INFLUENCE OF CHLOROPHENOXYISOBUTYRATE (CPIB) ON THYROID PARAMETERS

1969 ◽  
Vol 60 (2) ◽  
pp. 294-302 ◽  
Author(s):  
J. Mølholm Hansen
Keyword(s):  
Free Thyroxine ◽  
Term Therapy ◽  
Low Doses ◽  
Testosterone Metabolism ◽  
Pre Treatment ◽  
Long Term Therapy ◽  
Higher Doses

ABSTRACT Chlorophenoxyisobutyrate (CPIB) added to serum in vitro increases the quantity of dialysable thyroxine. The same effect can be obtained in vivo following large doses of the preparation. After low doses, increase in serum proteinbound iodine (PBI) is observed and with higher doses this increase is not observed, probably because of the thyroxine-displacing effect. Free thyroxine increases in practically all patients investigated. In long-term treated patients the alterations in dialysable thyroxine, serum proteinbound iodine and free thyroxine are transient; pre-treatment values being regained in the course of ½–4 months. 131I uptake in the thyroid gland is influenced irregularly and transiently possibly via inhibition of the thyrotrophin production in the hypophysis. The effect of CPIB on serum cholesterol appears, in long-term therapy, to be completely independent of the effect on these thyroid parameters. This observation is also supported by the fact that the 14C-testosterone metabolism is normal in patients receiving long-term therapy.

Long-term imatinib therapy promotes bone formation in CML patients

Blood ◽  
2008 ◽  
Vol 111 (5) ◽  
pp. 2538-2547 ◽  
Author(s):  
Stephen Fitter ◽  
Andrea L. Dewar ◽  
Panagiota Kostakis ◽  
L. Bik To ◽  
Timothy P. Hughes ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Growth Factor Receptor ◽  
Imatinib Therapy ◽  
Term Therapy ◽  
Bone Homeostasis ◽  
Bone Biopsies ◽  
Long Term Therapy

Imatinib inhibits tyrosine kinases important in osteoclast (c-Fms) and osteoblast (platelet-derived growth factor receptor [PDGF-R], c-Abl) function, suggesting that long-term therapy may alter bone homeostasis. To investigate this question, we measured the trabecular bone volume (TBV) in iliac crest bone biopsies taken from chronic myeloid leukemia (CML) patients at diagnosis and again after 2 to 4 years of imatinib therapy. Half the patients (8 of 17) showed a substantive increase in TBV (> 2-fold), after imatinib therapy, with the TBV in the posttreatment biopsy typically surpassing the normal upper limit for the patient's age group. Imatinib-treated patients exhibited reduced serum calcium and phosphate levels with hypophosphatemia evident in 53% (9 of 17) of patients. In vitro, imatinib suppressed osteoblast proliferation and stimulated osteogenic gene expression and mineralized-matrix production by inhibiting PDGF receptor function. In PDGF-stimulated cultures, imatinib dose-dependently inhibited activation of Akt and Crk-L. Using pharmacologic inhibitors, inhibition of PI3-kinase/Akt activation promoted mineral formation, suggesting a possible molecular mechanism for the imatinib-mediated increase in TBV in vivo. Further investigation is required to determine whether the increase in TBV associated with imatinib therapy may represent a novel therapeutic avenue for the treatment of diseases that are characterized by generalized bone loss.

Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells

2001 ◽  
Vol 7 (1) ◽  
pp. 43-47 ◽  
Author(s):  
Samia Ragheb ◽  
Sarah Abramczyk ◽  
Deena Lisak ◽  
Robert Lisak
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Glatiramer Acetate ◽  
Mechanisms Of Action ◽  
Term Therapy ◽  
In Vitro Proliferation ◽  
Long Term Therapy

Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and affect T-cells that are specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patients and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-b therapy on the in vitro proliferation of GA-responsive T-cells of MS patients. We found that GA induces the proliferation of T-cells isolated from individuals who have not been previously exposed to GA, and that long-term in vivo therapy of MS patients with GA abrogates the GA-induced proliferative response of T-cells. In GA-treated patients, there is no evidence of generalized immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative responses remain unaffected. We propose that prolonged in vivo exposure to GA may result in the eventual induction of anergy or deletion of a population of GA-responsive cells that may also be T-cells that are pathogenic in MS. This mechanism of action, in addition to other mechanisms that have been demonstrated, suggests that GA has pleiotropic effects on the immune system in MS.

scholarly journals Murine neonates develop vigorous in vivo cytotoxic and Th1/Th2 responses upon exposure to low doses of NIMA-like alloantigens

Blood ◽  
2008 ◽  
Vol 112 (4) ◽  
pp. 1530-1538 ◽  
Author(s):  
Shannon J. Opiela ◽  
Robert B. Levy ◽  
Becky Adkins
Keyword(s):  
Early Life ◽  
In Vitro Assays ◽  
Low Doses ◽  
Early Life Exposure ◽  
Donor Cells ◽  
Th2 Responses ◽  
In Vivo Cytotoxicity

AbstractEarly life exposure to noninherited maternal antigens (NIMAs) may occur via transplacental transfer and/or breast milk. There are indications that early life exposure to NIMAs may lead to lifelong tolerance. However, there is mounting evidence that exposure to NIMAs may also lead to immunologic priming. Understanding how these different responses arise could be critical in transplantation with donor cells expressing NIMAs. We recently reported that murine neonates that received a transplant of low doses of NIMA-like alloantigens develop vigorous memory cytotoxic responses, as assessed by in vitro assays. Here, we demonstrate that robust allospecific cytotoxicity is also manifest in vivo. Importantly, at low doses, NIMA-expressing cells induced the development of in vivo cytotoxicity during the neonatal period. NIMA-exposed neonates also developed vigorous primary and memory allospecific Th1/Th2 responses that exceeded the responses of adults. Overall, we conclude that exposure to low doses of NIMA-like alloantigens induces robust in vivo cytotoxic and Th1/Th2 responses in neonates. These findings suggest that early exposure to low levels of NIMA may lead to long-term immunologic priming of all arms of T-cell adaptive immunity, rather than tolerance.

Effect of long-term therapy with an oral contraceptive on some aspects of hepatic lipid metabolism in vitro

1975 ◽  
Vol 24 (17) ◽  
pp. 1583-1588 ◽  
Author(s):  
Ira Weinstein ◽  
Richard Belitsky ◽  
Susan Seedman ◽  
Melvin J. Fregly ◽  
Terry N. Thrasher
Keyword(s):  
Lipid Metabolism ◽  
Oral Contraceptive ◽  
Term Therapy ◽  
Hepatic Lipid Metabolism ◽  
Hepatic Lipid ◽  
Long Term Therapy

scholarly journals Long-Term Azithromycin Therapy in Cystic Fibrosis Patients: A Study on Drug Levels and Sputum Properties

2004 ◽  
Vol 11 (2) ◽  
pp. 151-155 ◽  
Author(s):  
Ulrich Baumann ◽  
Malcolm King ◽  
Ernst M App ◽  
Shusheng Tai ◽  
Armin König ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Low Dose ◽  
Term Therapy ◽  
High Dose ◽  
Drug Levels ◽  
Diffuse Panbronchiolitis ◽  
Underlying Mechanisms

BACKGROUND:Following reports on the treatment of diffuse panbronchiolitis (DPB), recent studies demonstrate that long term therapy with azithromycin (AZM) is effective in cystic fibrosis (CF) patients. However, the underlying mechanisms remain uncertain. Some macrolides, including AZM, display inhibition of virulence factors and other antipseudomonal effects at subinhibitory levels in vitro.OBJECTIVES:Drug doses used for CF and DPB therapy were investigated to determine whether they achieve corresponding sputum drug levels in CF patients in vivo.METHODS:In an open, prospective study, 14 CF patients with chronic Pseudomonas aeruginosa airway infection received 250 mg AZM either daily ('high dose') or twice weekly ('low dose') for 12 weeks. Viscoelasticity of sputum was assessed by magnetic microrheology.RESULTS:AZM accumulated in sputum by two orders of magnitude over a period of four weeks. In the following steady state, median AZM concentrations in sputum were 9.5 µg/mL (0.6 to 79.3 µg/mL, interquartiles 1.4 to 33.4 µg/mL) and 0.5 µg/mL (range less than 0.1 [below detection level] to 5.2 µg/mL, interquartiles 0.2 to 1.4 µg/mL) in the high and low dose groups, respectively. Viscoelasticity improved in all patients but one.CONCLUSIONS:The findings suggest that antipseudomonal activity has to be considered among the potential mechanisms of macrolide therapy. Further, viscoelasticity may be a valuable parameter in future clinical trials.

INFLUENCE OF OESTROGEN ADMINISTRATION IN VIVO AND IN VITRO ON THE RELEASE AND SYNTHESIS OF PROLACTIN FROM INCUBATED PITUITARIES

1977 ◽  
Vol 86 (4) ◽  
pp. 714-721 ◽  
Author(s):  
Marta E. Apfelbaum ◽  
S. Taleisnik
Keyword(s):  
Incubation Medium ◽  
Direct Action ◽  
Ovariectomized Rats ◽  
Spontaneous Release ◽  
Prolactin Cells ◽  
Oestradiol Benzoate ◽  
Pre Treatment ◽  
Higher Doses

ABSTRACT The release and synthesis of prolactin were studied in incubated adenohypophyses from ovariectomized rats. After a 4 h incubation period the prolactin concentration in the medium markedly increased whereas that in the gland was reduced. However, the concentration of prolactin in the system, tissue plus medium, after 4 h was almost twice as much as that present at the beginning of incubation indicating spontaneous synthesis. This spontaneous release and synthesis of prolactin was greatly increased in incubated glands from ovariectomized oestrogen-treated rats. Oestradiol benzoate was injected in doses of 2.5, 5.0 or 10.0 μg/rat 2 or 24 h before killing the animals. Lower effects were obtained in glands from 2 h-oestradiol-pre-treated rats than from 24 h-oestradiol-primed rats. Oestradiol-17β (55, 166, 500 and 1500 ng/ml) added to the incubation medium also enhanced the release and synthesis of prolactin and the effect was more marked in glands from oestrogen injected rats than in those of non-treated animals. The increase was dose-related although the higher doses were less effective. These results provide further evidence of the effect of oestrogen on the release and synthesis of prolactin by a direct action on the pituitary gland. They also show that oestradiol pre-treatment in vivo increase the response of the prolactin cells towards oestradiol in vitro.

scholarly journals The Dynamics of Human Cytomegalovirus Replication in Vivo

1999 ◽  
Vol 190 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Vincent C. Emery ◽  
Alethea V. Cope ◽  
E. Frances Bowen ◽  
Dehila Gor ◽  
Paul D. Griffiths
Keyword(s):  
Half Life ◽  
Doubling Time ◽  
Term Therapy ◽  
Intravenous Ganciclovir ◽  
Alternative Drug ◽  
Resistant Strains ◽  
Antiviral Chemotherapy ◽  
Long Term Therapy

Cytomegalovirus (CMV) is generally described as a slowly replicating virus. During studies of immunocompromised patients, we observed rapid changes in the quantity of CMV DNA present in serial blood samples by quantitative-competitive polymerase chain reaction commensurate with a doubling time of <2 d. To further investigate the dynamics of replication in vivo, patients in three distinct situations were studied in detail: (a) those receiving intravenous ganciclovir; (b) those in whom ganciclovir-resistant strains appeared during long-term therapy; and (c) those in whom ganciclovir-resistant strains disappeared with alternative drug therapy. In all cases, it was possible to provide accurate estimates of the doubling time of CMV and its half-life of disappearance after antiviral chemotherapy. The results from all three approaches demonstrated that the doubling time/half-life of CMV in blood is ∼1 d when frequent samples are collected. These results show that CMV DNA replication in vivo is a highly dynamic process. We conclude that the reputation of CMV as a slowly replicating virus based on the time taken to produce cytopathic effects in vitro is unwarranted. These findings have implications for the potency, dose, and duration of antiviral chemotherapy needed for the effective treatment of this important human pathogen.

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