scholarly journals Detection of Atypical porcine pestivirus in Swedish pigs with congenital tremor type A-II

2020 ◽  
Author(s):  
Hedvig Stenberg ◽  
Magdalena Jacobson ◽  
Maja Malmberg

Abstract Background Congenital tremor (CT) type A-II is a neurological disorder characterized by tremor of the head and body of new-born piglets. The suggested causative agent of the disease is the recently found atypical porcine pestivirus. The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far been performed in the Nordic countries. The overarching goal of this study was to investigate if atypical porcine pestivirus are present in the brain tissue of Swedish piglets suffering from congenital tremor. From June 2017 – June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of CT and 13 piglets with splay leg originating from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n=8) were also studied. Two APPV-specific RT-qPCR methods targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed on material from Swedish piglets with CT sampled in 2004 (n = 11) and 2011/2012 (n = 3) using the described APPV-specific RT-qPCR methods. The total number of piglets with signs of CT in this study was 29. Results Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV, whereas, all of the healthy controls (n = 11) were negative. The piglets with CT sampled 2017-2018 had an odds ratio of 271 (95% CI 12.1 to 6096.8, z = 3.5, P = 0.0004) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in the Swedish pig population. Conclusion This is the first description of atypical porcine pestivirus in piglets suffering from congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004. Keywords: congenital tremor, type A-II, atypical porcine pestivirus, splay legs, Sweden, pigs, piglets.

2020 ◽  
Author(s):  
Hedvig Stenberg ◽  
Magdalena Jacobson ◽  
Maja Malmberg

Abstract Background Congenital tremor (CT) type A-II is a neurological disorder characterized by tremor of the head and body of newborn piglets. The suggested causative agent of the disease is the recently found atypical porcine pestivirus (APPV). The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far been performed in the Nordic countries. The overarching goal of this study was to investigate if APPV is present in the brain tissue of Swedish piglets suffering from congenital tremor. From June 2017 – June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of congenital tremor and 13 piglets with splay leg originating from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n=8) were also investigated. Two APPV-specific RT-qPCR methods targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed on material from Swedish piglets with congenital tremor sampled in 2004 (n = 11) and 2011/2012 (n = 3) using the described APPV-specific RT-qPCR methods. The total number of piglets with signs of CT in this study was 29. Results Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV, whereas, all of the healthy controls (n = 11) were negative. The piglets with congenital tremor sampled 2017-2018 had an odds ratio of 91,8 (95% CI 3.9128 to 2153.7842, z = 2.807, P = 0.0050) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in the Swedish pig population. Conclusion This is the first description of atypical porcine pestivirus in piglets suffering from congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004.


2019 ◽  
Author(s):  
Hedvig Stenberg ◽  
Magdalena Jacobson ◽  
Maja Malmberg

Abstract Background Congenital tremor type A-II is a neurological disorder characterized by tremor of the head and body of new-born piglets. The suggestive causative agent of the disease is the recently found atypical porcine pestivirus. The virus has been detected in piglets suffering from congenital tremor in central Europe, South and North America and in China but no studies has so far not been performed in the Nordic countries, hence, the aim of this study was to investigate the prevalence of atypical porcine pestivirus in Swedish piglets. From June 2017 – June 2018, 15 piglets from four Swedish farms with ongoing outbreaks of congenital tremor, and 13 piglets with splay leg, from four different farms, were investigated for presence of APPV RNA in brain tissue. Matched healthy control piglets (n=8) were also studied. Two APPV-specific RT-qPCR:s targeting the NS3 and NS5B region, respectively, were used. A retrospective study was performed in the same manner on material from Swedish piglets with congenital tremor sampled in 2004 (n=11) and 2011/2012 (n=6). Results Atypical porcine pestivirus-RNA was detected in 93% (27/29) of the piglets suffering from congenital tremor. All samples from piglets with congenital tremor from 2004 (n = 11) and 2012 (n = 3) were PCR-positive with respect to APPV. All of the healthy controls (n=8) were negative for APPV. The piglets with congenital tremor sampled 2017-2018 had an odds ratio of 271 (95% CI 12.1 to 6096.8, z = 3.5, P = 0.0004) to test positive for APPV by qRT-PCR compared to the healthy piglets (Fishers exact test p < 0.0001). These findings make it interesting to continue investigating APPV in pigs in Sweden, as most of the virus details is unknown to date. Conclusion This is the first description of atypical porcine pestivirus in piglets with congenital tremor type A-II in Sweden and the Nordic countries. The virus has been present in the Swedish pig population since at least 2004.


2020 ◽  
Vol 10 (5) ◽  
pp. 654-661
Author(s):  
Qin Wang ◽  
Ting Wang

The purpose of current study was to explore the role and mechanism of microRNA-182-5p (miR182-5p) in neonatal hypoxic ischemic brain damage (HIBD). First, we established a hypoxic-ischemic (HI) rat model and assessed the neurological function of the rats using the Zea Longa score. Then, the level of miR-182-5p in brain tissue of neonatal rats was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Findings revealed that miR-182-5p was significantly down-regulated in the brain tissue of HI rat model. Next, we studied the target gene of miR-182-5p by using TargetScan and dual luciferase reporter assay. Results showed that CASP2 was a direct target gene of miR-182-5p, and the level of CASP2 was significantly up-regulated in the brain tissue of HI rat model. Immediately thereafter, we established an oxygen and glucose deprivation (OGD) cell model of primary cortical neurons, and demonstrated the changes of miR182-5p in cells treated with OGD by qRT-PCR. Finally, to determine the function of miR-182-5p in OGD subjected neuronal cells, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry (FCM) assays were used to study cell viability and apoptosis. The study found that compared with the OGD group, miR-182-5p mimic significantly increased nerve cell viability, reduced cell apoptosis and decreased cleaved-Caspase3/7/8 protein expression, however, all these changes were significantly reversed by overexpression of the CASP2 gene. Taken together, miR-182-5p might protect the nerve cells from ischemia and hypoxia by targeting CASP2, thereby playing a protective role in hypoxic ischemic encephalopathy, which might be a new effective target for neonatal hypoxic ischemic brain damage treatment.


1999 ◽  
Vol 10 (4) ◽  
pp. 854-863
Author(s):  
GEORGE METRY ◽  
BJÖRN WIKSTRÖM ◽  
SVEN VALIND ◽  
BO SANDHAGEN ◽  
TORBJÖRN LINDE ◽  
...  

Abstract. Full correction of anemia with recombinant human erythropoietin (rhEPO) has been reported to reduce the risk of cardiovascular morbidity and mortality and improve the quality of life in hemodialysis (HD) patients. Effects of normalization of hematocrit on cerebral blood flow and oxygen metabolism were investigated by positron emission tomography. Regional cerebral blood flow (rCBF), cerebral blood volume (rCBV), oxygen extraction ratio (rOER), and metabolic rate for oxygen (rCMRO2) were measured in seven HD patients before and after correction of anemia and compared with those in six healthy control subjects. In addition, blood rheology before and on rhEPO therapy was measured in HD patients, which included blood viscosity, plasma viscosity, erythrocyte fluidity, and erythrocyte aggregability. The results showed that plasma viscosity was high (1.51 ± 0.19 mPa · s) and erythrocyte fluidity was low (85.8 ± 4.8 Pa-1 · s-1), while whole blood viscosity was within the normal range (3.72 ± 0.38 mPa · s) before rhEPO therapy. After treatment, the hematocrit rose significantly from 29.3 ± 3.3 to 42.4 ± 2.2% (P < 0.001), accompanied by a significant increase in the whole blood viscosity to 4.57 ± 0.16 mPa · s, nonsignificant decrease in erythrocyte fluidity to 79.9 ± 7.4 mPa-1 · s-1 and nonsignificant change in plasma viscosity (1.46 ± 1.3 mPa · s). Positron emission tomography measurements revealed that by normalization of hematocrit, rCBF significantly decreased from 65 ± 11 to 48 ± 12 ml/min per 100 cm3 (P < 0.05). However, arterial oxygen content (caO2) significantly increased from 5.7 ± 0.7 to 8.0 ± 0.4 mmol/L (P < 0.0001), rOER of the hemispheres significantly increased from 44 ± 3 to 51 ± 6% (P < 0.05) and became significantly higher than healthy control subjects (P < 0.05). In addition, rCBV significantly increased from 3.5 ± 0.5 to 4.6 ± 0.6 ml/100 cc brain tissue. The results showed that oxygen supply to the brain tissue increased with normalization of hematocrit, but it was accompanied by increased oxygen extraction in the brain tissue. This may be assumed to be related to the decrease of erythrocyte velocity in the cerebral capillaries as a result of the decreased blood deformability and the increased plasma viscosity.


1997 ◽  
Vol 78 (03) ◽  
pp. 0990-0992 ◽  
Author(s):  
Andreas Hillarp ◽  
Bengt Zӧller ◽  
Peter J Svensson ◽  
Bjӧrn Dahlbäck

SummaryA dimorphism in the 3’-untranslated region of the prothrombin gene (G to A transition at position 20210) has recently been reported to be associated with increases in plasma prothrombin levels and in the risk of venous thrombosis (1). We have examined the prothrombin dimorphism among 99 unselected outpatients with phlebography verified deep venous thrombosis, and in 282 healthy controls. The prevalence of the 20210 A allele was 7.1% (7/99) in the patient group, and 1.8% (5/282) in the healthy control group (p = 0.0095). The relative risk of venous thrombosis was calculated to be 4.2 (95% Cl, 1.3 to 13.6), and was still significant when adjustment was made for age, sex and the factor V:R506Q mutation causing APC resistance [odds ratio 3.8 (95% Cl, 1.1 13.2)]. As previously reported, 28% of the patients were carriers of the factor V:R506Q mutation. Thus, 34% (one patient carried both traits) of unselected patients with deep venous thrombosis were carriers of an inherited prothrombotic disorder. To sum up, our results confirm the 20210 A allele of the prothrombin gene to be an important risk factor for venous thrombosis.


2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.


2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Felicitas Schulz ◽  
Ekkehart Jenetzky ◽  
Nadine Zwink ◽  
Charlotte Bendixen ◽  
Florian Kipfmueller ◽  
...  

Abstract Background Evidence for periconceptional or prenatal environmental risk factors for the development of congenital diaphragmatic hernia (CDH) is still scarce. Here, in a case-control study we investigated potential environmental risk factors in 199 CDH patients compared to 597 healthy control newborns. Methods The following data was collected: time of conception and birth, maternal BMI, parental risk factors such as smoking, alcohol or drug intake, use of hairspray, contact to animals and parental chronic diseases. CDH patients were born between 2001 and 2019, all healthy control newborns were born in 2011. Patients and control newborns were matched in the ratio of three to one. Results Presence of CDH was significantly associated with maternal periconceptional alcohol intake (odds ratio = 1.639, 95% confidence interval 1.101–2.440, p = 0.015) and maternal periconceptional use of hairspray (odds ratio = 2.072, 95% confidence interval 1.330–3.229, p = 0.001). Conclusion Our study suggests an association between CDH and periconceptional maternal alcohol intake and periconceptional maternal use of hairspray. Besides the identification of novel and confirmation of previously described parental risk factors, our study underlines the multifactorial background of isolated CDH.


2020 ◽  
Vol 11 (1) ◽  
pp. 147-160
Author(s):  
Ranyah Shaker M. Labban ◽  
Hanan Alfawaz ◽  
Ahmed T. Almnaizel ◽  
Wail M. Hassan ◽  
Ramesa Shafi Bhat ◽  
...  

AbstractObesity and the brain are linked since the brain can control the weight of the body through its neurotransmitters. The aim of the present study was to investigate the effect of high-fat diet (HFD)-induced obesity on brain functioning through the measurement of brain glutamate, dopamine, and serotonin metabolic pools. In the present study, two groups of rats served as subjects. Group 1 was fed a normal diet and named as the lean group. Group 2 was fed an HFD for 4 weeks and named as the obese group. Markers of oxidative stress (malondialdehyde, glutathione, glutathione-s-transferase, and vitamin C), inflammatory cytokines (interleukin [IL]-6 and IL-12), and leptin along with a lipid profile (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein levels) were measured in the serum. Neurotransmitters dopamine, serotonin, and glutamate were measured in brain tissue. Fecal samples were collected for observing changes in gut flora. In brain tissue, significantly high levels of dopamine and glutamate as well as significantly low levels of serotonin were found in the obese group compared to those in the lean group (P > 0.001) and were discussed in relation to the biochemical profile in the serum. It was also noted that the HFD affected bacterial gut composition in comparison to the control group with gram-positive cocci dominance in the control group compared to obese. The results of the present study confirm that obesity is linked to inflammation, oxidative stress, dyslipidemic processes, and altered brain neurotransmitter levels that can cause obesity-related neuropsychiatric complications.


2020 ◽  
Vol 31 (6) ◽  
pp. 806-812
Author(s):  
Simone Gasser ◽  
Lukas Stastny ◽  
Markus Kofler ◽  
Vitalijs Zujs ◽  
Christoph Krapf ◽  
...  

Abstract OBJECTIVES Immediate surgical repair for type A aortic dissection is gold standard and at most centres is performed by the surgeon on call during night-time and weekends. The objective was to evaluate whether emergency surgery during night-time or weekends has an influence on 30-day mortality. METHODS In 319 patients undergoing surgery for type A aortic dissection, skin incision was documented. Patients were divided into 2 groups according to the time point of skin incision (05:00 a.m. to 07:00 p.m. = daytime group; 07:01 p.m. to 04:59 a.m. = night-time group). We also noted whether their surgeries were started on weekdays (Monday 00:00 to Friday 23:59) or weekends (Saturday 00:00 to Sunday 23:59). RESULTS The median age was 61 years (interquartile range 49–70) and 69.6% (n = 222) were male. Almost 50% (n = 149) of patients presented in a critical preoperative state. Forty-one percent of patients (n = 131) underwent night-time surgery. There were no differences in baseline data, time from onset of symptoms to surgery or surgical treatment between groups, except from preferred femoral access for arterial cannulation during night-time. Advanced age [odds ratio 1.042, 95% confidence interval (CI) 1.014–1.070], preoperative malperfusion syndrome (odds ratio 2.542, 95% CI 1.279–5.051) and preoperative tamponade (odds ratio 2.562, 95% CI 1.215–5.404) emerged as risk factors for 30-day mortality. Night-time or weekend surgery did not have any impact on 30-day mortality when covariates were considered. CONCLUSIONS Based on the natural course of the disease and our results, surgery for type A aortic dissection should be performed as an emergency surgery regardless of time and day.


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