Acute phase proteins, interleukin 6, and heat shock protein 70 in broiler chickens administered with corticosterone

An experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CPN), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 d of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CPN, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP 70 density. Although CORT administration significantly increased feed intake, weight gain was significantly depressed. Administration of CORT also increased CORT, OVT, CPN, AGP, IL-6, and HSP 70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CPN and AGP. In conclusion, an elevation in CORT can induce an acute-phase response and HSP 70 expression. Thus, APP and HSP 70 may be of value as indicators of stress in poultry

Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis

Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet–fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders.Organismic and Evolutionary Biolog

Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality among Patients with COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial

Importance: Thrombotic events are commonly reported in critically ill patients with COVID-19. Limited data exist to guide the intensity of antithrombotic prophylaxis. Objective: To evaluate the effects of intermediate-dose vs standard-dose prophylactic anticoagulation among patients with COVID-19 admitted to the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized trial with a 2 � 2 factorial design performed in 10 academic centers in Iran comparing intermediate-dose vs standard-dose prophylactic anticoagulation (first hypothesis) and statin therapy vs matching placebo (second hypothesis; not reported in this article) among adult patients admitted to the ICU with COVID-19. Patients were recruited between July 29, 2020, and November 19, 2020. The final follow-up date for the 30-day primary outcome was December 19, 2020. Interventions: Intermediate-dose (enoxaparin, 1 mg/kg daily) (n = 276) vs standard prophylactic anticoagulation (enoxaparin, 40 mg daily) (n = 286), with modification according to body weight and creatinine clearance. The assigned treatments were planned to be continued until completion of 30-day follow-up. Main Outcomes and Measures: The primary efficacy outcome was a composite of venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days, assessed in randomized patients who met the eligibility criteria and received at least 1 dose of the assigned treatment. Prespecified safety outcomes included major bleeding according to the Bleeding Academic Research Consortium (type 3 or 5 definition), powered for noninferiority (a noninferiority margin of 1.8 based on odds ratio), and severe thrombocytopenia (platelet count <20 �103/µL). All outcomes were blindly adjudicated. Results: Among 600 randomized patients, 562 (93.7) were included in the primary analysis (median interquartile range age, 62 50-71 years; 237 42.2% women). The primary efficacy outcome occurred in 126 patients (45.7%) in the intermediate-dose group and 126 patients (44.1%) in the standard-dose prophylaxis group (absolute risk difference, 1.5% 95% CI,-6.6% to 9.8%; odds ratio, 1.06 95% CI, 0.76-1.48; P =.70). Major bleeding occurred in 7 patients (2.5%) in the intermediate-dose group and 4 patients (1.4%) in the standard-dose prophylaxis group (risk difference, 1.1% 1-sided 97.5% CI,-� to 3.4%; odds ratio, 1.83 1-sided 97.5% CI, 0.00-5.93), not meeting the noninferiority criteria (P for noninferiority >.99). Severe thrombocytopenia occurred only in patients assigned to the intermediate-dose group (6 vs 0 patients; risk difference, 2.2% 95% CI, 0.4%-3.8%; P =.01). Conclusions and Relevance: Among patients admitted to the ICU with COVID-19, intermediate-dose prophylactic anticoagulation, compared with standard-dose prophylactic anticoagulation, did not result in a significant difference in the primary outcome of a composite of adjudicated venous or arterial thrombosis, treatment with extracorporeal membrane oxygenation, or mortality within 30 days. These results do not support the routine empirical use of intermediate-dose prophylactic anticoagulation in unselected patients admitted to the ICU with COVID-19. Trial Registration: ClinicalTrials.gov Identifier: NCT04486508. © 2021 American Medical Association. All rights reserved

Acute phase proteins, heat shock protein and other blood parameters as physiological indicators of stress in poultry

Experiments were conducted to explore physiological aspect of stress in chickens. Acute phase proteins (APPs), heat shock protein (HSP) 70 and other blood parameters responses to various stressors were investigated. Activation of APPs by nonpathogenic stimulus is still unclear in poultry species. Thus, this research was conducted to elucidate the relationship between stress and APPs response in poultry. In Chapter 3, an experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CP), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 day (d) of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CP, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP70 density. Although CORT administration significantly increased feed intake, weight gain was significantly decreased. Administration of CORT also increased CORT, OVT, CP, AGP, IL-6, and HSP70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CP and AGP. An elevation in CORT can induce an APR and HSP70 expression. In Chapter 4, effect of feed deprivation on serum CORT, OVT, AGP and CP concentrations in broiler chickens was investigated. At 21 days of age, birds were subjected to one of five feed deprivation periods: (i) 0 h (ad libitum) (AL), (ii) 6 h, (iii) 12 h, (iv) 18 h, (v) 24 h, and (vi) 30 h. Upon completion of the deprivation period, blood samples were collected to determine CORT, OVT, AGP and CP. Results showed that feed deprivation for 24 h or more caused a marked elevation in CORT when compared to AL. However, significant increases in AGP, CP and OVT were only noted following 30 h of feed deprivation. Thus, elicitation of AGP, CP and OVT response may represent a more chronic stressful condition than CORT response in assessing the well-being of broilers. In Chapter 5, effect of different stocking densities on serum CORT, OVT, AGP and CP concentrations, brain HSP70 expression and performance in broiler chickens exposed to unheated and heated conditions was determined. Day-old chicks were stocked at 0.100m2/bird (low density (LD)) or 0.063m2/ bird (high density (HD)), in battery cages and housed in environmentally controlled rooms. From 21 to 35 days of age, birds from each stocking density group were exposed to either 24 or 32 °C. Growth performance was recorded during the heat treatment period, and blood and brain samples were collected to determine CORT, OVT, AGP, CP and HSP70 levels on day 35. Heat treatment but not stocking density was detrimental to growth performance. There were significant temperature×density interactions for CORT, CP and OVT on day 35. Although HD elevated CORT, CP and OVT when compared to LD, the effects of the former were more obvious under heated condition. Both temperature and density had significant effect on AGP and HSP70. In conclusion, irrespective of temperature, high stocking density was physiologically stressful to broiler chickens, as indicated by CORT, AGP, CP, OVT and HSP70, but not detrimental to growth performance and survivability. So AGP, CP and OVT could be useful biomarkers to determine the effect of overcrowding and high temperature on the welfare of broiler chickens. In Chapter 6, an experiment was conducted to determine the physiological response to feed restriction in female broiler breeders using a range of conventional and novel indicators. One hundred female breeders were subjected to one of five feeding regimens from d 28-42 as follows (i) ad libitum feeding (AL), (ii-v) 75, 60, 45 and 30% of ad libitum feed intake. Blood heterophil to lymphocyte ratio (HLR), and plasma circulating CORT, ghrelin (GHR), serotonin (5-HT) and dopamine (DA), and serum acute phase proteins (APP) concentrations, and brain HSP70 level were measured. The results showed a significant effect of feed restriction on blood HLR and plasma CORT, GHR, 5-HT, DA and brain HSP70 levels. However, feed restriction had no effect on serum levels of APP such as AGP, OVT and CP. Serum levels of 5-HT and GHR varied curvilinearly with the feed restriction level. The relationship between brain HSP70 and level of feed restriction was negligible. However, significant linear relationships between HLR, CORT, DA and level of feed restriction were noted. Thus, these three parameters appear to represent a straight forward relation with severity of feed restriction. In Chapter 7, the effect of inhibiting adrenal steroidogenesis on serum CORT, OVT, AGP and CP, IL-6 concentrations and brain HSP70 expression was elucidated in broiler chickens subjected to feed deprivation for 24 hours. On days 4, 5, and 6, equal numbers of birds were assigned to either ad libitum feeding (AL) or (2) 60% of ad libitum feed intake (60FR). On day 35, equal number of AL and 60FR birds were subjected to (i) ad libitum feeding (ALF), (ii) 48 h feed restriction (SFR), or (iii) 24 hours feed restriction with intramuscular injection of 1,1-bis(4-chlorophenyl)-2,2,2-trichloroethane (DDT) (an adrenal blocker) dissolved in corn oil at 100 mg/kg BW (SFR+DDT). The birds were injected with DDT 12 h prior to feed deprivation. Following feed withdrawal, samples were collected to determine CORT, OVT, AGP, CP, IL-6 and HSP70 levels. The earlier feeding regimen had no significant effect on CORT, AGP, OVT, CP, IL-6 and brain HSP70 concentration on day 36. The CORT, AGP, OVT, CP, IL-6 and brain HSP70 density of SFR birds following 24 h (day 36) of feed deprivation were significantly higher than their ALF and SFR+DDT counterparts. However, both ALF and SFR+DDT birds had similar values. It can be concluded that stress without concurrent elevation in the circulating level of corticosterone may not elicit APP, IL-6 and HSP 70 reactions. The linear relationship between DA and level of feed restriction suggests that this neurotransmitter is a potential marker of stress magnetite in feed restricted breeders. Serum levels of 5-HT and GHR are not clear indicators of feed restriction level

Impact of Glutamine in Drinking Water on Performance and Intestinal Morphology of Broiler Chickens under High Stocking Density

This work sought to look into the impacts of glutamine in drinking water on performance, intestinal morphology and corticosterone level of chickens under different stocking densities. A total 300 male chicks randomly were divided to battery cages as 10 birds/(normal stocking density) and 15 birds/(high stocking density). The chicks received feed as (i) control diet and (ii) control diet + 5g glutamine/ liter in drinking water under normal and high stocking density for the whole experiment. On d 42, 3 chicks from each cage were randomly selected and slaughtered to collect blood and duodenal samples. The results showed significant improvement in growth performance and longer villi when chicken were supplemented with glutamine via drinking water. High stocking density impaired performance of chicks in the control diet, but not in chicken supplemented with glutamine under high stocking density condition. Moreover, high stocking density increased the level of corticosterone in the both groups. More interestingly, the rate of mortality significantly decreased in chickens fed with glutamine supplemented diet (2% when supplemented with glutamine and 5.33% without supplementation). In conclusion, glutamine supplementation via drinking water resulted in better growth performance of birds subjected to high stocking density

Correlation between cystatin-C, acute phase reactants, and retinopathy severity in diabetic patients

AIM: To evaluate correlation of cystatin-C(Cys-C)with severity of diabetic retinopathy(DR)and acute phase reactants, including erythrocyte sedimentation rate(ESR)and high-sensitivity C-reactive protein(hs-CRP).METHODS: All diabetic patients who were referred for diabetic retinopathy(DR)screening during 1mo were enrolled. Demographic data were recorded. All patients have undergone full ophthalmic exam. At the same day, all patients were tested for hemoglobin A1c(HbA1c), ESR, hs-CRP, and Cys-C serum levels.RESULTS: Sixty seven diabetics were enrolled, including 19(28.3%)without retinopathy, 22(32.8%)non-proliferative retinopathy, and 26(38.8%)proliferative retinopathy patients. The mean age, sex distribution, mean duration of diabetes, prevalence of hypertension and dyslipidemia, smoking status and HbA1c levels were not significantly different among the three groups. The mean levels of Cys-C increase significantly as retinopathy progress \〖1.1±0.48; 1.22±0.38; 1.71±0.92(P=0.007), respectively\〗. In multiple regression analysis, just Cys-C was significantly associated with severity of DR(P=0.025).CONCLUSIONS: This study revealed that serum levels of Cys-C increase while DR progress independently of acute phase reactants. Therefore, it could be used as an associated marker by primary care physicians to distinguish patients at higher risk of severe DR. Larger randomized studies are warranted to confirm findings. Reviewing physiological role of the Cys-C, we proposed that the Cys-C may be a protective response to catalytic stress rather than being a pathogenic factor in microangiopathies

Relative Leistungsbewertung bei wiederholter Delegation

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