thymosin-beta(4) and Chronic-Disease

Substantial evidence demonstrates a link of increased plasminogen activator inhibitor-1 (PAI-1) and glomerulosclerosis and kidney fibrosis, providing a novel therapeutic option for prevention and treatment of chronic kidney diseases. Several mechanisms contributing to increased PAI-1 will be addressed, including classic key profibrotic factors such as the renin-angiotensin-system (RAS) and transforming growth factor-beta (TGF-b???and novel molecules identified by proteomic analysis, such as thymosin- b4. The fibrotic sequelae caused by increased PAI-1 in kidney depend not only on its classic inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA), but also its influence on cell migration.

Topics: Angiotensins; Animals; Chronic Disease; Disease Models, Animal; Fibrosis; Humans; Kidney Diseases; Mice; Oligopeptides; Organ Specificity; Plasminogen Activator Inhibitor 1; Renin-Angiotensin System; Thymosin; Transforming Growth Factor beta1

Tβ4 is an integral factor in repair of myocardium in animal models. To investigate whether Tβ4 is important in human cardiac disease and has a role in mediating the beneficial cardiac effects of bone-marrow-derived stem cell (BMSC) therapy, we measured serial plasma Tβ4 levels in patients enrolled on the REGENERATE-IHD cell therapy trial.. Plasma Tβ4 concentrations were measured in 13 patients who received BMSCs and 14 controls.. There was a significant increase in plasma Tβ4 in the BMSC group 24 h after intracardiac injection. Increases in Tβ4 levels were associated with improvement in New York Heart Association symptom class.. This exploratory study highlights the need for further study of Tβ4 in human cardiovascular disease.

Topics: Aged; Bone Marrow Cells; Cell Count; Chronic Disease; Female; Heart Failure; Heart Function Tests; Humans; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Stem Cell Transplantation; Thymosin; Treatment Outcome

The objective of this double-blind, placebo-controlled, dose-escalation study is to evaluate safety, tolerability, and enhancement on healing of thymosin beta-4 (Tbeta-4) administered topically in patients with venous ulcers. Three groups of patients, coming from 10 sites, 5 from Italy and 5 from Poland, will be enrolled sequentially. Twenty-four patients within each group will be randomized to Tbeta-4 or placebo in a 3:1 ratio and will be treated with increasing doses of Tbeta-4. When review safety data show no-dose-limiting adverse events, a new group will be enrolled. So, the study design comprehends 72 patients treated for 84 days and followed for 14 days at the end of treatment. Blood samples will be taken on day 0 and at the end of treatment visit to measure plasma levels of Tbeta-4. Every week each patient is visited and blood samples are taken for clinical chemistry, hematology, coagulation, and urinalysis. Each ulcer is treated with debridement, if necessary, and compression therapy with standard compression stockings class 2. Efficacy parameters are incidence of healing defined as the percentage of patients who have complete closure of the index ulcer at day 84 and, mean time to complete healing. Ulcer area will be calculated by digital planimetry and photographic analysis. The study is ongoing and a total of 21 patients have been enrolled so far in the first treatment group at the lower dose. Patients' compliance and motivated and well-trained teams seem to be the most suitable parameters of a successfully conducted study.

Topics: Chronic Disease; Dose-Response Relationship, Drug; Double-Blind Method; Europe; Humans; Placebos; Prospective Studies; Safety; Thymosin; Varicose Ulcer; Wound Healing

The therapeutic efficiency of recombinant thymosin β4 (rTβ4) synthesized by us was studied in vivo on spontaneous CBRB mouse model that is adequate to human chronic dermatitis. Three applications of the drug during a week significantly alleviated symptoms of the disease in female mice, and in complex with subsequent antibacterial and antifungal therapy led to a pronounced and lasting (2 months) therapeutic effect. The results attest to a possibility of using rTβ4 in combination with the known treatment protocols for chronic inflammatory diseases of the skin.

Topics: Animals; Chronic Disease; Dermatitis; Disease Models, Animal; Female; Mice; Recombinant Proteins; Thymosin

Topics: Aged, 80 and over; Chronic Disease; Compassionate Use Trials; Corneal Diseases; Diabetes Complications; Epithelium, Corneal; Female; Herpes Zoster Ophthalmicus; Humans; Male; Middle Aged; Ophthalmic Solutions; Thymosin