Culture supernatant of Shiga toxin-producing Escherichia coli strains provoke fluid accumulation in rabbit ileal loops

In the present study, in order to get a better insight into the mechanism of action of cyclophosphamide (CY) in rheumatoid arthritis (RA), we monitored the changes in lymphocytes' expression of leukocyte function associated antigen 1 (LFA-1). A group of 28 patients with refractory severe RA were treated with CY and methylprednisolone (MO) intravenously. Using flow cytometry we evaluated the changes in LFA-1 molecule expression on peripheral lymphocytes. In the analyzed group of patients the proportion of LFA-1 "dim" cells was reduced. After the treatment the ratio was partly normalized. Twelve months after cessation of the therapy high proportion of LFA-1 "dim" was observed only among CY/MP treated patients. The changes were related to clinical improvement. Based on the obtained data, it seems, that the treatment affecting the expression of LFA-1 may slow down lymphocyte migration and by that limit chronic inflammation within the synovium.     

Fluconazole sensitivities of Candida species isolated from the mouths of terminally ill cancer patients

BACKGROUND: It has been suggested that tumors respond differently after irradiation with 10 or more fractions than with less fractionated regimens and that extrapolation from experiments with only a few fractions to "curative" regimens may be invalid. To test this hypothesis, we compared hypofractionated-accelerated treatments with "curative" fractionation schedules in human squamous cell carcinoma in nude mice. MATERIAL AND METHODS: FaDu tumors were transplanted subcutaneously into the hindleg of NMRI nu/nu mice. TCD50 values, i.e., the dose necessary to control 50% of the tumors locally, were determined after irradiation under ambient blood flow conditions with 5 and 10 fractions in 5 days, 10 fractions in 10 days, and 30 fractions in 15 days, 6 weeks or 10 weeks. RESULTS: TCD50 values of the hypofractionated regimens were not significantly different and varied from 41 to 46 Gy. The number of fractions given in the same overall time had no measurable effect on local tumor control. The TCD50 after 30 fractions in 6 weeks was 30 Gy higher than after the hypofractionated regimens. This effect was caused by a substantial increase of TCD50 with overall treatment time, the dose recovered per day was 0.82 Gy (95% CI 0.66; 0.96). alpha/beta eff determined from all data was 58 Gy (13; infinite). CONCLUSIONS: The results of the present study compare well with our previous findings after different "curative" fractionation schedules in the same tumor. Thus, our study does not support that tumors respond differently after application of 10 or more fractions compared to less fractionated regimens. The biological mechanisms that govern the radiation response of FaDu tumors appear to be the same for hypofractionated-accelerated and "curative" regimens. Since only one tumor was investigated, these results cannot be generalized at the present time.     

Arterial stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: a randomised trial

BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent placement (PTAS) may be more effective. We undertook a randomised prospective study to compare PTA with PTAS in patients with ostial atherosclerotic renal-artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA failed immediately or during 6 months' follow-up. Analysis was by intention to treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one patient in the PTAS group was excluded from the study. Primary success rate (<50% residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients) for PTAS (difference between groups 31% [95% CI 12-50]). Complications were similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and 75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12 patients underwent secondary stenting for primary or late failure of PTA within the follow-up period: success was similar to that of primary PTAS. Evaluation based on intention to treat showed no difference in clinical results at six months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However, the burden of reintervention after PTA outweighs the potential saving in stents, so primary PTAS is a better approach to use.     

Cardiovascular responses mediated by protease-activated receptor-2 (PAR-2) and thrombin receptor (PAR-1) are distinguished in mice deficient in PAR-2 or PAR-1

We developed mice deficient in protease-activated receptor-2 (PAR-2) or PAR-1 to explore the pathophysiological functions of these receptors. In this report, we evaluated mean arterial pressure and heart rate (HR) changes in response to PAR-1 or PAR-2 activation in anesthetized wild-type (WT), PAR-1-deficient (PAR-1(-/-)), and PAR-2-deficient (PAR-2(-/-)) mice. In WT mice, TFLLRNPNDK, a PAR-1 selective activating peptide, caused hypotension and HR decreases at 1 micromol/kg. TFLLRNPNDK also caused secondary hypertension following L-NAME pretreatment. These responses were absent in PAR-1(-/-) mice. In WT mice, SLIGRL, a PAR-2 selective activating peptide, caused hypotension without changing HR at 0.3 micromol/kg. SLIGRL did not induce hypertension following Nomega-nitrol-arginine-methyl ester-HCl (L-NAME). The response to SLIGRL was absent in PAR-2(-/-) mice. SFLLRN, a nonselective receptor activating peptide caused hypotension and HR decreases in WT mice at 0.3 micromol/kg, as well as secondary hypertension following L-NAME. SFLLRN still induced hypotension in PAR-1(-/-) mice, but HR decrease and secondary hypertension following L-NAME were absent. The hypotensive and bradycardic responses to SFLLRN and TFLLRNPNDK in PAR-2(-/-) mice were accentuated compared with WT mice. By using mouse strains deficient in either PAR-1 or PAR-2, we confirmed the in vivo specificity of TFLLRNPNDK and SLIGRL as respective activating peptides for PAR-1 and PAR-2, and the distinct hemodynamic responses mediated by activation of PAR-1 or PAR-2. Moreover, the accentuated response to PAR-1 activation in PAR-2-deficient mice suggests a compensatory response and potential receptor cross-talk.     

Magnetic resonance spectroscopy for assessing myocardial rejection in the transplanted rat heart

Tandem duplication of a mitochondrial import leader sequence has been shown to markedly increase the efficiency of translocation of chimaeric precursors across mitochondrial membranes to the mitochondrial matrix. The principle of leader sequence duplication was applied to the protein secretion system of the yeast Saccharomyces cerevisiae and of Bacillus subtilis. The secretion signal sequences of yeast invertase and B. subtilis neutral protease were used to direct the secretion of human interferon alpha 4. Our results show that the duplication of these N-terminal signal sequences does not enhance secretion of interferon alpha 4 in either of the cell systems studied.