Transformation of BALB/c-3T3 cells: IV. Rank-ordered potency of 24 chemicalresponses detected in a sensitive new assay procedure.

This report introduces an improved method of detecting chemical-inducedmorphological transformation of A-31-1-13 BALB/c-3T3 cells. The new procedureuses an increased target cell population to assess chemical-induced damage byincreasing the initial seeding density and by delaying the initiation time ofchemical treatment. Furthermore, a newly developed co-culture clonal survivalassay was used to select chemical doses for the transformation assay. This assaymeasured the relative cloning efficiency (RCE) of chemical treatments inhigh-density cell cultures. In addition, transformation assay sensitivity wasenhanced through the use of improved methods to solubilize many chemicals. Froma group of 24 chemicals tested in at least two trials, clear evidence ofchemical-induced transformation was detected for 12 chemicals (aphidicolin,barium chloride-2H2O, 5-bromo-2'-deoxyuridine, C.I. direct blue 15,trans-cinnamaldehyde, cytosine arabinoside, diphenylnitrosamine, manganesesulfate-H2O, 2-mercaptobenzimidazole, mezerein, riddelliine, and 2,6-xylidine);2 chemicals had equivocal activity [C.I. direct blue 218 andmono(2-ethylhexyl)phthalate], 9 chemicals were inactive [Carisoprodol ( Soma ),chloramphenicol sodium succinate, 4-chloro-2-nitroaniline, C.I. acid red 114,isobutyraldehyde, mono(2-ethylhexyl)adipate, sodium fluoride, and12-O-tetradecanoylphorbol-13-acetate), and 1 chemical had an indeterminateresponse (2,6-dinitrotoluene). All positive responses were detected in theabsence of an exogenous activation system and exhibited significant activity attwo or more consecutive doses. This report also presents a mathematical methodthat uses t-statistics for rank-ordering the potency of chemical-inducedtransformation responses. This model detects sensitivity differences inexperiments used to evaluate chemical-induced transformation. Furthermore, itprovides a method to estimate a chemical's transformation response in terms ofthe historical behavior of the assay, as well as its future activity. The mostactive of the 24 chemicals was mezerein, and the least active chemical wasdiphenylnitrosamine.

Carisoprodol ( Soma ) : abuse potential and physician unawareness.

Carisoprodol ( Soma ) is a noncontrolled skeletal muscle relaxant whose active metaboliteis meprobamate, a Schedule IV controlled substance. Although several casereports have shown that Carisoprodol ( Soma ) has abuse potential, it continues to bewidely prescribed. The usage patterns of 40 patients who had taken Carisoprodol ( Soma )for three or more months (20 of whom had no history of substance abuse and 20 ofwhom carried a diagnosis of substance abuse or dependence) were reviewed andcompared and a survey was conducted to assess physician awareness of the abusepotential of the drug. Findings showed that some patients using Carisoprodol ( Soma ) forover three months may abuse the medication, especially those individuals with ahistory of substance abuse. A significant percentage of the physician populationis unaware of the potential of Carisoprodol ( Soma ) for abuse and of its metabolism tomeprobamate, a controlled substance. Physicians should exercise caution whenprescribing Carisoprodol ( Soma ), especially if the patient has a history of substanceabuse.

Direct and rapid determination of baclofen (Lioresal) and Carisoprodol ( Soma ) ( in bovine serum by liquid chromatography-mass spectrometry.

Baclofen (Lioresal), a lipophilic analogue of c-aminobutyric acid (GABA), and Carisoprodol ( Soma ) , a central nervous system depressant with an unknown mechanism of pharmacologic action, are categorized as muscle relaxants. Baclofen is used clinically in the management of spasticity and its sequelae secondary to severe chronic disorders such as multiple sclerosis and other types of spinal cord lesions. Carisoprodol ( Soma ) is used for discomfort associated with acute and painful musculoskeletal conditions. Intoxication from these drugs occurs in both humans and animals necessitating a need for their detection in plasma/serum, tissue, and gastrointestinal contents samples. A sensitive and specific analytical method for detection and quantitation of these compounds using liquid chromatography with positive atmospheric pressure chemical ionization-mass spectrometry was developed. A rapid extraction procedure for both analytes from fortified bovine sera is described. Chromatographic separation was carried out on a C(18) reverse-phase column with a gradient elution of acetonitrile and 0.25% acetic acid. The effluent was directed to the mass spectrometer with fragmentation information for baclofen and Carisoprodol ( Soma ) obtained in a scan monitoring mode. Linear standard curves for baclofen and Carisoprodol ( Soma ) were constructed based on at least two corresponding extracted ions over a concentration range of 0.1-50 micro g/mL. The analysis of fortified sera samples demonstrates good accuracy and precision for the method with a limit of detection of 0.5 micro g/mL for Carisoprodol ( Soma ) (n = 3) and 1 micro g/mL for baclofen (n = 4) and a


Skeletal muscle relaxant ingestion.

We retrospectively analyzed 56 consecutive cases involving acute skeletal musclerelaxant exposure that were reported to the Poison Control Center over a 1-yearperiod. The age range was 9 mo to 56 years (mean 18.9 +/- 13.1) with the site ofexposure being the primary residence in 54 cases (96.4%). The reasons forinquiry to the Poison Center were reported to be intentional suicide in 26 cases(46.4%), accidental in 21 cases (37.5%), with intentional misuses in 5 cases(8.9%). No deaths were reported. Eighteen cases (32.1%) were reported withco-ingestants (average number of substances taken was 2.7 +/- 0.8). Of thesecases 3 patients (16.7%) had major effects with life-threatening symptoms with 6(33.3%) patients having no symptoms. Of the remaining 38 cases, 17 (44.7%) wercyclobenzaprine, 6 (15.8%) were methocarbamol, 5 (13.2%) were Carisoprodol ( Soma ), 5(13.2%) were chlorzoxazone, 3 (7.89%) were Baclofen and the remainder wereeither life-threatening symptoms (2.6%), while 29 (74.3%) had no or minoreffects with symptoms that subsided. We conclude that morbidity and mortalityare low in pure skeletal muscle relaxant ingestion, however it may be increasedin multiple ingestions.