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Biomedical subjects

K Bolla

Publications and source records attributed to K Bolla.

At least 37 records · Page 2Linked to original sources

Thymopentin as adjuvant therapy to hepatitis B vaccination in formerly non-or hyporesponding hemodialysis patients.

Thirteen patients who were on chronic hemodialysis for renal failure received booster vaccination with 40 micrograms HB-Vax while receiving thymopentin as adjuvant therapy. A 50-mg dose of thymopentin was administered subcutaneously 3 times weekly for 3 weeks and vaccination was given after the first week's treatment. Seven of the 13 patients had never developed any measurable anti-HBs titers in spite of 4-5 previous vaccinations, although 6 out of these 7 had used interferon as adjuvants to their last vaccination. The remaining 6 patients were hyporesponders, but the antibodies had vanished in all before the study was started. Twelve out of the 13 patients developed anti-HBs after revaccination while on thymopentin adjuvant therapy. The antibody production started in most cases within 2 weeks after the booster HB-Vax and showed an increasing trend for up to 6 weeks. Protective titers persisted in the responder cases for the duration of the study (2-3 months). Thus thymopentin may represent a valuable tool to achieve a successful hepatitis B vaccination in hemodialysis patients.

Adjuvants, Immunologic↗

In vitro influence of thymopentin on proliferative responses and phytohemagglutinin-induced interleukin 2 production in normal human lymphocyte cultures.

Peripheral human blood lymphocytes from healthy blood donors were investigated in vitro to observe the influence of different doses of thymopentin on nonstimulated proliferation, candidin-stimulated proliferation, and phytohemagglutinin (PHA)-induced interleukin 2 (IL2) production. Concentrations of thymopentin ranging from 0.01 to 10,000 ng/ml were used. The proliferation response in non-stimulated cultures was significantly higher in the presence of 0.01, 1, 10, 1,000, and 10,000 ng/ml of thymopentin. There was no significant increase with 0.1 or 100 ng/ml of thymopentin. Thus, three separate peaks were present in these unstimulated cultures: at a concentration of 0.01 ng/ml; between 1 and 10 ng/ml, and between 1,000 and 10,000 ng/ml. These peaks possibly represent three different subpopulations with different sensitivities to different concentrations of thymopentin. Candidin-induced proliferation was significantly higher only at concentrations of 1 and 10 ng/ml of thymopentin, corresponding to the second peak in the unstimulated culture. No other thymopentin concentrations induced significant increase in the candidin-stimulated cultures. No IL2 production was observed in the unstimulated cultures, even in the presence of thymopentin. On the contrary, preincubation with different concentrations of thymopentin influenced PHA-induced IL2 production. A significant increase in the IL2 level was observed in the supernatant of the cultures if 1,000 ng/ml of thymopentin was used in the preculture period. This concentration corresponds to the third peak in the unstimulated cultures. No significant changes were observed with other concentrations of thymopentin. As the measured value of IL2 is a result of a balance between IL2 production and utilization, the above-mentioned findings need further investigation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic↗

Thymopentin treatment in a patient with pluriorificial pyoderma vegetans.

This paper presents longitudinal clinical and immunological findings in a patient with a life-long history of pluriorificial pyoderma vegetans, a disease characterized by a distinct immunodeficiency of T lymphocytes. After treatment with thymopentin, 50 mg s.c. three times weekly for 12 weeks, the number of T lymphocytes in peripheral blood normalized, while other impaired immunological functions failed to improve, however. The most impressive observation was the significant clinical improvement of the patient's condition.

Adjuvants, Immunologic↗

Thymopentin as adjuvant to hepatitis B vaccination. Results from three double-blind studies.

The influence of adjuvant thymopentin therapy on the effect of vaccination with HB-Vax was investigated in three independent double-blind studies in which three different time/dose schedules of the adjuvant therapy were used. The first study was conducted with 30 hemodialyzed patients who had previously been non- or hyporesponders. Forty and 26 nonvaccinated hemodialyzed patients were chosen for the two additional studies. A 50-mg dose of thymopentin or placebo was administered subcutaneously in all studies. In one study, in which only one adjuvant injection was administered simultaneously with each vaccine injection, thymopentin inhibited the antibody response. On the contrary, in the other two studies, in which three injections of adjuvant were administered during the week following the vaccination (in one of these studies three injections were also given before the vaccination), no difference in the effect of vaccination was observed in patients on either placebo or thymopentin. Comparison of the results of the present studies with those of earlier observations emphasizes the importance of time/dose schedules of adjuvant therapy in vaccination.

Adjuvants, Immunologic↗

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↗

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↗

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↗

Clinical experience and results of treatment with suprofen in pediatrics. 1st communication: Suprofen dosage for children/An open and a double-blind study with suprofen syrup.

The antipyretic effect of single doses of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) syrup, administered at dose levels of 1, 2, 3, 4, 5, 7.5, and 10 mg/kg b.w., was tested in a randomized double-blind and a subsequent open study. The test populations consisted of 100 children in the double-blind study and 40 patients in the open test (20 subjects/group). The patients' age ranged from 2 to 12 years; the lowest initial rectal temperature was 39.0 degrees C. The treatment groups were homogeneous as to demographic data. The temperature was reduced in all treatment groups. In the double-blind study the mean value dropped under the subfebrile threshold of 38.0 degrees C only in the group on 5 mg/kg and remained then constant for up to 6 h following administration. No sufficient antipyretic effect was obtained with lower doses. The results of the additional open study with doses of 7.5 and 10 mg/kg indicated good antipyretic effect. This effect was not, however, superior to that obtained with 5 mg/kg. Pulse and respiratory rates returned to normal within 1.5 h following administration, except in patients on 1 mg/kg. A total of 10 patients, homogeneously distributed in the treatment groups, experienced vomiting as an adverse reaction. Short-term hypotonia was seen in one subject on 7.5 mg/kg. The results obtained show that single doses of suprofen upward of 5 mg/kg b.w. exert satisfactory, long-lasting, antipyretic effect on children.

Body Temperature↗

[Acquired immunodeficiency syndrome, chronic coccidiosis and Salmonella typhimurium septicemia in a couple from Zaire. Immunological functions and attempt at immunostimulation by thymopentin].

A clinical review of a young couple from Zaïre with acquired immunodeficiency syndrome (AIDS) is reported. Both had opportunistic infections such as Salmonella typhimurium septicemia, genital herpes and digestive candidiasis. The husband was hospitalized for diarrhea from Isospora belli infection and for hemoptysis from an aspergilloma. His wife was admitted for a thoracic herpes zoster infection and left hemiplegia preceding subacute encephalitis. In both patients the biological immune functions were compatible with AIDS: presence of antibody against lymphadenopathy virus, decreased in OKT4+/OKT8+ ratio, and lack of lymphocyte response to mitogens which was partially restored in vitro after addition of interleukin 2 and thymopentin (TP-5) in the husband. In vitro monocyte cultures showed increased production of prostaglandins E2 (PGE2) and a slight decrease in interleukin 1 production. The symptomatic treatments and an attempt at immunostimulation with TP-5 in the husband are described.

Acquired Immunodeficiency Syndrome↗

[Treatment of recurrent herpes simplex with thymopoietin-pentapeptide].

Treatment resistant recurrent herpes simplex persisting for years in 7 patients was treated with thymopoietin pentapeptide for 6 weeks, 50 mg subcutaneously three times per week. During treatment and follow-up of 6 weeks a pronounced reduction of frequency and duration of recurrences were observed. There was some tendency for normalisation of deranged lymphocyte and granulocyte function. The mode of action of thymopoietin pentapeptide in recurrent herpes simplex remains uncertain. An indirect effect via stimulation of production of interferon may be assumed.

Adult↗

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↗

Immunomodulation with thymopentin in humans.

The effect of thymopentin administered i.v. or s.c. on the levels of circulating specific IgM and IgG KLH (key-hole limpet haemocyanine) antibodies and non-specific immunoglobulins were measured at weekly intervals in elderly volunteers for three subsequent weeks after vaccination with 500 micrograms KLH. As compared with the placebo group, specific IgM and IgG antibody responses significantly increased in the s.c. treated group, but remained at significantly lower levels in the i.v. treated groups. Increases in non-specific immunoglobulin levels were observed after vaccination in the placebo group; no such increases appeared in the groups treated with thymopentin. The results demonstrate the immunomodulatory effect of thymopentin in humans. It is assumed that, depending on the route of application (which indirectly represents different doses), thymopentin can either stimulate or inhibit immune processes. As an immunomodulator it may represent a new therapeutic tool for immunostimulation as well as for specific immunosuppression.

Adjuvants, Immunologic↗

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↗

Interim results on the clinical effects of i.v. administered thymopentin in active rheumatoid arthritis.

Forty-one patients with active rheumatoid arthritis entered a controlled, double-blind, randomized study; 21 received prolonged i.v. injections (10 min) of thymopentin 50 mg 3 times a week for 3 consecutive weeks; the other 20 received placebo under the same conditions. The groups were comparable at the start of the study. Statistical tests of changes within the treatment groups after 3 weeks showed that the improvement achieved in the thymopentin group was significant (p less than 0.05 or p less than 0.01) for each clinical parameter, except for left-hand grip strength. On the other hand, no significant improvement was observed for any parameter except morning stiffness in the patients on placebo. The intergroup comparison showed significant differences, favouring thymopentin over placebo treatment, in the Ritchie index, scores for swollen joints, assessment of severity of pain and scores for changes in the activity of the disease. Only minor side-effects were experienced in the two treatment groups. The present placebo-controlled double-blind study confirms the previous positive results achieved in open studies, i.e., the beneficial therapeutic effect of prolonged i.v. injections of thymopentin in patients with severe rheumatoid arthritis observed after 3 weeks of therapy. The drug appears to be safe at the dose regimen used.

Arthritis, Rheumatoid↗

Preliminary results on clinical and immunological effects of thymopentin in AIDS.

In an open study, 10 African patients with AIDS were treated with thymopentin 50 mg i.v. 3 times a week for 2 consecutive months: 1 month by i.v. direct injections and 1 month by 30-min i.v. infusions. In group A there were 6 patients with AIDS-lymphadenopathy characterized by weight loss, chronic fever, generalized lymphadenopathy and OKT-4 to OKT-8 ratio below 0.2. Group B consisted of 4 patients with AIDS and opportunistic infections. Immunological studies performed before, during and after therapy included lymphocyte count, T-cell subsets assessment, study of blastogenic response of lymphocytes to PHA and delayed hypersensitivity skin testing to 5 antigens. In group A, results after thymopentin i.v. direct injections showed a significant increase in OKT-3 and OKT-8 cells. After thymopentin i.v. infusion, blastogenic response to PHA increased significantly as compared with pretherapy values and to the values after i.v. direct injections. At the end of infusion therapy, skin tests became positive for 3 antigens (range 2-4). Furthermore, all 6 patients noted subjective improvement associated with significant weight gain and disappearance of fever. In contrast, in group B the clinical and immunological status worsened during therapy and two patients died from opportunistic infections. This preliminary study suggests that i.v. infusion with thymopentin may be useful in the early phase of the acquired immune deficiency syndrome as it produces symptomatic and immunological improvement.

Acquired Immunodeficiency Syndrome↗