Age-associated changes in the stimulatory effect of transforming growth factor beta on human osteogenic colony formation

Previous studies have indicated that the mitogenic responsiveness of human bone cells may change with age. In the present study, we examined whether aging affects the capacity of transforming growth factor beta (TGF-beta) to stimulate the colony formation of human osteoprogenitor cells. Outgrowths of bone cells from 98 iliac crest biopsies were plated at a density of 25 cells/cm2 and cultured for 3 weeks in the presence of 10% fetal calf serum. Approximately 5% of the plated cells gave rise to clonal colonies. TGF-beta (10(-11) M) significantly increased the estimated number of cells per colony. However, the stimulatory effect of TGF-beta significantly declined with donor age (r = -0.26, P = 0.01). Whereas TGF-beta raised the average number of cells per colony in cultures from donors below the age of 50 years by 136+/-50%, the average increase was only 43+/-16% in donors older than 60 years. These data raise the possibility that aging may be associated with a declining capacity of TGF-beta to enlarge the pool of bone cells that can be generated from a single human osteoblast progenitor cell.     

Degradable poly(anhydride ester) implants: effects of localized salicylic acid release on bone

Degradable poly(anhydride ester) implants in which the polymer backbone breaks down into salicylic acid (SA) were investigated. In this preliminary work, local release of SA from the poly(anhydride esters), thus classified as ‘active polymers', on healthy bone and tissue was evaluated in vivo using a mouse model. Degradable polyanhydrides that break down into inactive by-products were used as control membranes because of their chemical similarity to the active polymers. Small polymer squares were inserted over the exposed palatal bone adjacent to the maxillary first molars. Active polymer membranes were placed on one side of the mouth, control polymers placed on the contra lateral side. Intraoral clinical examination showed that active polymer sites were less swollen and inflamed than control polymer sites. Histopathological examination at day 1 showed essentially no difference between control and active polymers. After 4 days, active polymer sites showed epithelial proliferation to a greater extent than the polyanhydride controls. After 20 days, active polymer sites showed greater thickness of new palatal bone and no resorptive areas, while control polymer sites showed less bone thickness as well as resorption including lacunae involving cementum and dentine. From these preliminary studies, we conclude that active polymers, namely poly(anhydride esters), stimulated new bone formation.     

Ex vivo rapamycin generates Th1/Tc1 or Th2/Tc2 Effector T cells with enhanced in vivo function and differential sensitivity to post-transplant rapamycin therapy.

Rapamycin prevention of murine graft-versus-host disease (GVHD) is associated with a shift toward Th2- and Tc2-type cytokines. Recently, we found that use of rapamycin during ex vivo donor Th2 cell generation enhances the ability of adoptively transferred Th2 cells to prevent murine GVHD. In this study, using a method, without antigen-presenting cells, of T-cell expansion based on CD3,CD28 costimulation, we evaluated whether (1) rapamycin preferentially promotes the generation of Th2/Tc2 cells relative to Th1/Tc1 cells, (2) rapamycin-generated T-cell subsets induce cytokine skewing after allogeneic bone marrow transplantation (BMT), and (3) such in vivo cytokine skewing is sensitive to post-BMT rapamycin therapy. Contrary to our hypothesis, rapamycin did not preferentially promote Th2/Tc2 cell polarity, because rapamycin-generated Th1/Tc1 cells secreted type I cytokines (interleukin [IL]-2 and interferon-gamma) did not secrete type II cytokines (IL-4, IL-5, IL-10, or IL-13) and mediated fasL-based cytolysis. Rapamycin influenced T-cell differentiation, because each of the Th1, Th2, Tc1, and Tc2 subsets generated in rapamycin had increased expression of the central-memory T-cell marker, L-selectin (CD62L). Rapamycin-generated Th1/Tc1 and Th2/Tc2 cells were not anergic but instead had increased expansion after costimulation in vitro, increased expansion in vivo after BMT, and maintained full capacity to skew toward type I or II cytokines after BMT, respectively; further, rapamycin-generated Th1/Tc1 cells mediated increased lethal GVHD relative to control Th1/Tc1 cells. Rapamycin therapy after BMT in recipients of rapamycin-generated Th1/Tc1 cells greatly reduced Th1/Tc1 cell number, greatly reduced type I cytokines, and reduced lethal GVHD; in marked contrast, rapamycin therapy in recipients of rapamycin-generated Th2/Tc2 cells nominally influenced the number of Th2/Tc2 cells in vivo and did not abrogate post-BMT type II cytokine skewing. In conclusion, ex vivo and in vivo usage of rapamycin may be used to modulate the post-BMT balance of Th1/Tc1 and Th2/Tc2 cell subsets.     

Experimental evaluation of eye-blink parameters as a drowsiness measure

Drowsiness and increased tendency to fall asleep during daytime is still a generally underestimated problem. An increased tendency to fall asleep limits the efficiency at work and substantially increases the risk of accidents. Reduced alertness is difficult to assess, particularly under real life settings. Most of the available measuring procedures are laboratory-oriented and their applicability under field conditions is limited; their validity and sensitivity are often a matter of controversy. The spontaneous eye blink is considered to be a suitable ocular indicator for fatigue diagnostics. To evaluate eye blink parameters as a drowsiness indicator, a contact-free method for the measurement of spontaneous eye blinks was developed. An infrared sensor clipped to an eyeglass frame records eyelid movements continuously. In a series of sessions with 60 healthy adult participants, the validity of spontaneous blink parameters was investigated. The subjective state was determined by means of questionnaires immediately before the recording of eye blinks. The results show that several parameters of the spontaneous eye blink can be used as indicators in fatigue diagnostics. The parameters blink duration and reopening time in particular change reliably with increasing drowsiness. Furthermore, the proportion of long closure duration blinks proves to be an informative parameter. The results demonstrate that the measurement of eye blink parameters provides reliable information about drowsiness/sleepiness, which may also be applied to the continuous monitoring of the tendency to fall asleep. Electronic Publication     

Stellenwert der Herzglykoside in der Therapie der chronischen Herzinsuffizienz

Ohne ZusammenfassungAbkürzungen NYHA New York Heart Association - VF Vorhofflimmern - WPW-Syndrom Wolff-Parkinson-White-Syndrom     

The effect of rectal pH values on the absorption of methohexital

The factors underlying the unpredictability of the pharmacokinetics of rectally administered methohexitone remain unclear. The "pH partition hypothesis" offers an explanation. We investigated six children with rectal pH values ranging from 7.5 to 9.8, who were given 25 mg/kg methohexitone 10% via the rectal route under general anaesthesia. Blood samples were taken at zero, 3, 5, 7, 10, 15, 20, 30, 40, 60, 90 and 120 min; rectal pH was measured at zero and 1 min. The methohexitone plasma levels reached a maximum (Cmax) of 2.63 micrograms/ml (median) after 17.5 min (median). The elimination half-life ranged from 37 to 218 min. No positive correlation between lower pH and better resorption (AUC and Cmax) was found. The resorption kinetics of rectally administered methohexitone cannot be explained by its electrochemical properties alone.     

A TLC screening program for 170 commonly used pesticides using the corrected Rf value (R f c value)

Summary This article reports TLC data (corrected R_f values; R _f ^c values) of 170 commonly used pesticides which are regularly encountered in toxicological analysis. Silica gel was used as the stationary phase and three binary systems were chosen as solvents.