scholarly journals Physical properties and biocompatibility effects of doping SiO2 and TiO2 into phosphate-based glass for bone tissue engineering

2018 ◽  
Vol 33 (2) ◽  
pp. 271-280 ◽  
Author(s):  
Alaa Aldaadaa ◽  
Mustafa Al Qaysi ◽  
George Georgiou ◽  
Rachel MA Leeson ◽  
Jonathan C Knowles
Keyword(s):  
Synergistic Effect ◽  
Physical Properties ◽  
Mass Loss ◽  
Bone Substitutes ◽  
Glass Density ◽  
Biological Responses ◽  
Group 2 ◽  
Group Compositions ◽  
Group 1

Phosphate glass is continuing to gain more attention as potential bone substitutes. The ternary (P2O5-CaO-Na2O) is investigated in terms of both physical properties and biocompatibility by doping different percentages of SiO2 and TiO2. Two groups were prepared; the first has different percentages of TiO2 and SiO2, whereas the second group compositions have 5 mol% TiO2 and 5 mol% SiO2 being added to compensate the network-forming oxide P2O5 and the network-modifying oxide CaO. Density, mass loss, pH, DTA, XRD, and cation release experiments were performed to study the physicochemical properties of the compositions, while MG63 and hMS cells were used within in vitro cell culture to study their biocompatibility. Results showed that an increase in TiO2 content correlated with an increase in glass density, decreased mass loss, increased trend of Tg and Tm values, and Na+ and Ca2+ release in group 1. There was no improvement in the MG63 viability or the ability of hMSCs to differentiate into osteoblasts where TiO2 decreased in favour of SiO2. Furthermore, in group 2, 50P2O5–25CaO was less dense than 45P2O5–30CaO, degraded dramatically less, had lower Tg and Tm values and released less Na+ and Ca(2+). The synergistic effect of doping 5 mol% TiO2 and 5 mol% SiO2 increased the MG63 viability in both compositions and was found 45P2O5–30CaO to have promising results in terms of the ability of hMSCs to differentiate into osteoblasts. To conclude, substituting TiO2 in place of SiO2 improved the physical properties and the biocompatibility of (P2O5-CaO-Na2O) glass system, whereas doping 5 mol% SiO2 and 5 mol% TiO2 together in place of P2O5 and CaO had a synergistic effect in controlling their degradation rate and improving their biological responses.

scholarly journals Effect of Splinting in Accuracy of Two Implant Impression Techniques

2014 ◽  
Vol 40 (6) ◽  
pp. 633-639 ◽  
Author(s):  
Erica Dorigatti de Avila ◽  
Fernanda de Matos Moraes ◽  
Sabrina Maria Castanharo ◽  
Marcelo Antonialli Del'Acqua ◽  
Francisco de Assis Mollo
Keyword(s):  
Confidence Interval ◽  
Analysis Of Variance ◽  
Impression Material ◽  
Titanium Screw ◽  
Standard Preparation ◽  
Implant Abutment ◽  
Interface Gaps ◽  
Group 2 ◽  
Group 1

Because there is no consensus in the literature about the need for a splint between copings, the aim of this study was to evaluate, in vitro, the accuracy of 2 impression techniques for implant-supported prostheses. A master cast was fabricated with four parallel implant abutment analogs and a passive framework. Two groups with 5 casts each were formed: Group 1 (squared impression copings with no splint: S) and Group 2 (splinted squared impression copings, using metal drill burs and Pattern resin: SS). The impression material used was polyvinyl siloxane with open trays for standard preparation of the casts. For each cast, the framework was positioned, and a titanium screw was tightened with 10 N·cm torque in analog A, after which measurements of the abutment-framework interface gaps were performed at analogs C and D. This process was repeated for analog D. These measurements were analyzed using software. A one-way analysis of variance (ANOVA) with a confidence interval of 95% was used to analyze the data. Significant differences were detected between S and SS in relation to the master cast (P ≤ 0.05). The median values of the abutment-framework interface gaps were as follows: master cast: 39.64 μm; squared impression copings with no splint: 205.86 μm; splinted squared impression copings: 99.19 μm. Under the limitations of this study, the technique presented for Group 2 produces better results compared with the technique used for Group 1.

scholarly journals A Flexible Multidose GnRH Antagonist versus a Microdose Flare-Up GnRH Agonist Combined with a Flexible Multidose GnRH Antagonist Protocol in Poor Responders to IVF

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Gayem İnayet Turgay Çelik ◽  
Havva Kömür Sütçü ◽  
Yaşam Kemal Akpak ◽  
Münire Erman Akar
Keyword(s):  
Gnrh Agonist ◽  
Gnrh Antagonist ◽  
Poor Responders ◽  
Vitro Fertilization ◽  
Significant Difference ◽  
Gnrh Antagonist Protocol ◽  
Group 2 ◽  
Antagonist Protocol ◽  
Group 1

Objective. To compare the effectiveness of a flexible multidose gonadotropin-releasing hormone (GnRH) antagonist against the effectiveness of a microdose flare-up GnRH agonist combined with a flexible multidose GnRH antagonist protocol in poor responders to in vitro fertilization (IVF).Study Design. A retrospective study in Akdeniz University, Faculty of Medicine, Department of Obstetrics and Gynecology, IVF Center, for 131 poor responders in the intracytoplasmic sperm injection-embryo transfer (ICSI-ET) program between January 2006 and November 2012. The groups were compared to the patients’ characteristics, controlled ovarian stimulation (COH) results, and laboratory results.Results. Combination protocol was applied to 46 patients (group 1), and a single protocol was applied to 85 patients (group 2). In group 1, the duration of the treatment was longer and the dose of FSH was higher. The cycle cancellation rate was significantly higher in group 2 (26.1% versus 38.8%). A significant difference was not observed with respect to the number and quality of oocytes and embryos or to the number of embryos transferred. There were no statistically significant differences in the hCG positivity (9.5% versus 9.4%) or the clinical pregnancy rates (7.1% versus 10.6%).Conclusion. The combination protocol does not provide additional efficacy.

scholarly journals THU0227 CAFFEINE INTAKE MODULATES DISEASE ACTIVITY AND CYTOKINES LEVELS IN SYSTEMIC LUPUS ERYTHEMATOSUS PATIENTS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 340.2-341
Author(s):  
V. Orefice ◽  
F. Ceccarelli ◽  
C. Barbati ◽  
R. Lucchetti ◽  
G. Olivieri ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Caffeine Intake ◽  
Caffeine Consumption ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
The Impact ◽  
Group 1

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

scholarly journals Evaluation of Gingival Microleakage in Class II Composite Restorations with Different Lining Techniques: An In Vitro Study

Scientifica ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6
Author(s):  
Vedavathi Bore Gowda ◽  
B. V. Sreenivasa Murthy ◽  
Swaroop Hegde ◽  
Swapna Devarasanahalli Venkataramanaswamy ◽  
Veena Suresh Pai ◽  
...  
Keyword(s):  
Study Groups ◽  
Class Ii ◽  
Composite Liner ◽  
Flowable Composite ◽  
Composite Restorations ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

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.

CURRENT STATUS OF COMBINED ANTIBIOTIC THERAPY

PEDIATRICS ◽  
1958 ◽  
Vol 21 (6) ◽  
pp. 1000-1009
Author(s):  
Charles V. Pryles
Keyword(s):  
Synergistic Effect ◽  
Bacterial Resistance ◽  
Current Status ◽  
Causative Organism ◽  
In Vitro Tests ◽  
Aminosalicylic Acid ◽  
Tract Infections ◽  
Vitro Effect ◽  
Group 1

The use of combinations of drugs in "shotgun" fashion, on the theory if one will do something, two or three will accomplish more, is to be deplored. A single antibiotic can be used effectively in most infections caused by a single organism. Furthermore, a single wide-spectrum antibiotic may be used in many mixed infections. In certain infections, the value of combinations of antibiotics has been proved, both in the laboratory and in the clinic: (a) streptomycin plus one of the tetracyclines in brucellosis; (b) penicillin plus streptomycin in enterococcic endocarditis; (c) erythromycin plus chloramphenicol in serious staphylococcal infections in which the organism is resistant to penicillin; (d) streptomycin, isoniazid and para-aminosalicyclic acid in treatment of tuberculosis. In these infections, the proper combination should be used from the start and in full therapeutic dosage. Mixtures of antibiotics may occasionally be useful in individual cases outside this group but, in general, these mixtures do not produce a synergistic effect. If the infection does not fall into one of the four classes already cited, the in-vitro effect of combinations of various antibiotics should be studied, providing the patient's illness is such that a delay of 48 to 72 hours is warranted. The combination showing the greatest synergistic effect should then be used. Persisting urinary tract infections and endocarditis are examples of conditions in which this method is likely to produce results. Even here, it must be borne in mind that such in-vitro tests do not guarantee that a certain mixture of antibiotics will be effective clinically; in fact, they may be misleading. In accord with the recommendations of Dowling, if there is not sufficient time for an in-vitro study to be carried out, two antibiotics in Jawetz and Gunnison's Group 1 (see text) may be used together, if each alone is partially effective against the causative organism. If no two antibiotics in Group 1 fit this criterion, and a combination of an antibiotic from Group 1 and one from Group 2 does fit the criterion, this combination should be given in doses that will result in full therapeutic concentrations of each antibiotic at the site of infection. For delaying the emergence of resistant strains of tubercle bacilli, combinations of two or more of the following drugs are indicated: Streptomycin, isoniazid and para-aminosalicylic acid. A combination of chloramphenicol with erythromycin is also indicated to delay emergence of resistance of staphylococci to the batter antibiotics. In the treatment of seriously ill patients before a bacteriologic diagnosis is available, two or more antibiotics may properly be administered. Such illnesses include endocarditis, suspected staphylococcal pneumonia in infants, tuberculosis, brucellosis, and meningitis due to an unidentified organism. Combined antimicrobials should be given only after a careful clinical diagnosis has been made, and in doses that would be optimal for each drug if used alone. Readymade mixtures are not recommended for use systemically; certain combinations of agents, such as a mixture of bacitracin and polymyxin B, may have a place in topical therapy. Finally, there are several potentially harmful or undesirable effects that may result from the use of combinations of antimicrobials and these must be considered whenever their possible use arises. These include: (1) the tendency of fixed, "packaged" combinations to encourage inadequate therapy; (2) the possible increase in hypersensitivity and/or toxicity to one or more of the agents in a combination; (3) the probable emergence of bacterial resistance to either or both of the antibiotics in a mixture; (4) superinfection by originally resistant organisms not affected by the therapy; (5) the accumulation of antibiotic-resistant organisms within hospitals or other semiclosed communities; and (6) the possibility of interference of one antibiotic with the operation of another in a given combination.

scholarly journals Experimental Reproduction of Bovine Fetal Neospora Infection and Death with a Bovine Neospora Isolate

1994 ◽  
Vol 6 (2) ◽  
pp. 207-215 ◽  
Author(s):  
Bradd C. Barr ◽  
Joan D. Rowe ◽  
Karen W. Sverlow ◽  
Robert H. BonDurant ◽  
Alex A. Ardans ◽  
...  
Keyword(s):  
Uninfected Cell ◽  
In Utero ◽  
Pathogenic Potential ◽  
Group 4 ◽  
Fetal Infection ◽  
Group 3 ◽  
Group 2 ◽  
Protozoal Infection ◽  
Group 1

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.

scholarly journals Comparative Evaluation of Cleaning Efficacy of Three Different Single File Systems: An In Vitro Study

2021 ◽  
pp. 26-31
Author(s):  
Deebah Choudhary
Keyword(s):  
File Systems ◽  
In Vitro Study ◽  
Single File ◽  
Working Length ◽  
Group 3 ◽  
Group 2 ◽  
Cleaning Efficacy ◽  
Scanning Electron ◽  
Group 1

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.

scholarly journals Association Between Serum Oestradiol Level on the Human Chorionic Gonadotrophin Administration Day and Neonatal Birthweight After in Vitro Fertilization-embryo Transfer: A Retrospective Study of 3659 Singleton Live Births

2020 ◽  
Author(s):  
Yu Liu ◽  
Jing Li ◽  
Yihong Guo
Keyword(s):  
Retrospective Study ◽  
Chorionic Gonadotrophin ◽  
Human Chorionic Gonadotrophin ◽  
Vitro Fertilization ◽  
Group 4 ◽  
Group 3 ◽  
Group 2 ◽  
Ivf Et ◽  
Group 1

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.

scholarly journals Phytochemical Analysis and In-Vitro Effects of Ethanolic Tamarindus Indica Seed Extract on Snake Venom

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Soraya Ismail ◽  
Nur Farhana Azmi ◽  
Khin Maung Maung ◽  
Pakeer Oothuman
Keyword(s):  
Snake Venom ◽  
Seed Extract ◽  
Tamarindus Indica ◽  
Phytochemical Screening ◽  
Snake Species ◽  
Hydrolysable Tannins ◽  
Group 2 ◽  
In Vitro Effects ◽  
Group 1

Introduction: Snakebite has been categorised as a ‘neglected tropical disease’ by WHO in 2009 and it affects mainly the poorer countries like Africa and Asia. The standard treatment for snake envenomation is the anti-snake venom medication which can be very expensive, not readily available and specific against a snake species. This study was conducted to screen the phytochemical compounds of Tamarindus indica seed extract (TSE) and its in-vitro effects on snake venom of three snake species; namely Daboia russelli, Naja kaouthia and Ophiophagus hannah. Materials and method: Ethanolic Soxhlet extract of TSE was used. Phytochemical screening analysing for saponins, alkaloids, flavanoids, anthraquinone derivatives, arthraquinone glycosides, phenolic compounds, tannins, terpenoids, sterol and volatile oils were carried out. In-vitro enzymatic inhibition study on venom enzymes namely phospholipase A2 (PLA2), proteinase and phosphomonoesterase (PME) were studied by measuring the absorbance using the spectrophotometer. There were two main groups; Group 1: venom only; and Group 2: venom with TSE. The mean triplicate determination of venom enzyme activity post-exposure to TSE from Group 2 was taken and analysed against 100% venom enzyme activity from Group 1. Results: Phytochemical screening showed that the TSE has (+++) phenolics and (+++) hydrolysable tannins. TSE significantly reduced all venom enzymatic activities i.e. PLA2, proteinase and PME from the three snake species at 925 nm, 280 nm and 400 nm, respectively. SDS-PAGE experiment showed the disruption of venom protein bands from all three snake species when venom was exposed to 4.76 µg TSE. Conclusion: Ethanolic TSE contains mainly phenolics and hydrolysable tannins which can reduce the snake venom enzymatic activities. This is possibly due to the formation of tannin-protein complex rendering the venom less potent.

scholarly journals Pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, for COVID-19-related moderate pneumonia: a randomized, double-blind, placebo-controlled, phase IIa study

2021 ◽  
Author(s):  
Benjamin Gaborit ◽  
Eric Dailly ◽  
Bernard Vanhove ◽  
Régis Josien ◽  
Karine Lacombe ◽  
...  
Keyword(s):  
Adverse Events ◽  
High Serum ◽  
Serum Concentrations ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Good Tolerability ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

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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