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Results for “Therapeutic modulation”

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At least 55 records · Page 3Linked to original sources
PubMed2000

Therapeutic modulation of low-density lipoprotein size.

Small, dense LDL particles have been linked to atherosclerosis, often in a cluster of risk factors and affecting approximately 20% of adults. Over the past year, studies confirmed that small dense LDL is an autosomal dominant trait, influenced mainly by hypertriglyceridaemia and obesity, insulin resistance and diabetes mellitus and some incompletely investigated genetic loci. Compositional and functional differences have been observed in small LDL. Evidence is emerging that lifestyle as well as pharmacological intervention can modulate LDL size, but there is no proof yet that this is of clinical benefit.

Arteriosclerosis↗
PubMed2006

Therapeutic modulation of DMD splicing by blocking exonic splicing enhancer sites with antisense oligonucleotides.

Antisense oligonucleotides (AONs) can be used to correct the disrupted reading frame of Duchenne muscular dystophy patients (DMD). We have a collection of 121 AONs, of which 79 are effective in inducing the specific skipping of 38 out of the 79 different DMD exons. All AONs are located within exons and were hypothesized to act by steric hindrance of serine-arginine rich (SR) protein binding to exonic splicing enhancer (ESE) sites. Indeed, retrospective in silico analysis of effective versus ineffective AONs revealed that the efficacy of AONs is correlated to the presence of putative ESE sites (as predicted by the ESEfinder and RESCUE-ESE software). ESE predicting software programs are thus valuable tools for the optimization of exon-internal antisense target sequences.

Dystrophin↗
PubMed2003

The metabolic syndrome: peroxisome proliferator-activated receptor gamma and its therapeutic modulation.

By the end of this decade, it has been estimated that between 200 million and 300 million people worldwide will meet World Health Organization diagnostic criteria for diabetes mellitus. This epidemic of predominantly type 2 diabetes has largely been mediated by our shift toward a more sedentary lifestyle predisposing to obesity and insulin resistance. Affected individuals can also exhibit an array of associated undesirable traits such as hypertension, dyslipidemia, and hypercoagulability, leading to morbidity and mortality from atherosclerotic vascular disease. The coexistence of several of these traits with insulin resistance constitutes the metabolic syndrome. Accordingly, improving insulin sensitivity in this group, and thereby potentially ameliorating the excess vascular risk, is a primary goal of treatment. Recent interest has focused on the thiazolidinediones, a novel class of antidiabetic agents, which act as insulin sensitizers and, therefore, potentially target the underlying metabolic disturbance. These agents are high-affinity ligands for the nuclear receptor peroxisome proliferator-activated receptor gamma, and a large body of in vitro and in vivo data has evolved to support their increasing clinical use. Importantly, clinical and laboratory findings in human subjects harboring natural mutations and polymorphisms within the receptor have provided additional insights. Here, we focus on the consequences of inherited variation in the human peroxisome proliferator-activated receptor gamma gene, linking this receptor to disordered glucose homeostasis, adipogenesis, lipid metabolism, and blood pressure regulation. These studies provide further support for the future development of more selective receptor modulators, targeting specific pathways to ameliorate facets of the metabolic syndrome.

Adipose Tissue↗
PubMed2005

The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation.

There is a growing amount of evidence suggesting that cannabinoids may be neuroprotective in CNS inflammatory conditions. Advances in the understanding of the physiology and pharmacology of the cannabinoid system have increased the interest of cannabinoids as potential therapeutic targets. Cannabinoid receptors and their endogenous ligands, the endocannabinoids, have been detected in cells of the immune system, as well as in brain glial cells. In the present review it is summarized the effects of cannabinoids on immune reactivity and on the regulation of neuroinflammatory processes associated with brain disorders with special attention to chronic inflammatory demyelinating diseases such as multiple sclerosis.

Brain↗
PubMed1987

Therapeutic modulation of growth-promoting activity in platelets from diabetics.

Proliferation of vascular smooth muscle is thought to be involved in the major diabetic complication atherosclerosis. We have previously reported an increase of growth-promoting activity (GA) in platelets from insulin-dependent diabetics. In this study, GA was measured in the platelet extract (PE) from eight diabetic patients who had been treated by conventional insulin therapy. Vascular smooth muscle cells from rat aorta were cultured and used as an assay system for GA. Incorporation of [3H]thymidine into DNA of cultured cells was stimulated by diabetic PE significantly more (P less than .05) than by normal PE. Diabetic PE incubated with cells for 4 days increased cell numbers significantly more (P less than .05) than normal PE. These abnormalities were corrected by long-term intensive insulin treatments (continuous subcutaneous insulin infusion and Pen infuser). The decrease of platelet extract GA appeared to correlate with the amount of insulin administered before meals as short-acting boluses, whereas the level of basal or long-acting insulin appeared to correlate with an increase of PE GA. Thus, the growth-promoting potential of platelets can be normalized by intensive insulin therapy. The relationship of insulin levels to this activity needs further evaluation.

Adult↗
PubMed2003

Pharmacodynamics of FTY720, the first member of a new class of immune-modulating therapeutics in transplantation medicine.

FTY is a novel immunomodulator currently undergoing clinical investigation and has the potential of improving immunosuppressive therapy after organ transplantation. Previous experimental studies in animals have shown that FTY has a unique mechanism of action. We have studied the pharmacodynamic effects of FTY in stable renal allograft recipients taking part in a phase I clinical trial. As in various animal models including non-human primates, a single oral dose of FTY (0.25 - 3.5 mg) significantly reduced peripheral lymphocyte count by 30 - 70%. The peripheral lymphocyte count returned to baseline within 24 hours. Only in those patients treated with the highest dose of FTY (3.5 mg), did peripheral lymphopenia persist for more than 96 hours. FTY reduced all lymphocyte subsets, T cells more than B cells and CD4+ cells more than CD8+ cells. The reduction in CD3+CD62L+ cell counts was more pronounced, whereas CD3+CCR5+ cell counts were less affected in comparison to the total number of CD3+ lymphocytes. We found only slightly increased apoptosis rates (< 5%) in peripheral lymphocytes, and this change does not explain the marked reduction in lymphocyte count. In cultured human lymphocytes only suprapharmacological doses of 10 microM FTY induced apoptosis (20.6 +/- 2.8%) after a 4-h incubation. More important, clinically relevant doses of 0.1 microM FTY increased lymphocyte mobility 2-fold. No effect of FTY on anti-CD3mAb-stimulated lymphocyte proliferation was detected and there was no change in phagocytosis rates in whole-blood cultures incubated with FTY. Further studies are necessary to investigate the mechanism of action of FTY in detail.

Apoptosis↗
PubMed2000

Macrophage-mediated immunostimulation modulates therapeutic efficacy of interleukin-2 based chemoimmunotherapy in advanced metastatic melanoma patients.

The biological mechanisms of chemoimmunotherapy efficacy in vivo have not been fully clarified; furthermore, few data are available to predict its efficacy on the basis of clinical and immunological pretreatment factors. In this paper, pre- and post-treatment serum levels of cytokines (interleukin [IL]-6, IL-10, IL-12 and neopterin) and soluble IL-2 receptors (sIL-2R), as well as circulating levels of T-cell and NK subpopulations, were analysed according to clinical outcome in 66 advanced metastatic melanoma (MM) patients treated with subcutaneous IL-2 in association with interferon-alpha, cisplatin and tamoxifen. Our purpose was to correlate the immune modifications during treatment with the clinical response and to define pretreatment factors with predictive value for clinical outcome. The overall response rate was 35%, with a median overall survival of 11.3 months. During treatment, responding patients showed a common marked increase in IL-12 (mainly released by activated macrophages), sIL-2R and neopterin serum levels, associated with high levels of total lymphocytes and circulating natural killer lymphocytes; progressing patients were characterized by an increase in IL-6 serum levels (directly related to the increase in tumour burden). Multivariate analysis showed that high pretreatment IL-12 levels (P = 0.05) and, to a lesser extent, lactate dehydrogenase levels in the normal range (< or = 450 U/I; P = 0.061) are independent favourable prognostic factors for survival. Our results show that macrophage activation in an immunostimulating way either before or during treatment is associated with a better clinical response and improved survival in advanced MM patients treated with IL-2-based chemoimmunotherapy.

Adult↗
PubMedDate not supplied

Biological factors and therapeutic modulation in breast cancer radiotherapy.

The natural history and survival of breast cancer are extremely variable although the advances and improvement in treatment in recent years led to a lower mortality. In fact, in spite of the administration of systemic adjuvant therapy, women with metastatic lymph nodes at diagnosis have a risk of disease progression at 5 years of 40-50%. The disease heterogeneity and the intrinsic tumor cell resistance to therapies are determining factors of the problem. The role of parameters as tumor size, grading, vascular spread, axillary lymph node status, are well defined. However the increasingly early diagnosis and changes in clinical practice have led to the need for non morphologic parameters as estrogen and progesteron receptors, cell proliferation index, labelling index, growth factors tumor-dependent genes (p53, HER2), cell cycle regulators (cyclins). Specific cellular and molecular alterations are studied to identify diagnosticoinstrumental images (MRI) of tumor angiogenesis, the cause of the different tumor aggressiveness. In the surgical and consequently clinico-oncologic approach there is the problem of the interpretation and prognostic role of sentinel lymph node when it is positive for micrometastasis only, if diagnosed by immunohistochemistry.

Biological Factors↗
PubMedDate not supplied

Biological factors and therapeutic modulation in brain tumor radiotherapy.

Diagnosticotherapeutic approaches aimed at the improvement of prognosis of the most aggressive brain tumors tend to include new tools of investigation. Functional imaging, biologic markers, radiosensitizers, the combination of different modalities of radiation therapy and chemotherapy are being experimented. These new approaches to the neoplastic metabolism require increased resources and a close follow-up during treatment to better define the biological target volume. More sophisticated and aggressive techniques as intensity modulated radiation therapy or brachycurietherapy can be suitably included in combined modality therapy.

Biological Factors↗
PubMed1992

[Regulation and therapeutic modulation of T-lymphocytes adhesion].

LFA-1, Mac-1, and p150,95 are leukocyte adhesion proteins called beta 2 integrins. LFA-1 is expressed at the surface of all leukocytes. A rare disease caused by mutations of the gene encoding the integrin beta 2 subunit is characterized by defective expression of these leukocyte adhesion molecules. Affected individuals have profound immune deficiency with severe bacterial infections for which the only effective treatment is bone marrow transplantation. These patients are unable to reject a transplant from only partially "Human Leucocyte Antigen" (HLA) compatible donors. In vivo studies have demonstrated decreased transplant rejection after injection of anti-LFA-1 antibodies to patients with other immune deficiencies. Simultaneous administration of an anti-CD2 antibody that blocks the second major pathway of lymphocyte adhesion can be expected to reduce even further the rate of rejection episodes.

Antibodies↗
PubMed1982

Therapeutic modulation of bronchial hyperreactivity.

At the department of allergology is Göteborg clinical models have been developed for studies of the allergen-induced and histamine- (and metacholine-) induced bronchial hyperreactivity. The reproductability in carefully selected asthmatic patients has been found to be acceptable. One of the aims has been to evaluate the clinical effect of new anti-allergic drugs. The importance for clinical methods has increased as experimental studies in animals have been found to be of limited predicted value. In drugs such as KWD 2131 and ketotifen more than one fundamental mechanism of action has been found. In those drugs we have tried to separate the different anti-asthmatic effects by using bronchial histamine provocations in combination with allergen provocations. The presentation will include a discussion of the provocation models used and the results of clinical trials on anti-allergic drugs.

Asthma↗