Early Effects of Rhenium-188 Treatment on Proliferation, Migration, and Matrix Synthesis of Cultured Human Aortic Smooth Muscle Cells

BACKGROUND AND PURPOSE: Due to its properties rhenium-188 (188Re) seems to be a promising radionuclide for stent coating to reduce restenosis following percutaneous transluminal angioplasty (PTA). In order to characterize the early effects of local 188Re treatment, human aortic smooth muscle cells (HaSMCs) were incubated with different doses of 188Re. MATERIAL AND METHODS: 2 days after plating, HaSMCs were treated for a period of 5 days with 188Re. The total radiation doses applied were 1 Gy, 4 Gy, 8 Gy, 16 Gy, and 32 Gy. On days 1, 3, 5, and 7 (i.e., 2 days after the end of 188Re incubation), cell growth, clonogenic activity, cell migration, cell-cycle distribution, as well as matrix synthesis were evaluated. RESULTS: From the 1st day on, a dose-dependent growth inhibition was observed. Cumulative doses of > or = 8 Gy completely inhibited colony formation. The results of the migration tests were contradictory; on day 3 the migratory activity of all treated cells was increased compared to the controls, on day 5 it was reduced. Cumulative radiation doses of > or = 8 Gy resulted in an increased fraction of cells in G2/M-phase. The synthesis of the extracellular matrix protein tenascin was not affected by the treatment. CONCLUSION: Incubating human smooth muscle cells with 188Re for a period of 5 days (i.e., seven half-lives) results in an effective inhibition of muscle cell proliferation and colony formation. Partially, this is due to a radiation-induced G2/M-phase block. Cell migration and matrix synthesis were not effectively affected in the presented in vitro system.     

A cell-based approach to the minimization of immunosuppression in renal transplantation.

Five renal transplant recipients were preoperatively treated with transplant acceptance-inducing cells (TAICs) in a Phase-I safety study of TAICs as an adjunct immune-conditioning therapy in living-donor kidney transplantation. Initially, patients received anti-thymocyte globulin induction therapy in combination with tacrolimus and steroid immunosuppression. Over the course of 12 weeks, steroids were withdrawn and tacrolimus therapy was minimized. Three of the five patients were able to tolerate low-dose tacrolimus monotherapy and one patient was withdrawn from all immunosuppression for over 8 months. No acute or delayed adverse events were associated with the infusion of TAICs. Monitoring of the recipient anti-donor reactivity of TAIC-treated patients in mixed lymphocyte cultures demonstrated that, during periods of clinically stable graft function, recipient T-cell proliferation and cytokine secretion in response to stimulation with donor alloantigen was relatively suppressed. Therefore, although the TAIC-II trial did not provide conclusive evidence of a beneficial effect of preoperative TAIC treatment, the results were encouraging because they suggest that TAICs promote a state of alloantigen-specific unresponsiveness, which might allow safe minimization of pharmacological immunosuppression.     

Mild course of cystic fibrosis associated with heterozygosity for infrequent mutations in the first nucleotide-binding fold of CFTR

The mild clinical course of a patient with cystic fibrosis is presented who inherited the two mutations Gly551----Asp and Arg553----Stop in the cystic fibrosis transmembrane conductance regulator gene. The missense mutation Arg553----Stop discovered in American Blacks is also present on cystic fibrosis chromosomes of Caucasian ancestry.     

Carbapenem Activities against Pseudomonas aeruginosa: Respective Contributions of OprD and Efflux Systems

While meropenem MICs were strongly influenced by the presence or absence of the MexAB-OprM efflux pump in both OprD-proficient and -deficient strain backgrounds, MICs of imipenem and of ER-35786 remained unchanged, demonstrating that meropenem is a substrate of MexAB-OprM but not imipenem and ER-35786. In vitro, all three carbapenems selected loss of OprD as a first mechanism of resistance. However, in an OprD-deficient background, meropenem was able to select MexAB-OprM overproducers as a secondary resistance mechanism, while ER-35786 selected a mutant cross-resistant to sparfloxacin and cefpirome.     

Dichloro-[1-(hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes: testing on the human ovarian cancer cell lines NIH: OVCAR3 and SK OV 3.

The diastereoisomeric dichloro-[1-(2-, 3- and 4-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) complexes were tested on two human ovarian cancer cell lines NIH: OVCAR-3 and SK-OV-3, both resistant against cisplatin. Dichloro-[threo-1-(3-hydroxyphenyl)-2-phenylethylenediamine]platinum(II) (threo-5-PtCl2) proved to be the most active representative of the new series, producing cytocidal effects at a concentration range of 2.5 to 5.0 microM on the NIH: OVCAR-3 cell line. On the more resistant SK-OV-3 cell line, threo-5-PtCl2 was only moderately active, while in combination with BSO, a GSH level lowering compound, threo-5-PtCl2 showed a strong synergistic effect.     

A new mechanical sensor for activity controlled and body position dependent frequency adaptive pacemaker stimulation

In the past, the most important feature in the development of rate-responsive pacemaker systems was ensuring an adequate rate response to physical exercise. But there are other variables that modulate the rate of the healthy heart; examples include postural changes in heart rate in order to prevent orthostatic reactions, and the nightly decrease in intrinsic pacemaker rate. Therefore, we developed a sensor that could distinguish, not only rest and activity, but also discriminate between a supine and an upright position. This sensor is a multicontact tilt switch, which contains a small mercury ball. By measuring the number of openings and closures within the sensor as the ball touches the numerous sensor contacts it is possible to discriminate between different levels of exercise; the contact pins are circled around the base plate. There is an almost linear increase in the number of changes per time with increasing exercise. Besides measuring body activity from the number of contact changes per time, it is also possible to determine the body's posture from the count and positioning of the closed contacts within the casing. Based upon the results of 12 volunteers and nine pacemaker patients, a new algorithm is being prepared which enables the pacemaker to decrease stimulation rate in the supine position, to increase it in the upright position, and to correlate pacing rate with the increase in physical exercise. There is a good correlation between number of contact changes and the intrinsic heart rate (r = 0.87).