Acute graft pyelonephritis following renal transplantation.

BACKGROUND: Urinary tract infection is the most common form of bacterial infection encountered in a renal transplant recipient. Studies explaining the long-term consequences of acute graft pyelonephritis (AGPN) are few. METHODS: A total of 1022 consecutive renal allograft recipients were studied retrospectively over a period of 10 years for evidence of AGPN. These patients were classified into two groups according to the presence or absence of at least one AGPN episode. Only culture-proven infections were included in the study. RESULT: Of the 1022 renal transplant recipients, 169 patients (16.5%) developed AGPN. In the multivariate analysis with stepwise logistic regression, significant associations were observed between AGPN and placement of ureteric stent (odds ratio [OR]=4.6), urological malformations of native kidney (OR=2.1), cytomegalovirus (CMV) disease (OR=2.0), mycophenolate mofetil (MMF)-based regimen (OR=1.9), and acute rejection episodes (OR=1.5). However, age>40 years, female gender, induction therapy, anti-CD3 treatment, and hyperglycemia did not show such an association. In comparison with the non-AGPN group, these patients had a lower graft and patient survival (though it did not attain statistical significance). In the multivariate analysis using the Cox model for the entire study population, AGPN did not independently contribute to poor graft or patient survival. CONCLUSION: AGPN in the renal transplant setting is an ominous event, as these patients are also more prone to develop bacteremia, acute rejection, and CMV disease, which could then lead to poor graft and patient survival. Its association with MMF needs further clarification.

WR-1065, an active metabolite of the cytoprotector amifostine, affects phosphorylation of topoisomerase II alpha leading to changes in enzyme activity and cell cycle progression in CHO AA8 cells.

The effects of WR-1065 (2-((aminopropyl)amino)ethanethiol) on cell cycle progression, topoisomerase (topo) II alpha activity, and topo II alpha phosphorylation in Chinese hamster ovary (CHO) cells have been investigated. Exposure of CHO cells to 0.4 microM of WR-1065 for 30 min did not effect cell cycle progression nor topo II alpha activity and phosphorylation status. However, concentrations ranging from 4 microM to 4 mM were equally effective in significantly altering these three end points. Cell cycle progression was analysed by flow cytometry. Following a 30 min exposure to this range of concentrations, cells redistributed throughout the cell cycle with the most prominent changes being an accumulation of cells in G2. Topo II alpha activity was measured using a kinetoplast DNA (kDNA) decatenation assay. Enzyme activity was reduced by 50% relative to control levels throughout the 4 microM to 4 mM dose range tested. Likewise, topo II alpha phosphorylation levels, analysed using an immunoprecipitation assay and an antibody specific to the 170 kDa band of topo II, decreased between 42% to 48% of control levels. Inhibition of topo II alpha activity in cells exposed to WR-1065 is consistent with the associated observation of WR-1065 mediated cell cycle progression delay and build-up of cells in the G2 phase of the cell cycle.

Dipyrone enhances intracellular accumulation and cytotoxicity of adriamycin in human chronic myeloid leukemia cells.

The cytotoxicity induced by dipyrone alone, or in combination with adriamycin (ADR) was studied in human chronic myeloid leukemia (CML) cells. The inhibition of 3H-thymidine incorporation into DNA was taken as a measure of cytotoxicity. While dipyrone alone indicated marginal inhibition, its combination with ADR demonstrated a potentiating effect (p less than 0.001), which was found to be irreversible. The enhanced cytotoxicity of the combination was a result of an increased drug accumulation as studied by the uptake of 14C-adriamycin. Observations indicate that dipyrone can be used to enhance the cytotoxicity of ADR in human CML patients.

In vivo response of mitoxantrone and doxorubicin with dipyrone in parental and doxorubicin-resistant P388 leukemia.

The efficacy of dipyrone to modulate antitumor activity of mitoxantrone (MTN) and doxorubicin (DOX) was studied in vivo in mice bearing P388 murine lymphocytic leukemia sensitive (P388/S) and resistant P388/DOX) to DOX. P388/DOX-bearing mice demonstrated marginally higher sensitivity to dipyrone at 200 mg/kg when compared to P388/S-bearing mice. However, dipyrone could significantly enhance the antitumor activity of MTN and DOX in both P388/S and P388/DOX-tumor-bearing mice. MTN was cross-resistant to P388/DOX.

Mitoxantrone & adriamycin cytotoxicity enhanced by reserpine in human chronic myeloid leukaemia cells.

The effect of reserpine was studied alone and in combination with anticancer drugs on human chronic myeloid leukaemia (CML) cells. To study the effect of reserpine on anthracycline antibiotic adriamycin and anthracenedione mitoxantrone the extent of 3H-thymidine incorporation into the DNA was taken as the measure of cytotoxicity. The results indicate that reserpine enhances the cytotoxicity of mitoxantrone and adriamycin in mildly toxic concentrations (1 and 10 micrograms respectively), in CML cells. The mechanism of enhancement in drug sensitivity by reserpine in CML cells is due to enhanced intracellular accumulation of drug.

1,10-phenanthroline potentiates cytotoxicity of hydroxyurea in human chronic myeloid leukemia cells.

The effect of the divalent hydrophobic metal chelator 1,10-phenanthroline was evaluated alone and in combination with the antineoplastic agent hydroxyurea on human chronic myeloid leukemia cells. The compound at concentrations of 10 and 5 micrograms/ml significantly (p less than 0.001) potentiates DNA biosynthesis inhibiting the activity of hydroxyurea in vitro. Synergistic inhibition was obtained when both 1,10-phenanthroline and hydroxyurea was used in combination at relatively nontoxic concentrations. Cytotoxicity due to the combination was found to be partially reversible and was marginally reversible in the presence of Fe+2 and Zn. The results strongly suggest the utility of the iron-chelating agent along with hydroxyurea for further evaluation to achieve a better therapeutic result in the clinic.

Restoration of doxorubicin responsiveness in doxorubicin-resistant P388 murine leukaemia cells by dipyrone.

The effect of dipyrone along with doxorubicin and mitoxantrone was studied alone and in combination on the 3H-thymidine (3H-TdR) incorporation in P388 leukaemia sensitive (P388/S) and resistant (P388/ADR) to doxorubicin. Dipyrone 10(-4) M demonstrated minimal inhibitory effect on DNA biosynthesis in both the sensitive and resistant cells. Doxorubicin and mitoxantrone at equimolar concentrations, indicated time and dose-dependent inhibition in 3H-TdR incorporation in the sensitive cells. The inhibition was more at the higher drug concentrations at 4 h drug exposure. Mitoxantrone showed cross-resistance in P388/ADR compared to P388/S. Both the drugs along with 10(-4) M dipyrone in the incubating medium revealed synergistic inhibitory activity in P388/S and P388/ADR. Observations indicate circumvention of doxorubicin and mitoxantrone resistance in P388/ADR by dipyrone.

Practical multi-spectrum Hadamard transform spectrometer.

We have constructed a Hadamard transform spectrometer (HTS) which simultaneously obtains fifteen ir spectra, each having 255 spectral elements. Spectra are obtained essentially in real time through use of a minicomputer with 8K words of memory and a CRT display. This permits operation of the instrument in the field.