Effect of low-level laser irradiation on osteoblast proliferation and bone formation.

Applications of laser therapy in biostimulation and healing injured tissues are widely described in medical literature. The present study focuses on the effects of laser irradiation on the growth rate and differentiation of human osteoblast-like cells seeded on titanium or zirconia surfaces. Cells were laser irradiated with low therapeutical doses at different intervals and the effects of irradiation were evaluated at each time-point. After 3 hours lasered cells showed an enhanced mitogen activity compared to non-lasered control cells and a higher alkaline phosphatase activity, marker of bone formation. At the same time, the mRNA of RUNX2 and OSTERIX, two genes involved in osteoblast differentiation, showed a clear decrease in lasered cells. This reached the lowest value 6 to 12 hours after irradiation, after which the transcripts started to increase, indicating that the laser treatment did promote the osteogenic potential of growth-induced cells. These results indicate that Low Level Laser Treatment (LLLT) stimulates osteogenic cell proliferation.

Touch receptor of venous flytrap, Dionaea muscipula.

Numerous small structures (stellate trichomnes) protrude from the surface of marginal hairs, outer leaf surface, and stem of Dionaea muscipula Ellis. None are present inside the trap. Mechanical stimulation causes small action potentials and eventual closure of the trap, independently of the sensitive trigger hairs. Subthreshold stimulation of these structures appears to sensitize the trigger hairs and facilitate closure of the trap. This suiggests that these structures act as touch sensors or receptors.

When should the immune clock be reset? From circadian pharmacodynamics to temporally optimized drug delivery.

Immune defenses are organized along both 24-h and yearly time scales. Two circadian systems have been isolated in man, which can be desynchronized: (1) the circulation of T, B, or NK lymphocyte subsets in peripheral blood and (2) the density of epitope molecules (CD3, CD4, ...) at their surface, which may relate to cell reactivity to antigen exposure. The in vitro response of murine splenocytes to interleukin 2, interferon (IFN), or cyclosporin A strongly depended upon circadian time of exposure. Temporally optimized delivery of biologic response modifiers (BRM) may be guided by immunologic marker rhythms. An alternative yet complementary strategy was sought with IFN: since high doses were shown as more effective than low doses against several malignancies, this drug was given at the presumed less toxic time, so that its dose could be increased. Continuous drug delivery was circadian modulated in 8 cancer patients. Dose intensities twice to fourfold higher than those usually recommended were safely infused to ambulatory patients. Chronotherapy with BRM may represent a necessary step for optimizing the immunologic control of malignancies.

Subcutaneous recombinant interleukin-2 (rIL-2) in out-patients with metastatic renal cell carcinoma. Results of a multicenter SCAPP1 trial.

BACKGROUND: This multicenter phase II trial was conducted in order to evaluate the efficacy and toxicity of the subcutaneous route of administration of rIL-2 in the treatment of patients with metastatic renal cell carcinoma and to check whether an increased cumulative dose of rIL-2 increases efficacy. PATIENTS AND METHODS: Thirty-nine patients with metastatic renal cell carcinoma were included in this study. During the induction period, rIL-2 was administered subcutaneously 5 days a week for 8 weeks. The weekly dosages were 90 MIU during weeks 1 and 6;63 MIU during weeks 2 to 4 and 7 to 9. After evaluation, responders and patients with stable disease received maintenance treatment which was discontinued upon the appearance of disease progression or unacceptable toxicity. During the maintenance period, rIL-2 was administered 5 days a week for 4 weeks followed by a 2-week rest period. The weekly dosages were 90 MIU in week 1 and 63 MIU in weeks 2 to 4. RESULTS: After completion of induction treatment, 7 of 39 evaluable patients (18%) had objective responses (95% CI: 9% to 37%) with one complete response. Treatment was interrupted or reduced due to toxicity for seven patients: Neuropsychiatric symptoms (3 patients), joint pain (1 patient), major asthenia and anorexia (1 patient), stroke (1 patient), and septicemia (1 patient). Other systemic side effects in the remaining patients were acceptable. Seventeen patients received maintenance treatment. In none of the patients did the response status improve during this maintenance period. The median follow-up of all of the patients included was 19 months. The one- and two-year survivals were 65% and 33%, respectively, ad the median duration of response was 11 months (5 to 16+). CONCLUSIONS: This multicentric study confirms the efficacy of subcutaneously-administered rIL-2 in patients with metastatic renal cell carcinoma in terms of both response rate and survival. The role of a maintenance therapy needs further evaluation.

Production and manipulation of elevated temperatures in pig abdomen with a three-electrode capacitive heating device.

The ability of a three-electrode capacitive heating device operating at 13.56 MHz to produce and effect spatial redistribution of hyperthermic temperatures is demonstrated through abdominal heating studies conducted with 80 kg female and 65 kg male pigs. Temperature-time profiles over the respective heating periods were obtained in anterior and posterior superficial tissue and in selected abdominal organs. At selected times during heating, spatial redistribution of elevated temperatures was effected through adjustment of power settings for one or more of the three electrodes, i.e. through manipulation of the specific absorption rate (SAR) in-vivo.