scholarly journals M211. NEUROPROTECTIVE EFFECT OF SHI-ZHEN-AN-SHEN-TANG, A CHINESE HERB FORMULA ON MICE EXPOSED TO CUPRIZONE

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S216-S217
Author(s):  
Chao Ma ◽  
Yan Wu ◽  
Pei Chen ◽  
Yuan Jia ◽  
Dongqing Yin ◽  
...  
Keyword(s):  
Low Dose ◽  
Neuroprotective Effect ◽  
Chinese Herb ◽  
Large Body ◽  
High Dose ◽  
Neuregulin 1 ◽  
The Brain ◽  
Different Doses ◽  
Medium Dose

Abstract Background Our previous study indicated a therapeutic effect of Shi-Zhen-An-Shen-Tang (SZAST), a Chinese herb formula, on schizophrenia, but the related mechanism is unknown(citation). A large body of evidence suggests the important role of white matter of the brain in the pathophysiology of schizophrenia. This study was designed to evaluate the effect of SZAST on schizophrenia with demyelinated mice. Methods Male C57BL/6 mice were given mixed cuprizone (CPZ, a copper chelator, 0.2 %, w/w) rodent chow for six successive weeks to induce demyelination. During the last two weeks, mice were given an oral gavage of saline, or SZAST of three different doses (a low dose of 5.5g·kg-1·d-1, a medium dose of 8.24g·kg-1·d-1, or a high dose of 10.98 g·kg-1·d-1), or quetiapine, respectively. Behavioral tests were conducted after the last treatment. Meanwhile, the expression of myelin basic protein (MBP) and neuregulin-1(NRG1) in the brain was tested by immunohistochemistry staining or Western Blot. Results Mice exposed to CPZ for six weeks showed obvious schizophrenia-like behaviors, including lower nest-building activity, sensory gating activity, and higher locomotor activity. CPZ-fed mice also displayed a lower myelin density in the corpus callosum, hippocampus, and cerebral cortex and a reduction of MBP and NRG1 protein in the hippocampus compared with controls. Both quetiapine and SZAST significantly alleviated the abnormal schizophrenia-like behaviors and the impairment of myelin sheath in CPZ-fed mice, however, SZAST with medium dose showed better neuroprotective effect than the low dose or the high dose of SZAST. Furthermore, the expression of NRG1protein in the hippocampus was slightly, but not significantly increased in all SZAST-treated and quetiapine-treated groups. Discussion These results indicate that the neuroprotective effect of SZAST in demyelinated mice might partially relate to remyelination in the hippocampus in CPZ-fed mice.

Shedding of Angiostrongylus costaricensis larvae in the faeces of Swiss mice experimentally infected with different infective doses

2018 ◽  
Vol 94 ◽  
Author(s):  
C.C. Hermes ◽  
E. Benvegnú ◽  
M.M. Costa ◽  
R. Rodriguez ◽  
M.I.B. Vieira
Keyword(s):  
Low Dose ◽  
High Dose ◽  
Southern Brazil ◽  
Wild Rodents ◽  
Intermediate Hosts ◽  
Swiss Mice ◽  
Faecal Samples ◽  
Third Stage ◽  
Different Doses ◽  
Medium Dose

AbstractAbdominal angiostrongyliasis is an endemic zoonosis in southern Brazil caused by the nematode Angiostrongylus costaricensis, which uses terrestrial molluscs as intermediate hosts and wild rodents as final hosts. Humans can be infected by ingesting infectious A. costaricensis larvae. To date, correlations between shedding of first-stage larvae (L1) and different infective doses of third-stage larvae (L3) have not been elucidated. The aim of this study was to assess L1 faecal shedding levels in Swiss mice experimentally infected with different doses of A. costaricensis L3 and to determine whether infective doses are related to mortality. Thirty-two male Swiss mice were divided evenly into a non-infected control (NI-Con); low-dose infection (LD-Inf); medium-dose infection (MD-Inf) and high-dose infection (HD-Inf) groups infected with 0, 5, 15 and 30 A. costaricensis L3, respectively. Faecal samples were collected from each animal, starting at day 20 post infection. HD-Inf mice had greater faecal L1 shedding levels than LD-Inf mice, but not a significantly shortened survival. In conclusion, infective doses of A. costaricensis L3 affect L1 shedding levels without altering mortality in Swiss mice.

scholarly journals Effect of vitamin E on stroke-associated pneumonia

2020 ◽  
Vol 48 (9) ◽  
pp. 030006052094965
Author(s):  
Hongwei Shen ◽  
Bingyan Zhan
Keyword(s):  
Vitamin E ◽  
Low Dose ◽  
Nutritional Assessment ◽  
Mini Nutritional Assessment ◽  
High Dose ◽  
Duration Of Hospitalization ◽  
High Dose Vitamin ◽  
Different Doses ◽  
Better Than

Objective To study the role of vitamin E in stroke-associated pneumonia. Methods We selected 183 patients with stroke-related pneumonia who were divided into different nutrition groups according to the Mini Nutritional Assessment score. Patients were then administered different doses of vitamin E. Results CD55 and CD47 levels in patients taking vitamin E across different nutrition score groups were better than those in patients who did not use vitamin E. The levels of CD55 and CD47 and the duration of hospitalization were better in the high-dose vitamin E group than in the low-dose vitamin E group. Conclusion Vitamin E may have an auxiliary therapeutic effect in patients with stroke-associated pneumonia.

scholarly journals Evaluation of the BDNF, NGF, NT3 and NT4 Genes Expressions in the Brains of Neonatal Mice with Hypothyroidism

2017 ◽  
Vol 7 (1) ◽  
pp. 171
Author(s):  
Hamid Reza Adeli Bhroz ◽  
Kazem Parivar ◽  
Iraj Amiri ◽  
Nasim Hayati Roodbari
Keyword(s):  
Dose Group ◽  
Low Dose ◽  
Pure Water ◽  
Intervention Group ◽  
Control Group ◽  
High Dose ◽  
Endocrine Glands ◽  
Blood Samples ◽  
High Doses ◽  
The Brain

Background and Aim: Thyroid is one of the endocrine glands, (T3 and T4) play a significant role in the development of prenatal brain and the following stages. The study aimed to evaluate the effect of hypothyroidism on the amount of expression of NT4, NT3, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in brain of one-day rat neonates with hypothyroidism.Materials and Methods: In total, 25 mature mice of Albino NMRI race were selected after mating, divided into three group, control, as well as low-dose and high-dose intervention groups. Samples of the control group received pure water during pregnancy, whereas subjects of the intervention group with low and high doses of the medication were administered with 20 mg and 100 mg methimazole powder (dissolved in 100 cc water), respectively. After child delivery, blood samples were obtained from mother mice to determine the level of T3 and T4 in blood serum. Following that, the brain of one-day mice were removed by surgery and assessed to determine the amount of expression of NT4, NT3, NGF and BDNF using the complete kit of RT-PCR.Results: Levels of T4 and T3 in the control group were 28 ug/dl and 1.59 ug/dl, respectively. In the low-dose intervention group, the amounts of the mentioned hormones were 8 ug/dl and 0.85 ug/dl, significantly, indicating a significant reduction in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group. Moreover, T4 and T3 were 6 ug/dl and 0.79 ug/dl in the high-dose group, respectively, conveying a significant decrease in the expression of NT4, NT3, NGF and BDNF genes, compared to the control group (P<0.05).

Effect of Different Doses of Propofol and Nerve block Combined with General Anesthesia on The Intraoperative Anesthesia and Postoperative Awakening and Cognitive Function in Elderly Patients with Knee Osteoarthritis

2021 ◽  
Vol 7 (4) ◽  
pp. 697-705
Author(s):  
Jianhui Ma ◽  
Meimei Pang ◽  
Xin Ding ◽  
Shirong Fang ◽  
Lichao Chu
Keyword(s):  
Cognitive Function ◽  
Elderly Patients ◽  
General Anesthesia ◽  
Nerve Block ◽  
Dose Group ◽  
Low Dose ◽  
High Dose Group ◽  
High Dose ◽  
Knee Oa ◽  
Different Doses

Objective. To explore the effect of different doses of propofol and nerve block combined with general anesthesia on the intraoperative anesthesia and postoperative awakening and cognitive function in elder patients with knee osteoarthritis (OA). Methods. According to the inclusion criteria for research object, we selected 98 elderly patients with knee OA who needed surgery and were admitted to our hospital from January 2019 to January 2021 for the study. Patients were divided into the low dose group (given 2 mg/kg propofol by pumping under constant speed during surgery) and the high dose group (given 4 mg/kg propofol by pumping during surgery) by the number table method to compare their indicators including the intraoperative anesthesia effect, with 49 cases in each group. Results. No between-group difference was shown in the anesthesia time and postoperative VAS scores, but the awakening time of the low dose group was significantly shorter than that of the high dose group (P<0.05); the differences in heart rate (HR) values at various time points between the two groups were not obvious, but the high dose group obtained significantly higher HR values at T4 than the low dose group; the mean arterial pressure (MAP) values of both groups were significantly reduced at Ti and then returned to the level before anesthesia (P>0.05); the bispectral index scores (BIS) of both groups experienced a marked drop at Ti and then recovered gradually, but failed to return to the level at T0 till the end, and a between-group difference in BIS indexes presented at Ti; the plasma corticosterone (CORT) concentration at Ti of both groups were significantly lowered and then returned to the level at T0, with no between-group difference; and compared with the low dose group, the high dose group achieved slightly lower mini-mental state examination (MMSE) scores at 24-72 h after surgery, with no significant difference between them (P>0.05). Conclusion. The therapy of different doses of propofol and nerve block combined with general anesthesia has no significant effect on the cognitive function in elderly knee OA patients after surgery. With the nerve block improving the analgesic effect, a low dose of propofol is good for the postoperative awakening of patients. Different doses of propofol inhibited the stress response to a different degree and produced good anesthesia outcomes in elderly patients, but comparatively speaking, a low-dose propofol ensures more smooth indexes and less effect on the intraoperative hemodynamics.

scholarly journals CD8+ T Cells Mediate Recovery andImmunopathology in West Nile VirusEncephalitis

2003 ◽  
Vol 77 (24) ◽  
pp. 13323-13334 ◽  
Author(s):  
Yang Wang ◽  
Mario Lobigs ◽  
Eva Lee ◽  
Arno Müllbacher
Keyword(s):  
T Cells ◽  
Dose Group ◽  
Low Dose ◽  
Neuronal Degeneration ◽  
High Dose ◽  
West Nile ◽  
Activation Markers ◽  
High Doses ◽  
The Brain ◽  
Deficient Mice

ABSTRACT C57BL/6J mice infected intravenously with the Sarafend strain of West Nile virus (WNV) develop a characteristic central nervous system (CNS) disease, including an acute inflammatory reaction. Dose response studies indicate two distinct kinetics of mortality. At high doses of infection (108 PFU), direct infection of the brain occurred within 24 h, resulting in 100% mortality with a 6-day mean survival time (MST), and there was minimal destruction of neural tissue. A low dose (103 PFU) of infection resulted in 27% mortality (MST, 11 days), and virus could be detected in the CNS 7 days postinfection (p.i.). Virus was present in the hypogastric lymph nodes and spleens at days 4 to 7 p.i. Histology of the brains revealed neuronal degeneration and inflammation within leptomeninges and brain parenchyma. Inflammatory cell infiltration was detectable in brains from day 4 p.i. onward in the high-dose group and from day 7 p.i. in the low-dose group, with the severity of infiltration increasing over time. The cellular infiltrates in brain consisted predominantly of CD8+, but not CD4+, T cells. CD8+ T cells in the brain and the spleen expressed the activation markers CD69 early and expressed CD25 at later time points. CD8+ T-cell-deficient mice infected with 103 PFU of WNV showed increased mortalities but prolonged MST and early infection of the CNS compared to wild-type mice. Using high doses of virus in CD8-deficient mice leads to increased survival. These results provide evidence that CD8+ T cells are involved in both recovery and immunopathology in WNV infection.

Abstract P331: Angiotensin-salt Hypertension Requires Ouabain-sensitive Na + Pumps

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Ling Chen ◽  
Jerry B Lingrel ◽  
John M Hamlyn ◽  
Mordecai P Blaustein
Keyword(s):  
Low Dose ◽  
High Dose ◽  
Ang Ii ◽  
Wild Type ◽  
Dietary Salt ◽  
Endogenous Ligand ◽  
Ouabain Binding ◽  
Fab Fragments ◽  
Salt Hypertension ◽  
The Brain

Dietary salt is a major factor in the pathogenesis of essential hypertension (EH), but the underlying links are unresolved. Animal models indicate that angiotensin (Ang) II and high dietary salt (HS) are convergent signals that act via the brain to elevate blood pressure (BP). Low-dose sc Ang II+HS is a common model for EH. We tested the Na + pump ouabain binding site’s role in this model because it is crucial in some other hypertension models (e.g., ACTH and Nedd4-2-knockout +HS). Mice that express Na + pumps with a mutant, ouabain-resistant α2 catalytic subunit (α2 R/R ; cation transport is normal), and wild type (WT), ouabain sensitive controls (α2 S/S ) were studied. [80-90% of rodent artery myocyte Na + pumps are ouabain-resistant (α1 R/R ); only 10-20% are α2.] BP was measured by telemetry. First, 3 basal 24 hr BPs were recorded. Osmotic 4-week minipumps were then implanted sc in all mice to deliver vehicle (saline; Expt. #1,3), or 400 (Expt. #1,2) or 800 (Expt. #3) ng/kg/min Ang II; simultaneously, in Expt. #2, the diet was switched from 0.4% (standard) to 2% NaCl (HS). BPs were monitored every 3-4 days for up to 4 weeks. Also, in Expt. #2, on day 21, all mice received 2 ip injections, 4 hrs apart, of 10 mg/kg DigiFab, Fab fragments that immuno-neutralize ouabain, while BP was continuously monitored; on day 23, the mice received 2 ip injections of CroFab, anti-crotalus toxin (‘control’) Fab fragments. Results: 1. Basal mean BP (MBP) was 10±2 mm Hg higher in α2 R/R than in WT mice ( P <0.01; n =21 & 29; ANOVA). 2. In WT mice, 400 ng/kg/min sc Ang II and Ang II+HS raised MBP by 15±1 and 34±1 mm Hg, respectively ( P <0.01; n =7-8; ANOVA). 3. The MPB elevation in Ang II+HS α2 R/R (17±2 mm Hg) was only half that in WT mice ( P <0.01; n =7 each; ANOVA). 4. DigiFab rapidly (<1 hr) reduced MBP by 14±2 mm Hg in Ang II+HS hypertensive WT mice ( P <0.001; n =7; T-test), but not in α2 R/R mice ( P <0.01; n =7 each; ANOVA); CroFab did not lower MBP in either strain. 5. 800 ng/kg/min sc Ang II elevated systolic BP by 55±3 mm Hg in WT mice, but by only 37±3 mm Hg in α2 R/R mice ( P <0.05; n =3-5; ANOVA). Conclusions: Ouabain-sensitive α2 Na + pumps and their endogenous ligand are both required for full expression of low-dose Ang II-salt hypertension. Ouabain-sensitive α2 pumps apparently also contribute to high-dose Ang II-hypertension.

scholarly journals Validation of Pharmacological Protocols for Targeted Inhibition of Canalicular MRP2 Activity in Hepatocytes Using [99mTc]mebrofenin Imaging in Rats

Pharmaceutics ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 486
Author(s):  
Solène Marie ◽  
Irene Hernández-Lozano ◽  
Louise Breuil ◽  
Wadad Saba ◽  
Anthony Novell ◽  
...  
Keyword(s):  
Blood Flow ◽  
Biliary Excretion ◽  
Low Dose ◽  
Organic Anion ◽  
Liver Blood Flow ◽  
High Dose ◽  
Liver Uptake ◽  
Targeted Inhibition ◽  
Substrate Inhibitor

The multidrug resistance-associated protein 2 (MRP2) mediates the biliary excretion of drugs and metabolites. [99mTc]mebrofenin may be employed as a probe for hepatic MRP2 activity because its biliary excretion is predominantly mediated by this transporter. As the liver uptake of [99mTc]mebrofenin depends on organic anion-transporting polypeptide (OATP) activity, a safe protocol for targeted inhibition of hepatic MRP2 is needed to study the intrinsic role of each transporter system. Diltiazem (DTZ) and cyclosporin A (CsA) were first confirmed to be potent MRP2 inhibitors in vitro. Dynamic acquisitions were performed in rats (n = 5–6 per group) to assess the kinetics of [99mTc]mebrofenin in the liver, intestine and heart-blood pool after increasing doses of inhibitors. Their impact on hepatic blood flow was assessed using Doppler ultrasound (n = 4). DTZ (s.c., 10 mg/kg) and low-dose CsA (i.v., 0.01 mg/kg) selectively decreased the transfer of [99mTc]mebrofenin from the liver to the bile (k3). Higher doses of DTZ and CsA did not further decrease k3 but dose-dependently decreased the uptake (k1) and backflux (k2) rate constants between blood and liver. High dose of DTZ (i.v., 3 mg/kg) but not CsA (i.v., 5 mg/kg) significantly decreased the blood flow in the portal vein and hepatic artery. Targeted pharmacological inhibition of hepatic MRP2 activity can be achieved in vivo without impacting OATP activity and liver blood flow. Clinical studies are warranted to validate [99mTc]mebrofenin in combination with low-dose CsA as a novel substrate/inhibitor pair to untangle the role of OATP and MRP2 activity in liver diseases.

scholarly journals Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids, with Cranial and Caudal Extension

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Mahmood Mubasher ◽  
Aseel Sukik ◽  
Ahmed Hassan El Beltagi ◽  
Ali Rahil
Keyword(s):  
Spinal Cord ◽  
Lower Limbs ◽  
High Dose ◽  
Oral Corticosteroids ◽  
Dose Oral ◽  
Multiple Levels ◽  
Romberg Test ◽  
Brain And Spinal Cord ◽  
The Brain

A 23-year-old lady presented with vertigo and imbalance in walking, blurring of vision, diplopia, and headache, in addition to numbness in the lower limbs over a period of six days. On examination patient had nystagmus, ataxia, positive Romberg test, and hyperreflexia. MRI examination of the brain and spinal cord showed evidence of faint bright signal intensity foci in T2/FLAIR involving bilateral cerebral hemispheres, subcortical deep white matter, bilateral thalami, posterior pons and left brachium pontis, and basal ganglia, with small nodular enhancement that aligned along curvilinear structures; those lesions also were apparent along the spinal cord at multiple levels. The clinical and radiological features suggested CLIPPERS (chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids) syndrome. Symptoms improved dramatically with high dose oral corticosteroids. Our report addresses the radiological and clinical pattern of a case of CLIPPERS rhombencephalitis, with added superior and inferior extension to involve the brain and spinal cord, which is to emphasize the importance of raising the awareness of this disease and the combined role of radiologist and physicians for the diagnosis of this potentially treatable entity, responsive to glucocorticosteroid immunosuppression.

Renal ammoniagenic response to chronic acid loading: role of glucocorticoids

1988 ◽  
Vol 254 (1) ◽  
pp. F134-F138 ◽  
Author(s):  
T. C. Welbourne ◽  
G. Givens ◽  
S. Joshi
Keyword(s):  
Production Rate ◽  
Low Dose ◽  
High Dose ◽  
Ammonium Excretion ◽  
Ammonia Production ◽  
Total Ammonia ◽  
High Doses ◽  
Reduced Rate ◽  
Acid Loading

Adrenalectomized (ADX) animals exhibit a blunted renal response to chronic acid loading. To determine whether this response truly reflects impaired renal ammoniagenesis from glutamine, urinary ammonium excretion was compared with acid intake in ADX, intact, and ADX rats supplemented with either a low dose (4 micrograms.100 g-1.day-1) or a high dose (40 micrograms.100 g-1.day-1) of triamcinolone. ADX rats consumed similar amounts of acid as did intact controls yet excreted only 37% of the load as ammonium; in contrast intact controls returned 86% and triamcinolone-supplemented animals returned 98 and 88% for low and high doses, respectively. Nor could the reduced ammonium excretion be attributed to increased renal venous release, since total ammonia production, the sum of renal venous and urine ammonium, was reduced to 49% of the intact controls; low- and high-dose triamcinolone restored and markedly increased the production rate. Underlying the impaired ammonia production rate in ADX rats was a reduced rate of glutamine extraction, 350 +/- 49 vs. 896 +/- 102 and 1,260 +/- 247 and 1,448 +/- 112 nmol.min-1.100 g-1 for intact and low and high doses, respectively. Unlike intact acidotic and glucocorticoid-supplemented ADX acidotic rats, glutamine extraction was disassociated from the delivered glutamine load consonant with the role of glucocorticoid in coupling cellular glutamine transport to its metabolic utilization.

scholarly journals Dosing of thromboprophylaxis and mortality in critically ill COVID-19 patients

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Sandra Jonmarker ◽  
Jacob Hollenberg ◽  
Martin Dahlberg ◽  
Otto Stackelberg ◽  
Jacob Litorell ◽  
...  
Keyword(s):  
Body Weight ◽  
Confidence Intervals ◽  
Critically Ill ◽  
Low Dose ◽  
Cox Proportional Hazards ◽  
High Dose ◽  
Thromboembolic Events ◽  
Risk Of Death ◽  
Dosing Strategy ◽  
Medium Dose

Abstract Background A substantial proportion of critically ill COVID-19 patients develop thromboembolic complications, but it is unclear whether higher doses of thromboprophylaxis are associated with lower mortality rates. The purpose of the study was to evaluate the association between initial dosing strategy of thromboprophylaxis in critically ill COVID-19 patients and the risk of death, thromboembolism, and bleeding. Method In this retrospective study, all critically ill COVID-19 patients admitted to two intensive care units in March and April 2020 were eligible. Patients were categorized into three groups according to initial daily dose of thromboprophylaxis: low (2500–4500 IU tinzaparin or 2500–5000 IU dalteparin), medium (> 4500 IU but < 175 IU/kilogram, kg, of body weight tinzaparin or > 5000 IU but < 200 IU/kg of body weight dalteparin), and high dose (≥ 175 IU/kg of body weight tinzaparin or ≥ 200 IU/kg of body weight dalteparin). Thromboprophylaxis dosage was based on local standardized recommendations, not on degree of critical illness or risk of thrombosis. Cox proportional hazards regression was used to estimate hazard ratios with corresponding 95% confidence intervals of death within 28 days from ICU admission. Multivariable models were adjusted for sex, age, body mass index, Simplified Acute Physiology Score III, invasive respiratory support, and initial dosing strategy of thromboprophylaxis. Results A total of 152 patients were included: 67 received low-, 48 medium-, and 37 high-dose thromboprophylaxis. Baseline characteristics did not differ between groups. For patients who received high-dose prophylaxis, mortality was lower (13.5%) compared to those who received medium dose (25.0%) or low dose (38.8%), p = 0.02. The hazard ratio of death was 0.33 (95% confidence intervals 0.13–0.87) among those who received high dose, and 0.88 (95% confidence intervals 0.43–1.83) among those who received medium dose, as compared to those who received low-dose thromboprophylaxis. There were fewer thromboembolic events in the high (2.7%) vs medium (18.8%) and low-dose thromboprophylaxis (17.9%) groups, p = 0.04. Conclusions Among critically ill COVID-19 patients with respiratory failure, high-dose thromboprophylaxis was associated with a lower risk of death and a lower cumulative incidence of thromboembolic events compared with lower doses. Trial registration Clinicaltrials.gov NCT04412304 June 2, 2020, retrospectively registered.

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