Stability of Interleukin 1β (IL-1β) in Aqueous Solution: Analytical Methods,Kinetics, Products,and Solution Formulation Implications

The thermal stability of IL-1 in aqueous solution as a function of temperature (5–60°C), pH (2–9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 at or above 39°C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30°C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5°C suggests that a solution formulation may be feasible for IL-1.     

Assessment of quality of life in the elderly assisted at home through a Tele-Check service

This study evaluates the effects of a Tele-check/Tele-emergency service on the quality of life in the elderly. Through telephone interviews a questionnaire has been repeatedly administered to explore various psychological, somatic, and social aspects in a random sample of 574 subjects aged 65 years and over (mean = 76.8 years). The findings suggest that the elderly helped by the service (in its control functioning) make less demands on health facilities (GPs visits, number of days in hospital) as compared to controls. Implications are presented and discussed.     

Very large peroxisomes in distinct peroxisomal disorders (rhizomelic chondrodysplasia punctata and acyl-CoA oxidase deficiency): novel data

Summary We report very large hepatic peroxisomes (d-circle >1 m) in a patient with rhizomelic chondrodysplasia punctata and a patient with acyl-CoA oxidase deficiency. The effects of peroxisomal enlargement on the enzymatic activity are discussed. As increase in peroxisomal size is also reported in at least 12 other patients with peroxisomal disorders, we propose, a relationship between the enlargement of the organelles and their functional deficiency.     

The value of retrograde urethrography in the diagnosis of sub-urethral diverticula in women]

Urethral diverticulum in women is not a frequent disease. The diagnosis of this lesion is based on history and careful physical examination looking for a swelling on the anterior vaginal wall. A study of 15 cases is reported. The authors insist on investigations as a help to confirm and localise the diverticulum. A new technique of retrograde urethrography using a prehension cannula ("Bomelaer") is described. By this well tolerated and minimally invasive test, the visualisation of the urethral diverticulum was obtained in 14/15 patients. Associated with intravenous urography, it is certainly the most adapted strategy for diagnosis and management.     

Comparison of renal function and psychomotor performance in workers exposed to elemental mercury

Summary Renal function and psychomotor performance (eye-hand coordination, arm-hand steadiness) of a group of 43 workers exposed to mercury vapor were examined. Their mean age and average duration of exposure to mercury were 38 and 5 years, respectively. The results were compared with those obtained in a matched group of 47 control workers. Increased proteinuria and albuminuria were found slightly more prevalent in the Hg-exposed group than in the control workers. These results are in agreement with those found during a previous study carried out in another group of workers also exposed to elemental mercury (Bucket et al. 1980). The scores of the psychomotor tests were less satisfactory in the Hg workers than in the control workers, the arm-hand steadiness test being more discriminative than the eye-hand coordination test. Preclinical changes in psychomotor function can be detected independently of the presence of signs of renal dysfunction. No clear-cut relationships were found between the prevalence of abnormal psychomotor scores and the level of mercury in blood (HgB) or in urine (HgU). Increased prevalences of abnormal psychomotor scores seem however to occur for HgB between 1 and 2 g/100 ml and for HgU between 50 and 100 g/g creatinine. Therefore, a biologic threshold limit value of 50 g/g creatinine is proposed for urinary mercury to prevent the development of preclinical effects on the central nervous system. A similar critical HgU level based on renal dysfunction prevalences has been suggested in a previous study.This study was supported by a grant from the Commission of the European Communities     

Reactivation of acetylcholinesterase inhibited by methamidophos and analogous (di)methylphosphoramidates

Reactivation of electric eel acetylcholinesterase (AChE) inhibited by MeO(NH₂)P(O)SMe (methamidophos) and by MeS(NH₂)P(O)SMe was studied at pH 7.5 and 25° C. The former inhibited enzyme shows a rather rapid spontaneous reactivation (t_1/2=3.7 h); this reactivation is accelerated by 1 M of the bispyridinium oximes TMB4 and obidoxime, and, to a lesser extent, by the monopyridinium oximes P2S and its 1-benzyl analogue (benzyl-P2A). The latter inhibited enzyme shows rapid aging (t_1/2=0.6 h). Reactivation with 1 mM of the bispyridinium oximes is incomplete and reactivation with 1 mM of the monopyridinium oximes proceeds very slowly. These large differences between the properties of the two inhibited enzymes indicate that the methylthio group is the leaving group during inhibition of AChE by methamidophos. Additional support is afforded by the observation of induced aging of the former inhibited enzyme by thiourea.Upon comparison of the reactivation of AChE inhibited by methamidophos with that of AChE inhibited by an N-methyl analogue, cruf ornate, and an N,N-dimethyl analogue, tabun, it appears that the rate of spontaneous reactivation decreases with increasing alkylation of the P-NH₂ group. Whereas benzyl-P2A is somewhat less active than P2S for reactivation of AChE inhibited by methamidophos, it is superior to P2S for reactivation of AChE inhibited by crufomate and also superior to P2S and to the bispyridinium oximes for AChE inhibited by tabun.     

Clinical effects and plasma levels of Δ9-Tetrahydrocannabinol (Δ9-THC) in heavy and light users of cannabis

⁹-Tetrahydrocannabinol (⁹-THC) was administered in a crossover design by smoking and IV injection to groups of heavy and light users of marihuana. Plasma concentrations of ⁹-THC were similar for the groups after IV injection of 5.0 mg ⁹-THC, but the AUC_{0–240 min} showed a trend towards lower values for the heavy user group. To achieve a maximum desired high, both groups smoked similar amounts (about 13 mg) of ⁹-THC. Heavy users tended to have higher plasma levels than light users. The systemic availability of smoked ⁹-THC was significantly higher for the heavy users (heavy users 23±16% vs 10±7% for light users). These results also indicate that heavy cannabis users smoke more efficiently than casual smokers.Both light and heavy users showed more clinical effect following IV administration than after smoking. The response of the heavy users, both with respect to effect on heart and high, was quite comparable to that of light users.The present study does not suggest that tolerance readily develops in heavy users.     

Effect of short-term administration of lead to pregnant rats.

Lead was administred to adult female rats in drinking water (0;0.1:1 and 10 ppm) for 3 weeks before mating, during pregnancy and during 3 weeks after delivery. On day 21 after delivery the mothers and their newborns were sacrified and various parameters of blood -- lead concentration on (Pb-B), hematocrit (Htc), hemoglobin (Hb), free erythrocyte porphyrins (FEP), delta0aminolevulinate dehydratase (ALAD) -- and tissue -- ALAD, free tissue porphyrins (FTP), lead concentration (Pb-T) -- were determined. In mothers a significant increase in Pb-B and Pb concentration in kidney was found in the 10 ppm group, but this increase in lead concentration was not associated with any statistically significant modification of the biochemical parameters. In newborns, lead concentration in blood and in kidney was also significantly increased in the 10 ppm group and this lead exposure was associated with a decrease of the ALAD activity in blood and an increase of FTP in kidney. On the basis of the biochemical parameters investigated one can therefore conclude that the developing organism is more susceptible to the biological action of lead than the organism of adult animals and that the "no-effect" level of lead administered during pregnancy and in the neonatal period is around 1 ppm.     

Radiosurgery in the treatment of the glottic plane carcinoma

During the last 20 years, various conservative surgical techniques have been proposed to treat larynx cancer. On the basis of our various experiences and of the ultrastructural data on the tissues treated with radiowaves, we decided to also use radiosurgery in operations under direct microlaryngoscopy. We select 18 patients suffering from epidermoid carcinoma. These patients had been referred to our ENT clinic at the Polichnico of Palermo between 1999 and 2001. The authors describe the surgical procedures used and emphasize the advantages of radiosurgery in the treatment of larynx cancer.     

Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols.

PURPOSE: To determine demographic data and define prognostic factors for long-term outcome in patients presenting with high-grade osteosarcoma of bone with clinically detectable metastases at initial presentation. PATIENTS AND METHODS: Of 1,765 patients with newly diagnosed, previously untreated high-grade osteosarcomas of bone registered in the neoadjuvant Cooperative Osteosarcoma Study Group studies before 1999, 202 patients (11.4%) had proven metastases at diagnosis and therefore were enrolled onto an analysis of demographic-, tumor-, and treatment-related variables, response, and survival. The intended therapeutic strategy included pre- and postoperative multiagent chemotherapy as well as aggressive surgery of all resectable lesions. RESULTS: With a median follow-up of 1.9 years (5.5 years for survivors), 60 patients were alive, 37 of whom were in continuously complete surgical remission. Actuarial overall survival rates at 5 and 10 (same value for 15) years were 29% (SE = 3%) and 24% (SE = 4%), respectively. In univariate analysis, survival was significantly correlated with patient age, site of the primary tumor, number and location of metastases, number of involved organ systems, histologic response of the primary tumor to preoperative chemotherapy, and completeness and time point of surgical resection of all tumor sites. However, after multivariate Cox regression analysis, only multiple metastases at diagnosis (relative hazard rate [RHR] = 2.3) and macroscopically incomplete surgical resection (RHR = 2.4) remained significantly associated with inferior outcomes. CONCLUSION: The number of metastases at diagnosis and the completeness of surgical resection of all clinically detected tumor sites are of independent prognostic value in patients with proven primary metastatic osteosarcoma.