367 INFLUENCE OF SUPERESTIMULATION AND HORMONAL DEPRIVATION PROTOCOLS ON IN VITRO PRODUCTION OF NELORE EMBRYOS (BOS TAURUS INDICUS)

2006 ◽  
Vol 18 (2) ◽  
pp. 291 ◽  
Author(s):  
C. M. Barros ◽  
M. M. G. Ferreira ◽  
J. R. Potiens ◽  
B. G. Eberhardt ◽  
D. S. Melo ◽  
...  

There are indications in the literature that delaying the period between ovarian superestimulation and ovum pickup (OPU) will induce follicles to a condition of initial atresia, which could be beneficial to oocyte development. Blondin et al. (2002 Biol. Reprod. 66, 38–43) superstimulated (FSH) Holstein heifers and delayed OPU for 48 h, i.e. they induced initial atresia in these follicles deprived of FSH (starvation) for 48 h. Additionally, 6 h before OPU, LH was administered to accelerate follicular maturation. This protocol yielded a surprisingly high blastocyst rate (80.4 ± 9.4%). In the present work, Blondin’s protocol was simultaneously compared to other protocols used for OPU and in vitro production of embryos (IVP), in Nelore cattle. Nelore cows (n = 18) were randomly allocated in three groups: Group 1 (just OPU), Group 2 (superestimulation and OPU), and Group 3 (superestimulation associated with FSH deprivation and OPU). Three OPU were performed, and the animals were switched to a different group each time in such a way that at the end of the experiment all cows received the three protocols. At a random stage of the estrous cycle (D2), follicles ≥6 mm were aspirated to induce a new follicular wave 2 days afterward (D0). In Group 1, OPU was performed on D2 and oocytes were processed to IVP. In Group 2, starting on D0, cows were superestimulated (pFSH, Folltropin®, 30 mg administered daily, IM, during 3 consecutive days; Bioniche Animal Health, Belleville, Ontario, Canada), and 6 h after the last FSH dose they received exogenous LH (12.5 mg, Im, Lutropin®, D3; Bioniche Animal Health). OPU was performed 6 h after LH administration, i.e. 12 h after the last dose of FSH. Animals in Group 3 received the same treatment as in Group 2, except that LH was administered 36 h after the last dose of FSH, and OPU occurred 6 h later. Therefore, in this Group, follicles were deprived of FSH during 48 h. Both cleavage and blastocyst rates were similar (P > 0.05, logistic regression) among oocytes from Groups 1, 2, and 3, respectively: 77.4% (144/185) and 42.70% (79/185); 75.54% (105/139) and 31.65% (44/139); 63.52% (101/159) and 33.33% (53/159). However, hatched blastocyst rate was higher (P < 0.01) in Group 1 (30.27%, 56/185) when compared to Group 2 (11.51%, 16/139) or 3 (15.72%, 25/159). It is concluded that, contrary to previous work on European breeds (taurus), ovarian superestimulation associated with deprivation of FSH and OPU (Group 3) do not increase IVP of Nelore embryos (indicus). Additionally, the highest hatched blastocyst rates were observed in oocytes from non superstimulated cows (Group 1).

2014 ◽  
Vol 26 (1) ◽  
pp. 217
Author(s):  
X. Q. Lv ◽  
J. H. Xue ◽  
Y. L. Zhu ◽  
H. B. Liang ◽  
B. H. Xuan

Juvenile in vitro embryo transfer can markedly reduce animal generation intervals. The purpose of this study was to investigate the ovarian response of juvenile calves and in vitro oocyte developmental capacity after superstimulation. Experiments on calves were performed in accordance with the Animal Welfare Regulations. A total of 36 donor juvenile calves on standard nutrition and in a disease-free environment, were selected from the breeding farm of the Beijing Dairy Cattle Center. At 60 days of age, calves were randomly assigned into three groups of four calves each, replicated three times. On day 1, Group 1 received a progesterone vaginal insert (CIDR, 300 mg per device); Group 2 received a CIDR and 0.5 mg oestrogen benzoate (China); Group 3 received a CIDR, 0.5 mg oestrogen benzoate, and 50 mg progesterone (China). Then, calves were injected with FSH (Folltropin-V, Bioniche Animal Health, Belleville, ON, Canada) twice daily on days 5 (40 mg/40 mg) and 6 (30 mg/30 mg) at 12 h intervals. Cumulus–oocyte complexes (COCs) were recovered from the superstimulated calves 12 to 14 h after the final FSH treatment. COCs were considered usable unless they were damaged or had expanded cumulus layers. Usable COCs were matured in vitro for 24 h in maturation medium consisting of TCM199, 10% FBS, 10 μg mL–1 FSH, 1 μg mL–1 LH, 1 μg mL–1 E2–17β, 100 IU mL–1 penicillin, 100 μg mL–1 streptomycin, with (+Cys) or without (–Cys) 100 μM Cysteamine. Each calf oocyte was cultured in one well. The final concentration added to each fertilization drop was 5 × 106 sperm mL–1. Sperm and oocytes were co-cultured in IVF-100 medium (BO liquid+10 μg mL–1 heparin, Japan) at 38.5°C, 5% CO2 and a saturated humidity for 6 to 8 h. Blastocyst production rates were determined after 7 and 8 d of in vitro culture in CR1aa medium without the addition of cysteamine. Differences among treatments in each experiment were determined by one-way ANOVA and a multiple range test. Superstimulatory results indicated that more follicles were aspirated (63.2 per calf) and more usable oocytes were recovered (48.0 per calf) in Group 1 than in the other two groups (Group 2–45.2 and 31.8, respectively; Group 3–35.4 and 28.3, respectively; P < 0.05). No difference was observed between Groups 2 and 3. Superstimulation of calves twice at 30 day intervals in Group 2 (n = 12) did not affect the number of follicles or usable oocytes (overall, 44.2 and 28.0 per calf). Maturation rates (86.5% v. 85.0%, respectively) and cleavage rates (84.4% v. 80.0%, respectively) did not differ whether cysteamine was not (–Cys; n = 318) or was (+Cys; n = 330) added to the maturation medium. However, the blastocyst rate differed significantly (12.9% v. 35.2%, respectively; P < 0.01). This study established a protocol for the superstimulation of juvenile calves with an average of 48 oocytes obtained per calf. Superstimulation and surgical oocyte recovery twice at an interval of 30 days had no adverse effect on follicle development or oocyte recovery. The novelty of this research is that the blastocyst production rate of calf oocytes (35.2%) in maturation medium supplemented with cysteamine was similar to that reported in the cow.


2014 ◽  
Vol 26 (1) ◽  
pp. 181
Author(s):  
L. Berté ◽  
L. Vasconcelos ◽  
L. Hatamoto-Zervoudakis ◽  
W. Yamazaki ◽  
L. Yamazaki ◽  
...  

Bovine growth hormone (bGH) has been used to improve the results for in vitro production of bovine embryos. Inclusion of bGH in the maturation medium increases both rate of cleavage and frequency of blastocyst development. Thus, the purpose of the present study was to evaluate the effect of recombinant bovine somatotropin (rBST) on cleavage and blastocyst development of bovine embryos when included during in vitro maturation (IVM) only (Group 1), during both IVM and in vitro culture (IVC; Group 2), during IVC only (Group 3), or not included during either IVM or IVC (Group 4). Specifically, in Group 1, oocytes were matured in TCM 199 (Earle's salts) supplemented with 10% FCS, LH, FSH, oestradiol, and amikacin (IVM medium), plus 100 ng mL–1 of rBST and cultured in SOFaaci supplemented with essential amino acids, tri-sodium citrate, myo-inositol, and 5% FBS. In group 2, oocytes were matured in IVM medium containing 100 ng mL–1 of rBST and cultured in SOFaaci supplemented with essential amino acid, tri-sodium citrate, myo-inositol, 5% FBS; on Day 5, rBST (50 ng mL–1) was added. In Group 3, oocytes were matured in IVM medium without rBST; on Day 5, rBST (50 ng mL–1) was added. Group 4 was the control, without rBST supplementation. The treatment groups were analysed using the SAS® (SAS Institute Inc., Cary, NC, USA) in a completely randomised design (P < 0.05). Somatotropin has receptors in cumulus cells and in the zona pellucida acting directly in the oocyte; however, the increase in cleavage rate seen in previous studies after rBST treatment was not observed in the present study. Supplementation of culture medium with rBST during Day 2 to 6 of IVC has been shown to increase the number of trophoblast and subsequent pregnancy rate following transfer. However, in the present study, addition of 50 and 100 ng mL–1 of rBST to the maturation or culture medium did not affect the cleavage rate of embryos and blastocyst production. Table 1.Analysis of the meaning and percentages related to cleavage and production of embryos


2004 ◽  
Vol 16 (2) ◽  
pp. 146
Author(s):  
Y.S. Kim ◽  
S.A. Ock ◽  
S.L. Lee ◽  
S.Y. Choe ◽  
G.J. Rho

The present study compared the development of cloned porcine embryos following different activation treatments. Cumulus-oocyte complexes (COCs) were aspirated from slaughterhouse ovaries and cultured for 22h in NCSU#23 medium supplemented with 10% porcine follicular fluid, 0.57mM cysteine, 0.5μgmL−1 LH, 0.5μgmL−1 FSH and 10ngmL−1 EGF. The COCs were further cultured for an additional 22h in the same medium at 39°C in an atmosphere of 5% CO2 in air, without hormonal supplements. Primary cultures of fibroblasts from a female fetus on Day 40 of gestation were established in DMEM +15% FCS. For nuclear donation, cells at the 5th-6th passage were cultured in DMEM+0.5% FCS for 5 days in order to arrest the cells in G0/G1. Following enucleation, oocytes were reconstructed by transfer of donor cells and fusion by means of three DC pulses (1.4kVcm−1, 30μs) delivered by a BTX 200, in 0.28M mannitol containing 0.01mM CaCl2 and 0.01mMMgCl2. Eggs were then divided into three treatment groups; control (without further treatment, Group 1), eggs cultured in 10μgmL−1 cycloheximide (CHX) for 5h (Group 2), and eggs cultured in 1.9mM6-dimethylaminopurine (6-DMAP) for 5h (Group 3). The eggs were then cultured in sets of 30in 60μL drops of NCSU#23 supplemented with 4μgmL BSA (essentially fatty acid free) until Day 7 at 39°C in a humidified atmosphere of 5% CO2. On Day 4 the culture were fed by adding 20μL NCSU#23 supplemented with 10% FBS. All experiments were performed as 4 replicates and statistical analysis was performed by one-way ANOVA (P&lt;0.05). Blastocyst development rates were significantly higher (P&lt;0.05) in Group 3 embryos compared to Group 1 controls (27.6±2.7% v. 20.1±4.1%, respectively), but rates did not differ in Group 2 (23.8±5.7%) compared to control. Total cell number in Group 3 blastocysts was, however, significantly higher (P&lt;0.05) than in Groups 1 and 2 (44.6±2.4 v. 19.9±1.9 and 21.9±2.1, respectively). These results suggest that 6-DMAP is more efficient than cycloheximide in the activation of electrically fused NT oocytes during in vitro production of cloned porcine embryos. [Supported by High Technology Development Project for Agriculture and Forestry Korea, MAF-SGRP, 300012-05-3-SB010 and Cho-A Pharm. Co. LTD.]


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.2-341
Author(s):  
V. Orefice ◽  
F. Ceccarelli ◽  
C. Barbati ◽  
R. Lucchetti ◽  
G. Olivieri ◽  
...  

Background:Systemic lupus erythematosus (SLE) is an autoimmune disease mainly affecting women of childbearing age. The interplay between genetic and environmental factors may contribute to disease pathogenesis1. At today, no robust data are available about the possible contribute of diet in SLE. Caffeine, one of the most widely consumed products in the world, seems to interact with multiple components of the immune system by acting as a non-specific phosphodiesterase inhibitor2.In vitrodose-dependent treatment with caffeine seems to down-regulate mRNA levels of key inflammation-related genes and similarly reduce levels of different pro-inflammatory cytokines3.Objectives:We evaluated the impact of caffeine consumption on SLE-related disease phenotype and activity, in terms of clinimetric assessment and cytokines levels.Methods:We performed a cross-sectional study, enrolling consecutive patients and reporting their clinical and laboratory data. Disease activity was assessed by SLE Disease Activity Index 2000 (SLEDAI-2k)4. Caffeine intake was evaluated by a 7-day food frequency questionnaire, including all the main sources of caffeine. As previously reported, patients were divided in four groups according to the daily caffeine intake: <29.1 mg/day (group 1), 29.2-153.7 mg/day (group 2), 153.8-376.5 mg/day (group 3) and >376.6 mg/day (group 4)5. At the end of questionnaire filling, blood samples were collected from each patient to assess cytokines levels. These were assessed by using a panel by Bio-Plex assays to measure the levels of IL-6, IL-10, IL-17, IL-27, IFN-γ, IFN-α and Blys.Results:We enrolled 89 SLE patients (F/M 87/2, median age 46 years, IQR 14; median disease duration 144 months, IQR 150). The median intake of caffeine was 195 mg/day (IQR 160.5). At the time of the enrollment, 8 patients (8.9%) referred a caffeine intake < 29.1 mg/day (group 1), 27 patients (30.3%) between 29.2 and 153.7 mg/day (group 2), 45 patients (51%) between 153.8 and 376.5 mg/day (group 3) and 9 patients (10.1%) >376.6 mg/day (group 4). A negative correlation between the levels of caffeine and disease activity, evaluated with SLEDAI-2K, was observed (p=0.01, r=-0.26). By comparing the four groups, a significant higher prevalence of lupus nephritis, neuropsychiatric involvement, haematological manifestations, hypocomplementemia and anti-dsDNA positivity was observed in patients with less intake of caffeine (figure 1 A-E). Furthermore, patients with less intake of caffeine showed a significant more frequent use of glucocorticoids [group 4: 22.2%,versusgroup 1 (50.0%, p=0.0001), group 2 (55.5%, p=0.0001), group 3 (40.0%, p=0.009)]. Moving on cytokines analysis, a negative correlation between daily caffeine consumption and serum level of IFNγ was found (p=0.03, r=-0.2) (figure 2A); furthermore, patients with more caffeine intake showed significant lower levels of IFNα (p=0.02, figure 2B), IL-17 (p=0.01, figure 2C) and IL-6 (p=0.003, figure 2D).Conclusion:This is the first report demonstrating the impact of caffeine on SLE disease activity status, as demonstrated by the inverse correlation between its intake and both SLEDAI-2k values and cytokines levels. Moreover, in our cohort, patients with less caffeine consumption seems to have a more severe disease phenotype, especially in terms of renal and neuropsychiatric involvement. Our results seem to suggest a possible immunoregulatory dose-dependent effect of caffeine, through the modulation of serum cytokine levels, as already suggested byin vitroanalysis.References:[1]Kaul et alNat. Rev. Dis. Prim.2016; 2. Aronsen et alEurop Joul of Pharm2014; 3. Iris et alClin Immun.2018; 4. Gladman et al J Rheumatol. 2002; 5. Mikuls et alArth Rheum2002Disclosure of Interests:Valeria Orefice: None declared, Fulvia Ceccarelli: None declared, cristiana barbati: None declared, Ramona Lucchetti: None declared, Giulio Olivieri: None declared, enrica cipriano: None declared, Francesco Natalucci: None declared, Carlo Perricone: None declared, Francesca Romana Spinelli Grant/research support from: Pfizer, Consultant of: Novartis, Gilead, Lilly, Sanofi, Celgene, Speakers bureau: Lilly, cristiano alessandri Grant/research support from: Pfizer, Guido Valesini: None declared, Fabrizio Conti Speakers bureau: BMS, Lilly, Abbvie, Pfizer, Sanofi


2011 ◽  
Vol 75 (3) ◽  
pp. 429-433 ◽  
Author(s):  
F.G. Leivas ◽  
D.S. Brum ◽  
S.S. Fialho ◽  
W.P. Saliba ◽  
M.T.T. Alvim ◽  
...  

Scientifica ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Vedavathi Bore Gowda ◽  
B. V. Sreenivasa Murthy ◽  
Swaroop Hegde ◽  
Swapna Devarasanahalli Venkataramanaswamy ◽  
Veena Suresh Pai ◽  
...  

Aim. To compare the microleakage in class II composite restorations without a liner/with resin modified glass ionomer and flowable composite liner.Method. Forty standardized MO cavities were prepared on human permanent mandibular molars extracted for periodontal reasons and then divided into 4 groups of ten specimens. The cavity preparations were etched, rinsed, blot dried, and light cured and Adper Single Bond 2 is applied. Group 1 is restored with Filtek P60 packable composite in 2 mm oblique increments. Group 2 is precure group where 1 mm Filtek Z350 flowable liner is applied and light cured for 20 sec. Group 3 is the same as Group 2, but the liner was cocured with packable composite. In Group 4, 1 mm RMGIC, Fuji Lining LC is applied and cured for 20 sec. All the teeth were restored as in Group 1. The specimens were coated with nail varnish leaving 1 mm around the restoration, subjected to thermocycling, basic fuchsin dye penetration, sectioned mesiodistally, and observed under a stereomicroscope.Results. The mean leakage scores of the individual study groups were Group 1 (33.40), Group 2 (7.85), Group 3 (16.40), and Group 4 (24.35). Group 1 without a liner showed maximum leakage. Flowable composite liner precured was the best.


1994 ◽  
Vol 6 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Bradd C. Barr ◽  
Joan D. Rowe ◽  
Karen W. Sverlow ◽  
Robert H. BonDurant ◽  
Alex A. Ardans ◽  
...  

Studies were conducted to determine the pathogenic potential of the recently isolated bovine Neospora protozoa (BPA-1) for the bovine fetus. Cows chosen for study had Neospora titers < 160 using an indirect immunofluorescent antibody (IFA) test. Four experimental groups were studied. In group 1, 2 fetuses were inoculated in utero at 118 days gestation with culture-derived Neospora tachyzoites. A pregnant control cow was housed in the same pen, observed daily and screened serologically for evidence of exposure to Neospora. In group 2, 2 cows were infected with Neospora tachyzoites at 138 or 161 days gestation, and 1 control cow was given uninfected cell culture suspension simultaneously at 154 days gestation. Groups 3 (85 days gestation) and 4 (120 days gestation) each consisted of 2 cows infected with Neospora tachyzoites and 1 control cow given uninfected material at the same stage of gestation. Dead fetuses were surgically removed from the infected cows in group 1 on postinfection day (PID) 17. The histopathology was compatible with protozoal fetal infection, and protozoa were identified by immunohistochemistry. Viable fetuses were removed surgically from cows in group 2 on PID 28-30. The histopathology was compatible with protozoal fetal infection, protozoa were identified by immunoperoxidase techniques, and Neospora tachyzoites were reisolated in vitro from tissues of the 2 infected fetuses. In groups 3 and 4, the control fetus and 1 infected fetus were removed surgically between PID 26 and PID 33. The remaining infected cows were observed until fetal death or abortion occurred. In group 3, the fetus that was surgically removed from 1 infected cow had no pathologic abnormalities, and parasites were not found (PID 26). The second fetus in group 3 died in utero, and expulsion of a mummified fetus was induced on PID 67. Brain histopathology was compatible with protozoal infection, and parasites were identified by immunoperoxidase techniques. The fetus that was surgically removed (PID 32) from 1 infected cow in group 4 had lesions compatible with protozoal infection, and Neospora tachyzoites were reisolated in vitro from fetal tissues. The second infected cow in group 4 produced a full-term live calf that had a precolostral Neospora titer of 20,480. Clinically, this calf had depressed conscious proprioception in all limbs. Very mild lesions were found in the central nervous system, but protozoa were not found in the tissues. The results demonstrate that the bovine Neospora protozoa can be transplacentally transmitted, resulting in fetal infection and death, and mimics the naturally occurring fetal disease.


Author(s):  
Deebah Choudhary

Aim: The aim of this study was to evaluate the canal cleaning efficacy of these three file systems using scanning electron microscopy. Place and Duration of Study: The study was conducted in the Department of Conservative dentistry and Endodontics, Institute of Dental Sciences Sehora, between October 2020 and December 2020. Materials and Methods: Access cavity preparation was performed on sixty extracted human mandibular premolar teeth and working length was determined. The samples were randomly divided into three groups (n=20) depending upon the file system used i.e. Group 1 (Reciproc Blue), Group 2 (Waveone Gold) and Group 3 (F360). Samples were split into two halves by creating longitudinal grooves on the buccal and lingual surfaces. The samples were sputter-coated with gold and examined under scanning electron microscope at 5000X. The dentinal wall of root canal at coronal, middle and apical thirds of each sample were evaluated for the presence of determining the canal cleanliness and then analyzed using a five-score index. Results: The results of this study revealed that Group 1 (Reciproc Blue) exhibited better cleaning efficacy than samples of Group 2 (WaveOne Gold) and Group 3 (F360) at different locations in the canal i.e. coronal, middle and apical. The mean debris present was highest in coronal area for both group 2 and group 3 i.e. 2.1 and least was seen in apical area of group 1 i.e. 0.3. (p<0.05) Conclusion: Reciproc Blue single-file showed highest cleaning efficacy followed by Waveone Gold and F360. Reciproc file also showed effective cleaning in the apical third of the canal.


2020 ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Yihong Guo

Abstract BackgroundOestradiol, an important hormone in follicular development and endometrial receptivity, is closely related to clinical outcomes of fresh in vitro fertilization-embryo transfer (IVF-ET) cycles. A supraphysiologic E2 level is inevitable during controlled ovarian hyper-stimulation (COH), and its effect on the outcome of IVF-ET is controversial. The aim of this retrospective study is to evaluate the association between elevated serum oestradiol (E2) levels on the day of human chorionic gonadotrophin (hCG) administration and neonatal birthweight after IVF-ET cycles.MethodsThe data of 3659 infertile patients with fresh IVF-ET cycles were analysed retrospectively between August 2009 and February 2017 in First Hospital of Zhengzhou University. Patients were categorized by serum E2 levels on the day of hCG administration into six groups: group 1 (serum E2 levels≤1000 pg/mL, n=230), group 2 (serum E2 levels between 1001 and 2000 pg/mL, n=524), group 3 (serum E2 levels between 2001 and 3000 pg/mL, n=783), group 4 (serum E2 levels between 3001 and 4000 pg/mL, n = 721), group 5 (serum E2 levels between 4001 and 5000 pg/mL, n=548 ), and group 6 (serum E2 levels > 5000 pg/mL, n=852). Univariate linear regression was used to evaluate the independent correlation between each factor and outcome index. Multiple logistic regression was used to adjust for confounding factors.ResultsThe LBW rates were as follows: 3.0% (group 1), 2.9% (group 2), 1.9% (group 3), 2.9% (group 4), and 2.0% (group 6) (P =0.629), respectively. There were no statistically significant differences in the incidences of neonatal LBW among the six groups. We did not detect an association between peak serum E2 level during ovarian stimulation and neonatal birthweight after IVF-ET.ConclusionThe results of this retrospective cohort study showed that serum E2 peak levels during ovarian stimulation were not associated with birth weight during IVF cycles. In addition, no association was found between higher E2 levels and increased LBW risk. Our observations suggest that the hyper-oestrogenic milieu during COS does not seem to have adverse effects on the birthweight of offspring after IVF.


Author(s):  
Benjamin Gaborit ◽  
Eric Dailly ◽  
Bernard Vanhove ◽  
Régis Josien ◽  
Karine Lacombe ◽  
...  

Objective: We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2, in COVID-19-related moderate pneumonia. To evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. Methods : In this phase 2a trial, adults with COVID-19-related moderate pneumonia of ≤10 days duration were randomized to infusion of XAV-19 0.5mg/kg at day 1 and day 5 (group 1), 2mg/kg at day 1 and day 5 (group 2), 2mg/kg at day 1 (group 3) or placebo. Results : Eighteen patients (n=7 for group 1, n=1 for group 2, n=5 for group 3, and n=5 for placebo) were enrolled. Baseline characteristics were similar across groups, XAV-19 serum concentrations (μg/mL, median, range) at C max and at day 8 were 9.1 (5.2-18.1) and 6.4 (2.8-11.9), 71.5 and 47.2, and 50.4 (29.1-55.0) and 20.3 (12.0-22.7) for groups 1, 2 and 3, respectively (p=0.012). Terminal half-life (median, range) was estimated at 11.4 (5.5-13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 μg/mL (tow fold the in vitro 100% inhibitory concentration [IC 100 ]) from the end of perfusion to more than 8 days for XAV-19 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, there was no discontinuation for adverse events and no serious adverse events related to study drug. Conclusions : Single intravenous dose of 2mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. Trial registration: ClinicalTrials.gov Identifier: NCT04453384


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