scholarly journals Response of methylenetetrahydrofolate levels to methotrexate in Krebs ascites cells

1983 ◽  
Vol 216 (2) ◽  
pp. 295-298 ◽  
Author(s):  
P Sur ◽  
M T Doig ◽  
D G Priest
Keyword(s):  
Thymidylate Synthase ◽  
Rapid Growth ◽  
Ternary Complex ◽  
Kidney Tissue ◽  
Tumour Cells ◽  
Post Transplantation ◽  
Tissue Extracts ◽  
Time Period ◽  
Liver And Kidney ◽  
The Impact

Levels of methylenetetrahydrofolate in Krebs ascites cells subsequent to transplantation and the effects of methotrexate on these levels have been measured. To directly measure methylenetetrahydrofolate in tissue extracts, the cofactor was incorporated into a covalent ternary complex with thymidylate synthase and 3H-labelled fluorodeoxyuridine monophosphate. A 3-4-day lag preceded rapid growth of the tumour cells, and this same kinetic behaviour was observed for methylenetetrahydrofolate levels in the tumour cells. Liver and kidney tissue from the same animals also showed an increase in methylenetetrahydrofolate over the same time period. The impact of methotrexate on methylenetetrahydrofolate in the tumour cells depended upon concentration and the post-transplantation time at which treatment was initiated. Levels of methylenetetrahydrofolate in the tumour cells were most sensitive to the drug at the beginning of the rapid growth phase and were more sensitive to a given level of methotrexate in the presence of phospholipids. A slight but significant increase in methylenetetrahydrofolate occurred in some cases in response to the presence of methotrexate.

scholarly journals Effects of Substitution and High-Dose Thyroid Hormone Therapy on Deiodination, Sulfoconjugation, and Tissue Thyroid Hormone Levels in Prolonged Critically Ill Rabbits

Endocrinology ◽  
2008 ◽  
Vol 149 (8) ◽  
pp. 4218-4228 ◽  
Author(s):  
Yves Debaveye ◽  
Björn Ellger ◽  
Liese Mebis ◽  
Theo J. Visser ◽  
Veerle M. Darras ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Hormone Therapy ◽  
Critically Ill ◽  
Kidney Tissue ◽  
High Dose ◽  
Reverse T3 ◽  
Hormone Levels ◽  
Liver And Kidney ◽  
Thyroid Hormone Levels ◽  
The Impact

To delineate the metabolic fate of thyroid hormone in prolonged critically ill rabbits, we investigated the impact of two dose regimes of thyroid hormone on plasma 3,3′-diiodothyronine (T2) and T4S, deiodinase type 1 (D1) and D3 activity, and tissue iodothyronine levels in liver and kidney, as compared with saline and TRH. D2-expressing tissues were ignored. The regimens comprised either substitution dose or a 3- to 5- fold higher dose of T4 and T3, either alone or combined, targeted to achieve plasma thyroid hormone levels obtained by TRH. Compared with healthy animals, saline-treated ill rabbits revealed lower plasma T3 (P = 0.006), hepatic T3 (P = 0.02), and hepatic D1 activity (P = 0.01). Substitution-dosed thyroid hormone therapy did not affect these changes except a further decline in plasma (P = 0.0006) and tissue T4 (P = 0.04). High-dosed thyroid hormone therapy elevated plasma and tissue iodothyronine levels and hepatic D1 activity, as did TRH. Changes in iodothyronine tissue levels mimicked changes in plasma. Tissue T3 and tissue T3/reverse T3 ratio correlated with deiodinase activities. Neither substitution- nor high-dose treatment altered plasma T2. Plasma T4S was increased only by T4 in high dose. We conclude that in prolonged critically ill rabbits, low plasma T3 levels were associated with low liver and kidney T3 levels. Restoration of plasma and liver and kidney tissue iodothyronine levels was not achieved by thyroid hormone in substitution dose but instead required severalfold this dose. This indicates thyroid hormone hypermetabolism, which in this model of critical illness is not entirely explained by deiodination or by sulfoconjugation.

scholarly journals Changes in the spectrum of proteins and phospholipids in tissues of rats exposed to thiosulfonates

2018 ◽  
Vol 9 (4) ◽  
pp. 495-500 ◽  
Author(s):  
V. I. Lubenets ◽  
V. V. Havryliak ◽  
A. Z. Pylypets ◽  
A. V. Nakonechna
Keyword(s):  
Blood Plasma ◽  
Total Protein ◽  
Methyl Esters ◽  
Kidney Tissue ◽  
Total Content ◽  
Ethyl Esters ◽  
Short Term ◽  
Wide Range ◽  
Liver And Kidney ◽  
The Impact

Esters of thiosulfoacids demonstrate a wide range of biological activity. One of their effects is the influence on the metabolism of proteins and lipids in the body. Therefore, the purpose of our experiment was to study the impact of synthesized thiosulfonates on the total content of proteins and phospholipids, as well as their spectrum in the blood, liver, and kidney of rats. For the experiment, allyl, ethyl, and methyl esters of thiosulfoacid were used. The protein profile of rat tissues was investigated by electrophoresis, and the ratio of different fractions of phospholipids by thin-layer chromatography. Our results have shown that short-term administration of thiosulfonates in a dose of 300 mg/kg of body weight did not cause significant changes in the content of total protein and its fractions in liver tissue, whereas the effect of allyl and ethyl esters of thiosulfoacid was accompanied by an increase in the total protein and albumin in the blood plasma. The decrease in total protein was found in the kidney tissue of rats injected with allyl- and methyl thiosulfonates. The newly synthesized compounds did not lead to significant changes in the total content of phospholipids in blood plasma and tissues of rats, except for methyl thiosulfonate, the effect of which was accompanied by an increase in the total phospholipids in the liver of rats. These data may indicate an adaptive reaction of the rat’s organism. Tissue-specific features of the phospholipid spectrum were detected in rats after short-term exposure to thiosulfonates. The most significant effect on the phospholipid profile in the blood was shown for allyl- and ethyl esters of thiosulfoacid. Their action was accompanied by a decrease in the phosphatidylserine and phosphatidylinositol fractions, while phosphatidylethanolamine and phosphatidylcholine increased, respectively. Esters of thiosulfoacid significantly influenced the ratio of different fractions of phospholipids in the liver and kidney tissues. The phospholipid composition of the liver was more influenced by the allyl and methyl esters of thiosulfoacid, whereas for the kidney tissue a greater effect was observed for ethyl and methyl esters. Thus, the action of allyl ester of thiosulfoacid caused a decrease in the asymmetry coefficient of hepatocyte membranes, indicating an elevation of the lipid bilayer saturation and the increase of membrane microviscosity. Similar changes were found in the kidney of rats treated with allyl- and ethyl thiosulfonates.

Epigenetic Studies in Psychotherapy: A Systematic Review

2020 ◽  
Vol 16 (2) ◽  
pp. 86-92
Author(s):  
Rafael Penadés ◽  
Bárbara Arias ◽  
Mar Fatjó-Vilas ◽  
Laura González-Vallespí ◽  
Clemente García-Rizo ◽  
...  
Keyword(s):  
Systematic Review ◽  
Dna Methylation ◽  
Mental Disorders ◽  
Epigenetic Modifications ◽  
Symptom Improvement ◽  
Epigenetic Changes ◽  
Main Hypothesis ◽  
Psychological Treatments ◽  
Time Period ◽  
The Impact

Background: Epigenetic modifications appear to be dynamic and they might be affected by environmental factors. The possibility of influencing these processes through psychotherapy has been suggested. Objective: To analyse the impact of psychotherapy on epigenetics when applied to mental disorders. The main hypothesis is that psychological treatments will produce epigenetic modifications related to the improvement of treated symptoms. Methods: A computerised and systematic search was completed throughout the time period from 1990 to 2019 on the PubMed, ScienceDirect and Scopus databases. Results: In total, 11 studies were selected. The studies were evaluated for the theoretical framework, genes involved, type of psychotherapy and clinical challenges and perspectives. All studies showed detectable changes at the epigenetic level, like DNA methylation changes, associated with symptom improvement after psychotherapy. Conclusion: Methylation profiles could be moderating treatment effects of psychotherapy. Beyond the detected epigenetic changes after psychotherapy, the epigenetic status before the implementation could act as an effective predictor of response.

scholarly journals Development of the Circular Bioeconomy: Drivers and Indicators

2021 ◽  
Vol 13 (1) ◽  
pp. 413
Author(s):  
Maximilian Kardung ◽  
Kutay Cingiz ◽  
Ortwin Costenoble ◽  
Roel Delahaye ◽  
Wim Heijman ◽  
...  
Keyword(s):  
Circular Economy ◽  
Food Production ◽  
Conceptual Analysis ◽  
Green Economy ◽  
Political Agenda ◽  
Analysis Framework ◽  
Stakeholder Consultation ◽  
Time Period ◽  
The Impact ◽  
The Eu

The EU’s 2018 Bioeconomy Strategy Update and the European Green Deal recently confirmed that the bioeconomy is high on the political agenda in Europe. Here, we propose a conceptual analysis framework for quantifying and analyzing the development of the EU bioeconomy. The bioeconomy has several related concepts (e.g., bio-based economy, green economy, and circular economy) and there are clear synergies between these concepts, especially between the bioeconomy and circular economy concepts. Analyzing the driving factors provides important information for monitoring activities. We first derive the scope of the bioeconomy framework in terms of bioeconomy sectors and products to be involved, the needed geographical coverage and resolution, and time period. Furthermore, we outline a set of indicators linked to the objectives of the EU’s bioeconomy strategy. In our framework, measuring developments will, in particular, focus on the bio-based sectors within the bioeconomy as biomass and food production is already monitored. The selected indicators commit to the EU Bioeconomy Strategy objectives and conform with findings from previous studies and stakeholder consultation. Additionally, several new indicators have been suggested and they are related to measuring the impact of changes in supply, demand drivers, resource availability, and policies on sustainability goals.

scholarly journals Rijeka as a socialist port: Insights from Jugolinija's early years, 1947-1960

2021 ◽  
Vol 33 (1) ◽  
pp. 193-208
Author(s):  
Brigitte Le Normand
Keyword(s):  
Rapid Growth ◽  
Foreign Currency ◽  
Global Market ◽  
Early Years ◽  
The Political ◽  
State Socialism ◽  
Privileged Access ◽  
Shipping Line ◽  
The World ◽  
The Impact

To understand the distinctiveness of ports under state socialism, it is necessary to shift the focus from the built environment to flows of people, goods, knowledge and capital. In so doing, this article examines the operation of Yugoslavia's main shipping line, Jugolinija, from its inception in 1947 until 1960. This enterprise was based in the port of Rijeka, with both firm and port experiencing rapid growth during this period. The impact of state socialism can be seen in the primacy of the political over the profitability of the firm, with Jugolinija used to advance Yugoslavia's foreign trade and foreign policy, its interests being subordinated to the project of building self-managed socialism. It can also be seen in the unique challenges posed by having to operate at the intersection of the global market and a highly regulated economy – a situation that also created opportunities for the firm as a whole, as well as for its employees, who had access to foreign currency, travel and knowledge of the world. Jugolinija's privileged access to the world in what was still very much a closed society also created opportunities for ‘leaks’ of personnel and goods. Finally, socialist ideology left its imprint on Jugolinija's operations and shaped the ways in which its employees understood their work and the place of the firm within the Yugoslav economy. While it is tempting to see state socialism as ‘getting in the way’ of Jugolinija's business, in actuality the firm was remarkably successful both at operating within the Yugoslav socialist state framework, and capitalizing on the opportunities provided by access to the global market. Jugolinija's employees, in turn, profited from the mobility that came with working for the firm, sometimes at the expense of the enterprise and the state.

scholarly journals The Value of Vaccination in Older Adults: The Why

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 806-807
Author(s):  
Philip Buck
Keyword(s):  
Older Adults ◽  
Time Horizon ◽  
Pneumococcal Disease ◽  
Population Aging ◽  
Indirect Costs ◽  
Health Behavior Change ◽  
Vaccine Preventable Diseases ◽  
Time Period ◽  
The Us ◽  
The Impact

Abstract The incidence of vaccine-preventable diseases remains high among older adults in the US, despite longstanding immunization recommendations, and is projected to increase as the population ages. The impact of US population aging on the burden of four vaccine-preventable diseases (influenza, pneumococcal disease, shingles, and pertussis) was modeled over a 30-year time horizon, with cumulative direct and indirect costs increasing from $378 billion over 10 years to $1.28 trillion over 30 years. Compared to current levels of vaccination coverage, increasing coverage was predicted to avert over 33 million cases of disease and greater than $96 billion in disease-associated costs, with a corresponding increase in vaccination costs of approximately $83 billion over the entire 30-year time period. Specific examples of cost-effectiveness analyses that assess the epidemiologic and economic impact of vaccination against shingles and pertussis in older adults will be discussed. Part of a symposium sponsored by the Health Behavior Change Interest Group.

An Analysis of Procedural Medicare Reimbursement Rates in Hand Surgery: 2000 to 2019

Hand ◽  
2021 ◽  
pp. 155894472199080
Author(s):  
Danielle A Thornburg ◽  
Nikita Gupta ◽  
Nathan Chow ◽  
Jack Haglin ◽  
Shelley Noland
Keyword(s):  
Consumer Price Index ◽  
Hand Surgery ◽  
The United States ◽  
Medicare Reimbursement ◽  
Reimbursement Rate ◽  
Time Period ◽  
Long Term Trends ◽  
Fee Schedule ◽  
Procedure Codes ◽  
The Impact

Background: Medicare reimbursement trends across multiple surgical subspecialties have been analyzed; however, little has been reported regarding the long-term trends in reimbursement of hand surgery procedures. The aim of this study is to analyze trends in Medicare reimbursement for commonly performed hand surgeries. Methods: Using the Centers for Medicare and Medicaid Services Physician and Other Supplier Public Use File, we determined the 20 hand surgery procedure codes most commonly billed to Medicare in 2016. Reimbursement rates were collected and analyzed for each code from The Physician Fee Schedule Look-Up Tool for years 2000 to 2019. We compared the change in reimbursement rate for each procedure to the rate of inflation in US dollars, using the Consumer Price Index (CPI) over the same time period. Results: The reimbursement rate for each procedure increased on average by 13.9% during the study period while the United States CPI increased significantly more by 46.7% ( P < .0001). When all reimbursement data were adjusted for inflation to 2019 dollars, the average reimbursement for all included procedures in this study decreased by 22.6% from 2000 to 2019. The average adjusted reimbursement rate for all procedures decreased by 21.92% from 2000 to 2009 and decreased by 0.86% on average from 2009 to 2019 ( P < .0001). Conclusion: When adjusted for inflation, Medicare reimbursement for hand surgery has steadily decreased over the past 20 years. It will be important to consider the implications of these trends when evaluating healthcare policies and the impact this has on access to hand surgery.

Labour-use Efficiency of Assam Gramin Vikash Bank: Branch- and District-level Analysis

2021 ◽  
pp. 232102222110243
Author(s):  
Mohuya Deb Purkayastha ◽  
Joyeeta Deb ◽  
Ram Pratap Sinha
Keyword(s):  
Efficiency Score ◽  
Significant Variable ◽  
Data Envelopment ◽  
Tobit Regression ◽  
Second Stage ◽  
Time Period ◽  
Use Efficiency ◽  
The Mean ◽  
The Impact ◽  
Observation Period

The present study estimated labour-use efficiency of 48 branches of Assam Gramin Vikash Bank at its branch level, covering three districts of Barak Valley, which falls under Silchar region of the bank for the time period from 2010–2011 to 2017–2018. The study applied data envelopment analysis for estimating labour-use efficiency. In the second stage, the study applied censored Tobit regression for determining the impact of several contextual variables on efficiency. The study reveals that the mean labour-use efficiency score of the selected branches is 76% when averaged for the in-sample branches over the observation period. Results of the Tobit regression identified cluster 2 and total business of the branches as the significant factors for determining efficiency and the number of employees as a significant variable influencing inefficiency. JEL Classifications: G2, G20, G21, J3

scholarly journals Imaging NAD(H) Redox Alterations in Cryopreserved Alveolar Macrophages from Ozone-Exposed Mice and the Impact of Nutrient Starvation during Long Lag Times

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 767
Author(s):  
He N. Xu ◽  
Joanna Floros ◽  
Lin Z. Li ◽  
Shaili Amatya
Keyword(s):  
Oxidative Stress ◽  
Alveolar Macrophages ◽  
Redox State ◽  
Redox Status ◽  
Nutrient Starvation ◽  
Ozone Exposure ◽  
Reduced Form ◽  
Time Period ◽  
Lag Times ◽  
The Impact

Employing the optical redox imaging technique, we previously identified a significant redox shift of nicotinamide adenine dinucleotide (NAD and the reduced form NADH) in freshly isolated alveolar macrophages (AM) from ozone-exposed mice. The goal here was twofold: (a) to determine the NAD(H) redox shift in cryopreserved AM isolated from ozone-exposed mice and (b) to investigate whether there is a difference in the redox status between cryopreserved and freshly isolated AM. We found: (i) AM from ozone-exposed mice were in a more oxidized redox state compared to that from filtered air (FA)-exposed mice, consistent with the results obtained from freshly isolated mouse AM; (ii) under FA exposure, there was no significant NAD(H) redox difference between fresh AM that had been placed on ice for 2.5 h and cryopreserved AM; however, under ozone exposure, fresh AM were more oxidized than cryopreserved AM; (iii) via the use of nutrient starvation and replenishment and H2O2-induced oxidative stress of an AM cell line, we showed that this redox difference between cryopreserved and freshly isolated AM is likely the result of the double “hit”, i.e., the ozone-induced oxidative stress plus nutrient starvation that prevented freshly isolated AM from a full recovery after being on ice for a prolonged time period. The cryopreservation technique we developed eliminates/minimizes the effects of oxidative stress and nutrient starvation on cells. This method can be adopted to preserve lung macrophages from animal models or clinical patients for further investigations.

scholarly journals Clinical Relevance of Corticosteroid Withdrawal on Graft Histological Lesions in Low-Immunological-Risk Kidney Transplant Patients

2021 ◽  
Vol 10 (9) ◽  
pp. 2005
Author(s):  
Domingo Hernández ◽  
Juana Alonso-Titos ◽  
Teresa Vázquez ◽  
Myriam León ◽  
Abelardo Caballero ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Rejection Rate ◽  
Open Label ◽  
Post Transplantation ◽  
Protocol Biopsy ◽  
Corticosteroid Withdrawal ◽  
Transplant Patients ◽  
Prospective Phase ◽  
Kidney Transplant Patients ◽  
The Impact

The impact of corticosteroid withdrawal on medium-term graft histological changes in kidney transplant (KT) recipients under standard immunosuppression is uncertain. As part of an open-label, multicenter, prospective, phase IV, 24-month clinical trial (ClinicalTrials.gov, NCT02284464) in low-immunological-risk KT recipients, 105 patients were randomized, after a protocol-biopsy at 3 months, to corticosteroid continuation (CSC, n = 52) or corticosteroid withdrawal (CSW, n = 53). Both groups received tacrolimus and MMF and had another protocol-biopsy at 24 months. The acute rejection rate, including subclinical inflammation (SCI), was comparable between groups (21.2 vs. 24.5%). No patients developed dnDSA. Inflammatory and chronicity scores increased from 3 to 24 months in patients with, at baseline, no inflammation (NI) or SCI, regardless of treatment. CSW patients with SCI at 3 months had a significantly increased chronicity score at 24 months. HbA1c levels were lower in CSW patients (6.4 ± 1.2 vs. 5.7 ± 0.6%; p = 0.013) at 24 months, as was systolic blood pressure (134.2 ± 14.9 vs. 125.7 ± 15.3 mmHg; p = 0.016). Allograft function was comparable between groups and no patients died or lost their graft. An increase in chronicity scores at 2-years post-transplantation was observed in low-immunological-risk KT recipients with initial NI or SCI, but CSW may accelerate chronicity changes, especially in patients with early SCI. This strategy did, however, improve the cardiovascular profiles of patients.

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