The Effect of Dietary Cholesterol on Platelet Survival in the Rabbit – A Study Using 14C-Serotonin and 51Chromium Double-Labelled Platelets

1984 ◽  
Vol 52 (01) ◽  
pp. 085-089 ◽  
Author(s):  
Ian R Wanless
Keyword(s):  
Ex Vivo ◽  
Dietary Cholesterol ◽  
The Other ◽  
Cholesterol Feeding ◽  
Control Groups ◽  
Platelet Survival ◽  
Double Label ◽  
And Control

SummaryHypercholesterolemic men and monkeys have shortened platelet survival but attempts to demonstrate this in rabbits have been unsuccessful. The present study examines platelet survival in cholesterol-fed rabbits. Platelets were double-labelled in vitro with 51Cr and 14C-serotonin or in vivo by intravenous injection of 14C-serotonin.In the double-label experiments 51Cr survival was always shorter than 14C survival but changes in survival of one label were accompanied by similar changes in the other label. Survival was shortened after 4 and 7 weeks of cholesterol feeding. This was demonstrated when the donor platelets were from normal rabbits for both cholesterol and control recipients but no shortening was demonstrated when cholesterol-rich platelets were injected into cholesterol-fed recipients and normal platelets were injected into the control rabbits. When 14C-serotonin was injected intravenously 14C survival was the same as when platelets were labelled ex vivo prior to injection and 14C survival was shortened in rabbits fed cholesterol for 1,2, and 6 weeks.These results indicate that cholesterol-feeding shortens platelet survival. This effect may be masked if the test platelets are not identical in both test and control groups.

scholarly journals Efficacy and Pharmacokinetics of Fosmanogepix (APX001) in the Treatment of Candida Endophthalmitis and Hematogenous Meningoencephalitis in Non-neutropenic Rabbits

2020 ◽  
Author(s):  
Ruta Petraitiene ◽  
Vidmantas Petraitis ◽  
Bo Bo Win Maung ◽  
Robert S. Mansbach ◽  
Michael R. Hodges ◽  
...  
Keyword(s):  
Aqueous Humor ◽  
Fungal Pathogens ◽  
Rabbit Model ◽  
Control Groups ◽  
Highly Active ◽  
Fungal Enzyme ◽  
Plasma Pharmacokinetics ◽  
And Control

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.

Activity of the sesquiterpene lactone goyazensolide against Trypanosoma cruzi in vitro and in vivo

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 ◽  
...  
Keyword(s):  
Trypanosoma Cruzi ◽  
Sesquiterpene Lactone ◽  
Selectivity Index ◽  
H9c2 Cells ◽  
Therapeutic Activity ◽  
Control Groups ◽  
Disease Treatment ◽  
And Control

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.

scholarly journals Hydatid Cyst Protoscolices Induce Cell Death in WEHI-164 Fibrosarcoma Cells and Inhibit the Proliferation of Baby Hamster Kidney FibroblastsIn Vitro

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Hossein Yousofi Darani ◽  
Narges Soozangar ◽  
Soliman Khorami ◽  
Fatomeh Taji ◽  
Mortaza Yousofi ◽  
...  
Keyword(s):  
Hydatid Cyst ◽  
Anticancer Activity ◽  
Cell Types ◽  
Baby Hamster Kidney ◽  
Control Groups ◽  
Cell Counts ◽  
Fibrosarcoma Cells ◽  
And Control

Bothin vitroandin vivomodels have demonstrated that some parasites can interfere with tumor cell growth. The present study investigates the anticancer activity of hydatid cyst protoscolices on WEHI-164 fibrosarcoma cells and baby hamster kidney (BHK) fibroblast cellsin vitro. Those above two cell types were treated with live hydatid cyst protoscolices or left untreated for control groups. After 48 h, lactate dehydrogenase (LDH) and cell counts were assayed for both treated cells and control groups. Following treatment with hydatid cyst protoscolices, cell proliferation of both cell types was inhibited, and lysis of fibrosarcoma cells increased. Based on these results, it appears that hydatid cyst protoscolices have strong anticancer activity, and additional studies are needed to further clarify the mechanisms of this activity.

scholarly journals Preliminary screening of the possible protective effect of Moroccan propolis against chromium-induced nephrotoxicity in animal model

2020 ◽  
Vol 13 (7) ◽  
pp. 1327-1333
Author(s):  
Soukaina El-Guendouz ◽  
Soumia Zizi ◽  
Youssef Elamine ◽  
Badiaa Lyoussi
Keyword(s):  
Animal Model ◽  
Protective Effect ◽  
Creatinine Clearance ◽  
Potassium Dichromate ◽  
Treated Group ◽  
Control Groups ◽  
Before And After ◽  
And Control

Background and Aim: Hexavalent chromium (Cr (VI)) compounds have been shown to induce nephrotoxicity associated with oxidative stress in humans and animals. The aim of the present study was to investigate the nephroprotective effect of bee propolis, as highly antioxidant natural product, in vivo using an animal model. Materials and Methods: First of all, total phenol and flavonoid contents of propolis sample were estimated in vitro. Afterward, to study the protective effect of propolis on renal damages caused by an injection of a single dose of potassium dichromate (15 mg/kg b.wt), 24 male Wister rats were divided into test and control groups. Propolis treatment was performed by oral gavage of 100 mg/kg b.wt/day, while the control groups received water instead. The 24 h urine was collected and blood samples were withdrawn before and after each treatment for further analysis. Results: Propolis revealed to be rich in polyphenols and flavonoids. Chromate provoked a nephrotoxic effect expressed by a drastic decrease in glomerular filtration assessed by creatinine clearance. However, the administration of propolis attenuated the renal damages induced by the chromate. This attenuation can be seen by the increase of creatinine clearance when comparing propolis treated group to the non-treated group. Conclusion: Propolis showed a protective potential against chromate-induced nephrotoxicity through the amelioration of chromate's toxic effects. It might be concluded that propolis could be effective as chemoprotectant in the management of potassium dichromate-induced nephrotoxicity.

scholarly journals The Effect of Growth Differentiation Factor 8 (Myostatin) on Bone Marrow–Derived Stem Cell–Coated Bioactive Sutures in a Rabbit Tendon Repair Model

Hand ◽  
2018 ◽  
Vol 15 (2) ◽  
pp. 264-270 ◽  
Author(s):  
Kunihide Muraoka ◽  
Wei Le ◽  
Anthony W. Behn ◽  
Jeffrey Yao
Keyword(s):  
Bone Marrow ◽  
Quantitative Polymerase Chain Reaction ◽  
Tendon Repair ◽  
Tendon Healing ◽  
Gap Formation ◽  
Control Groups ◽  
Differentiation Factor ◽  
And Control

Background: We have reported that bioactive sutures coated with bone marrow–derived mesenchymal stem cells (BMSCs) enhance tendon repair strength in an in vivo rat model. We have additionally shown that growth differentiation factor 8 (GDF-8, also known as myostatin) simulates tenogenesis in BMSCs in vitro. The purpose of this study was to determine the possibility of BMSC-coated bioactive sutures treated with GDF-8 to increase tendon repair strength in an in vivo rabbit tendon repair model. Methods: Rabbit BMSCs were grown and seeded on to 4-0 Ethibond sutures and treated with GDF-8. New Zealand white rabbits’ bilateral Achilles tendons were transected and randomized to experimental (BMSC-coated bioactive sutures treated with GDF-8) or plain suture repaired control groups. Tendons were harvested at 4 and 7 days after the surgery and subjected to tensile mechanical testing and quantitative polymerase chain reaction. Results: There were distinguishing differences of collagen and matrix metalloproteinase RNA level between the control and experimental groups in the early repair periods (day 4 and day 7). However, there were no significant differences between the experimental and control groups in force to 1-mm or 2-mm gap formation or stiffness at 4 or 7 days following surgery. Conclusions: BMSC-coated bioactive sutures with GDF-8 do not appear to affect in vivo rabbit tendon healing within the first week following repair despite an increased presence of quantifiable RNA level of collagen. GDF-8’s treatment efficacy of the early tendon repair remains to be defined.

Inhibition by saccharin of glucose-6-phosphatase: effects of alloxan in vivo and deoxycholate in vitro

1976 ◽  
Vol 54 (6) ◽  
pp. 587-590 ◽  
Author(s):  
David G. Lygre
Keyword(s):  
Kinetic Parameters ◽  
Rat Liver ◽  
Control Groups ◽  
Major Significance ◽  
Significant Difference ◽  
Hepatic Glucose ◽  
And Control

Inhibition by saccharin of rat liver glucose-6-phosphatase (EC 3.1.3.9) generally decreased as the pH increased in the range pH 4–8. This pattern was exhibited by homogenates from control and alloxan-treated animals assayed each in the absence and presence of 0.2% (w/v) deoxycholate. Saccharin inhibited in competitive fashion with respect to glucose-6-phosphate (glucose-6-P). There was a small increase in Km (glucose-6-P) but not Ki (saccharin) values in alloxan-treated rats when assays were conducted in the absence of deoxycholate. In the presence of this detergent there was no significant difference in these kinetic parameters between the alloxan-treated and control groups. Deoxycholate decreased Km (glucose-6-P) and increased Ki (saccharin) values. Calculations using these kinetic parameters indicate that, under usual hepatic glucose-6-P concentrations and relatively high levels of saccharin in liver, the inhibition by saccharin of glucose-6-phosphatase is unlikely to be of major significance in vivo.

Effects Of Bay g 6575 On Platelets And On Vascular PGI2 Production

1981 ◽  
Author(s):  
D E MacIntyre ◽  
E W Salzman
Keyword(s):  
Vascular Tissue ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Duration Of Action ◽  
Antithrombotic Activity ◽  
Vascular Rings ◽  
And Control ◽  
Induced Aggregation

Bay g 6575 (1-[2-(β-naphthyloxy) ethyl]-3-methy1-2-pyrazolin-5-one) exerts a protective effect in several animal models of thrombosis. To elucidate its mechanism of action, we examined the effects of Bay g 6575 on platelets and on vascular PGI2 production. In vitro addition of Bay g 6575 (200 μM) to human citrated platelet rich plasma (PRP) did not inhibit aggregation induced by ADP or U44069, or augment inhibition of ADP-induced aggregation by PGD2, PGE1, PGI2 or papaverine. When added to isolated human or rat vascular rings, Bay g 6575 (200 μM) did not stimulate production of PGI2 or 6-oxo-PGF1α. Ex vivo studies one hour after administration of Baya g 6575 to rabbits (10 mg/kg, i.a.) or rats (100 mg/kg, p.o.) revealed no inhibition of ADP-induced aggregation or enhancement of the level of “circulating” PGI2 as measured by bio-immunoassay. When production of anti-aggregating activity by vascular rings from Bay g 6575 treated (B) and Control (C) rats were compared, in 6 of 8 experiments B inhibited more than C and B produced more 6-oxo-PGF1α than C (mean increase in B ± s.d.=74.3 ± 35.7%, range 42-135%). Production of antiaggregatory activity by “exhausted” C rings was enhanced by B>C platelet free plasma. In all cases, the inhibitor of aggregation produced by B and C rings acted on both human and rat PRP, and its effects could be reversed by anti-PGI1 antibodies that neutralize PGI2>6-oxo-PGE1>PGD2. When exogenous PGI2 was incubated with (exhausted) aspirin treated vascular rings, the duration of action of PGI2 was longer in the presence of B rings than C rings.Bay g 6575 has no direct effects on platelets or on vascular tissue. Its antithrombotic activity appears to be caused by regulation of PGI2 synthesis and metabolism, an effect mediated by factors, possibly Bay g 6575 metabolites, present in plasma after in vivo administration.

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
Keyword(s):  
Subcutaneous Tissue ◽  
Ovarian Tissue ◽  
Control Group ◽  
Control Groups ◽  
Hybrid Strain ◽  
Tissue Grafts ◽  
And Control

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.

50 PRE-MATURATION OF BOVINE OOCYTES SUBMITTED TO NUCLEAR TRANSFER: EFFECTS ON IN VIVO DEVELOPMENT

2010 ◽  
Vol 22 (1) ◽  
pp. 183
Author(s):  
T. H. C. De Bem ◽  
P. R. Adona ◽  
R. Rochetti ◽  
F. F. Bressan ◽  
M. S. Miranda ◽  
...  
Keyword(s):  
Nuclear Transfer ◽  
Total Cell ◽  
Control Group ◽  
Control Groups ◽  
Cell Numbers ◽  
Fragmented Dna ◽  
And Control ◽  
Bovine Oocytes

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.

scholarly journals HPV Lesions and Other Issues in the Oral Cavity Treatment and Removal without Pain

2021 ◽  
Vol 22 (20) ◽  
pp. 11158
Author(s):  
Salima El Moussaoui ◽  
Mireia Mallandrich ◽  
Núria Garrós ◽  
Ana Cristina Calpena ◽  
Maria José Rodríguez Lagunas ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Well Being ◽  
In Vitro Test ◽  
Ketorolac Tromethamine ◽  
Applied Dose ◽  
Permeation Studies ◽  
And Control ◽  
High Degree

Due to different oral and dental conditions, oral mucosa lesions such as those caused by the human papilloma virus and temporomandibular joint pathologies often have to be treated by surgical, ablative or extractive procedures. The treatment and control of pain and inflammation during these procedures is essential to guarantee the patient’s well-being. For the foregoing reason, a hydrogel based on sodium alginate and hyaluronic acid containing 2% of ketorolac tromethamine has been developed. We characterized it physically, mechanically and morphologically. The rheological results suggest that the formulation can be easily and gently applied. Ex vivo permeation studies show that Ketorolac Tromethamine is able to penetrate through the buccal and sublingual mucosae, in addition to being retained in the mucosae’s structure. Through an in vitro test, we were able to evaluate the role that saliva plays in the bioavailability of the drug, observing that more than half of the applied dose is eliminated in an hour. The histological and cytotoxic studies performed on pigs in vivo showed the excellent safety profile of the formulation, as well as its high tolerability. In parallel, a biomimetic artificial membrane (PermeaPad®) was evaluated, and it showed a high degree of correlation with the oral and sublingual mucosa.

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