scholarly journals Intrahepatic Arterial Delivery of Sorafenib Eluting Beads: A Pharmacokinetics Study

2020 ◽  
Vol 3 (2) ◽  
pp. 17
Author(s):  
Eerdunbagena Ning ◽  
Zhijun Wang

 Objective: To determine the slow-release effect of Sorafenib carried beads and its impact on the normal liver of dogs. Materials and Methods: (1) To obtain the maximal drug-carrying of beads, different sizes of beads (300-500 μm and 500-700 μm) were tried. Five bottles of different sizes of beads were added into 75% solution of Sorafenid-alcohol with different concentrations: Bottle a,50mg/20ml; Bottle b, 100mg/20ml; Bottle c, 100 mg/40ml; Bottle d, 200mg/40m; Bottle e, 250mg/50ml. (2) In vivo study: 12 dogs were randomly divided into four groups [group A, Sorafenib carried bead (500-700μm); group B, only bead (300-500μm) ; group C, Lipiodol-sorafenib and four dogs in each group. Each group was treated with TAE with emulsion mentioned above. Sorafenib concentration in plasma and liver tissue was determined with HPLC respectively. Result: (1) In vitro research: Sorafenib can be dissolved into 75% alcohol and the best concentration for drug-carrying was 100mg/20ml. (2) In vivo study: ① Compared with group D, the Cmax and AUC in plasma in group A and B has a significant statistics difference(p<0.05). ② Sorafenib concentration in liver tissue could be determined in group A in the 3rd day and even after one week while it could not be determined in group D. Conclusion: Sorafenib can be carried in DC-Bead in a certain condition. Compared with emulsion with Sorafenib and lipiodol, DC-bead has a definite slow-release function and it is superior to lipiodol.

2014 ◽  
Vol 26 (1) ◽  
pp. 182
Author(s):  
S. Matoba ◽  
S. Sugimura ◽  
H. Matsuda ◽  
Y. Aikawa ◽  
M. Ohtake ◽  
...  

Previously, it was reported that a high rate of good quality blastocysts were produced by IVF of in vivo-matured oocytes, obtained by ovum pick up (OPU) after superstimulation in Holstein cows, using X-sorted sperm (Matoba et al. 2012 Reprod. Domest. Anim. 47, 515). In this system, an early first cleavage within 28 h after IVF was found to be a potent marker for the selection of embryos with high developmental competence (Matoba et al. 2013 Reprod. Fertil. Dev. 25, 266). However, we have limited knowledge on the timing and normality of embryonic cleavages in in vitro-matured oocytes after IVF. The purpose of the present study was to compare the kinetics and patterns of the first cleavage of in vivo- and in vitro-matured bovine oocytes after IVF with X-sorted sperm. In vivo-matured oocytes (Group A) were collected by OPU from non-lactating Holstein cows just before ovulation after superstimulation. Immature oocytes were either collected by OPU without hormonal treatment or by aspiration of ovaries at the local abattoir and matured in vitro (Group B or C). All the oocytes were inseminated with 5 × 106 sperm mL–1 of X-sorted sperm, except half of oocytes in Group C inseminated by non-sorted sperm (Group D) and cultured in CR1aa supplemented with 5% calf serum and 0.25 mg mL–1 of linoleic acid albumin at 38.5°C in 5% CO2, 5% O2, and 90% N2 for 216 h. Embryo kinetics were observed individually using a microwell culture dish and time-lapse cinematography (Sugimura et al. 2010 Biol. Reprod. 83, 970–978). Photographs of each embryo were taken in every 15 min during the IVC period and analysed by time-lapse cinematography software. Cleavage pattern was categorized as normal (2 even blastomeres without fragment or protrusion) or abnormal (2 uneven blastomeres, with fragment or protrusion and those dividing into 3–5 blastomeres) at the first cleavage. Data were analysed by ANOVA, chi-squared, or discriminant function. A total of 268 cleaved embryos were used. The blastocyst rate in Group A was higher than in Groups B and C (61.3 v. 40.0 and 25.0%, respectively; P < 0.05). The timing of first cleavage was longer in Group A compared with Groups C and D (28.3 ± 3.8 v. 27.6 ± 3.8 and 26.7 ± 1.9 h, respectively) and in Group B (28.1 ± 4.0 h) compared with in Group D (P < 0.05). Higher rates of normal cleavage were observed in Groups A, B, and D than in Group C (53.5, 44.4, and 54.8 v. 16.7%, respectively; P < 0.01). The frequency of blastocysts derived from the early (28.3 h) and normal pattern cleaving oocytes were greater in Groups A and B than in Group C (29.0 and 20.0 v. 8.3%, respectively; P < 0.05) and similar in Group D (22.6%). Our results reveal that IVF embryos produced from in vivo-matured oocytes with sex-sorted sperm had superior normality than those produced from in vitro-matured oocytes and similar normality to embryos inseminated with non-sorted sperm. Supported by the Research and Development projects for application in promoting new policy of agriculture, forestry and fisheries (22016) and by JSPS and HAS under the Japan-Hungary Research Cooperative Program.


2018 ◽  
Vol 47 (1) ◽  
pp. 212-221 ◽  
Author(s):  
Cecilia Pascual-Garrido ◽  
Elizabeth A. Aisenbrey ◽  
Francisco Rodriguez-Fontan ◽  
Karin A. Payne ◽  
Stephanie J. Bryant ◽  
...  

Background: In this study, we investigate the in vitro and in vivo chondrogenic capacity of a novel photopolymerizable cartilage mimetic hydrogel, enhanced with extracellular matrix analogs, for cartilage regeneration. Purpose: To (1) determine whether mesenchymal stem cells (MSCs) embedded in a novel cartilage mimetic hydrogel support in vitro chondrogenesis, (2) demonstrate that the proposed hydrogel can be delivered in situ in a critical chondral defect in a rabbit model, and (3) determine whether the hydrogel with or without MSCs supports in vivo chondrogenesis in a critical chondral defect. Study Design: Controlled laboratory study. Methods: Rabbit bone marrow–derived MSCs were isolated, expanded, encapsulated in the hydrogel, and cultured in chondrogenic differentiation medium for 9 weeks. Compressive modulus was evaluated at day 1 and at weeks 3, 6, and 9. Chondrogenic differentiation was investigated via quantitative polymerase reaction, safranin-O staining, and immunofluorescence. In vivo, a 3 mm–wide × 2-mm-deep chondral defect was created bilaterally on the knee trochlea of 10 rabbits. Each animal had 1 defect randomly assigned to be treated with hydrogel with or without MSCs, and the contralateral knee was left untreated. Hence, each rabbit served as its own matched control. Three groups were established: group A, hydrogel (n = 5); group B, hydrogel with MSCs (n = 5); and group C, control (n = 10). Repair tissue was evaluated at 6 months after intervention. Results: In vitro, chondrogenesis and the degradable behavior of the hydrogel by MSCs were confirmed. In vivo, the hydrogel could be delivered intraoperatively in a sterile manner. Overall, the hydrogel group had the highest scores on the modified O’Driscoll scoring system (group A, 17.4 ± 4.7; group B, 13 ± 3; group C, 16.7 ± 2.9) ( P = .11) and showed higher safranin-O staining (group A, 49.4% ± 20%; group B, 25.8% ± 16.4%; group C, 36.9% ± 25.2%) ( P = .27), although significance was not detected for either parameter. Conclusion: This study provides the first evidence of the ability to photopolymerize this novel hydrogel in situ and assess its ability to provide chondrogenic cues for cartilage repair in a small animal model. In vitro chondrogenesis was evident when MSCs were encapsulated in the hydrogel. Clinical Relevance: Cartilage mimetic hydrogel may offer a tissue engineering approach for the treatment of osteochondral lesions.


1976 ◽  
Vol 85 (6_suppl) ◽  
pp. 2-32 ◽  
Author(s):  
Thomas R. Van De Water

An experiment was designed to answer the question as to whether or not the neural elements of the statoacoustic ganglion complex have a trophic effect upon the histodifferentiation of the sensory structures of the embryonic mouse inner ear anlage as it develops in vitro. The embryonic inner ear anlage with associated otic mesenchyme and statoacoustic ganglion complex was excised from 11, 12, and 13-day CBA/C57 mouse embryos. The inner ear explants of each gestational age group were further divided into two groups: the first group “A” (with) statoacoustic ganglion was explanted to the organ culture system without further surgical intervention; the second group “B” (without) statoacoustic ganglion underwent further surgical manipulation during which their statoacoustic ganglion complexes were dissected away prior to explantation to in vitro. The explanted embryonic inner ears were allowed to develop in organ culture until the equivalent of gestation day 21 in vivo was reached for each group; then all cultures were fixed and histologically processed and stained by a nerve fiber stain, in combination with a stain for glucoprotein membranes. Each specimen was code labeled and scored for histodifferentiation of sensory structures. Light microscopic observations confirmed that in group “A” cultures, statoacoustic ganglion neurons and their nerve fibers were present in association with the developed sensory structures; neither ganglion cell neurons nor their nerve fibers were found to be present in the sensory structures that developed in the group “B” organ culture specimens. Quantification revealed no consistent trend of greater occurrence of any sensory structure in the groups of explants analyzed. The presence of such a trend would have signified the probable existence of a trophic effect of the statoacoustic ganglion neural elements upon development of inner ear sensory structures in the group “A” explants of the 11, 12, and 13-day embryo inner ear organ culture specimens when compared to the aganglionic group “B” cultures. Microscopic comparison of the sensory structures and their sensory hair cells that developed in the organ cultures revealed no differences in the quality of the histodifferentiation of either group “A” or group “B” explants. A base to apex pattern of histodifferentiation of the organ of Corti sensory structures, which has been described to occur in vivo, was noted to occur in the in vitro developed cochlear ducts of all of the explanted inner ears without respect to whether neural elements were present (“A”) or absent (“B”) during development. It was concluded from the quantification of histodifferentiation data and the above observation on the pattern of differentiation of Corti's organ that no trophic effect of neural elements of the statoacoustic ganglion complex influencing the histodifferentiation of sensory structures of 11, 12, and 13-gestation day mouse embryo inner ear explants as they differentiate in vitro could be demonstrated.


2017 ◽  
Vol 8 (3) ◽  
pp. 83-89
Author(s):  
Johnny Holanda De Gauw ◽  
Lara Maria Melo Costa ◽  
Rodrigo Neves Silva ◽  
Natanael Barbosa Santos ◽  
Maria Dânia Holanda Tenorio

Objective: This study aimed to evaluate the effect of ferrous sulfate (FS) on demineralized and non-demineralized human deciduous teeth. Additionally, it was evaluated the penetration extent of FS and its remineralizing effect on the enamel of deciduous teeth using Polarized Light Microscopy (PLM). Method: The sample comprised 44 human deciduous teeth. The 44 crowns were divided randomly into four groups: group A (FS after demineralization), group B (FS without demineralization), group C (only demineralization), and group D (control group). FS at 0.45 mol/L-1 was used daily (15 days) and demineralization was done by pH cycling (7 days). Then, three longitudinal slices of the crowns were photographed using PLM. The degree of penetration of the lesion or stain was measured in micrometers, as well as the distance between the external enamel surface and the core of lesion. Results: Group A showed a dark stain on the outer surface of enamel larger than the group B. It is suggested, a remineralizing effect when comparing groups, A and C. The mean depth and standard deviation for groups A, B, and C were 4.27µm (±1.49), 3.72 µm (±1.68) and 5.00 µm (±1.84), respectively. No dark stains were observed in group D. Conclusion: FS stained the demineralized and non-demineralized human deciduous teeth. However, dark stains in the non-demineralized teeth were smaller or absent, than in the demineralized teeth. Therefore, FS may have a protective effect against demineralization.


2020 ◽  
Vol 7 (10) ◽  
pp. 2041
Author(s):  
Neha Thilak ◽  
Sundeep K. Hedge ◽  
Sham S. Bhat

Background: The aim of the study is to compare the erosive potential of three different commonly used pediatric syrups on deciduous teeth enamel. The objectives of the study were to assess the endogeneous pH and titratable acidity of mefenamic acid syrup (meftal P), cetrizine syrup (alerid) and multivitamin syrup (zincovit) and to evaluate the microhardness of the enamel after successive immersion cycles in each of the syrups.Methods: 40 non carious deciduous teeth were included for the study The samples were then randomly allocated into 4 groups (10 in each group): Group A- mefenemic acid syrup (meftal P), Group B- cetrizine syrup (alerid), group C- multivitamin syrup (zincovit) and group D- control (distilled water). The samples were then subjected to the immersion cycles in the syrups. Assessment of enamel surface microhardness was done using Vickers hardness tester at 7th day and 14th day. The pH and titrable acidity of the syrups were also assessed. One way analysis of variance (ANOVA) and post hoc tests were used for the statistical analysis.Results: Out of the test groups, group C showed the lowest pH of around 4.2 and exhibited the largest titrable acidity (22.8 ml) compared with 21 ml in group A and 15.5 ml in group B. At the end of 14th day, group A had microhardness of about 293.43.84±6.34, group B had 299.930±6.85, group C had 313.380±6.23 and group D had 334.190±5.51.Conclusions: All the pediatric liquid medications assessed in the study, meftal P, alerid and zincovit showed acidic pH, high titrable acidities and all the syrups showed loss of microhardness after exposure to the syrups for 14 days. Loss of microhardness was highest for meftal P followed by alerid and least for zincovit.


2015 ◽  
Vol 42 (3) ◽  
pp. 202-208 ◽  
Author(s):  
Wen-Jian Jiang ◽  
Yong-Chao Cui ◽  
Jin-Hua Li ◽  
Xiu-Hui Zhang ◽  
Huan-Huan Ding ◽  
...  

Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium. We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at 4 months in group C, and at 6 months in group D. Each collected sample was divided into 2 parts, one for calcium-content measurement by means of atomic-absorption spectroscopy, and one for morphologic and histopathologic examinations. When compared with the autologous pericardium, calcium levels in the heterologous pericardium were higher in groups B, C, and D (P &lt;0.0001, P &lt;0.0002, and P &lt;0.0006, respectively). As embedding time increased, calcium levels in the heterologous pericardium increased faster than those in the autologous, especially in group D. Disorganized arrangements of collagenous fibers, marked calculus, and ossification were seen in the heterologous pericardium. Inflammatory cells—mainly lymphocytes and small numbers of macrophages—infiltrated the heterologous pericardium. The autologous pericardium showed a stronger ability to resist calcification. Our results indicate that autologous pericardium might be a relatively better choice for valvuloplasty.


Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1383-1388 ◽  
Author(s):  
LL Lenny ◽  
R Hurst ◽  
J Goldstein ◽  
LJ Benjamin ◽  
RL Jones

Abstract Full-unit transfusions of RBC enzymatically converted from group B to group O by treatment with alpha-galactosidase (ECO RBC) to group O and A normal healthy individuals exhibit excellent in vivo survival times (24-hour survival 95.1% +/- 2.3%, T50 36.9 +/- 4.6 days). These results confirm our earlier findings describing ECO RBC in vitro viability and normal in vivo survival time after small-volume infusions. No significant increase in pretransfusion anti-B titer or score is observed in either group O or A subjects provided that sufficient enzyme is used to treat the cells: Cells transfused to group O recipients require higher levels of enzyme (185 to 200 U/mL RBC) than those infused to group A (90 U/mL RBC). Two separate single-unit transfusions of ECO RBC to one group O recipient (4.5 months apart) also survived normally (24-hour survival 96% and 92%, T50 40 and 36 days) and did not increase preexisting anti-B levels in this subject. ECO RBC were not agglutinated or lysed by recipient sera before or after transfusion. Similarly, no antibody development to the alpha- galactosidase used in cell treatment (and washed from the product before transfusion) could be detected in any subject. The sustained increase in hemoglobin levels after transfusion of ECO RBC suggests that this product will be useful in treatment of acute and chronic anemia.


2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Shan Chen ◽  
Yu-Tong Jin ◽  
Zheng-Yang Zhu ◽  
Ling-Tao Wu ◽  
Ping Yang ◽  
...  

Objective. To investigate the site of action of sinapine thiocyanate (ST), following acupoint herbal patching (AHP). Methods. Twenty Wistar rats were randomized into five groups (groups A, B, C, D, and E), and all groups received the same AHP in vivo. Skin samples were excised at 2 h, 4 h, 6 h, 10 h, and 26 h after AHP administration from group A to group E separately and the concentrations of ST in the skin were determined using a liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method. A pharmacokinetic profile of ST following AHP was performed at the same time in a group of five Wistar rats to detect plasma levels at the same time intervals. Results. The mean ± SD ST concentrations (ng/ml) at 2 h (group A), 4 h (group B), 6 h (group C), 10 h (group D), and 26 h (group E) after AHP administration were 250.01±61.99, 61.01±30.41, 40.12±26.94, 78.66±59.43, and 19.55±18.95, respectively. No ST was detected in rats’ plasma samples at the same time points. Conclusions. The site of action of ST following AHP is in the skin.


2019 ◽  
Vol 31 (1) ◽  
pp. 198
Author(s):  
F. Kotarski ◽  
B. Zimmer ◽  
C. Wrenzycki

The sex ratio of newborn calves and embryos produced in vivo is ~1:1. However, numerous studies on bovine in vitro-produced embryos suggest that the sex ratio may differ from 1:1 and that the rate of development may be influenced by the sex of the embryo under certain culture conditions. The duration of sperm-oocyte interaction and sperm pre-incubation also affect the sex ratio of bovine embryos produced in vitro. It is well documented that in vitro male embryos reach the more advanced stages earlier than do their female counterparts. Selection of developmentally more advanced embryos in anticipation that they have a greater developmental capacity may be one of the underlying causes of the disproportionate number of males among offspring born after transfer of in vitro-produced embryos. The aim of the present study is to test whether a pre-incubation of sperm before IVF might improve the developmental rates and also influence the sex ratio of the resulting embryos. Bovine cumulus-oocyte complexes were recovered from abattoir-derived ovaries by the slicing method. After 24h of maturation, fertilization was realised using a standard protocol. Prior to IVF, sperm cells from 2 different bulls were treated as follows: sperm within group A were pre-incubated in IVF medium for one hour. This step was omitted for sperm in group B (control). After 19h of co-culture of COC and sperm, presumptive zygotes were cultured in SOFaa for a period of 7 days. Cleavage and developmental rates were recorded at Day 3 and 7 (Day 0=IVF). Day 7 blastocysts from all groups were sexed using bovine and Y chromosome-specific primers. Data were analysed by ANOVA. As shown in Table 1, sperm pre-incubation did not affect the cleavage and developmental rates for the individual bull (P&gt;0.05). On average, at Day 7 of development a higher number of blastocysts was determined when embryos had been produced from pre-incubated sperm (P ≤ 0.05). This held true for both bulls. The shift in favour of male embryos was detectable in all groups of embryos, with a drastic one for bull 1 after sperm pre-incubation. In conclusion, sperm pre-incubation accelerated embryo development and possibly enhanced the proportion of male embryos, which was already shifted toward males. Table 1.Developmental rates, developmental kinetics and sex ratio of embryos after sperm pre-incubation before IVF (mean±standard deviation)


2021 ◽  
Vol 12 (1) ◽  
pp. 144-152
Author(s):  
Minal Gopal Tulsani ◽  
Dhanraj Ganapathy ◽  
Divya Rupawat ◽  
Sanjana Devi

Aim: To evaluate the effectiveness of midazolam and zolpidem on postoperative pain perception in patients undergoing implant placement. Materials and Methods: In the present in vivo study 60 patients undergoing implant placement were selected based on the inclusion criteria framed and were randomly allocated using sequentially numbered, opaque, and sealed envelope (SNOSE) method into 3 groups with 20 patients each after obtaining informed consent. Group A was the control group, Group B received midazolam 7.5 mg 30 minutes before the procedure. Group C received zolpidem 5 mg 30 minutes before the procedure. The anxiety level of patients was recorded using the Corah scale and postoperative pain was recorded after 2 hours of implant placement using the VAS scale. Statistical analysis was done using analysis of variance (ANOVA), one-way multivariate analysis of variance (one-way MANOVA), and then Tukey’s Honestly Significant Difference (HSD) test for comparison among groups at the 0.05 level of significance. Results: Group A had a mean anxiety level of 16 ± 1.451, Group B had a mean anxiety level of 11.2 ± 2.858, and Group C had a mean anxiety level of 13 ± 2.9019 and a statistically significant difference between the groups was observed ( P < .05). The mean for the postoperative pain perception for Group A was 6.8 ± 1.1965, for Group B was 3.8 ± 1.3611, and Group C was 5 ± 1.451 and a statistically significant difference between the groups was observed ( P < .05). Conclusion: This study concluded that both midazolam and zolpidem significantly reduced anxiety levels and postoperative pain in patients undergoing implant placement.


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