Search results for "Methotrexate"
showing 10 items of 111 documents
Methotrexate specifically modulates cytokine production by T cells and macrophages in murine collagen-induced arthritis (CIA): a mechanism for methot…
1999
SUMMARYImmunosuppressive therapy with methotrexate (MTX) has been established as effective treatment for patients with rheumatoid arthritis. To analyse the therapeutic potential and mechanisms of action of MTX, we determined serum cytokine levels and cytokine production by splenic T cells and macrophages in untreated and MTX-treated mice. Furthermore, we assessed the role of MTX in a murine model of experimental arthritis induced by collagen type II (CIA). MTX reduced spontaneous and IL-15-induced tumour necrosis factor (TNF) production by splenic T cells but not by macrophages from healthy mice in vitro in a dose-dependent manner. In contrast, interferon-gamma (IFN-γ) production was less s…
Impact of Undernutrition on the Pharmacokinetics and Pharmacodynamics of Anticancer Drugs: A Literature Review
2017
The etiology of undernourishment in cancer patients is multifactorial: tumor-related mechanisms (such as obstruction, metabolic abnormalities, and functionality changes) in addition to the influence of anticancer therapies, which can induce or worsen undernutrition. The evident role of undernutrition in cancer treatment outcomes suggests the need of considering nutritional status when evaluating anticancer drugs. In order to merge the available data and offer researchers and clinicians a global view of this phenomenon, the present manuscript reviews on a drug-by-drug basis the undernutrition-related pharmacokinetic and pharmacodynamic aspects of anticancer treatments. This review notes inte…
Photogenotoxicity of folic acid.
2013
Folic acid (FA), also named vitamin B9, is an essential cofactor for the synthesis of DNA bases and other biomolecules after bioactivation by dihydrofolate reductase (DHFR). FA is photoreactive and has been shown to generate DNA modifications when irradiated with UVA (360 nm) in the presence of DNA under cell-free conditions. To investigate the relevance of this reaction for cells and tissues, we irradiated three different cell lines (KB nasopharyngeal carcinoma cells, HaCaT keratinocytes, and a melanoma cell line) in the presence of FA and quantified cytotoxicity and DNA damage generation. The results indicate that FA is phototoxic and photogenotoxic by two different mechanisms. First, ext…
Exploring the cellular uptake of hectorite clay mineral and its drug carrier capabilities.
2022
In the last years, the use of clay minerals for pharmaceutical purposes has increased due to their interesting properties. Hectorite (Ht) is a clay belonging to the smectite group which has attracted attention for applications in biology, tissue engineering and as drug carrier and delivery system. However, the mechanisms involved in Ht cellular uptake and transport into cells, are still unclear. Herein, we used a labeled Ht (Ht/1Cl) to study both the cellular uptake, by confocal laser scanning microscopy, and internalization pathways involved in the cellular uptake, by various endocytosis-inhibiting studies and fluorescence microscopy. These studies highlighted that Ht can penetrate the cel…
OP0023 Targeted Polymeric Nanoparticles as Diagnostic and Therapeutic Tool for Rheumatoid Arthritis
2016
Background Rheumatoid arthritis (RA) is a chronic, systemic autoimmune disease affecting joints due to the persistent synovial tissue inflammation. RA treatment has dramatically evolved in the last 20 years due to the production of biological Disease Modifying Antirheumatic Drugs (bDMARDs). However, side effects and the high costs of biological drugs are holding back their widespread usage. Moreover, some patients fail to respond to bDMARDs, for all of these reasons, DMARDs remains the main desired strategy for the treatment of RA, and Methotrexate (MTX) is still the “anchor” drug to treat RA. A successful treatment depends also on the early diagnosis, treating patients as soon as possible …
On the activity of trifluoperazine and palmitoylcarnitine in mice: Delayed hypersensitivity models
2001
Abstract The effect of pre- and post-challenge treatments with trifluoperazine and palmitoylcarnitine, two protein kinase C (PKC) inhibitors characterised by their interaction with the phospholipid enzyme cofactor, on the inflammation caused by delayed hypersensitivity (DTH) to dinitrofluorobenzene (DNFB) and sheep red blood cells (SRBC) in mice is reported. The activity of dexamethasone and two immunosupressors, azathioprine and methotrexate, is also evaluated. The effectiveness of pre-treatment with each of the test drugs diminished when the DNFB challenge dose increased, whereas trifluoperazine and azathioprine were more active when administered after the challenge at the high DNFB dose.…
Influence of Pharmacokinetic Variations on the Pharmacological Properties of Adriamycin
1972
Whenever it appears impossible to modify the chemical structure of drugs with a high and established therapeutic activity but a low chemotherapeutic index, pharmacological research has to find other ways of improving the chemotherapeutic index. This problem is particularly important in the case of antitumor drugs, thus justifying research into the most suitable choice of dosage and routes of administration, as well as into the pharmacological associations which enable tumor cells to be hit at various stages of the reproductive cycle. Alternatively, the therapeutic index could be improved by the use of antagonistic compounds (like, for example, methotrexate and folinic acid) which act upon t…
Aging Successfully: The Role of Genetics and Environment in the Era of the Aging-Boom. Potential Therapeutic Implications
2019
Aging is one of the main health-related challenges in the world. The average life expectancy of the global population at birth is increasing up to 72 years, in 2016 and it increases about two years every decade. The healthcare costs in many countries are very high because of the increased number of unhealthy populations, and the consequent increase of severe age-related disabilities [1]. Therefore, the goal of the future should be the achievement of the so-called “health-span” (healthy-life-span), more than the treatment of age-related disease to prevent the collapse of the health system. In order to achieve this objective, it is necessary to identify new targets and biomarkers and to addre…
Trattamento medico della gravidanza ectopica diagnosticata precocemente:nostra esperienza.
2006
Gli autori hanno trattato con il methotrexate (MTX) in un'unica somministrazione seguita da una seconda identica dose dop il 7° giorno, se i livelli ematici di B-hCG non diminuiscono tra il 4° e il 7° giorno di almeno il 15%, un gruppo di 20 pazienti affette da gravidanza ectopica diagnosticata precocemente. In 16 pazienti, pari all'80% dei casi, i livelli ematici iniziali di B-hCG sono >1000 U.I./ml e 2000 e <5000 U.I./ml. L'esame ecografico eseguito per via transvaginale in 18 pazienti (pari al 90% dei casi) ha evidenziato una cavità uterina senza camera gestazionale con reazione deciduale ben rappresentata; in 2 pazienti pari al 10%, una massa annessiale di diametro <3cm. In 15 casi (75%…
Chromosomenuntersuchungen aus Lymphocyten und Knochenmark von Psoriasis-Kranken nach Langzeitbehandlung mit Methotrexat
1970
4 Psoriasis-Patienten, 3 davon mit zuruckliegender Arsenexposition, hatten Gesamtmengen zwischen 570 und 2735 mg Methotrexat erhalten. Bei diesen Patienten wurden Chromosomendarstellungen aus dem Knochenmark und aus Lymphocytenkulturen durchgefuhrt. Im Knochenmark (ohne Kultur in vitro) fanden sich keine eindeutigen Aberrationen, wahrend in den Lymphocyten in 2 Fallen gehauft (24%) ein Chromosom regellos fehlte, und bei einem Patienten einzelne Bruche zu finden waren. Soweit aus diesen Beobachtungen in Verbindung mit den Daten der Literatur Schlusse gezogen werden durfen, werden sie bezuglich der Chromosomenmutationen diskutiert.