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PubMed1989

[Stimulation of immunogenesis by neurotensin, pentagastrin and thymopentin and ways of its realization].

In experiments on mice and in vitro the influence of neurotensin pentagastrin and thymopentin on the immune response, the phagocytosis of staphylococcus aureus by polymorphoneutrophil leucocytes and enzymatic activity of these cells by NBT-test were investigated. It was shown that neurotensin and thymopentin increase enzymatic and phagocytic function of polymorphoneutrophil leucocytes. Pentagastrin, as well as thymopentin stimulates the immune response, enzymatic but not phagocytic function of polymorphoneutrophil leucocytes. Immunostimulating effect of the studied peptides was realized by facility differentiation of mouse bone marrow cells into T-lymphocytes and by the interaction of the peptides with T-cells.

Adjuvants, Immunologic↗
PubMed1985

Thymopentin treatment of herpes simplex infections. An open, monitored, multicenter study.

Twenty-seven patients suffering from long-standing, severe, recurrent herpes simplex (14 labial and 13 genital) who had not responded adequately to prior therapy were recruited for this open, monitored study. They were treated with thymopentin 50 mg subcutaneously three times weekly for a period of 6 weeks. Clinical controls were performed once a week and then again 6 weeks after cessation of therapy; laboratory investigations were done at time points 0, 3, and 6 weeks. Additionally, information was collected with regard to the clinical course during the following year. Thirteen of 14 patients with labial infection and 10 of the 13 with genital herpes improved markedly (p less than 0.05) as shown by decrease in the relapse rate of at least 50%, shorter relapse episodes, and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than 4 months after cessation of therapy. These favorable results were paralleled by a statistically significant increase in the T cell helper/suppressor ratio. This finding indicates that thymopentin acts as an immunodomulator; it is assumed that the activation of T helper cells induces-presumable via interleukin 2-the proliferation of cytotoxic T lymphocytes and natural killer cells which play a major role in the natural immune defense. No serious side effects of thymopentin were recorded.

Adjuvants, Immunologic↗
PubMed1985

Thymopentin in chronic Trichophyton rubrum infection.

The case histories of 2 patients with chronic Trichophyton rubrum infections are presented. Both subjects had previously been treated systemically with griseofulvin, but had to be dropped from therapy due to adverse reactions. Topical treatment alone yielded unsatisfactory results. Thymopentin, 50 mg, administered subcutaneously three times weekly for a period of 6 weeks, induced rapid improvement within 3 weeks and almost complete remission 3 weeks later, although the fungi were still present on the skin. This beneficial effect lasted for up to 7 months after cessation of thymopentin therapy. Reinstitution of treatment produced the same response pattern. The clinical and immunological implications of these findings are briefly discussed; thymopentin is believed to enhance the suggested impaired cellular immunity in patients with chronic T. rubum infections.

Adjuvants, Immunologic↗
PubMed1985

Safety of thymopentin. Data from European clinical studies.

The safety data collected from 196 patients treated with thymopentin during the clinical development of this compound in Europe are reviewed and compared with the incidence of adverse drug reactions experienced when using a commercial nonsteroid anti-inflammatory drug. Quantitatively side effects are reported in the same range for both drugs, however, they appear to be quite different when classified by body systems. Some patients complained about somnolence, and it is speculated whether this symptom might be related to thymopentin's known effect on the neuromuscular junction. The general conclusion is that thymopentin is an extremely well tolerated drug when used according to the dose regimens recommended.

Animals↗
PubMed1985

Thymopentin in active rheumatoid arthritis. An open, monitored study in 16 patients.

The present paper reports on 16 patients with active rheumatoid arthritis who were treated with thymopentin administered as intravenous prolonged injections (one push of 5 mg every minute for 10 min) three times weekly for 3 consecutive weeks. Thirteen patients were evaluated, including a follow-up period of 2 months. Most patients improved clinically already after 5 injections. The overall data showed a statistically significant improvement (p less than 0.05) at the end of treatment; this favorable effect lasted for 6-7 weeks after thymopentin was discontinued. Standard laboratory tests and immunological parameters did not reveal any meaningful findings, hence, it can only be speculated about thymopentin's mechanism of action. It is suggested that the dose regimen is very critical as to therapeutic outcome when using an immunomodulating drug in clinical medicine.

Adjuvants, Immunologic↗
PubMed1985

Modulation of immune response in aged humans through different administration modes of thymopentin.

Thymopentin, a synthetic pentapeptide corresponding to the active site of thymopoietin, has been shown to restore antibody production in old mice. A decrease in immune response can also be observed in elderly humans, which is mainly caused by defective T cell function. The present study shows that the immunomodulating properties of thymopentin involve both specific and nonspecific responses in a population of elderly people vaccinated with keyhole limpet hemocyanin (KLH) antigen. Furthermore, it is demonstrated that these effects depend upon the mode of administration of thymopentin: The specific KLH antibodies (IgM and IgG), measured by solid-phase radioimmunoassay, reach the highest titers after subcutaneous injection. The lowest titers are produced after intravenous injections, whereas the responses to placebo are between these two ranges. The nonspecific immunoglobulin production, measured by nephelometry, does not follow the same pattern, suggesting that different regulatory mechanisms are involved. Future implications of these findings are discussed.

Adjuvants, Immunologic↗
PubMed1984

The effect of thymopentin treatment on the relapse rate in frequently relapsing herpes simplex virus infections.

Twenty-four patients suffering from longstanding severe recurrent herpes simplex, who had not responded to prior therapy, were treated with s.c. thymopentin injections 50 mg, three times weekly, over a period of six weeks. They were followed up at weekly intervals over this period and then six weeks later. Moreover, the longest relapse-free period observed in the year after the treatment was recorded in the investigator's documentation. Thirteen of the 14 patients with labial herpes simplex and 10 of the 13 patients with genital herpes simplex improved markedly as shown by a decrease in the relapse rate of at least 50%, shorter episodes of relapse and improvement of symptoms such as pain and itching. Fourteen of these 27 patients experienced no relapse for a period longer than four months after cessation of the therapy. No serious side-effects were observed. Laboratory examinations before, during and after thymopentin did not reveal significant alterations except for an increase in the T-helper/T-suppressor ratio. The effect of thymopentin is assumed to be due to T-helper cell activation resulting in enhanced interleukin-2 production with subsequent proliferation of cytotoxic T lymphocytes and natural killer cells which are capable of producing immune interferon.

Adult↗
PubMed1984

First observations on high-dosed and long-term thymopentin treatment in active rheumatoid arthritis.

In this pilot study carried out in two centres, six male and two female patients with severe active rheumatoid arthritis (RA) (average duration over 10 years) were treated with thymopentin 50 mg in the form of prolonged i.v. injection (over 10 min), 3 times weekly for 3 to 20 weeks. Two of these patients were subsequently treated with different s.c. doses of thymopentin in a crossover fashion for more than two years, including periods without any treatment or treatment with placebo. The overall clinical efficacy was judged by assessing pain patterns and joint status and the functional stage of the patients according to Steinbrocker; in addition, the sedimentation rate was measured before and after the therapy. Seven out of eight patients showed definite improvement in their clinical status as assessed by the Steinbrocker scale. Most of the symptoms, particularly pain, capsular swelling, tenderness and morning stiffness, were remarkably reduced within 3 weeks of thymopentin treatment. Sedimentation rate decreased in five out of eight patients. Prolonged i.v. injections seemed to have somewhat better effects than s.c. administration; in the latter group the highest dose (3 X 100 mg/week or higher) produced the best results. During placebo treatment and during the medication-free intervals both groups of patients got worse. No side-effects occurred during the study.

Adult↗
PubMed1995

[Role of thymopentin in the prevention of post-splenectomy infections].

The Authors evaluated the efficacy of thymopentin in the prevention of post-splenectomy infections. 14 splenectomized patients treated by thymopentin (50 mg s.c. every other day in the 4 weeks following splenectomy) were compared with 14 splenectomized control patients. Clinical evaluations and measurement of CD4 and CD8 lymphocyte subpopulations were made preoperatively and then after 3 and 6 months from splenectomy. Hyperthermia (37.5-38 degrees C) "sine materia", which disappeared spontaneously in 4-5 weeks, was observed in the post-operative phase in 4 control patients and in 1 patient treated by thymopentin. No statistical difference was demonstrated comparing pre- and post-operative percentages of CD4 and CD8 lymphocytes in the treated and control groups.

Adolescent↗
PubMed1994

[Prevention of immunodeficiency and postoperative infective complications in patients undergoing surgical resection for carcinoma of the colon-rectum. Clinical study on 50 cases, using thymus hormones and thymopentin in particular].

As well as being related to the spread of the tumour, cancer patients present a state of immunodeficiency which is linked to age, malnutrition which is often present, particular in cases of cancer of the gastroenteric tract, surgery and the possibility of associated chemo- or radiotherapy. The authors studied two groups of 25 patients with colorectal cancer. In addition to antibiotic prophylaxis, group A received immunostimulating therapy with thymopentin-TP5. Group B was treated with antibiotic therapy alone. Cell-mediated immunity was checked preoperatively and after 15 days on the basis of skin reaction to 7 booster antigens (Multitest-IMC). Strictly surgical infective complications were more frequent in group B patients (28.1%) receiving antibiotic treatment alone compared to subjects in group A (21.6%). Infections in a non-surgical site were more than double in the absence of perioperative immune therapy. Of the 25 patients examined in group A, 3-4 postoperative infections and as many long-distance infections were reported, all of which resolved without sequelae within a few days. There was a greater and faster recovery of body weight in those subjects receiving thymopentin treatment in addition to antibiotic therapy. In colorectal cancer surgery antibiotic prophylaxis alone is without doubt a valid surgical antisepsis but, above all in hypoergic patients, it is significantly enhanced by perioperative treatment with thymopentin. This association reduces both postoperative infectious complications, in particular postoperative abdominal abscess, and infections in other areas, such as respiratory complications.

Adult↗
PubMed1997

[Recurrent urinary tract infections. Biological suppositions and clinical treatment with thymopentin].

BACKGROUND: Urinary tract infections (UTI) are a common usual pathological event. They relapse often due to the periurethral colonization of microorganisms from the intestinal bacterial flora. They also constitute an important and considerable social and clinical problem. The absence of inducing organic conditions or an infective focus at the base of the pathogenetic mechanism suggests the existence of alterations of the immune response of the subject. MATERIALS AND METHODS: In this work we wanted to verify if, in those subjects with relapsing UTI (more than four events every year) cure with "biological" response modifiers, particularly "thymopentin", meaningfully reduced the number of events. RESULTS: The results obtained confirm that for those cases in which the chemo-antibiotic therapy did not have the expected results, it is rational to support it with an immune-modulating drug (thymopentin). In fact the post-therapy reduction of UTI observed during two years of follow-up is statistically significant when compared to the average of UTI before therapy. CONCLUSIONS: The "cost-benefits" analysis should prove to be a saving in favour of the use of thymopentin, taking into consideration the reduction of chemo-antibiotics consumption and the lower number of working hours lost every year.

Adjuvants, Immunologic↗
PubMed1988

In vivo immunopotentiating activity of thymopentin in aging humans: modulation of IL-2 receptor expression.

The effect of thymopentin treatment was investigated in immunocompromised elderly subjects. Thymopentin was able to increase IL-2 production and IL-2 receptor expression, as assessed on PHA-activated blasts by percentage of Tac-positive cells and response to exogenous IL-2. After treatment, an increased precursor frequency, estimated by limiting dilution analysis, of PHA-responding lymphocytes was observed in two out of six subjects tested. In vitro experiments with thymopentin show that the drug was able to enhance blastogenesis by PHA of elderly lymphocytes but not of adult cells. These results indicate that (a) the increased IL-2 synthesis/IL-2 receptor expression may be the crucial mechanism of the immunopotentiating activity of the drug in elderly subjects and (b) an increased intrinsic T-cell responsiveness seems to be responsible for this immunopotentiating activity, although an increase in the size of the responsive T-cell pool could not be excluded.

Adjuvants, Immunologic↗
PubMed1988

Arg-Lys-Asp-Val-Tyr (thymopentin) accelerates the cholinergic-induced inactivation (desensitization) of reconstituted nicotinic receptor.

1. The thymic hormone thymopoietin blocks neuromuscular transmission and was proposed (Goldstein, 1974) as a modulator of synaptic conductivity. 2. The cholinergic-induced inactivation of nicotinic receptor reconstituted into asolectin lipid vesicles was studied in the presence and in the absence of thymopentin, a synthetic pentapeptide corresponding to positions 32-36 of thymopoietin. 3. The present data show that thymopentin accelerates desensitization of the nicotinic acetylcholine receptor, supporting the aforementioned physiological role proposed for thymopoietin. 4. They also suggest that the hormone itself and/or a yet unidentified hormine-derived peptide fragment may act as an endogenous ligand for nicotinic acetylcholine receptor desensitization.

Animals↗
PubMed1985

Thymopentin structure and relation to thymic factors.

High-performance liquid chromatography (HPLC) was used to evaluate the purity and batch-to-batch consistency of four commercially available thymic extracts and thymopentin, the synthetic pentapeptide corresponding to the biologically active region of the thymic hormone thymopoietin. The thymus extracts were all extremely heterogeneous, differing one from the other. Additionally, they showed high batch-to-batch variation. In contrast, thymopentin was homogeneous and this homogeneity was consistent in different batches.

Animals↗
PubMed1985

Thymopentin: stability considerations and potency by various routes of administration.

Thymopentin, the synthetic pentapeptide Arg-Lys-Asp-Val-Tyr corresponding to amino acids 32-36 of thymopoietin, was rapidly degraded in human plasma (T 1/2 = 30 s) and this was shown to be due to proteolytic enzymes in plasma. The biological potency of thymopentin varied greatly with the route of administration, a finding possibly related to its short half-life. Intravenous infusion provided the most potent and bolus intraperitoneal injection the least potent mode of administration. Thus the route and rate of administration are critical factors in determining the effective dose being received by the animal.

Action Potentials↗
PubMed1985

Thymopentin treatment in patients with chemotherapy-resistant lepromatous leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae; it is chiefly involving the skin and peripheral nerves. In lepromatous leprosy there are widespread loose infiltrates with M. leprae multiplying extensively in the skin macrophages and Schwann cells of peripheral nerves. Such patients reveal a decrease of circulating T helper cells, which is still more pronounced in the cutaneous lesions. Due to the ever increasing bacterial resistance to classical dapsone and combined chemotherapy as well, an immunomodulatory approach seemed reasonable: Eight patients with long-lasting (5-40 years) disease who had become resistant to combined chemotherapy were treated with thymopentin, 50 mg s.c., 3 times weekly for 5 weeks and thereafter combined with dapsone and clofazimine for 5 months. During the trial a statistically significant increase in E-rosette-forming cells (p less than 0.05) was observed, along with a steady improvement of the bacterial status of the nasal mucus. Although the skin lesions did not disappear within the observation period of the study, it is important to realize that long-term improvement of such lesions is always initiated by clearance of bacilli from the nasal mucus, hence, thymopentin treatment appears to be a promising approach to chemotherapy-resistant lepromatous lepra.

Adjuvants, Immunologic↗
PubMed1985

Rationale for thymopentin as therapeutic agent in rheumatoid arthritis.

Etiology and pathogenesis of rheumatoid arthritis (RA) is reviewed, with special emphasis on immunological factors. A common feature in active RA seems to be the decreased T cell suppressor/cytotoxic response, also reflected in an increased OKT4/OKT8 ratio. As the presence of several subgroups in patients is possible, the therapeutic approach may differ accordingly. Different disease-modifying antirheumatic drugs (DMARDs) are discussed in this context; their most characteristic features are slow onset of action (i.e., after several months) and improvement in immunological parameters. Although thymopentin does possess the latter property, it is not considered a DMARD at the present time. The action of thymopentin sets in within a few weeks, and it is speculated whether this may be due to its possible hormonal effects (via beta-endorphins, prostaglandins, etc.).

Adjuvants, Immunologic↗
PubMed2006

Preparation and evaluation of lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin.

The purpose of this study was to design and evaluate lectin-conjugated PLGA nanoparticles for oral delivery of thymopentin. Thymopentin loaded PLGA nanoparticles (TP5-NPs) were prepared by a double emulsion-solvent evaporation technique. Novel WGA-PLGA conjugates were synthesized by coupling the amino groups of wheat germ agglutinin (WGA) to the carbodiimide-activated carboxylic groups of PLGA, and were incorporated into nanoparticles preparation to take mucoadhesive properties. Important characteristics such as particle size, zeta potential, entrapment efficiency, storage stability, as well as in vitro drug release behavior were investigated. The retention of biorecognitive activity of WGA after covalent coupling was confirmed by haemagglutination test. In vitro experiments with pig mucin (PM) demonstrated that the conjugation of WGA enhanced the interaction about 1.8-4.2 fold compared with that of the non-conjugated nanoparticles, and still exhibited sugar specificity. The pharmacodynamical studies on oral administration of WGA-TP5-NPs were performed in FACScan flow cytometry. The values of CD4(+)/CD8(+) ratios were significantly increased compared with that of TP5-NPs (p<0.01). The enhanced uptake was related to the increasing of WGA content on nanoparticles. These results confirmed that the conjugation of WGA onto PLGA nanoparticles effectively improved the intestinal absorption of TP5 due to specific bioadhesion on GI cell membrane.

Adjuvants, Immunologic↗