Single-dose intranasal subunit vaccine rapidly clears secondary sepsis in a high-dose pneumonic plague infection

Vaccine ◽  
2021 ◽  
Vol 39 (9) ◽  
pp. 1435-1444
Author(s):  
Christina D'Arco ◽  
Alison A. McCormick ◽  
Paul M. Arnaboldi
Keyword(s):  
Single Dose ◽  
Subunit Vaccine ◽  
High Dose ◽  
Pneumonic Plague

Anticoagulation profile of high-dose vs. standard-dose enoxaparin for percutaneous coronary intervention

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Z Liu ◽  
Q Chen ◽  
J Li ◽  
X Zhu ◽  
L Xu ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Single Dose ◽  
Dose Group ◽  
Standard Dose ◽  
Coronary Intervention ◽  
High Dose ◽  
Funding Source ◽  
Minor Bleeding ◽  
Therapeutic Anticoagulation ◽  
Percutaneous Coronary

Abstract Background Although enoxaparin 0.5 mg/kg is a recommended anticoagulation regimen for percutaneous coronary intervention (PCI), a randomized study demonstrated that more patients receiving enoxaparin 0.75 mg/kg compared to those receiving 0.5 mg/kg achieved therapeutic anticoagulation without increase of major bleeding. However, no detailed data regarding the anticoagulation profile of enoxaparin 0.75 mg/kg was reported in the study. Purpose This study prospectively assessed the anticoagulation profile of enoxaparin 0.75 mg/kg vs. 0.5 mg/kg in troponin-negative patients undergoing elective trans-radial coronary angiography (CAG). Methods Eligible patients were randomly assigned to the Planned Single-dose group (0.75 mg/kg) or the Planned Staged-dose group (0.5±0.25 mg/kg). In the Planned Single-dose group, all patients received enoxaparin 0.75 mg/kg before CAG irrespective of their indication for subsequent PCI. In the Planned Staged-dose group, enoxaparin 0.5 mg/kg was administered to all patients before CAG and additional 0.25 mg/kg was given only to those undergoing subsequent PCI immediately before PCI. Patients without indication for subsequent PCI in each group were defined as High-dose (0.75 mg/kg) and Standard-dose (0.5 mg/kg) groups, respectively. Anti-Xa levels were assessed at 0 min (immediately before), 10 min, and 90 min after enoxaparin administration. Therapeutic anticoagulation was defined as anti-Xa level of 0.5–1.8 IU/ml. Bleeding was according to the thrombolysis in myocardial infarction (TIMI) criteria. Results In 170 randomized patients, 48 of 85 patients in the Planned Single-dose group and 47 of 85 patients in the Planned Staged-dose group were included in the High-dose and Standard-dose groups, respectively. The baseline characteristics were well balanced between the two groups. The anti-Xa levels were higher in the High-dose vs. Standard-dose group both at 10 min (1.354±0.228 IU/ml vs. 0.976±0.213 IU/ml, p<0.001) and 90 min (0.827±0.195 IU/ml vs. 0.583±0.169 IU/ml, p<0.001) (Figure 1). The percentages of patients with therapeutic anticoagulation were similar at 10 min (100% [46/46] vs. 100% [46/46], p=1.000) but higher at 90 min (100% [41/41] vs. 75% [33/44], p=0.001) in the High-dose vs. Standard-dose group. No TIMI major or minor bleeding occurred within 24 h of randomization in both groups. Conclusions Enoxaparin 0.75 mg/kg compared to 0.5 mg/kg provided higher anticoagulation which was adequate for up to 90 min of administration. Enoxaparin 0.75 mg/kg would be a superior anticoagulation regimen for PCI, especially when the procedure duration is long. Figure 1. High-dose vs. Standard-dose Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): 2016 Peking Union Medical College Hospital (PUMCH) Science Fund for Junior Faculty

scholarly journals Identification of E2 with improved secretion and immunogenicity against CSFV in piglets

2020 ◽  
Author(s):  
Huiling Xu ◽  
Yanli Wang ◽  
Guangwei Han ◽  
Weihuan Fang ◽  
fang he
Keyword(s):  
Single Dose ◽  
Signal Peptide ◽  
Classical Swine Fever Virus ◽  
Subunit Vaccine ◽  
Classical Swine Fever ◽  
Cost Effective ◽  
Fever Virus ◽  
Economic Losses ◽  
Swine Industry ◽  
Virus Challenge

Abstract Background: Outbreaks of Classical swine fever virus (CSFV) cause significant economic losses in the swine industry. Vaccination is the major method to prevent and control the disease. As live attenuated vaccines fail to elicit differentiable immunity between infected and vaccinated animals, subunit vaccine was considered as an alternative candidate to prevent and eradicate CSFV. Subunit vaccines present advantages in DIVA immunogenicity and safety. The technology was limited due to the low yield and the high cost with multiple and large doses. The native E2 signal peptide has not been well defined before. Here, the aim of this study is to develop a cost-effective and efficacious E2 vaccine candidate against CSFV with signal peptide and E2 sequence selection. Results: A novel CSFV E2 sequence (E2ZJ) was identified from an epidemic strain of Zhejiang for outstanding secretion in baculovirus and enhanced immunogenicity. E2 secretion induced with the selected signal peptide, SPZJ (SP23), increase at least 50% as compared to any other signal peptides tested. Besides, unique antigenic features were identified in E2ZJ. E2ZJ elicited CSFV antibodies at the earlier stage than other E2 types tested in mice. Moreover, higher level of neutralization antibodies against both genotypes 1 and 2 CSFV with E2ZJ was detected than other E2s with the same dosage. Further, in piglets, E2ZJ successfully elicited neutralizing immunity. A single dose of 5 μg of E2ZJ was sufficient to induce protective antibodies against CSFV in piglets and provided 100% protection against lethal virus challenge. Conclusions: Our studies provide evidence that E2ZJ guided by a novel E2 signal peptide (SPZJ) was efficiently secreted and presented significantly improved immunogenicity than conventional E2 vaccines. Moreover, a single dose of 5 μg E2ZJ is efficacious against CSFV in piglets. Keywords: Classical swine fever virus; novel signal peptide; SPZJ-E2ZJ; subunit vaccine; protective immunity

Ameliorative Effects of Quercetin in Cyclophosphamide-Induced Vascular Toxicity in Rats

2021 ◽  
Author(s):  
EMİN ŞENGÜL ◽  
VOLKAN GELEN ◽  
SEMİN GEDİKLİ ◽  
ELİF ERBAS ◽  
ASLIHAN ATASEVER
Keyword(s):  
Superoxide Dismutase ◽  
Single Dose ◽  
Corn Oil ◽  
Endothelial Damage ◽  
Control Group ◽  
High Dose ◽  
Protective Effects ◽  
Vascular Toxicity ◽  
Relaxation Responses

Abstract Cyclophosphamide (CYP) causes vascular toxicity and endothelial damage. In this study aimed the determination of the protective effects of Quercetin (Q) in the CYP-induced vascular toxicity in rats. The rats were randomly divided into the following five groups: Control, CYP, Q50+CYP, Q100+CYP and Q100. The control group was given intragastric (i.g.) corn oil for seven days. The CYP group received i.g. corn oil for seven days and a single dose (200 mg/kg) of CYP via intraperitoneal (i.p.) injection on the seventh day. The rats in the three Q-treated groups received Q for seven days. On the seventh day after the Q treatment, the Q50+CYP, and Q100+CYP groups were injected to single dose (200 mg/kg, i.p.) of CYP. The CYP-treatment both worsen the Phenylephrine (PE)-induced contractions and acetylcholine (ACh)-induced relaxation responses in isolated thoracic aorta of rats, and the application of Q corrected these responses. The malondialdehyde (MDA) levels were significantly higher in the CYP-treated groups. The both dose of Q decreased the MDA level. Superoxide dismutase (SOD) and glutathione (GSH) activities were significantly decreased in the CYP group, whereas the high dose of Q increased SOD and GSH activities. Q treatment attenuated CYP-induced pathologies, and endothelial damage. According to results, Q has protective effects against CYP-induced vascular toxicity in rats.

scholarly journals Is Once-Daily High-Dose Ceftriaxone plus Ampicillin an Alternative for Enterococcus faecalis Infective Endocarditis in Outpatient Parenteral Antibiotic Therapy Programs?

2020 ◽  
Vol 65 (1) ◽  
pp. e02099-20
Author(s):  
Laura Herrera-Hidalgo ◽  
Arístides de Alarcón ◽  
Luis Eduardo López-Cortes ◽  
Rafael Luque-Márquez ◽  
Luis Fernando López-Cortes ◽  
...  
Keyword(s):  
Single Dose ◽  
Infective Endocarditis ◽  
Antibiotic Therapy ◽  
Enterococcus Faecalis ◽  
High Dose ◽  
Synergistic Activity ◽  
Parenteral Antibiotic ◽  
Once Daily ◽  
Content Type ◽  
Outpatient Parenteral Antibiotic Therapy

ABSTRACTCeftriaxone administered as once-daily high-dose short infusion combined with ampicillin has been proposed for the treatment of Enterococcus faecalis infective endocarditis in outpatient parenteral antibiotic therapy programs (OPAT). This combination requires synergistic activity, but the attainment of ceftriaxone synergic concentration (Cs) with the regimen proposed for OPAT has not been studied. This phase II pharmacokinetic study enrolled healthy adult volunteers who underwent two sequential treatment phases. During phase A, volunteers received 2 g of ceftriaxone each 12 h during 24 h followed by a 7-day wash-out. Then the participants received phase B, which consisted of a single dose of 4 g of ceftriaxone. Throughout both phases, each volunteer underwent intensive pharmacokinetic (PK) sampling over 24 h. Ceftriaxone total and unbound concentrations were measured. Twelve participants were enrolled and completed both phases. Mean ceftriaxone total and free concentrations 24 h after the administration of 2 g each 12 h were 86.44 ± 25.90 mg/liter and 3.59 ± 1.35 mg/liter, respectively, and after the 4-g single dose were 34.60 ± 11.16 mg/liter and 1.40 ± 0.62 mg/liter, respectively. Only 3 (25%) patients in phase A maintained unbound plasma concentrations superior to the suggested Cs = 5 mg/liter during 24 h, and none (0%) in phase B. No grade 3 to 4 adverse events or laboratory abnormalities were observed. Ceftriaxone optimal exposure combined with ampicillin to achieve maximal synergistic activity against E. faecalis required for the treatment of infective endocarditis remains unknown. However, the administration of a single daily dose of 4 g of ceftriaxone implies a reduction in the time of exposure to the proposed Cs. (This study has been registered in the European Union Drug Regulating Authorities Clinical Trials [EudraCT] database under identifier 2017-003127-29.)

Efficacy and safety of a single-dose veterinary preparation of ivermectin versus 7-day high-dose albendazole for chronic strongyloidiasis

2008 ◽  
Vol 31 (1) ◽  
pp. 46-49 ◽  
Author(s):  
Yupin Suputtamongkol ◽  
Nuntakorn Kungpanichkul ◽  
Saowaluk Silpasakorn ◽  
Nicholas J. Beeching
Keyword(s):  
Single Dose ◽  
High Dose ◽  
Efficacy And Safety

scholarly journals Fractionated versus single-dose total body irradiation at low and high dose rates to condition canine littermates for DLA-identical marrow grafts

Blood ◽  
1994 ◽  
Vol 83 (11) ◽  
pp. 3384-3389 ◽  
Author(s):  
R Storb ◽  
RF Raff ◽  
FR Appelbaum ◽  
HJ Deeg ◽  
TC Graham ◽  
...  
Keyword(s):  
Dna Repair ◽  
Single Dose ◽  
Dose Rate ◽  
Total Body Irradiation ◽  
High Dose Rate ◽  
Lymphoid Cells ◽  
High Dose ◽  
Dose Rates ◽  
Total Body ◽  
Allogeneic Marrow

Abstract We explored in dogs the immunosuppressive properties of 450 cGy total body irradiation (TBI) delivered from two opposing 60Co sources, as assessed by the criterion of successful engraftment of allogeneic genotypically DLA-identical littermate marrow. Two questions were asked in this study. Firstly, does dose rate affect the immunosuppressive effect of TBI when administered in a single dose? Secondly, does fractionation alter the immunosuppression of TBI when delivered at a very fast dose rate? Dose rates studied included 7 and 70 cGy/min, and fractionation involved four fractions of 112.5 cGy each, with 6-hour minimum interfraction intervals. Six of 7 dogs receiving 450 cGy single- dose TBI at 70 cGy/min showed sustained engraftment of the allogeneic marrow, compared with 1 of 7 dogs receiving single-dose TBI at 7 cGy/min (P = .01). Fractionated TBI at 70 cGy/min resulted in sustained allogeneic engraftment in 3 of 10 dogs, a result that was statistically significantly worse than that with single-dose TBI at 70 cGy/min (P = .03) and not statistically different (P = .24) from that with fractionated TBI delivered at 7 cGy/min (0 of 5 dogs engrafted). A single dose of 450 cGy of TBI delivered at a rate of 70 cGy/min is significantly more immunosuppressive than the same total dose delivered at 7 cGy/min. Fractionated TBI at 70 cGy/min is significantly less immunosuppressive than single-dose TBI at 70 cGy/min and not significantly different from fractionated TBI administered at 7 cGy/min. Results are consistent with the notion that significant DNA repair in lymphoid cells is possible during interfraction intervals at the relatively high dose rate of 70 cGy/min.

scholarly journals Systematic Review and Meta-analysis: Optimal Salvage Therapy in Acute Severe Ulcerative Colitis

2019 ◽  
Vol 25 (7) ◽  
pp. 1169-1186 ◽  
Author(s):  
Matthew C Choy ◽  
Dean Seah ◽  
David M Faleck ◽  
Shailja C Shah ◽  
Che-Yung Chao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Ulcerative Colitis ◽  
Single Dose ◽  
Salvage Therapy ◽  
Meta Analysis ◽  
Optimal Dose ◽  
High Dose ◽  
Free Survival ◽  
Severe Ulcerative Colitis ◽  
The Impact

AbstractBackgroundInfliximab is an effective salvage therapy in acute severe ulcerative colitis; however, the optimal dosing strategy is unknown. We performed a systematic review and meta-analysis to examine the impact of infliximab dosage and intensification on colectomy-free survival in acute severe ulcerative colitis.MethodsStudies reporting outcomes of hospitalized steroid-refractory acute severe ulcerative colitis treated with infliximab salvage were identified. Infliximab use was categorized by dose, dose number, and schedule. The primary outcome was colectomy-free survival at 3 months. Pooled proportions and odds ratios with 95% confidence intervals were reported.ResultsForty-one cohorts (n = 2158 cases) were included. Overall colectomy-free survival with infliximab salvage was 79.7% (95% confidence interval [CI], 75.48% to 83.6%) at 3 months and 69.8% (95% CI, 65.7% to 73.7%) at 12 months. Colectomy-free survival at 3 months was superior with 5-mg/kg multiple (≥2) doses compared with single-dose induction (odds ratio [OR], 4.24; 95% CI, 2.44 to 7.36; P < 0.001). However, dose intensification with either high-dose or accelerated strategies was not significantly different to 5-mg/kg standard induction at 3 months (OR, 0.70; 95% CI, 0.39 to 1.27; P = 0.24) despite being utilized in patients with a significantly higher mean C-reactive protein and lower albumin levels.ConclusionsIn acute severe ulcerative colitis, multiple 5-mg/kg infliximab doses are superior to single-dose salvage. Dose-intensified induction outcomes were not significantly different compared to standard induction and were more often used in patients with increased disease severity, which may have confounded the results. This meta-analysis highlights the marked variability in the management of infliximab salvage therapy and the need for further studies to determine the optimal dose strategy.

Sign in / Sign up

Export Citation Format

Share Document