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.

scholarly journals Asialoglycoprotein Receptor-Targeted Superparamagnetic Perfluorooctylbromide Nanoparticles

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yang Li ◽  
Chao Feng Yang ◽  
Hui Zuo ◽  
Ao Li ◽  
Sushant Kumar Das ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Rat Liver ◽  
Liver Parenchyma ◽  
Asialoglycoprotein Receptor ◽  
Enhancement Effect ◽  
Receptor Imaging ◽  
Significant Difference ◽  
Mean Size

Background. The decrease in asialoglycoprotein receptor (ASGPR) levels is observed in patients with chronic liver disease and liver tumor. The aim of our study was to develop ASGPR-targeted superparamagnetic perfluorooctylbromide nanoparticles (M-PFONP) and wonder whether this composite agent could target buffalo rat liver (BRL) cells in vitro and could improve R2 ∗ value of the rat liver parenchyma after its injection in vivo. Methods. GalPLL, a ligand of ASGPR, was synthesized by reductive amination. ASGPR-targeted M-PFOBNP was prepared by a film hydration method coupled with sonication. Several analytical methods were used to investigate the characterization and safety of the contrast agent in vitro. The in vivo MR T2 ∗ mapping was performed to evaluate the enhancement effect in rat liver. Results. The optimum concentration of Fe3O4 nanoparticles inclusion in GalPLL/M-PFOBNP was about 52.79 µg/mL, and the mean size was 285.6 ± 4.6 nm. The specificity of GalPLL/M-PFOBNP for ASGPR was confirmed by incubation experiment with fluorescence microscopy. The methyl thiazolyl tetrazolium (MTT) test showed that there was no significant difference in the optical density (OD) of cells incubated with all GalPLL/M-PFOBNP concentrations. Compared with M-PFOBNP, the increase in R2 ∗ value of the rat liver parenchyma after GalPLL/M-PFOBNP injection was higher. Conclusions. GalPLL/M-PFOBNP may potentially serve as a liver-targeted contrast agent for MR receptor imaging.

Effect of starvation on gonadotrophin secretion and on in vitro release of LRH from the isolated median eminence of the male rat

1983 ◽  
Vol 103 (3) ◽  
pp. 293-301 ◽  
Author(s):  
Michael Warnhoff ◽  
Gunter Dorsch ◽  
Karl M. Pirke
Keyword(s):  
In Vitro Release ◽  
Basic Mechanism ◽  
Male Rat ◽  
Gonadotrophin Secretion ◽  
Significant Difference ◽  
Lh Release ◽  
And Control ◽  
Vitro Release

Abstract. A perfusion system was developed in which isolated median eminences (ME) were stimulated in vitro by depolarizing agents such as potassium and veratridine. Potassium concentrations between 30 and 80 mm released increasing amounts of luteinizing hormone-releasing hormone (LRH) from the MEs of starved and control rats. Veratridine at a concentration of 50 μm caused a more prolonged LRH release in both starved and control animals. LRH secretion in vitro was slightly, though not under all conditions, significantly greater in rats starved for 5 days. The testosterone (T)-LH feedback was studied by castrating the animals and substituting various doses of T through implantation of T-releasing capsules of different sizes. The concentration in plasma, which can prevent the castration-induced much smaller in starved than in control rats. The in vitro release of LRH evoked by 80 mm potassium was not different for starved and fed rats under various feedback conditions. Both groups revealed decreased in vitro release of LRH when castrated animals were not substituted with T. The effect of castration was studied from 1 to 28 days. The plasma LH values rapidly increased in starved and control animals, indicating that the hypothalamic responsestration is not delayed by starvation. The release in vitro of LRH decreased from the first to the fifth day and remained constant thereafter. No significant difference between starved and fed rats was observed. The experiments indicate that the 'releasable pool' of LRH in vitro is greater under conditions of reduced LH release in vivo. The basic mechanism of depolarization-induced exocytosis of LRH from the ME is intact in starved animals.

scholarly journals Inhibition and Induction by Poziotinib of Different Rat Cytochrome P450 Enzymes In Vivo and in an In Vitro Cocktail Method

2021 ◽  
Vol 11 ◽  
Author(s):  
Jinhui Wang ◽  
Feifei Chen ◽  
Hui Jiang ◽  
Jia Xu ◽  
Deru Meng ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Rat Liver ◽  
Clinical Investigation ◽  
Liver Microsomes ◽  
Pharmacokinetic Parameters ◽  
Rat Liver Microsomes ◽  
Cytochrome P450 Enzymes ◽  
Significant Difference

Poziotinib is an orally active, irreversible, pan-HER tyrosine kinase inhibitor used to treat non-small cell lung cancer, breast cancer, and gastric cancer. Poziotinib is currently under clinical investigation, and understanding its drug-drug interactions is extremely important for its future development and clinical application. The cocktail method is most suitable for evaluating the activity of cytochrome P450 enzymes (CYPs). As poziotinib is partially metabolized by CYPs, cocktail probes are used to study the interaction between drugs metabolized by each CYP subtype. Midazolam, bupropion, dextromethorphan, tolbutamide, chlorzoxazone, phenacetin, and their metabolites were used to examine the effects of poziotinib on the activity of cyp1a2, 2b1, 2d1, 2c11, 2e1, and 3a1/2, respectively. The in vitro experiment was carried out by using rat liver microsomes (RLMs), whereas the in vivo experiment involved the comparison of the pharmacokinetic parameters of the probes after co-administration with poziotinib to rats to those of control rats treated with only probes. UPLC-MS/MS was used to detect the probes and their metabolites in rat plasma and rat liver microsomes. The in vitro results revealed that the half-maximal inhibitory concentration values of bupropion and tolbutamide in RLMs were 8.79 and 20.17 μM, respectively, indicating that poziotinib showed varying degrees of inhibition toward cyp2b1 and cyp2c11. Poziotinib was a competitive inhibitor of cyp2b1 and cyp2c11, with Ki values of 16.18 and 17.66 μM, respectively. No time- or concentration-dependence of inhibition by poziotinib was observed toward cyp2b1 and cyp2c11 in RLMs. Additionally, no obvious inhibitory effects were observed on the activity of cyp1a2, cyp2d1, cyp2e1, and cyp3a1/2. In vivo analysis revealed that bupropion, tolbutamide, phenacetin, and chlorzoxazone showed significantly different pharmacokinetic parameters after administration (p < 0.05); there was no significant difference in the pharmacokinetic parameters of dextromethorphan and midazolam. These results show that poziotinib inhibited cyp2b1 and cyp2c11, but induced cyp1a2 and cyp2e1 in rats. Thus, poziotinib inhibited cyp2b1 and cyp2c11 activity in rats, suggesting the possibility of interactions between poziotinib and these CYP substrates and the need for caution when combining them in clinical settings.

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 Latex and nonlatex orthodontic elastics: In vitro and in vivo evaluations of tissue compatibility and surface structure

2015 ◽  
Vol 86 (2) ◽  
pp. 278-284 ◽  
Author(s):  
Sara Martínez-Colomer ◽  
Patrícia Gaton-Hernández ◽  
Fábio Lourenço Romano ◽  
Andiara De Rossi ◽  
Sandra Yasuyo Fukada ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Surface Structure ◽  
Null Hypothesis ◽  
Microscopic Analysis ◽  
Plasma Extravasation ◽  
Control Groups ◽  
Tissue Compatibility ◽  
Significant Difference

ABSTRACT Objective:  To test the null hypothesis that there is no difference between latex and nonlatex orthodontic elastics with respect to tissue compatibility and surface structure. Materials and Methods:  Latex and nonlatex elastics were implanted in the subcutaneous connective tissue of 45 Wistar rats. In the control groups, no material was implanted (sham). After 24 hours, 3, 7, 14, and 21 days, the animals were euthanized; tissue samples were processed and analyzed by descriptive and semi-quantitative microscopic analysis and quantification of plasma extravasation. The surface structure of elastics was evaluated by scanning electron microscopy (SEM). The results were analyzed by analysis of variance (ANOVA), Tukey test and Kruskal-Wallis test at 5% significance level. Results:  Peri-implant plasma extravasation was significantly higher (P < .05) in the animals that received latex elastics compared with those with nonlatex elastics and those that were control animals. The microscopic analysis revealed a more intense inflammatory infiltrate in the initial periods without statistically significant difference (P > .05) between the experimental and control groups. The SEM analysis revealed that the latex elastics presented microspheres and porosities, while the nonlatex elastics exhibited crystals on their surface and absence of porosities. Conclusion:  The null hypothesis was rejected since the latex elastics were more irritating to the connective tissue than the nonlatex elastics in the initial periods and presented a more porous surface.

scholarly journals Evaluation of Antimalarial Activity of Methanolic Root Extract of Myrica salicifolia A Rich (Myricaceae) Against Plasmodium berghei–Infected Mice

2020 ◽  
Vol 25 ◽  
pp. 2515690X2092053 ◽  
Author(s):  
Zemene Demelash Kifle ◽  
Getnet Mequanint Adinew ◽  
Mestayet Geta Mengistie ◽  
Abyot Endale Gurmu ◽  
Engidaw Fentahun Enyew ◽  
...  
Keyword(s):  
Crude Extract ◽  
Plasmodium Berghei ◽  
Antimalarial Activity ◽  
Effective Vaccine ◽  
Root Extract ◽  
Honestly Significant Difference ◽  
Significant Difference ◽  
And Control

Background. The management and control of malaria has become gradually challenging due to the spread of drug-resistant parasites, lack of effective vaccine, and the resistance of vector to insecticides. Consequently, novel agents are urgently needed from different sources including from medicinal plants. In Ethiopia and Uganda, Myrica salicifolia root is traditionally claimed for the treatment of malaria. The aim of this study was to evaluate the in vivo antimalarial activity of root crude extract of M salicifolia. Methods. The parasite, Plasmodium berghei was used in this study since it is an appropriate parasite that is most commonly used because of its higher accessibility. A 4-day suppressive test was employed to evaluate the antimalarial effect of crude extract against early infection. The curative and prophylactic effect of the crude extract was further tested by Rane’s test and residual infection procedure. Parasitemia, survival time, packed cell volume, body weight, and rectal temperature of mice were used as evaluation parameters. Windows SPSS version 24 was used to analyze the data and analysis of variance followed by Tukey’s honestly significant difference to compare results between groups. Results. The root crude extract of M salicifolia significantly ( P < .05-.0001) suppressed parasitemia. The crude extract exhibited a chemosuppression of 40.90. Conclusion. The development of new antimalarial agents and the finding supports the traditional claims and previous in vitro studies.

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.

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