scholarly journals Antithyroid activity of some 6-(alkylsulfanyl)-9H-purines

2011 ◽  
Vol 76 (10) ◽  
pp. 1355-1364
Author(s):  
Fatima Ismat ◽  
Munawar Munawar ◽  
Affia Tasneem ◽  
Sarwat Jahan ◽  
Mibahul Khan ◽  
...  
Keyword(s):  
Charge Transfer ◽  
Histological Study ◽  
Formation Constants ◽  
Alkyl Aryl ◽  
Antithyroid Activity ◽  
Charge Transfer Complexation ◽  
Almost All ◽  
Derivatives Of

Some alkyl and aryl derivatives of 9H-purine-6-thiol were synthesized and evaluated in vitro and in vivo for potential antithyroid effects. Spectrophotometric studies demonstrated 1:1 charge transfer complexation between iodine and these compounds with quite high values of the formation constants. The blood assays of rats treated with these compounds revealed significant antithyroid activity for almost all the compounds, which was further supported by a histological study of the thyroid tissues of the animals. These compounds are expected to provide less toxic alternative of the existing medicines as the sulfa group, which is known to be a cause of toxicity of many drugs, is blocked by alkyl/aryl substituents.

Derivatives of Deoxypodophyllotoxin Induce Apoptosis Through Bcl-2/Bax Proteins Expression

2020 ◽  
Vol 20 ◽  
Author(s):  
Ya-Nan Li ◽  
Ni Ning ◽  
Lei Song ◽  
Yun Geng ◽  
Jun-Ting Fan ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtt Method ◽  
Anthriscus Sylvestris ◽  
Anti Tumor Activity ◽  
Derivatives Of ◽  
Toxicity In Vitro ◽  
Ht 29 ◽  
Mcf 7

Background: Deoxypodophyllotoxin, isolated from theTraditional Chinese Medicine Anthriscus sylvestris, is well-known because of its significant antitumor activity with strong toxicity in vitro and in vivo. Objective: In this article, we synthesized a series of deoxypodophyllotoxin derivatives, and evaluated their antitumor effectiveness.Methods:The anti tumor activity of deoxypodophyllotoxin derivatives was investigated by the MTT method. Apoptosis percentage was measured by flow cytometer analysis using Annexin-V-FITC. Results: The derivatives revealed obvious cytotoxicity in the MTT assay by decreasing the number of late cancer cells. The decrease of Bcl-2/Bax could be observed in MCF-7, HepG2, HT-29 andMG-63 using Annexin V-FITC. The ratio of Bcl-2/Bax in the administration group was decreased, which was determined by the ELISA kit. Conclusion: The derivatives of deoxypodophyllotoxin could induce apoptosis in tumor cell lines by influencing Bcl-2/Bax.

Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin

2014 ◽  
Vol 74 ◽  
pp. 742-750 ◽  
Author(s):  
Chengyuan Liang ◽  
Juan Xia ◽  
Dong Lei ◽  
Xiang Li ◽  
Qizheng Yao ◽  
...  
Keyword(s):  
Schiff Base ◽  
Antitumor Activity ◽  
Schiff Base Derivatives ◽  
In Vivo Antitumor Activity ◽  
Derivatives Of

Investigation of the Thermal and Injury Behavior During Microwave Thermal Therapy of Porcine Kidney

2002 ◽  
Author(s):  
Xiaoming He ◽  
Shawn Mcgee ◽  
James E. Coad ◽  
Paul A. Iaizzo ◽  
David J. Swanlund ◽  
...  
Keyword(s):  
Thermal Model ◽  
Histological Study ◽  
Kidney Cortex ◽  
Cellular Injury ◽  
Bioheat Equation ◽  
Tissue Slices ◽  
Thermal Histories ◽  
Microwave Probe

In this paper, we report on the characterization of microwave therapy of normal porcine kidneys both in vitro and in vivo. This technology is being developed for eventual use in the treatment of small renal cell carcinoma (RCC) by minimally invasive procedures. During experiments, microwave energy was applied through an interstitial microwave probe (Urologix, Plymouth, MN) to the kidney cortex with occasional involvement of the kidney medulla. The thermal histories at several locations were recorded. After treatment, the kidneys were bisected and small tissue slices were cut out at approximately the same depth as the thermal probes. The tissue slices were further processed for histological study. Both cellular injury and the area of microvascular stasis were quantitatively evaluated by histology. Absolute rate kinetic models of cellular injury and vascular stasis were developed and fit to this data. A 3-D finite element thermal model based on the Pennes Bioheat equation was developed and solved using a commercial software package (ANSYS, V5.7). The Specific Absorption Rate (SAR) of the microwave probe was measured experimentally in tissue equivalent gel-like solution. The thermal model was first validated by the measured in vitro thermal histories. It was then used to determine the blood perfusion term in vivo.

Synthesis, characterization and in vitro and in vivo anticancer activity of Pt(iv) derivatives of [Pt(1S,2S-DACH)(5,6-dimethyl-1,10-phenanthroline)]

2017 ◽  
Vol 46 (21) ◽  
pp. 7005-7019 ◽  
Author(s):  
Benjamin W. J. Harper ◽  
Emanuele Petruzzella ◽  
Roman Sirota ◽  
Fernanda Fabiola Faccioli ◽  
Janice R. Aldrich-Wright ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Biological Evaluation ◽  
Synthesis And Biological Evaluation ◽  
Derivatives Of

Synthesis and biological evaluation in vitro and in vivo of functionalized Pt(iv) derivatives of Pt56MeSS.

METABOLISM OF RAM TESTICULAR SPERMATOZOA IN THE PRESENCE OF TESTOSTERONE AND RELATED STEROIDS

1970 ◽  
Vol 65 (3) ◽  
pp. 565-576 ◽  
Author(s):  
J. K. Voglmayr ◽  
R. N. Murdoch ◽  
I. G. White
Keyword(s):  
Aerobic Glycolysis ◽  
Rete Testis ◽  
Glycolytic Metabolism ◽  
Anaerobic Conditions ◽  
Aerobic Conditions ◽  
Testicular Spermatozoa ◽  
Almost All ◽  
Oxidation Of Glucose

ABSTRACT The effects of testosterone* and related steroids on the oxidative and glycolytic metabolism of freshly collected ram testicular spermatozoa and of spermatozoa stored under air in rete testis fluid for 3 days at 3°C have been studied. When freshly collected testicular spermatozoa were incubated with glucose under aerobic conditions only a small proportion of the utilized glucose could be accounted for as lactate. The addition of a number of steroids, including testosterone, androstanedione, 5β-androstanedione, androsterone, epiandrosterone and 5β-androsterone, greatly increased aerobic glycolysis, the oxidation of the substrate and the proportion of the utilized substrate converted to lactic acid. After 3 days storage at 3°C, testicular spermatozoa respired at a greater rate than spermatozoa freshly collected from the testes. Although the stimulating effect of steroids on aerobic glycolysis increased after storage, they depressed rather than stimulated the oxidation of glucose by stored testicular spermatozoa. With the exception of androstanedione, which slightly stimulated glycolysis, storage of testicular spermatozoa for 3 days in the presence of steroids did not significantly influence their subsequent metabolism when washed free of the steroids. Both freshly collected and stored ram testicular spermatozoa displayed a marked Pasteur effect, and utilized more glucose and produced more lactate under anaerobic than under aerobic conditions. In the absence of oxygen the steroids did not stimulate glycolysis to any extent. However, epiandrosterone depressed the glycolysis of freshly collected spermatozoa under anaerobic conditions and after storage, 5β-androsterone had a similar effect. Androstanedione, 5β-androstanedione, epiandrosterone and 5β-androsterone were the most effective steroids in altering the metabolism of testicular spermatozoa and, under almost all conditions of incubation, depressed the synthesis of amino acids from glucose. The results suggest that the effects of testosterone and related steroids in vitro may depend on the age of the spermatozoa after their release from the Sertoli cells; the steroid effects may have important consequences in vivo in relation to sperm maturation.

scholarly journals Medicinal Plants Used for the Traditional Management of Diabetes in the Eastern Cape, South Africa: Pharmacology and Toxicology

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 2759 ◽  
Author(s):  
Samuel Odeyemi ◽  
Graeme Bradley
Keyword(s):  
South Africa ◽  
Medicinal Plants ◽  
Scientific Evidence ◽  
Traditional Healers ◽  
Bioactive Molecules ◽  
Eastern Cape ◽  
Insulin Mimetic ◽  
Almost All

The use of medicinal plants for the management of diabetes mellitus is on the rise in the developing countries, including South Africa. There is increasing scientific evidence that supports the claims by the traditional healers. In this review, we compare the families of previously reported anti-diabetic plants in the Eastern Cape by rating the anti-diabetic activity, mode of action and also highlight their therapeutic potentials based on the available evidence on their pharmacology and toxicity. Forty-five plants mentioned in ethnobotanical surveys were subjected to a comprehensive literature search in the available electronic databases such as PubMed, ScienceDirect, Google Scholar and Elsevier, by using “plant name” and “family” as the keywords for the primary searches to determine the plants that have been scientifically investigated for anti-diabetic activity. The search returned 25 families with Asteraceae highly reported, followed by Asphodelaceae and Alliaceae. Most of the plants have been studied for their anti-diabetic potentials in vivo and/or in vitro, with most of the plants having a higher percentage of insulin release and inhibition against carbohydrate digesting enzymes as compared with insulin mimetic and peripheral glucose uptake. Almost all the investigated plants also inhibit oxidative stress as part of their hypoglycemic activity with less toxicity. However, the isolation of their bioactive molecules is still lacking. This review provides a resource to enable thorough assessments of the therapeutic profiles of available medicinal plants used for the management of diabetes in the Eastern Cape, South Africa. Further studies such as the identification of the active ingredients of potent plants still need to be carried out; this may lead to new molecules in drug discovery and development.

scholarly journals Stem-loops direct precise processing of 3′ UTR-derived small RNA MicL

2018 ◽  
Author(s):  
Taylor B Updegrove ◽  
Andrew B Kouse ◽  
Katarzyna J Bandyra ◽  
Gisela Storz
Keyword(s):  
Small Rna ◽  
Cleavage Site ◽  
Differential Sensitivity ◽  
Rnase E ◽  
Small Regulatory Rnas ◽  
Regulatory Rnas ◽  
Derivatives Of

AbstractIncreasing numbers of 3′UTR-derived small, regulatory RNAs (sRNAs) are being discovered in bacteria, most generated by cleavage from longer transcripts. The enzyme required for these cleavages has been reported to be RNase E, the major endoribonuclease in enterica bacteria. Previous studies investigating RNase E have come to a range of different conclusions regarding the determinants for RNase E processing. To understand the sequence and structure determinants for the precise processing of the 3′ UTR-derived sRNAs, we examined the cleavage of multiple mutant and chimeric derivatives of the 3′ UTR-derived MicL sRNA in vivo and in vitro. Our results revealed that tandem stem-loops 3′ to the cleavage site define optimal, correctly-positioned cleavage of MicL and likely other similar sRNAs. Moreover, our assays of MicL, ArcZ and CpxQ showed that sRNAs exhibit differential sensitivity to RNase E, likely a consequence of a hierarchy of sRNA features recognized by the endonuclease.

scholarly journals Cycle initiation and colony formation in culture by murine marrow cells with long-term reconstituting potential in vivo

Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4149-4158 ◽  
Author(s):  
M Trevisan ◽  
XQ Yan ◽  
NN Iscove
Keyword(s):  
Colony Formation ◽  
Interleukin 1 ◽  
Methyl Cellulose ◽  
Culture Conditions ◽  
Liquid Suspension ◽  
Almost All ◽  
Marrow Cells

Abstract This investigation was directed at separating long-term reconstituting (LTR) stem cells in normal murine marrow from hematopoietic precursors detectable in short-term assays in vitro and in vivo, and then at determining whether purified LTR cells could themselves form colonies in culture. To do so, it was first necessary to identify culture conditions that would induce their growth while preserving their long- term reconstituting capacity. Marrow was cultured with various cytokines in liquid suspension for 4 days, after which the surviving LTR activity was quantitated in a competitive in vivo assay. Activity was preserved near input levels with combined murine c-kit ligand (KL), interleukin-1 (IL-1), IL-6, and IL-11. When the cultures also included tritiated or unlabeled thymidine, LTR potential was eliminated, indicating that essentially all LTR cells were induced into cell cycle with these cytokines. To purify them, marrow was sorted on the basis of Ly6A expression and Rhodamine 123 retention. The Ly6AhiRh123ls fraction contained 85% of total recovered LTR activity but only 1% of the recovered cells measured by multilineage colony formation in spleens or in vitro. This fraction was cultured in methyl cellulose with KL, IL-1, IL-6, and IL-11 for 4 to 6 days, after which colonies were isolated and injected into mice. High levels of permanent reconstitution were achievable in sublethally irradiated W41/W41 mice after the injection of a single reconstituting unit, and limiting dilution analysis estimated the frequency of multilineage LTR at 1 in 11,200 unpurified adult marrow cells. In either lethally irradiated normal or sublethally irradiated W41/W41 mice, 1-year lymphomyeloid reconstitutions were obtained from 1 in 65 to 84 colonies of 2 to 16 dispersed cells, but not from larger colonies or those with clumped cells. The results establish that resting marrow LTR cells can be separated from almost all of the more advanced clonogenic cells that are still pluripotential, can be induced to cycle in culture by defined cytokines with preservation of their reconstituting potential, and can be manipulated and assayed efficiently at single-cell and colony levels.

scholarly journals DIPG-07. HIGH THROUGHPUT DRUG SCREENING IDENTIFIES POTENTIAL NEW THERAPIES FOR DIFFUSE INTRINSIC PONTINE GLIOMAS (DIPGs)

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii288-iii288
Author(s):  
Dannielle Upton ◽  
Santosh Valvi ◽  
Jie Liu ◽  
Nicole Yeung ◽  
Sandra George ◽  
...  
Keyword(s):  
High Throughput ◽  
Apoptotic Cell ◽  
Safety Data ◽  
Biologically Active ◽  
Orthotopic Model ◽  
High Throughput Drug Screening ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
Almost All

Abstract DIPGs are the most devastating of all brain tumors. There are no effective treatments, hence almost all children will die of their tumor within 12 months. There is an urgent need for novel effective therapies for this aggressive tumor. We performed a high-throughput drug screen with over 3,500 biologically active, clinically approved compounds against a panel of neurosphere-forming DIPG cells. We identified 7 compounds- auranofin, fenretinide, ivermectin, lanatoside, parthenolide, SAHA and mefloquine- that were confirmed to have potent anti-tumor activity against a panel of DIPG-neurospheres, with minimal effect on normal cells. Using cytotoxicity and clonogenic assays, we found that these drugs were able to inhibit DIPG-neurosphere proliferation and colony formation in-vitro. To determine whether the in-vitro efficacy could be replicated in-vivo, we tested the activity of each of these compounds in an orthotopic DIPG model. Of the agents tested, fenretinide and SAHA were the most active anti-tumor agents, significantly enhancing the survival of tumor bearing animals. Mechanistic studies showed fenretinide enhancing apoptotic cell death of DIPG cells via inhibition of PDGFRa transcription and downregulation of the PI3K/AKT/MTOR pathway. We therefore examined the therapeutic efficacy of fenretinide using a second orthotopic model with PDGFRa amplification. We used two different Fenretinide formulations (LYM-X-Sorb and NanoMicelle) which were found to enhance survival. Fenretinide is clinically available with safety data in children. Validation of the activity of Fenretinide in PDGFRa-amplified or overexpressed DIPGs will lead to the development of a clinical trial, allowing the advancement of fenretinide as potentially the first active therapy for DIPG.

scholarly journals Postprandial transfer of colostral extracellular vesicles and their protein and miRNA cargo in neonatal calves

2019 ◽  
Author(s):  
Benedikt Kirchner ◽  
Dominik Buschmann ◽  
Vijay Paul ◽  
Michael W. Pfaffl
Keyword(s):  
Extracellular Vesicles ◽  
Expression Profiles ◽  
Bovine Milk ◽  
Cell Types ◽  
Specific Protein ◽  
In Vivo Experiments ◽  
Neonatal Calves ◽  
Almost All

Abstract Background Extracellular vesicles (EVs) such as exosomes are key regulators of intercellular communication that can be found in almost all bio fluids. Although studies in the last decade have made great headway in discerning the role of EVs in many physiological and pathophysiological processes, the bioavailability and impact of dietary EVs and their cargo still remain to be elucidated. Due to its widespread consumption and high content of EV-associated microRNAs and proteins, a major focus in this field has been set on EVs in bovine milk and colostrum. Despite promising in vitro studies in recent years that show high resiliency of milk EVs to degradation and uptake of milk EV cargo in a variety of intestinal and blood cell types, in vivo experiments continue to be inconclusive and sometimes outright contradictive. Results To resolve this discrepancy, we assessed the potential postprandial transfer of colostral EVs to the circulation of newborn calves by analysing colostrum-specific protein and miRNAs, including specific isoforms (isomiRs) in cells, EV isolations and unfractionated samples from blood and colostrum. Our findings reveal distinct populations of EVs in colostrum and blood from cows that can be clearly separated by density, particle concentration and protein content (BTN1A1, MFGE8). Postprandial blood samples of calves show a time-dependent increase in EVs that share morphological and protein characteristics of colostral EVs. Analysis of miRNA expression profiles by Next-Generation Sequencing gave a different picture however. Although significant postprandial expression changes could only be detected for calf EV samples, expression profiles show very limited overlap with highly expressed miRNAs in colostral EVs or colostrum in general. Conclusions Taken together our results indicate a selective uptake of membrane-associated protein cargo but not luminal miRNAs from colostral EVs into the circulation of neonatal calves.

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