Acute physiological stress down-regulates mRNA expressions of growth-related genes in coho salmon

Growth and development in fish are regulated to a major extent by growth-related factors, such as liver-derived insulin-like growth factor (IGF) -1 in response to pituitary-secreted growth hormone (GH) binding to the GH receptor (GHR). Here, we report on the changes in the expressions of gh, ghr, and igf1 genes and the circulating levels of GH and IGF-1 proteins in juvenile coho salmon (Oncorhynchus kisutch) in response to handling as an acute physiological stressor. Plasma GH levels were not significantly different between stressed fish and prestressed control. Plasma IGF-1 concentrations in stressed fish 1.5 h post-stress were the same as in control fish, but levels in stressed fish decreased significantly 16 h post-stress. Real-time quantitative PCR (qPCR) analysis showed that ghr mRNA levels in pituitary, liver, and muscle decreased gradually in response to the stressor. After exposure to stress, hepatic igf1 expression transiently increased, whereas levels decreased 16 h post-stress. On the other hand, the pituitary gh mRNA level did not change in response to the stressor. These observations indicate that expression of gh, ghr, and igf1 responded differently to stress. Our results show that acute physiological stress can mainly down-regulate the expressions of growth-related genes in coho salmon in vivo. This study also suggests that a relationship between the neuroendocrine stress response and growth-related factors exists in fish.Peer reviewed: YesNRC publication: Ye

Intravenous alteplase for stroke with unknown time of onset guided by advanced imaging: systematic review and meta-analysis of individual patient data

Background: Patients who have had a stroke with unknown time of onset have been previously excluded from thrombolysis. We aimed to establish whether intravenous alteplase is safe and effective in such patients when salvageable tissue has been identified with imaging biomarkers. Methods: We did a systematic review and meta-analysis of individual patient data for trials published before Sept 21, 2020. Randomised trials of intravenous alteplase versus standard of care or placebo in adults with stroke with unknown time of onset with perfusion-diffusion MRI, perfusion CT, or MRI with diffusion weighted imaging-fluid attenuated inversion recovery (DWI-FLAIR) mismatch were eligible. The primary outcome was favourable functional outcome (score of 0–1 on the modified Rankin Scale [mRS]) at 90 days indicating no disability using an unconditional mixed-effect logistic-regression model fitted to estimate the treatment effect. Secondary outcomes were mRS shift towards a better functional outcome and independent outcome (mRS 0–2) at 90 days. Safety outcomes included death, severe disability or death (mRS score 4–6), and symptomatic intracranial haemorrhage. This study is registered with PROSPERO, CRD42020166903. Findings: Of 249 identified abstracts, four trials met our eligibility criteria for inclusion: WAKE-UP, EXTEND, THAWS, and ECASS-4. The four trials provided individual patient data for 843 individuals, of whom 429 (51%) were assigned to alteplase and 414 (49%) to placebo or standard care. A favourable outcome occurred in 199 (47%) of 420 patients with alteplase and in 160 (39%) of 409 patients among controls (adjusted odds ratio [OR] 1·49 [95% CI 1·10–2·03]; p=0·011), with low heterogeneity across studies (I2=27%). Alteplase was associated with a significant shift towards better functional outcome (adjusted common OR 1·38 [95% CI 1·05–1·80]; p=0·019), and a higher odds of independent outcome (adjusted OR 1·50 [1·06–2·12]; p=0·022). In the alteplase group, 90 (21%) patients were severely disabled or died (mRS score 4–6), compared with 102 (25%) patients in the control group (adjusted OR 0·76 [0·52–1·11]; p=0·15). 27 (6%) patients died in the alteplase group and 14 (3%) patients died among controls (adjusted OR 2·06 [1·03–4·09]; p=0·040). The prevalence of symptomatic intracranial haemorrhage was higher in the alteplase group than among controls (11 [3%] vs two [<1%], adjusted OR 5·58 [1·22–25·50]; p=0·024). Interpretation: In patients who have had a stroke with unknown time of onset with a DWI-FLAIR or perfusion mismatch, intravenous alteplase resulted in better functional outcome at 90 days than placebo or standard care. A net benefit was observed for all functional outcomes despite an increased risk of symptomatic intracranial haemorrhage. Although there were more deaths with alteplase than placebo, there were fewer cases of severe disability or death. Funding: None

Effects of the aromatase inhibitor Fadrozole on plasma sex steroid secretion and ovulation rate in female coho salmon, oncorhynchus kisutch, close to final maturation

Abstract In male teleosts, plasma oestrogen levels are undetectable, or when detectable, are present in very low amounts. Several studies have shown that the testes are incapable of secreting oestrogens. In contrast, other studies have demonstrated that oestrogen can be formed in the male brain, and that oestrogens are involved with neuroendocrine and behavioral responses. Therefore, Ž this study evaluated the effects of inhibiting oestrogen production in male coho salmon Oncor-. Ž . hynchus kisutch during sexual maturation using the aromatase inhibitor Fadrozole AI . Groups of fish, which were approximately 1.5 months before natural spawning, received injections of 1.0 or 10.0 mg AIrkg or five weekly injections of 10 mg AIrkg. Plasma sex steroid hormones Ž Ž . 17b-oestradiol, testosterone, 17,20b-dihydroxy-4-pregnen-3-one 17,20b-P and 11-keto-. testosterone were determined before and during 32 days after injection. Injection with AI inhibited 17b-oestradiol secretion by the brain. Fish injected with 10 mg AIrkg or 10 mg AIrkg Ž weekly presented significantly higher plasma 17,20b-P levels 12.11 " 1.75 and 11.98 " 2.85 . Ž ngrml, respectively at 6 h after injection than before injection 0.19 " 0.19 and 1.00 " 0. O.B. Afonso et al.r Aquaculture 188 2000 175-187 176 . ngrml, respectively . At 16 days after injection, the groups injected with 10 mg AIrkg or 10 mg AIrkg weekly were already spermiating at significantly higher rates than the vehicle group. Ž . Gonadosomatic index GSI and sperm motility were not different among the groups. This study demonstrated that Fadrozole inhibited 17b-oestradiol in the brain, and prematurely increased plasma 17,20b-P levels.