Characterization of metronidazole-phosphate, a water-soluble metronidazole derivative, as a radiosensitizer of hypoxic cells.

A water-soluble derivative of metronidazole (Flagyl) was synthetized with the purpose to overcome some practical difficulties in the clinical administration of the drug. The derivative, a phosphate ester of metronidazole, was characterized for different physical-chemical properties. It had a low toxicity both in vitro and in vivo. In vitro, it retained a radiosensitizing effect specific for hypoxic cells which was, however, decreased in comparison with the parent compound. The decreased sensitization was related to a decreased one-electron reduction potential and octanol/water partition coefficient. In mice, metronidazole-phosphate had a prolonged blood life in comparison to metronidazole.     

A new combination chemotherapy for resistant trophoblastic disease.

Six patients with gestational trophoblastic neoplasia resistant to triple chemotherapy (methotrexate, actinomycin D, and Cytoxan: MAC) treated with a new chemotherapeutic regimen (modified Bagshawe protocol: MBP) are presented. Five of the six patients are alive without evidence of recurrent disease with negative β-subunit human chorionic gonadotropin (HCG) titers from 2 to 18 months after completion of therapy. The MBP regimen would appear to be less toxic than triple chemotherapy (MAC) in this group of patients. A critical analysis of the MBP regimen is presented.     

Participation of gonads in chronic poisonings with heavy metals

On the basis of clinical examinations in 23 of 37 patients with chronic heavy metal intoxications hypofunctions of the gonads were proved in the sense of a deficitary spermatogenesis. By application of gonadotropic hormones the spermatogenesis could be stimulated, so that a deficient excretion of hormones in toxic lesion of the hypothalamo-hypophysary structures of the patients is to be taken into consideration.     

Helicobacter-like organisms in gastroduodenal diseases

The incidence of the Helicobacter-like organisms (HLO) was investigated on biopsy specimens of antral gastric mucosa, stained by the Wayson technique, in 509 patients with various gastric and duodenal diseases. The incidence of HLO was: 72.8 percent in gastric ulcer, 69.6 percent in duodenal ulcer, 69.2 percent in bulbitis, 61.0. percent in chronic gastritis, 37.5 percent in the postoperative stomach, 50 percent in gastric cancer, and 34.3 percent on healthy controls. The HLO were present over the whole year, with a peak in March. Sex and age had little influence on the HLO incidence. The Wayson staining technique proved to be a good technique of detection of HLO on gastric mucosa smears.     

Cell kinetics in the spleen of ehrlich ascites tumor-bearing mice

Summary During the period of 18 days after transplantation the uptake of ³H-thymidine into DNA was significantly increased in the spleen of Ehrlich ascites tumor-bearing Swiss and NMRI mice. Adenosine deaminase activity was within the control limits in tumor-bearing Swiss mice and significantly increased for the tumor-bearers of the NMRI strain. However, the increase in the DNA content, which is associated to splenic hyperplasia, was evident only for the Swiss strain. The time course of the retention of ³H-DNA revealed that the half life of spleen cells ranged from 41 to 46 h in normal and tumor-bearing Swiss mice and normal NMRI mice. For tumor-bearing NMRI mice the rate of cell depletion was significantly increased (t _1/2=32 h) compared with that found in normal NMRI mice (t _1/2=44h). The mean survival time was 23.0 days for the tumor-bearing Swiss mice and 24.6 days for the NMRI mice. These data suggest that the immune responses were similar in both strains of mice, although cell kinetics was different in the spleen of tumor-bearing Swiss and NMRI mice.     

Nutrition in preschool children from Băile-Herculane

In the effected study we investigated the feeding quality in Baile-Herculane, during the period 2003-2004. The study was realised in two samples consisted in 659 preschool children (55% girls and 45% boys) and 359 children (65% girls and 35% boys) respectively, homogenous and statistical representative. The method consisted in feeding investigation using based on food lists consulting, effected 2 times in a year, in the winter season (November) and in the spring season (April). The inquiry period was 10 days consequently, in each season. We had established the nutritive value of feeding portions in two months (November and April), counted the average of the nutritive ration for the both investigated periods and compared them with nutritional necessity established for the same age group. We investigated the menu structure and diversity. In the first period of feeding investigation (November 2000) we established a decreased intake of foods which determine a small intake of calories, proteins, minerals and vitamins under the nutritional necessities. In April the nutritive value of the consumed food was less than in November. The decreased consumption of milk, cheese, eggs, vegetables and fruits determined a less intake of calories, fats, minerals and vitamins than nutritional necessities. The increased intake of bread, cereals and meat caused increased values of carbohydrates, vitamin B1 and iron. The menu was divided in two meals and a snack (breakfast - 15%, snack - 15%, lunch 50%). The menu variation and courses' succession were in line with the hygienic-sanitation rules.     

CD8+CD28− T suppressor cells and the induction of antigen-specific, antigen-presenting cell-mediated suppression of Th reactivity

Summary: Human CD8⁺CD28⁻ suppressor T cells (Ts) are a subset of T cells generated in the course of in vitro and in vivo immunizations. Ts recognize MHC class I:peptide complexes and inhibit the reactivity of T helper cells (Th) with cognate antigen specificity. We have demonstrated for the first time that CD8⁺CD28⁻ Ts represent a unique subset of regulatory cells that induces the differentiation of tolerogenic antigen-presenting cells, initiating a suppressive loop which results in the induction and spreading of Th unresponsiveness.     

Oxidized low density lipoproteins: The bridge between atherosclerosis and autoimmunity. Possible implications in accelerated atherosclerosis and for immune intervention in autoimmune rheumatic disorders

Atherosclerotic vasculopathy is a multifactorial process causing vessels damage and cardiovascular diseases, the leading causes of death worldwide. Atherosclerotic plaque is the asymptomatic primary, elementary, lesion of atherosclerotic vasculopathy. Accumulation of the oxidized low-density lipoprotein (oxLDL) at sub endothelial sites is now recognized as one of the major trigger events in plaque formation. The concomitant presence at the plaque site of cells belonging to either natural or adaptive immunity, the detection of autoantibodies to oxLDL, the cross-reactivity of oxLDL with anti-phospholipid antibodies, in addition to the clinical evidence of increased rates of cardiovascular events in several rheumatic diseases, has stimulated intensive research to define interconnections between the immune system and traditional risk factors at the molecular levels in order to explain accelerated atherosclerosis. Here, we critically review the results of previous and recent studies, which have disclosed molecules of both innate or adaptive immunity involved in atherosclerosis, focusing primarily on B cells and autoantibodies, where data are more consolidated. Particular attention has also been paid to molecules that may be predictive markers of atherosclerosis progression and can be potential targets for immune intervention to delay the atherosclerotic process. The latter include CD20 antigen, molecules involved in the BAFF-BAFF receptor axis, inflammatory molecules and modified LDL. The successful results of a recent randomized controlled clinical trial targeting inflammasome with anti-IL1β monoclonal antibody in non-autoimmune conditions, prove that specific immunotherapy can be a promising and effective strategy to control atherosclerosis in rheumatic diseases as well.     

Non-infusional vs intravenous consolidation chemotherapy in elderly patients with acute myeloid leukemia: final results of the EORTC-GIMEMA AML-13 randomized phase III trial.

In this trial, acute myeloid leukemia patients (pts) aged 61-80 years received MICE (mitoxantrone, etoposide and cytarabine) induction chemotherapy in combination with different schedules of granulocyte colony-stimulating factor administration. Pts in complete remission were subsequently randomized for two cycles of consolidation therapy: mini-ICE regimen (idarubicin, etoposide and cytarabine) given according to either an intravenous (i.v.) or a 'non-infusional' schedule. Among the 346 pts randomized for the second step, 331 pts received consolidation-1 and 182 consolidation-2. A total of 290 events (255 relapses, 35 deaths in first CR) have been reported. The median follow-up was 4.4 years. No significant differences were detected in terms of disease-free survival (median 9 vs 10.4 months, P=0.15, hazard ratio (HR) =1.18, 95% confidence interval (CI) 0.94-1.49) - primary end point - and survival (median 15.7 vs 17.8 months, P=0.19, HR=1.17, 95% CI 0.92-1.50). In the 'non-infusional' arm grade 3-4 vomiting (10 vs 2%; P=0.001) and diarrhea (10 vs 4%; P=0.03) were higher than in the 'i.v.' arm, whereas time to platelet recovery >20 x 10(9)/l (median: 19 vs 23 days; P=0.02) and duration of hospitalization (mean: 15 vs 27 days; P<0.0001) was shorter. The 'non-infusional' consolidation regimen resulted in an antileukemic effect similar to the intravenous regimen, which was less myelosuppressive and associated with less hospitalization days.