Effect of warfarin on formation and growth of pre-neoplastic lesions in chemically induced colorectal cancer in the rat

Anticoagulant drugs are known to have an effect on tumour growth. However, the mechanisms by which they act are poorly understood, and have therefore been investigated in this study. Wistar rats were given eight weekly subcutaneous injections of azoxymethane, at a dose of 10 mg kg-1 week-1. Following this they were randomized into two groups: a control group, which received no further treatment, and a warfarin treated group, which received warfarin at 'non-therapeutic' doses in their drinking water, for a further 8 weeks. Pairs of rats from each group were killed at 5-weekly intervals from 10 to 35 weeks after the first azoxymethane injection. At 40 weeks all remaining rats were killed. Samples of colonic mucosa from the descending colon and rectum were taken for scanning electron microscopy. The number of microadenomas per low power field was determined in both groups at each time interval. Tumour incidence and distribution were noted in animals killed at 40 weeks. The median number of microadenomas was significantly lower in warfarin treated animals than in controls at all time intervals. Tumour number was also significantly decreased by warfarin treatment (27 in azoxymethane treated animals, 10 in animals receiving azoxymethane and warfarin, P less than 0.05). The distribution of tumours along the colon was similar to that seen previously, following 12 weeks of azoxymethane. These effects occurred despite the non-concurrent administration of azoxymethane and warfarin.     

Cryptococcal meningoencephalitis. Case report and review of Italian literature

A case of cryptococcal meningoencephalitis, as presented by a hypertensive hydrocephalus, is described. To our knowledge, this is the 24th case described in Italy since 1953. The diagnosis was made with ventricular fluid examination: the patient was successfully treated with amphotericin B and 5-fluorocytosine, thus avoiding the risks of surgical treatment of hydrocephalus. Early diagnosis and proper therapy are necessary in order to decrease the high lethality of cryptococcosis.     

A comparison of parenteral loxapine and haloperidol in hostile and aggressive acutely schizophrenic patients

In a parallel groups, double-blind study, 54 acutely psychotic schizophrenics were given loxapine or haloperidol parenterally for 24 to 72 hours, then orally for a total study period of up to 10 days. Dosage ratios of loxapine to haloperidol ranged from a minimum of 2.7:1 to a maximum of 4.4:1. Both groups showed significant and rapid improvement from baseline. Forty-eight percent of the loxapine patients and 33% of the haloperidol patients achieved and maintained a global severity of illness rating of mild or better. By the end of the study, 84% of the loxapine patients and 63% of the haloperidol patients had achieved an improvement rating of moderate or marked. This difference approached significance (p less than .10). The most frequently reported adverse experiences were dystonic reactions and akathisia. The number and severity of adverse experiences did not differ significantly between drug groups. Intramuscular loxapine was at least as effective as haloperidol in the initial management of hostile and aggressive schizophrenic patients. The maintenance of therapeutic response after conversion to oral concentrate was comparable with the two drugs.     

Calcium paradox in skeletal muscles: physiologic and microscopic observations

Immersion of rat hemidiaphragms in Ca2+-free Krebs solution (KS) containing Ca2+ chelator in vitro leads to separation of basal lamina from the plasma membrane, as well as transient contracture and rapid loss of twitch response [calcium paradox (CP) phase 1]. Subsequent immersion in regular KS results in necrosis of muscle fibers accompanied by slowly increasing contracture (CP phase 2). This contracture could be prevented or reduced by using either Ca2+-free KS or calcium channel blockers, but not by dantrolene sodium, implying that after drastic reduction of extracellular and sarcolemmal Ca2+ during CP phase 1, the sarcolemma has lost its ability to control normal Ca2+ fluxes. Contracture did not develop at 21 degrees C. CP is a convenient model to study calcium-induced muscle cell death and the role of Ca2+ in maintaining sarcolemmal integrity.     

In vitro metabolism and toxicity assessment of toxin T-514 (Peroxisomicine A1) of Karwinskia humboldtiana in microsomes and primary cultured hepatocytes.

T-514 (Peroxisomicine A(1)) from Karwinskia humboldtiana is a dimeric hydroxyanthracenone with a highly selective cytotoxic effect on tumor cells. We evaluated the metabolism of this compound in two in vitro systems (liver microsomes and hepatocytes) and assessed the cytotoxicity of its metabolites on normal and tumor cells. Microsomes (12.5, 125 and 250 microg of protein/ml) and hepatocytes (1 x 10(6) cells/ml) were incubated with the toxin (25 microM) for 0.5, 1, 3, 6, 9, 12 and 24 h and the samples were examined using chromatographic analysis and UV spectra. Two metabolites (M1 and M2) were detected in the rat microsomes and one (M1) in the monkey microsomes. The retention times and UV spectra of the peaks were very similar to those of the toxin T-514. M1 was isolated and identified as a mixture of two isomers. The cytotoxicity of the metabolites was evaluated in Chang liver and Hep G2 cells but they did not show the selective cytotoxic effect on tumor cells seen in the original compound.     

Is there a role for reconstructive techniques to prevent periodontal defects after third molar surgery?

PURPOSE: Among patients at high risk for second molar (M2) periodontal defects after third molar (M3) removal, does active treatment at the time of extraction, when compared with no treatment, alter the risk of postextraction M2 periodontal defects? MATERIALS AND METHODS: We used a prospective cohort study design and a sample composed of subjects at high risk for developing M2 periodontal defects after M3 extraction, that is, age > or = 26 years, pre-existing periodontal defects (attachment level [AL] > or = 3 mm), and mesioangular or horizontal M3 impaction. The predictor variable was treatment status of the M3 extraction site. The M3 extraction sites were reconstructed with demineralized bone powder (DBP), bioresorbable guided tissue regeneration (GTR) therapy, or no treatment. The outcome variable was ALs measured at the M2 distobuccal line angle preoperatively and 26 weeks after extraction. Appropriate univariate, bivariate, and multivariate statistics were computed, and statistical significance was set at a value P < .05. RESULTS: The cohort was composed of 12 subjects contributing 18 high-risk M3s. Twenty-six weeks after M3 removal, the ALs for GTR-treated (3.0 +/- 1.2 mm), DBP-treated (1.4 +/- 0.5 mm), and control (3.8 +/- 0.9) M3 sites were statistically significantly different ( P = .002). Tukey post-hoc comparisons revealed a statistically significant difference between control and DBP ALs ( P = .001) and GTR-treated and DBP-treated ALs ( P = .037). There was no statistically significant difference in ALs between control and GTR-treated M3s ( P = .35). CONCLUSIONS: The results of this study suggest that subjects at high risk for developing M2 periodontal defects after M3 removal may benefit from the use of DBP placed at the time of M3 extraction to enhance periodontal healing.