock(P
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Expression of prepro-orexin gene in the hypothalamus was decreased in rats with dietary obesity,and has no correlation with serum corticosterone concentration.Expression of orexin receptor-2 in adrenal was increased in obese rats,and was positively correlated to expression of CRH mRNA and inversely correlated to serum corticosterene concentration.
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Objective:To study the effect of melatonin(Mel),a potent antioxidant,on the oxidative stress and the activity of hypothalamo-pituitary-adrenal axis in diabetic rats.Methods:Male SD rats were assigned to the following 4 groups:normal control(treated with 2% ethyl alcohol lavage\[NC,n=6\]),diabetes mellitus control(treated with 2% ethyl alcohol lavage \[DM,n=7\]),diabetes mellitus model group 1(treated with Mel lavage \[10 mg?kg-1?d-1,DM+Mel1,n=6\]),diabetes mellitus model group 2(treated with Mel lavage \[0.2 mg?kg-1?d-1,DM+Mel2,n=6\]).Diabetes in DM group,DM+Mel1 group and DM+Mel2 group was induced by intraperitoneal injection of streptozotacin(65 mg/kg).Blood glucose,body weight and adrenal gland weight/body weight(AW/BW)were determined in the 4 groups 12 weeks later;malondialdehyde(MDA)was examined with visible spectrophotometry;blood total cholesterol(TC)and triglyceride(TG)were examined with enzymology method;blood corticotrophin-releasing hormone(CRH),adreno-corticotrophic hormone(ACTH)and corticosterone(CORT)were examined with radioimmune method.Results:Blood glucose,MDA,TC,TG,CRH,ACTH,CORT and AW/BW in DM group were significantly higher than those in NC group(P