scholarly journals 221.Effects of exogenous gonadotrophin stimulation on ovarian tissue grafts in the mouse

2004 ◽  
Vol 16 (9) ◽  
pp. 221
Author(s):  
H. Yang ◽  
S. Cox ◽  
J. Shaw ◽  
G. Jenkin

Ovarian tissue grafts commonly contain only limited numbers of follicles. The functional life span and ability to retrieve as many mature oocytes as possible from ovarian grafts is important when grafting is used to restore fertility. This study aimed to determine whether ovarian grafts responded to exogenous hormones in a similar manner to that of in situ ovaries. Ovaries of C57BlxCBA F1 mice were cut in half and grafted to one of three different graft sites in females of the same F1 line; bursal capsule (BC, n = 12), kidney capsule (KC, n = 6), subcutaneous tissue (SC, n = 24). Three weeks after grafting, half of the graft recipients in each group were treated with 5IU PMSG followed by 5IU hCG 48 hours later. Oocytes were collected directly from the grafted ovaries 10 hours after the hCG injection and fertilized in vitro. Oocytes from the ovaries of superovulated normal mice (n = 4) of the same hybrid strain were used as controls. Two-cell embryos were transferred to pseudopregnant recipients and collected at day 15 of gestation or the animals were allowed to go to term. Mature fertilisable MII oocytes were retrieved from stimulated grafts from all graft sites, however, the number (BC 9, KC 5, SC 2 oocytes per ovary) and proportion of two-cell embryos in each grafted group (BC 52%, KC 32%, SC 32%) was significantly (P < 0.05) lower than in the in vivo matured control (16 oocytes, 85% two-cell). The fetal and placental weights of fetuses produced from graft-derived oocytes were not significantly different to the control group. Phenotypically normal pups were born in each of the graft and control groups. In conclusion, ovarian grafts treated with exogenous gonadotrophins produce significantly fewer mature oocytes and two cell embryos compared to in situ ovaries. Work supported by ARC and NIH RFA.

2010 ◽  
Vol 22 (1) ◽  
pp. 183
Author(s):  
T. H. C. De Bem ◽  
P. R. Adona ◽  
R. Rochetti ◽  
F. F. Bressan ◽  
M. S. Miranda ◽  
...  

In vitro embryo production by somatic cell nuclear transfer (SCNT) still presents low efficiency and blastocyst production rates are around 20%. Pre-maturation with cell cycle inhibitors is one alternative that has been studied to improve oocyte competence for use in in vitro production systems. The neurotrophin brain-derived neurotrophic factor (BDNF) has been reported to improve oocyte maturation. The aim of this work was to optimize the in vitro pre-maturation culture of bovine oocytes and its use in SCNT. Oocytes that were submitted to meiosis block before IVM (BL group) were cultured in TCM-199 medium supplemented with 10 ng mL-1 BDNF and 10 μM butyrolactone I for 24 h and then matured in IVM medium (TCM-199, 10% FCS, 0.5 μg mL-1 FSH, 5.0 μg mL-1 LH, 2.0 mM pyruvate, and 50 μg mL-1 gentamicin). Control oocytes (control group) were matured in IVM medium. After 19 h of IVM, oocytes from both groups were denuded with 0.2% hyarulonidase, enucleated, and reconstructed. Reconstructed embryos were chemically activated with ionomycin (5 min) and 6-DMAP (3h) and cultured in vitro in SOF medium for 7 or 8 days. Statistical analyses were performed by using BIOSTATS v.4.0 software. In vitro development variables [1st polar body (PB), fusion, cleavage, and blastocyst rates on Days 7 and 8] and in vivo development rates on Days 35, 60, 90, and 120 of pregnancy were analyzed by chi-square test. Total cell numbers and cells with fragmented DNA were analyzed by ANOVA. A level of 5% significance was considered. Extrusion of 1st PB (BL: n = 693; 69.3% and control: n = 639; 63.5%) and fusion rates (BL: n = 397; 79.2% and control: n = 345; 72.9%) were higher (P < 0.05) in the BL group. There were no differences between treatments for cleavage rates (BL: n = 268; 67.5% and control: n = 228; 66.1%) or blastocyst rates on Day 7 (BL: n = 77; 19.4% and control: n = 69; 20.0%) and Day 8 (BL: n = 81; 20.4% and control: n = 73; 21.2%). Cloned blastocysts from both groups were submitted to TUNEL reaction (Day 8 blastocysts, n = 15 for BL and control groups) for DNA fragmentation analysis or were transferred to synchronized recipients (Day 7 blastocysts, n = 26 and n = 28 for BL and control groups, respectively) for in vivo development analysis. No differences were observed (P > 0.05) between BL and control groups for total cell numbers (n = 127 and n = 138, respectively) and cells with fragmented DNA (0.0209 and 0.0188, respectively). Pregnancy rates at 35 (BL: n = 5; 19.2% and control: n = 9; 32.1%), 60 (BL: n = 3; 11.5 and control: n = 3; 10.7), 90 (BL: n = 3; 11.5 and control; n = 3; 10.7), and 120 days (BL: n = 3; 11.5 and control: n = 3; 10.7) also did not differ (P > 0.05) between treatments. In conclusion, pre-maturation enhanced 1st PB extrusion and fusion rates of oocytes submitted to SCNT, and moreover, it was able to establish pregnancies until 120 days, similarly to the control group. Financial support: FAPESP and CNPQ, Brazil.


2020 ◽  
pp. 155335062097800
Author(s):  
Ian A. Makey ◽  
Nitin A. Das ◽  
Samuel Jacob ◽  
Magdy M. El-Sayed Ahmed ◽  
Colleen M. Makey ◽  
...  

Background. Retained hemothorax (RH) is a common problem in cardiothoracic and trauma surgery. We aimed to determine the optimum agitation technique to enhance thrombus dissolution and drainage and to apply the technique to a porcine-retained hemothorax. Methods. Three agitation techniques were tested: flush irrigation, ultrasound, and vibration. We used the techniques in a benchtop model with tissue plasminogen activator (tPA) and pig hemothorax with tPA. We used the most promising technique vibration in a pig hemothorax without tPA. Statistics. We used 2-sample t tests for each comparison and Cohen d tests to calculate effect size (ES). Results. In the benchtop model, mean drainages in the agitation group and control group and the ES were flush irrigation, 42%, 28%, and 2.91 ( P = .10); ultrasound, 35%, 27%, and .76 ( P = .30); and vibration, 28%, 19%, and 1.14 ( P = .04). In the pig hemothorax with tPA, mean drainages and the ES of each agitation technique compared with control (58%) were flush irrigation, 80% and 1.14 ( P = .37); ultrasound, 80% and 2.11 ( P = .17); and vibration, 95% and 3.98 ( P = .06). In the pig hemothorax model without tPA, mean drainages of the vibration technique and control group were 50% and 43% (ES = .29; P = .65). Discussion. In vitro studies suggested flush irrigation had the greatest effect, whereas only vibration was significantly different vs the respective controls. In vivo with tPA, vibration showed promising but not statistically significant results. Results of in vivo experiments without tPA were negative. Conclusion. Agitation techniques, in combination with tPA, may enhance drainage of hemothorax.


Sensors ◽  
2021 ◽  
Vol 21 (22) ◽  
pp. 7490
Author(s):  
Nattapong Sirintawat ◽  
Tanyaporn Leelaratrungruang ◽  
Pongsakorn Poovarodom ◽  
Sirichai Kiattavorncharoen ◽  
Parinya Amornsettachai

This study aimed to investigate and compare the reliability and accuracy of tooth shade selection in the model using 30 milled crowns via five methods: (1) digital single-lens reflex (DSLR) camera with twin flash (TF) and polarized filter (DSLR + TF), (2) DSLR camera with a ring flash (RF) and polarized filter (DSLR + RF), (3) smartphone camera with light corrector and polarized filter (SMART), (4) intraoral scanner (IOS), and (5) spectrophotometer (SPEC). These methods were compared with the control group or manufacturer’s shade. The CIE Lab values (L, a, and b values) were obtained from five of the methods to indicate the color of the tooth. Adobe Photoshop was used to generate CIE Lab values from the digital photographs. The reliability was calculated from the intraclass correlation based on two repetitions. The accuracy was calculated from; (a) ΔE calculated by the formula comparing each method to the control group, (b) study and control groups were analyzed by using the Kruskal–Wallis test, and (c) the relationship between study and control groups were calculated using Spearman’s correlation. The reliability of the intraclass correlation of L, a, and b values obtained from the five methods showed satisfactory correlations ranging from 0.732–0.996, 0.887–0.994, and 0.884–0.999, respectively. The ΔE from all groups had statistically significant differences when compared to the border of clinical acceptance (ΔE = 6.8). The ΔE from DSLR + TF, DSLR + RF, SMART, and SPEC were higher than clinical acceptance (ΔE > 6.8), whereas the ΔE from IOS was 5.96 and all of the L, a, and b values were not statistically significantly different from the manufacturer’s shade (p < 0.01). The ΔE of the DSLR + RF group showed the least accuracy (ΔE = 19.98), whereas the ∆E of DSLR + TF, SMART, and SPEC showed similar accuracy ∆E (ΔE = 10.90, 10.57, and 11.57, respectively). The DSLR camera combined with a ring flash system and polarized filter provided the least accuracy. The intraoral scanner provided the highest accuracy. However, tooth shade selection deserves the combination of various techniques and a professional learning curve to establish the most accurate outcome.


2013 ◽  
Vol 25 (1) ◽  
pp. 273
Author(s):  
K. Imai ◽  
S. Sugimura ◽  
M. Ohtake ◽  
Y. Aikawa ◽  
Y. Inaba ◽  
...  

We previously reported that follicular wave synchronization and follicular growth treatment (FGT) before ovum pick-up (OPU) were effective in improving oocyte competence, which was associated with an increase in related embryos obtained by somatic cell nuclear transfer (Sugimura et al. 2012 Cell. Reprogram. 14, 29–37). However, oxygen consumption in oocytes remained unknown. The present study was designed to examine the differences in oxygen consumption between bovine oocytes obtained by OPU with or without FGT after in vitro maturation. Holstein dry cows (n = 8) were reared under the same feeding and environmental conditions. Two OPU sessions were conducted in each cow to collect immature oocytes, as described by Sugimura et al. (2012). The first OPU session (OPU group) was performed in cows on arbitrary days of the oestrous cycle, using a 7.5-MHz linear transducer with the needle connected to an ultrasound scanner. Follicles larger than 8 mm in diameter were then aspirated and a controlled internal drug release device (CIDR) was inserted on Day 5 (the day of the first OPU session = Day 0). Then 30 Armour units (AU) of FSH (Antrin, Kyoritsu Seiyaku, Tokyo, Japan) was administrated to cows twice a day from Day 7 to 10 in decreasing doses (6, 6, 4, 4, 3, 3, 2, 2 AU day–1). Cloprostenol (prostaglandin F2α; 0.75 mg) was administered in the morning of Day 9. The second OPU session (FGT-OPU group) was performed 48 h after prostaglandin F2α administration (Day 11), and only follicles larger than 5 mm in diameter were aspirated. The CIDR was removed from the cows just before OPU. Collected cumulus–oocyte complexes in the OPU and FGT-OPU groups were matured in vitro as described by Imai et al. [2006 J. Reprod. Dev. 52(Suppl.), S19–S29]. To collect in vivo-matured oocytes (control group), the CIDR was inserted into the cows on arbitrary days of the oestrous cycle (= Day 0), and oestradiol benzoate (0.8 mg) was administered on Day 1. The cows received the FGT treatment (as described above) from Day 6 to 10; however, the CIDR was removed in the evening of Day 8. Buserelin (gonadotropin-releasing hormone; 200 µg) was then administrated in the morning of Day 10, and OPU was performed at 24 h after gonadotropin-releasing hormone administration (Day 11). Oxygen consumption of matured oocytes was measured noninvasively with a scanning electron microscopy system (HV-405SP; Hokuto Denko Co., Tokyo, Japan). Data were analysed by ANOVA followed by a Tukey-Kramer test. There was no difference in the mean oxygen consumption between the FGT-OPU group (0.34 ± 0.02 × 10–14 mol–1, mean ± SEM) and control group (0.40 ± 0.01 × 10–14 mol–1). However, oxygen consumption in the FGT-OPU and control groups was significantly lower (P < 0.01) than that in the OPU group (0.50 ± 0.02 × 10–14 mol–1). These results revealed significantly lower oxygen consumption in OPU-derived in vitro-matured bovine oocytes after FGT treatment compared with those obtained without FGT treatment. Oxygen consumption of oocytes obtained from FGT-OPU was similar to that of in vivo-matured oocytes, which may reflect their cytoplasmic maturation status with high developmental competence.


Zygote ◽  
2019 ◽  
Vol 27 (3) ◽  
pp. 166-172 ◽  
Author(s):  
Linying Jia ◽  
Bo Ding ◽  
Chong Shen ◽  
Shiwei Luo ◽  
Yanru Zhang ◽  
...  

SummaryRabbits play an important role in people’s lives due to their high nutritional value and high-quality hair that can be used as raw material for textiles. Furthermore, rabbits are an important animal model for human disease, as genome-edited animals are particularly valuable for studying gene functions and pathogenesis. Somatic cell nuclear transfer (SCNT) is an important technique for producing genome-edited animals and it has great value in saving endangered species and in clone stem cell therapy. However, the low efficiency of SCNT limits its application, with the selection of suitable rabbit oocytes being crucial to its success. In the present study, we collected oocytes from ovarian follicles and stained them with 26 μM brilliant cresyl blue (BCB). We then matured the oocytes in vitro and used them for SCNT. Comparison of the BCB-positive oocytes with BCB-negative oocytes and the control group showed that the BCB-positive group had a significantly higher maturation rate (81.4% vs. 48.9% and 65.3% for the negative and control groups, respectively), cleavage rate (86.6% vs. 67.9% and 77.9%), blastocyst rate (30.5% vs. 12.8% and 19.6%), total number of blastocysts (90±7.5 vs. 65.3±6.3 and 67.5±5.7), and inner cell mass (ICM)/ trophectoderm (TE) index (42.3±4.2 vs. 30.2±2.1 and 33.9±5.1) (P<0.05). The BCB-positive group had a significantly lower apoptosis index (2.1±0.6 vs. 8.2±0.9 and 6.7±1.1 for the negative and control groups, respectively) (P<0.05). These findings demonstrate that BCB-positive oocytes have a higher maturation ability and developmental competence in vitro, indicating that BCB staining is a reliable method for selecting oocytes to enhance the efficiency of SCNT.


Zygote ◽  
2014 ◽  
Vol 24 (1) ◽  
pp. 48-57 ◽  
Author(s):  
Iana S. Campelo ◽  
Alexsandra F. Pereira ◽  
Agostinho S. Alcântara-Neto ◽  
Natalia G. Canel ◽  
Joanna M.G. Souza-Fabjan ◽  
...  

SummaryThe present study investigated the effects of crotamine, a cell-penetrating peptide from rattlesnake venom, at different exposure times and concentrations, on both developmental competence and gene expression (ATP1A1, AQP3, GLUT1 and GLUT3) of in vitro fertilized (IVF) bovine embryos. In Experiment 1, presumptive zygotes were exposed to 0.1 μM crotamine for 6, 12 or 24 h and control groups (vehicle and IVF) were included. In Experiment 2, presumptive zygotes were exposed to 0 (vehicle), 0.1, 1 and 10 μM crotamine for 24 h. Additionally, to visualize crotamine uptake, embryos were exposed to rhodamine B-labelled crotamine and subjected to confocal microscopy. In Experiment 1, no difference (P > 0.05) was observed among different exposure times and control groups for cleavage and blastocyst rates and total cells number per blastocyst. Within each exposure time, mRNA levels were similar (P > 0.05) in embryos cultured with or without crotamine. In Experiment 2, concentrations as high as 10 μM crotamine did not affect (P > 0.05) the blastocyst rate. Crotamine at 0.1 and 10 μM did not alter mRNA levels when compared with the control (P > 0.05). Remarkably, only 1 μM crotamine decreased both ATP1A1 and AQP3 expression levels relative to the control group (P < 0.05). Also, it was possible to visualize the intracellular localization of crotamine. These results indicate that crotamine can translocate intact IVF bovine embryos and its application in the culture medium is possible at concentrations from 0.1–10 μM for 6–24 h.


Reproduction ◽  
2006 ◽  
Vol 131 (5) ◽  
pp. 851-859 ◽  
Author(s):  
Hsiao Yun Yang ◽  
Shae-Lee Cox ◽  
Graham Jenkin ◽  
Jock Findlay ◽  
Alan Trounson ◽  
...  

Ovarian tissue cryopreservation and subsequent transplantation can restore fertility in cancer patients. This study used a mouse ovarian grafting model to investigate whether the graft site (bursal cavity, the kidney capsule or subcutaneous) influences the number, fertilization rate and developmental potential of oocytes recovered from grafts and whether using a standard gonadotrophin stimulation protocol would increase oocyte yield from the grafts. Mouse ovarian tissue was grafted into four week old mice and collected three weeks later. Graft recipients were treated either with or without exogenous gonadotrophin stimulation prior to graft collection. Grafted ovaries yielded oocytes that were either at the germinal vesicle (GV) stage or mature metaphase II (MII) stage at collection. These GV oocytes were matured beforein vitrofertilization (IVF), while the MII oocytes underwent IVF immediately. Oocytes collected from the oviducts of non-grafted superovulated mice of the same age served as controls. Two-cell embryos were transferred to pseudopregnant recipients and recovered at day 15 of gestation or left to go to term. Graft retrieval and the number of oocytes from each graft were lowest from the subcutaneous graft site. The number of two-cell embryos produced was significantly higher for oocytes from the grafts to the bursa as compared with the other sites. All graft sites gave rise to embryos with comparable implantation rates and developmental potential to fetuses and offspring following transfer. However, the oocytes from grafted ovaries had a significantly lower developmental potential when compared with the control group. Stimulation with exogenous gonadotrophins did not significantly increase oocyte yield from grafted ovaries but did enhance oocyte maturation and development. In conclusion, graft site affects the number and quality of oocytes produced from ovarian grafts.


2015 ◽  
Vol 1 (1) ◽  
pp. 94 ◽  
Author(s):  
Ananto Ali Alhasyimi ◽  
Siti Sunarintyas ◽  
Marsetyawan HNE Soesatyo

Mini screw orthodontics merupakan alat yang digunakan dalam perawatan ortodonsia untuk kasus yang membutuhkan absolute anchorage. Mini screw yang tersedia terbuat dari logam nikel titanium atau stainless steel yang pada beberapa pasien menyebabkan reaksi pada jaringan. Uji implantasi adalah uji yang dilakukan untuk menentukan biokompatibilitas medical device yang berkontak langsung dengan jaringan hidup. Respon jaringan terhadap jejas pasca implantasimempengaruhi derajat pembentukan jaringan granulasi, reaksi benda asing, dan fibrosis. Penelitian ini bertujuan untuk mengetahui efek lokal implantasi kobalt kromium sebagai alternatif bahan mini screw orthodontics terhadap jaringan subkutan kelinci albino. Subjek penelitian berupa 20 ekor kelinci jantan albino yang digunakan untuk 2 kelompok(perlakuan dan kontrol negatif). Kobalt kromium dibuat lempengan diameter 10 mm dan ketebalan 1 mm. Pada kelompok perlakuan, material diimplankan pada jaringan subkutan dorsum kelinci dengan insisi sampai terbentuk poket subkutan, dasar poket tidak lebih dari 10 mm dari garis awal insisi dan dilakukan suturing. Kelompok kontrol hanya dilakukanincisi kemudian disuturing. Secara makroskopis 24 jam pasca implantasi, daerah implan diamati terjadinya edema, hematoma, enkapsulasi dan tanda-tanda inflamasi. Evaluasi secara mikroskopis pada hari ke 14 pasca implantasi, diamati perubahan histopatologis infiltrasi sel-sel inflamasi, kemudian rerata hasil diuji dengan uji independent samplet-test untuk mengetahui apakah ada perbedaan jumlah sel-sel inflamasi pada kelompok perlakuan dan kontrol. Hasil pengamatan makroskopis, kelompok perlakuan maupun kontrol hanya terlihat tanda inflamasi ringan berupa eritema. Rerata dan Simpangan baku jumlah PMN, limfosit, sel plasma, makrofag, giant cell, neovaskularisasi, fibrosis kobalt kromium dan kontrol berturut turut yaitu (0,6 ± 0,49; 0,7 ± 0,48); (0,9 ± 0,87; 1,0 ± 0,67); (0,6 ± 0,24; 0,6 ± 0,21); (1,4 ± 0,84; 0,9 ± 0,74); (0,5 ± 0,27; 0); (0,6 ± 0,33; 0,7 ± 0,48); (0,5 ± 0,27; 0,1 ± 0,02). Hasil t-test menunjukkan perbedaan yang tidak signifikan (p>0,05) pada 6 parameter inflamasi sedangkan parameter giant cell menunjukkan perbedaan yang signifikan (p<0,05). Kesimpulan penelitian ini adalah implantasi subkutan logam kobalt kromium menyebabkan reaksi jaringan berupa infiltrasi giant cell selama 14 hari pasca implantasi sebagai respon tehadap benda asing. Effect Of Subcutaneous Implantation Of Cobalt Chromium As An Alternative Material For Mini Screw Orthodontics Against Albino Rabbit’s Tissue. Mini screw orthodontics is an instrument which is used in orthodontic treatment for some cases that require absolute anchorage. Available mini screws are made of nickel titanium or stainless steel alloy which in some patients may cause a reaction to the tissues. Implantation test is a test performed to determine the biocompatibility of medical devices that are directly contacted to the living tissue. Tissue response to injury after implantation affects the degree of formation of granulation tissue, foreign body reaction, and fibrosis. The aim of this study is to determine the local effect of implantation of cobalt chromium as an alternative material for mini screw orthodontic against the subcutaneous tissue of albino rabbits. The subjects of study were 20 male albino rabbits divided into two groups (treatment and negative control groups). Cobalt chromium was made in the form of discs with 10 mm in diameter and 1 mm in thickness. In the treatment group, the material was implanted in the subcutaneous tissue of the dorsum of the rabbits with an incision to form a subcutaneous pocket. The pocket base was not more than 10 mm from the initial line of incision then suturing was performed. The control group only had incision then sutured to maintain aseptic conditions. Macroscopically 24 hours after implantation, the implant area was observed related to the occurrence of oedema, haematoma, encapsulation and signs of inflammation. The evaluation on day 14 post-implantation shows the histopathologic changes observed by the infiltration of inflammatory cells types. The average of the results was analyzed using independent sample t-test. The results of the macroscopic observation shows that the treatment and control group were only seen of mild inflammatory signs included erythema. The mean and standard deviation of the amount of PMN, lymphocyte, plasma cells, macrophage, giant cell, neovascularisation, and fibrosis from cobalt chromium and control groups were (0.6 ± 0.49; 0.7 ± 0.48); (0.9 ± 0.87; 1.0 ± 0.67); (0.6 ± 0.24; 0.6 ± 0.21); (1.4 ± 0.84; 0.9 ± 0.74); (0.5 ± 0.27; 0); (0.6 ± 0.33; 0.7 ± 0.48); (0.5 ± 0.27; 0.1 ± 0.02). The results of t-test show a significant difference in giant cell (p<0.05), while the six others did not (p>0.05). The conclusion of this study is that the cobalt chromium alloy can affect the subcutaneous tissue by inducing giant cell infiltration on day 14 post-implantation as the result of foreign body reactions.


Author(s):  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Bo Bo Win Maung ◽  
Robert S. Mansbach ◽  
Michael R. Hodges ◽  
...  

Candida endophthalmitis is a serious sight-threatening complication of candidemia that may occur before or during antifungal therapy. Hematogenous Candida meningoencephalitis (HCME) is also a serious manifestation of disseminated candidiasis in premature infants, immunosuppressed children, and immunocompromised adults. We evaluated the antifungal efficacy and pharmacokinetics of the prodrug fosmanogepix (APX001) in a rabbit model of endophthalmitis/HCME. Manogepix (APX001A), the active moiety of prodrug fosmanogepix, inhibits the fungal enzyme Gwt1, and is highly active in vitro and in vivo against Candida spp., Aspergillus spp., and other fungal pathogens. Plasma pharmacokinetics of manogepix after oral administration of fosmanogepix on Day-6 at 25, 50, and 100 mg/kg resulted in plasma Cmax of 3.96±0.41, 4.14±1.1, and 11.5±1.1 μg/ml, respectively, and AUC0-12 of 15.8±3.1, 30.8±5.0, 95.9±14 μg·h/ml, respectively. Manogepix penetrated into the aqueous humor, vitreous, and choroid with liquid to plasma ratios ranging from 0.19 to 0.52, 0.09 to 0.12, and 0.02 to 0.04, respectively. These concentrations correlated with a significant decrease in Candida albicans burden in vitreous (>101-103) and choroid (>101-103) (P≤0.05 and P≤0.001, respectively). Aqueous humor had no detectable C. albicans in treatment and control groups. The tissue/plasma concentration ratios of manogepix in meninges, cerebrum, cerebellum, and spinal cord were approximately 1:1, which correlated with a >102-104 decline of C. albicans in tissue vs control (P≤0.05). Serum and CSF (1→3)-β-D-glucan levels demonstrated significant declines in response to fosmanogepix treatment. These findings provide an experimental foundation for fosmanogepix in treatment of Candida endophthalmitis and HCME and de-risk the clinical trials of candidemia and invasive candidiasis.


Parasitology ◽  
2019 ◽  
Vol 147 (1) ◽  
pp. 108-119 ◽  
Author(s):  
Matheus Marques Milagre ◽  
Renata Tupinambá Branquinho ◽  
Maira Fonseca Gonçalves ◽  
GMP de Assis ◽  
Maykon Tavares de Oliveira ◽  
...  

AbstractBackground:The current drugs for Chagas disease treatment present several limitationsMethods:The sesquiterpene lactone goyazensolide (GZL) was evaluated regarding to cytotoxicity and trypanocidal activity against amastigotes, selectivity index (SI) in vitro, acute toxicity and anti-Trypanosoma cruzi activity in vivo.Results:The in vitro cytotoxicity in H9c2 cells was observed at doses >250 ng mL−1 of GZL and the SI were of 52.82 and 4.85 (24 h) and of 915.00 and 41.00 (48 h) for GZL and BZ, respectively. Nephrotoxicity and hepatotoxicity were not verified. Treatment with GZL of mice infected with CL strain led to a significant decrease of parasitaemia and total survival at doses of 1 and 3 mg kg−1 day−1 by oral and IV, respectively. This last group cured 12.5% of the animals (negativation of HC, PCR, qPCR and ELISA). Animals infected with Y strain showed significant decrease of parasitaemia and higher negativation in all parasitological tests in comparison to BZ and control groups, but were ELISA reactive, as well as the BZ group, but mice treated with 5.0 mg kg−1 day−1 by oral were negative in parasitological tests and survived.Conclusion:GZL was more active against T. cruzi than benznidazole in vitro and presented important therapeutic activity in vivo in both T. cruzi strains.


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