Effect of deferrioxamine and diethyldithiocarbamate on paracetamol-induced hepato- and nephrotoxicity. The role of lipid peroxidation

In mice subjected to glutathione depletion by pretreatment with phorone (diisopropylidene acetone, 200 mg/kg i.p. in 10 ml/kg olive oil) paracetamol (acetaminophen, 300 mg/kg p.o. in 10 ml/kg tylose 2 h later) led to a marked hepatotoxicity as evidenced by increased plasma activities of the liver-specific enzymes sorbitol dehydrogenase (SDH) and glutamate-pyruvate-transaminase (GPT) 3 and 24 h after treatment. Nephrotoxicity was also indicated at both timepoints by an increased creatinine concentration in plasma, while neither the urine volume nor its content in gamma-glutamyl transpeptitase over 20 h were affected. Hepato- and nephrotoxicity were also assessed histomorphologically. In vivo lipid peroxidation (LPO), as measured by ethane exhalation over 3 h, was clearly enhanced by paracetamol. Malondialdehyde content was increased and glutathione concentration diminished in the liver, but not in the kidney. Diethyldithiocarbamate (DTC, 200 mg/kg i.p.) or deferrioxamine (DFO, 500 mg/kg i.p.) both given 30 min before PA, inhibited in vivo LPO. However, only DTC was capable of antagonizing the hepato- and nephrotoxic effects of paracetamol, while DFO only delayed the onset of nephrotoxicity but left the hepatotoxicity unaffected. Both agents inhibited the rise in hepatic malondialdehyde-content, but only DTC prevented paracetamol-induced glutathione depletion. These results indicate that LPO is not mainly responsible for paracetamol toxicity towards liver or kidney.     

Microstructure of the lung: diffusion measurement of hyperpolarized 3Helium

Imaging methods to study the lung are traditionally based on x-ray or on radioactive contrast agents. Conventional magnetic resonance imaging (MRI) has only limited applications for lung imaging because of the low tissue density of protons concentration of hydrogen atoms, which are usually the basis for the imaging. The introduction of hyperpolarized noble gases as a contrast agent in MRI has opened new possibilities for lung diagnosis. The present paper describes this new technique. Diffusion-weighted MRI for assessment of the lung microstructure is presented here as an example of the new possibilities of functional imaging. Studies to determine the sensitivity of the diffusion measurement and regarding the correlation with traditionally established methods are also presented, along with results of the measurement of the reproducibility determined in a clinical pilot study on healthy volunteers and patients. Furthermore, a pilot measurement of the 3He diffusion tensor in the lung is presented.     

Influence of (+)-Catechin and Dithiocarb on the Pharmacokinetics of Phenprocoumon, Tolbutamide and Three Inhalation Anesthetics in rats

Pretreatment with (+)-catechin ((+)-cyanidanol-3, Catergen) (200 mg/kg p.o.) did not alter the elimination of intravenously injected phenprocoumon (0.6 mg/kg) or tolbutamide (100 mg/kg) in rats, while dithiocarb (Sodium diethyl-dithiocarbamate) (200 mg/kg p.o.) prolonged only the elimination half-life of phenprocoumon to a small extent. The metabolism of halothane (100 ppm), enflurane (100 ppm) or methoxyflurane (300 ppm) was studied by measuring the disappearance of the compounds from the atmosphere of a closed exposure system. Pretreatment with (+)-catechin did not impair the metabolic removal of all three anesthetics; in the case of enflurane (+)-catechin caused a small, but significant shortening of the elimination half-life, for enflurane and methoxyflurane the uptake of the compounds into the rats seemed to be impaired under the influence of (+)-catechin. Dithiocarb strongly impaired the in vivo metabolism of halothane and methoxyflurane, whereas that of enflurane remained unaffected.     

Effect of smoking on cadmium and lead concentrations in human amniotic fluid

The amniotic fluids of 155 pregnant women, non-smokers (n = 128) and smokers (n = 27), were investigated on their cadmium (Cd) and lead (Pb) concentrations. The mean +/- s range of Cd in the amniotic fluid of non-smokers amounted to 2.58 +/- 1.36 ng/l, that of smokers to 7.29 +/- 2.39 micrograms/l. Moreover, there was a correlation between the extent of daily cigarette consumption and Cd levels. With Pb, higher concentrations were found ranging between 23.98 +/- 9.41 ng/l for non-smokers and 21.53 +/- 7.16 micrograms/l for smokers. No correlations were seen between age, week of pregnancy, blood pressure, disorders of pregnancy and the amniotic Cd or Pb concentrations. Thus, the maternal and fetal risks of the higher Cd levels in the amniotic fluid of smoking women remain unanswered.     

In-vitro Shear Bond Strength of Self-etching versus Traditional Adhesives for Orthodontic Luting

OBJECTIVE: To determine the enamel shear bond strength (SBS) of various established (Resulcin Aqua Prime & Monobond N [RA], Prompt L-Pot III [PLP]) and experimental (AC-Bond [AC], AC-Bond + Desensitizer [ACD]) self-etching adhesives in comparison to fourth (Total Etch, Primer and Bonding have separate liquids; OptiBond FL [FL]) and fifth-generation (Total Etch, Primer and Bonding "One Bottle"; Excite [EX], Gluma Comfort Bond [CB]) adhesives. MATERIALS AND METHODS: All adhesives were applied on flattened human enamel surfaces following the manufacturers' instructions and light-cured using a quartz-tungsten-halogen curing device. 3.5 x 2.0 mm Tetric Ceram A2 composite cylinders were sheared off (Zwick Universal-testing-machine 1445, 1 mm/min) after thermocycling (5-55 degrees C, 5000x). Normal distribution was tested for all groups and analysis of variance was conducted. The t-test (5% level, Bonferroni-correction) was used for statistical analysis to evaluate intergroup differences. RESULTS: Shear bond strength in enamel: Resulcin Aqua Prime & Monobond N: 27.0 +/- 5.8 MPa, Prompt L-Pop III: 15.9 +/- 3.4 MPa, AC-Bond: 28.1 +/- 4.4 MPa, AC-Bond + Desensitizer: 22.2 +/- 4.1 MPa, OptiBond FL: 33.2 +/- 3.2 MPa, Excite: 30.5 +/- 5.1 MPa, Gluma Comfort Bond: 30.1 +/- 3.7 MPa. OptiBond FL demonstrated significantly higher SBS (p < 0.002) in enamel than Resulcin Aqua Prime & Monobond N, AC-Bond, AC-Bond + Desensitizer and Prompt L-Pop III. Resulcin Aqua Prime & Monobond N performed significantly better than Prompt L-Pop III, but did not differ from AC-Bond or AC-Bond + Desensitizer. The SBS values of Excite and Gluma Comfort Bond were both on the same level of significance as AC-Bond and Resulcin Aqua Prime & Monobond N, but the former showed superior results to AC-Bond + Desensitizer and Prompt L-Pop III. Prompt L-Pop III yielded significantly lower SBS-values than all the other products evaluated. CONCLUSION: Resulcin Aqua Prime & Monobond N and AC-Bond did not differ significantly from established 5th-generation products. Further in-vivo studies are required to investigate intra-oral stability and resistance against changing forces and force directions.     

Severe non-haematological toxicity after treatment with gemcitabine

The authors report that 4 out of a series of 56 patients (7.1%) treated with gemcitabine developed an unexplained non-cardiogenic pulmonary distress syndrome most likely related to gemcitabine. One further patient developed ventricular arrhythmia immediately after gemcitabine exposure, leading to cardiac arrest. Between 1995 and 1998 56 patients with locally advanced or metastatic carcinoma were treated with gemcitabine. The patients suffered from breast cancer (n = 17), pancreatic cancer (n = 17), lung cancer (n = 12), cancer of unknown primary (n = 5), ovarian cancer (n = 2), oral cavity cancer (n = 2) and cancer of the bladder (n = 1). Their median age was 55 years, and there were 33 female and 23 male patients. Fifteen patients had been pretreated with radiation therapy: 2 had received radiation therapy involving the mediastinum as treatment for non-small-cell lung cancer and cancer of unknown origin respectively, 11 patients had had prior neoadjuvant or adjuvant radiation therapy of the chest wall for breast cancer and 2 patients had received radiation therapy for head/neck cancer. All patients received gemcitabine on days 1, 8 and 15 and this was repeated on day 29 at a dose of 1000 mg/m² as a 30-min infusion in 250 ml isotonic NaCl. In 4 patients gemcitabine treatment was combined with cisplatinum, in 7 patients with a somatostatin analogue and in 1 patient with epirubicin. All other patients received gemcitabine as a single agent. We assume that the pulmonary or cardiac toxicity of 5 patients was related to gemcitabine. In 3 patients re-exposure resulted in repeated toxicity. One patient did not receive gemcitabine again because of the life-threatening nature of the primary response. Two patients had received prior radiation to the mediastinum with 62 Gy and 50 Gy respectively, 3 years and 1 year before gemcitabine application. In our experience pulmonary toxicity after gemcitabine treatment is more common than initially anticipated. Gemcitabine should be used with caution in patients who have received prior radiation to the mediastinum. Received: 5 May 1999 / Accepted: 2 June 1999     

Laser ablation of lung metastases: results according to diameter and location

Lung tumour ablation with a thin-calibre laser applicator system was evaluated. We quantified feasibility, technical success and complication rates in relation to lesion diameter and location. Forty-two patients with 64 lung tumours were treated (39 patients with metastases and three with primary tumours). Mean follow-up was 7.6 months (range 6 weeks to 39 months). Eighty-six percent of treatments were technically successful in the first session. Pneumothorax was the main complication and occurred in 50% of the first 20 patients and in 35% of the rest. Two patients required a chest tube. Fourteen lesions were central and 50 were peripheral. It took several weeks for the effect of the therapy to become apparent on follow-up CT. Thirty-nine percent of all lesions increased in size immediately after treatment. Gross reduction in size with scar formation was seen in 50% of the lesions and cavitation in 13%. Local tumour control was achieved in 51 lesions. Progression after therapy was seen in 9% of lesions <1.5 cm but in more than 11% of larger lesions. Progression was also more frequent in lesions located in the basal parts of the lung (47%). Sixteen patients died due to systemic progression. Our results suggest that successful laser ablation of lung lesions is possible with a miniaturized applicator.