scholarly journals Single and combined effects of cisplatin and doxorubicin on the human and mouse ovary in vitro

Reproduction ◽  
2020 ◽  
Vol 159 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Federica Lopes ◽  
Jin Liu ◽  
Stephanie Morgan ◽  
Rebecca Matthews ◽  
Lucy Nevin ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Combined Effects ◽  
Limited Information ◽  
Human Ovary ◽  
Chemotherapy Drugs ◽  
Stromal Tissue ◽  
The Individual ◽  
Multiplicative Effects ◽  
Human And Mouse

Chemotherapy drugs are administered to patients using combination regimens, and as such the possibility of multiplicative effects between drugs need to be investigated. This study examines the individual and combined effects of the chemotherapy drugs cisplatin and doxorubicin on the human ovary. Although cisplatin and doxorubicin are known to affect female fertility, there is limited information about their direct effects on the human ovary, and none examining the possibility of combined, multiplicative effects of co-exposure to these drugs. Here, human ovarian biopsies were obtained from 14 women at the time of caesarean section, with 38 mouse ovaries also obtained from neonatal C57Bl/6J mice. Tissue was cultured for 6 days prior to analyses, with chemotherapy drugs added to culture medium on the second day of culture only. Treatment groups of a single (5 μg/mL human; 0.5 μg/mL mouse) or double (10 μg/mL human; 1.0 μg/mL mouse) dose of cisplatin, a single (1 μg/mL human; 0.05 μg/mL mouse) or double (2 μg/mL human; 0.01 μg/mL mouse) dose of doxorubicin or a combination of a single dose of both drugs together were compared to controls without drug exposure. Exposure to cisplatin or doxorubicin significantly decreased follicle health in human and mouse, supporting the suitability of the mouse as a model for the human ovary. There was also a significant reduction of mouse follicle number. Human ovarian stromal tissue exhibited increased apoptosis and decreased cell proliferation. Crucially, there was no evidence indicating the occurrence of multiplicative effects between cisplatin and doxorubicin.

scholarly journals In Vitro Evaluation of the Individual and Combined Cytotoxic and Estrogenic Effects of Zearalenone, Its Reduced Metabolites, Alternariol, and Genistein

2021 ◽  
Vol 22 (12) ◽  
pp. 6281
Author(s):  
Adrienn Balázs ◽  
Zelma Faisal ◽  
Rita Csepregi ◽  
Tamás Kőszegi ◽  
Balázs Kriszt ◽  
...  
Keyword(s):  
Dietary Supplements ◽  
Filamentous Fungi ◽  
Combined Effects ◽  
In Vitro Evaluation ◽  
Estrogenic Effects ◽  
Toxic Metabolites ◽  
Alternaria Toxins ◽  
The Individual

Mycotoxins are toxic metabolites of filamentous fungi. Previous studies demonstrated the co-occurrence of Fusarium and Alternaria toxins, including zearalenone (ZEN), ZEN metabolites, and alternariol (AOH). These xenoestrogenic mycotoxins appear in soy-based meals and dietary supplements, resulting in the co-exposure to ZEN and AOH with the phytoestrogen genistein (GEN). In this study, the cytotoxic and estrogenic effects of ZEN, reduced ZEN metabolites, AOH, and GEN are examined to evaluate their individual and combined impacts. Our results demonstrate that reduced ZEN metabolites, AOH, and GEN can aggravate ZEN-induced toxicity; in addition, the compounds tested exerted mostly synergism or additive combined effects regarding cytotoxicity and/or estrogenicity. Therefore, these observations underline the importance and the considerable risk of mycotoxin co-exposure and the combined effects of mycoestrogens with phytoestrogens.

scholarly journals How Can the Combination of Pasta and Wine Affect the Digestibility of Polyphenols? A Simulated Digestion Study to Assess the Meal Antioxidant Properties

Proceedings ◽  
2020 ◽  
Vol 70 (1) ◽  
pp. 53
Author(s):  
Natalia S. Podio ◽  
Mariana S. Lingua ◽  
Daniel A. Wunderlin ◽  
María V. Baroni
Keyword(s):  
Antioxidant Properties ◽  
Limited Information ◽  
Total Polyphenol ◽  
Phenolic Profile ◽  
Simulated Digestion ◽  
Whole Wheat ◽  
Bioavailable Fraction ◽  
Before And After ◽  
The Individual

There is limited information about how the co-digestion of different food matrices can affect the digestibility, bioaccessibility, and, hence, the effectiveness of their health beneficial compounds, such as polyphenols. This work aimed to study the effect of the co-digestion of a whole-wheat pasta dish and a glass of red wine on their individual antioxidant properties. Thus, changes in the total polyphenol content by Folin Ciocalteu, phenolic profile by HPLC-ESI-MS/MS, and in vitro antioxidant capacity (AC) by ABTS and FRAP methods were evaluated before and after simulated gastrointestinal digestions. Additionally, a final step of dialysis was included to verify the fraction of polyphenols that are potentially bioaccessible. Separate digestions of pasta and wine were used as controls. The results showed that the co-digestion increased the AC of the bioavailable fraction (measured by ABTS) with respect to the sum of the individual digestions. Moreover, differences in the bioaccessibility of some phenolics were also found, with an increase of 4 compounds characteristic of pasta and 5 of wine. This study shows that the co-ingestion of pasta and wine improves the antioxidant properties of individual food/beverage, pointing out the importance of further studies on co-digestion with different combinations of food/beverages containing bio-active compounds.

Hormonal Correlates of Follicular Development in the Human Ovary

1981 ◽  
Vol 34 (3) ◽  
pp. 249 ◽  
Author(s):  
Kenneth P McNatty
Keyword(s):  
Menstrual Cycle ◽  
Individual Cell ◽  
Follicular Development ◽  
Cell Types ◽  
Follicular Phase ◽  
Follicle Cells ◽  
Human Ovary ◽  
The Individual

This review summarizes recent studies pertaining to follicular development in the human ovary. Some of these studies were concerned with characterizing the steroidogenic capacity of the individual cell types of the follicle in relation to whether the follicle was healthy or atretic. Other studies covered in this review concern the oocyte and its hormonal environment both in vivo and in vitro, the effects of steroids and gonadotrophins on the steroidogenic potentials of follicle cells and also some endocrine and non-endocrine responses of thecal and granulosa cells after being separated and then recombined in vitro. The data are integrated in relation to the development of a follicle during the follicular phase of the menstrual cycle.

scholarly journals Individual and Combined In Vitro Effects of Deoxynivalenol and Zearalenone on Boar Semen

Toxins ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 495
Author(s):  
Panagiotis D. Tassis ◽  
Ioannis A. Tsakmakidis ◽  
Veronika Nagl ◽  
Nicole Reisinger ◽  
Eleni Tzika ◽  
...  
Keyword(s):  
Functional Status ◽  
Semen Analysis ◽  
Computer Assisted ◽  
Combined Effects ◽  
Main Trial ◽  
Acridine Orange Staining ◽  
Boar Semen ◽  
In Vitro Effects ◽  
The Individual

Mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) can negatively affect pig health. However, little is known about their effects on boar semen. We assessed the individual and combined effects of DON and ZEN on boar semen in vitro. In a pretrial, we determined the minimum dose (MiD) of each mycotoxin that induces a significant alteration of sperm progressive motility, as investigated using computer-assisted semen analysis (CASA). In the main trial, the individual and combined effects of each mycotoxin’s MiD on sperm motility and kinetics (CASA analysis), morphology (SpermBlue staining), viability (calcein-propidium iodide staining), membrane functional status (hypoosmotic swelling test), and chromatin integrity (acridine orange staining) were analyzed. Pretrial results suggested a MiD of 50.6 μM and 62.8 μM for DON and ZEN, respectively. In the main trial, DON and ZEN administered at MiD significantly affected CASA parameters (e.g., increase of immotile spermatozoa, reduction of progressive motile spermatozoa), decreased sperm viability, and affected sperm morphology (head abnormalities) and membrane functional status. DON and ZEN showed less than additive effects on most parameters tested and a synergistic effect on viability and on two CASA parameters. In conclusion, DON and ZEN showed individual and combined toxic effects on boar semen in vitro.

Some Structural Features of Metaphase Chromosomes of Mice and Men

1967 ◽  
Vol 25 ◽  
pp. 190-191
Author(s):  
Godfrey C. Hoskins ◽  
Betty B. Hoskins
Keyword(s):  
Electron Microscopy ◽  
Electron Micrographs ◽  
Structural Features ◽  
Metaphase Chromosomes ◽  
The Future ◽  
Of Mice And Men ◽  
Mouse Cells ◽  
Human And Mouse

Metaphase chromosomes from human and mouse cells in vitro are isolated by micrurgy, fixed, and placed on grids for electron microscopy. Interpretations of electron micrographs by current methods indicate the following structural features.Chromosomal spindle fibrils about 200Å thick form fascicles about 600Å thick, wrapped by dense spiraling fibrils (DSF) less than 100Å thick as they near the kinomere. Such a fascicle joins the future daughter kinomere of each metaphase chromatid with those of adjacent non-homologous chromatids to either side. Thus, four fascicles (SF, 1-4) attach to each metaphase kinomere (K). It is thought that fascicles extend from the kinomere poleward, fray out to let chromosomal fibrils act as traction fibrils against polar fibrils, then regroup to join the adjacent kinomere.

Ultrastructural Changes in Tumor Cells During Human Peripheral Blood Monocyte-Mediated Cytotoxicity

1981 ◽  
Vol 39 ◽  
pp. 452-453
Author(s):  
K. E. Muse ◽  
D. G. Fischer ◽  
H. S. Koren
Keyword(s):  
Target Cell ◽  
Human Peripheral Blood ◽  
Mononuclear Phagocytes ◽  
Ultrastructural Changes ◽  
Target Cells ◽  
Limited Information ◽  
Blood Monocytes ◽  
Tumoricidal Activity ◽  
Activated State

Mononuclear phagocytes, a pluripotential cell line, manifest an array of basic extracellular functions. Among these physiological regulatory functions is the expression of spontaneous cytolytic potential against tumor cell targets.The limited observations on human cells, almost exclusively blood monocytes, initially reported limited or a lack of tumoricidal activity in the absence of antibody. More recently, freshly obtained monocytes have been reported to spontaneously impair the biability of tumor target cells in vitro (Harowitz et al., 1979; Montavani et al., 1979; Hammerstrom, 1979). Although the mechanism by which effector cells express cytotoxicity is poorly understood, discrete steps can be distinguished in the process of cell mediated cytotoxicity: recognition and binding of effector to target cells,a lethal-hit stage, and subsequent lysis of the target cell. Other important parameters in monocyte-mediated cytotoxicity include, activated state of the monocyte, effector cell concentrations, and target cell suseptibility. However, limited information is available with regard to the ultrastructural changes accompanying monocyte-mediated cytotoxicity.

scholarly journals In VitroAnalyses of the Effects of Heparin and Parabens on Candida albicans Biofilms and Planktonic Cells

2011 ◽  
Vol 56 (1) ◽  
pp. 148-153 ◽  
Author(s):  
Marisa H. Miceli ◽  
Stella M. Bernardo ◽  
T. S. Neil Ku ◽  
Carla Walraven ◽  
Samuel A. Lee
Keyword(s):  
Candida Albicans ◽  
Metabolic Activity ◽  
Biofilm Formation ◽  
High Dose ◽  
Dependent Manner ◽  
Planktonic Cells ◽  
Content Type ◽  
Heparin Sodium ◽  
The Individual

ABSTRACTInfections and thromboses are the most common complications associated with central venous catheters. Suggested strategies for prevention and management of these complications include the use of heparin-coated catheters, heparin locks, and antimicrobial lock therapy. However, the effects of heparin onCandida albicansbiofilms and planktonic cells have not been previously studied. Therefore, we sought to determine thein vitroeffect of a heparin sodium preparation (HP) on biofilms and planktonic cells ofC. albicans. Because HP contains two preservatives, methyl paraben (MP) and propyl paraben (PP), these compounds and heparin sodium without preservatives (Pure-H) were also tested individually. The metabolic activity of the mature biofilm after treatment was assessed using XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] reduction and microscopy. Pure-H, MP, and PP caused up to 75, 85, and 60% reductions of metabolic activity of the mature preformedC. albicansbiofilms, respectively. Maximal efficacy against the mature biofilm was observed with HP (up to 90%) compared to the individual compounds (P< 0.0001). Pure-H, MP, and PP each inhibitedC. albicansbiofilm formation up to 90%. A complete inhibition of biofilm formation was observed with HP at 5,000 U/ml and higher. When tested against planktonic cells, each compound inhibited growth in a dose-dependent manner. These data indicated that HP, MP, PP, and Pure-H havein vitroantifungal activity againstC. albicansmature biofilms, formation of biofilms, and planktonic cells. Investigation of high-dose heparin-based strategies (e.g., heparin locks) in combination with traditional antifungal agents for the treatment and/or prevention ofC. albicansbiofilms is warranted.

scholarly journals Impacts of stroke and cognitive impairment on activities of daily living in the Taiwan longitudinal study on aging

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pi-Hsia Lee ◽  
Ting-Ting Yeh ◽  
Hsin-Yen Yen ◽  
Wan-Ling Hsu ◽  
Valeria Jia-Yi Chiu ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Longitudinal Study ◽  
Activities Of Daily Living ◽  
Daily Living ◽  
Skill Training ◽  
Community Dwelling ◽  
Combined Effects ◽  
Stroke Group ◽  
The Individual ◽  
Community Dwelling Older Adults

AbstractStroke and cognitive impairment are common in older population. They often occur together and their combined effects significantly increase disability in both basic (BADLs) and instrumental (IADLs) activities of daily living. We investigated the individual and combined impacts of stroke and cognitive impairment on BADLs and IADLs. A total of 3331 community-dwelling older adults were enrolled from the Taiwan longitudinal study on aging in 2011. Both BADLs and IADLs were analyzed. Combination of stroke and cognitive impairment increased severity of ADL disabilities, but similar prevalence, similar numbers of summed BADL and IADL tasks with disability, and similar levels of difficulty for each BADL and IADL task were found between the stroke group and cognitive impairment group. The former had more difficult in dressing while the latter had more difficult in using the telephone, transport, and managing finances. A hierarchy of ADLs was also observed in all groups. ADL skill training supplemented with cognitive and physical interventions should focus on secondary prevention of dementia and improve motor functional capacity to reduce loss of ADLs.

Independent and combined effects of biotin and hemolysis on high-sensitivity cardiac troponin assays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Kellisha Harley ◽  
Sarah Bissonnette ◽  
Rosanna Inzitari ◽  
Karen Schulz ◽  
Fred S. Apple ◽  
...  
Keyword(s):  
Cardiac Troponin ◽  
Clinical Laboratory ◽  
Troponin T ◽  
High Sensitivity ◽  
Combined Effects ◽  
Over The Counter ◽  
Heparin Plasma ◽  
Abbott Architect ◽  
Roche Cobas

Abstract Objectives This study compared the independent and combined effects of hemolysis and biotin on cardiac troponin measurements across nine high-sensitivity cardiac troponin (hs-cTn) assays. Methods Parallel cTn measurements were made in pooled lithium heparin plasma spiked with hemolysate and/or biotin using nine hs-cTn assays: Abbott Alinity, Abbott ARCHITECT i2000, Beckman Access 2, Ortho VITROS XT 7600, Siemens Atellica, Siemens Centaur, Siemens Dimension EXL cTnI, and two Roche Cobas e 411 Elecsys Troponin T-hs cTnT assays (outside US versions, with and without increased biotin tolerance). Absolute and percent cTn recovery relative to two baseline concentrations were determined in spiked samples and compared to manufacturer’s claims. Results All assays except the Ortho VITROS XT 7600 showed hemolysis and biotin interference thresholds equivalent to or greater than manufacturer’s claims. While imprecision confounded analysis of Ortho VITROS XT 7600 data, evidence of biotin interference was lacking. Increasing biotin concentration led to decreasing cTn recovery in three assays, specifically both Roche Cobas e 411 Elecsys Troponin T-hs assays and the Siemens Dimension EXL. While one of the Roche assays was the most susceptible to biotin among the nine studied, a new version showed reduced biotin interference by approximately 100-fold compared to its predecessor. Increasing hemolysis also generally led to decreasing cTn recovery for susceptible assays, specifically the Beckman Access 2, Ortho VITROS XT 7600, and both Roche Cobas e 411 Elecsys assays. Equivalent biotin and hemolysis interference thresholds were observed at the two cTn concentrations considered for all but two assays (Beckman Access 2 and Ortho VITROS XT 7600). When biotin and hemolysis were present in combination, biotin interference thresholds decreased with increasing hemolysis for two susceptible assays (Roche Cobas e 411 Elecsys and Siemens Dimension EXL). Conclusions Both Roche Cobas e 411 Elecsys as well as Ortho VITROS XT assays were susceptible to interference from in vitro hemolysis at levels routinely encountered in clinical laboratory samples (0–3 g/L free hemoglobin), leading to falsely low cTn recovery up to 3 ng/L or 13%. While most assays are not susceptible to biotin at levels expected with over-the-counter supplementation, severely reduced cTn recovery is possible at biotin levels of 10–2000 ng/mL (41–8,180 nmol/L) for some assays. Due to potential additive effects, analytical interferences should not be considered in isolation.

scholarly journals Controllable Drug Delivery by Na+/K+ ATPase α1 Targeting Peptide Conjugated DSPE-PEG Nanocarriers for Breast Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382110278
Author(s):  
Yayan Yang ◽  
Qian Feng ◽  
Chuanfeng Ding ◽  
Wei Kang ◽  
Xiufeng Xiao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Click Reaction ◽  
Chemotherapy Drugs ◽  
Targeting Peptide ◽  
And Migration

Although Epirubicin (EPI) is a commonly used anthracycline for the treatment of breast cancer in clinic, the serious side effects limit its long-term administration including myelosuppression and cardiomyopathy. Nanomedicines have been widely utilized as drug delivery vehicles to achieve precise targeting of breast cancer cells. Herein, we prepared a DSPE-PEG nanocarrier conjugated a peptide, which targeted the breast cancer overexpression protein Na+/K+ ATPase α1 (NKA-α1). The nanocarrier encapsulated the EPI and grafted with the NKA-α1 targeting peptide through the click reaction between maleimide and thiol groups. The EPI was slowly released from the nanocarrier after entering the breast cancer cells with the guidance of the targeting NKA-α1 peptide. The precise and controllable delivery and release of the EPI into the breast cancer cells dramatically inhibited the cells proliferation and migration in vitro and suppressed the tumor volume in vivo. These results demonstrate significant prospects for this nanocarrier as a promising platform for numerous chemotherapy drugs.

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