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The components of carbonless copy paper (CCP) and the chemistry involved in its manufacture are reviewed. Claims that the routine use of CCP can cause health problems ranging from skin, eye, and lung irritation to severe headaches and neurological damage are described; yet no definitive studies have been conducted that show correlation between CCP use and these symptoms. The toxicological properties of CCP components, many of them precursors to the dye-containing microcapsules or dye solvents that may be causing these problems, are discussed. Recommendations for the minimization of possible physiological reactions to CCP include reduction of usage time; use of the CCP in a well-ventilated area; storing large quantities of CCP, both new or archived, away from work area; and the practice good hand hygiene.

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UNLABELLED: The goal of this study was to examine the relationship between D2 dopamine receptor density and levodopa dosage, disease duration and dyskinesia in Parkinson's disease (PD). METHODS: Iodine-123-iodobenzamide SPECT scans were obtained from 14 PD patients and 12 age-matched controls using a three-headed camera in conjunction with MRI and a fiducial-based image registration system to define regions of interest. Basal ganglia/cerebellum counts/voxel ratios in dorsal and ventral head of caudate and anterior and posterior putamen were measured at 30, 60, 120 and 180 min postinjection. As in 11C-raclopride studies, ratios obtained at that time when they asymptomatically approach a maximum value (180 min) were accepted as the best measure of receptor density. RESULTS: Among PD patients, a trend towards an inverse correlation between regional basal ganglia/cerebellum ratios and levodopa dosage achieved significance in ventral caudate (F = 6.244, p = 0.037); similarly, an inverse correlation between these ratios and disease duration achieved significance in anterior putamen (F = 13.144, p = 0.007). Ratios were significantly lower in anterior putamen in patients with dyskinesia (t = 3.068, p = 0.042). CONCLUSION: In PD, the previously observed inverse correlation between levodopa dosage and D2-receptor density appears to be most prominent in the least dopamine-depleted region, ventral caudate. There may be a genuine effect of disease duration on receptor density in putamen and reduced receptor density in anterior putamen may be associated with dyskinesia.

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Radioiodinated-SCH 23982 is a potential agent for the imaging of dopamine D-1 receptors in the human brain. In vivo binding of [125I]SCH 23982 to D-1 receptors in rat brain was determined over 4 hr. The ratio of activity in striatum and frontal cortex to that in cerebellum increased over the first 2 hr to maximum values of 4.4:1 and 2.1:1, respectively. The percent injected dose in whole brain at 0.5 and 2 hr were 0.62 and 0.15, respectively. Administration of the antagonists propranolol (beta-1), prazosin (alpha-1), haloperidol (D-2) and ketanserin (5HT-2) did not significantly alter the striatum/cerebellum ratio; however, SCH 23390, a D-1 antagonist, totally blocked ligand uptake by striatum and frontal cortex. Biologic distribution data in the rat were determined after injection of 3 microCi of [125I]SCH 23982. 76% of the injected dose was excreted in 48 hr via the liver and kidneys. Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads and red bone marrow were calculated for humans using the physical decay data for 123I. The critical organ was found to be the lower large intestine which received 1.1 rad/mCi of the administered dose. The total-body dose was 63 mrad/mCi. The data indicate that [123I]SCH 23982 should be a suitable agent for imaging the D-1 dopamine receptor in the human brain by single photon emission computed tomography.

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In vivo binding of [125I]-2-[beta-(3-iodo-4-hydroxyphenyl)ethylaminomethyl tetralone) ([125I]HEAT) to alpha-1 adrenoceptors in the rat brain was determined over 4 hr. Uptake in the thalamus and frontal cortex was approximately 0.1% injected dose per gram tissue. Thalamus/cerebellum ratios of 10:1 and frontal cortex/cerebellum ratios of 5:1 were found at 4 hr. Pretreatment with prazosin, an alpha-1 antagonist, completely inhibited the accumulation of [125I]HEAT in thalamus and frontal cortex; yet uptake of radioactivity was not significantly affected by antagonists and agonists for other receptors classes (propranolol, beta-1; apomorphine, D-1; spiperone, D-2). Binding of [125I]HEAT is saturable. At 4 hr, [125I]HEAT or [123I]HEAT was shown to be the only radioactive material in rat thalamus and frontal cortex. Iodine-123 HEAT and [125I]HEAT were synthesized as radiopharmaceuticals within 3 hr in 99% radiochemical purity.

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Biologic distribution data in the rat were obtained for the alpha-1 adrenoceptor imaging agent (+/-) 2-[beta-(iodo-4-hydroxyphenyl)ethylaminomethyl]tetralone (HEAT) labeled with [125I]. The major excretory routes were through the liver (67%) and the kidney (33%). Internal radiation absorbed dose estimates to nine source organs, total body, the GI tract, gonads, and red bone marrow were calculated for the human using the physical decay data for [123I]. The critical organ was found to be the lower large intestine, receiving 1.1 rad per mCi of [123I]HEAT administered. The total-body dose was found to be 58 mrad per mCi.

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In studies of the regiospecific metabolism of lauric acid by monooxygenase enzymes, incubation medium from the reaction of [14C] lauric acid and microsomes is routinely acidified and extracted with ethyl ether. Separation of products by HPLC shows the formation of omega(12)- and omega-1(11)-hydroxylauric acids by rat liver microsomes. In a comparison of several extraction solvents, we observed that the extraction of incubation media with ethyl acetate alone was associated with the appearance of a major new metabolite peak concomitant with loss of the 12- and 11-hydroxylaurate peaks by 62 and 23%, respectively. No difference was observed between extraction procedures in the per cent recovery of radiolabel. Similar results were observed with extraction of lauric acid metabolites formed by fish liver microsomes. Acidification of the incubation media prior to ethyl acetate extraction prevented formation of the new metabolite peak. In experiments to identify the new metabolite(s), 11- and 12-hydroxylaurate products formed by rat liver microsomes were acetylated and found to show an HPLC retention time similar to that of the unknown metabolite peak formed with ethyl acetate extraction. Mass spectrometric analysis further showed that the methyl esters of 11- and 12-acetoxylauric acids were very similar to that of the methyl ester derivative of the unknown metabolite fraction. Thus, data indicate that the acetoxy derivatives of 11- and 12-hydroxylauric acids were formed by direct reaction of ethyl acetate with the laurate products formed by microsomal monooxygenase enzymes. This extraction procedure can produce a major shift in the amount and ratio of omega- and omega-1-hydroxylaurates measured in the incubation media.

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The urinary concentrations of o-hydroxymandelic acid, m-hydroxymandelic acid, p-hydroxymandelic acid, homovanillic acid and vanillylmandelic acid were determined in 57 healthy children and 9 patients with neuroblastoma. The concentrations of o-hydroxymandelic acid and p-hydroxymandelic were not significantly different for both groups whereas the concentrations of m-hydroxymandelic acid, homovanillic acid and vanillylmandelic acid were elevated 20- to 30-fold in the neuroblastoma patients.

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The development of a radiochemical enzyme assay for p-octopamine in 1969 led to its identification in a large number of invertebrate nerve systems and in mammalian sympathetic nerves. The original method by which p-octopamine was measured has now been found to be nonspecific; however, modifications of this procedure can determine both m- and p-octopamine. We recently developed a new specific method for the unequivocal identification and quantitative determination in tissue of the six octopamine and synephrine isomers. With this method--negative chemical ionization gas chromatography-mass spectrometry--the more physiologically active m-octopamine has been found in association with p-octopamine in 10 organs of the rat. m-Octopamine is present in concentrations equal to those of p-octopamine in heart, spleen, and liver and in concentrations from 30 to 60% of p-octopamine in adrenals, vas deferens, brain, kidney, large intestine, bladder, and lungs. In vivo inhibition of monoamine oxidase markedly increased the concentrations of both m- and p-octopamine in all organs examined. Both amines were virtually absent from all organs except the adrenals following chemical sympathectomy with 6-hydroxydopamine, thereby establishing that m- and p-octopamine are localized within sympathetic nerve endings.

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The urine of three patients with neuroblastoma was found to have a 3 to 5-fold elevation of m-octopamine concentration. The concentration of m-synephrine was normal in two cases and slightly elevated in the third. These findings were attributed to an increased formation of m-octopamine by this tumor.

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m-Hydroxyphenylglycol (MHPG) has been identified in mammalian urine by gas chromatography mass spectrometry selected ion monitoring. (2H0) MHPG and (2H5) MHPG were synthesized for use as authentic sample and internal standard, respectively. After acid hydrolysis or treatment with sulfatase, the glycol was extracted from urine with ethyl acetate, converted to its tris-pentafluoropropionyl (PFP) derivative and identified by comparison of the retention times and relative intensities of the characteristic ions, m/z 592, m/z 428 and m/z 415, with those from the authentic sample. Using the internal standard the following quantitative results were obtained: 10 normal human adults excreted 7 ng MHPG mg-1 creatinine (range 2-18) as a sulfate conjugate. Ten rats excreted 0.8 micrograms day-1 (range 0.5-1.1) of MHPG also in the conjugated form. Urinary m-hydroxymandelic acid (MHMA) was also measured quantitatively. The ratio MHMA:MHPG was 1:1 in the rat and 6:1 in the human. This indicates that the overall reductive pathway of m-octopamine and m-synephrine metabolism is more important in the rat than in the human. o-Hydroxyphenylglycol (OHPG) and the three isomeric monomethoxy phenylglycols could not be detected in human or rat urine by these techniques.

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o-Hydroxymandelic acid (OHMA), m-hydroxymandelic acid (MHMA) and p-hydroxymandelic acid (PHMA) were measured in the urine of 42 normotensive and 54 hypertensive patients. Patients having high urinary MHMA levels were all found to be ingesting medications containing m-synephrine (phenylephrine). These patients also had high levels of urinary m-synephrine which was excreted as the glucuronide. When patients ingesting m-synephrine were excluded from the analysis, no significant differences were observed between the two groups for the urinary excretion of OHMA, MHMA and PHMA.

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o-Hydroxymandelic acid has been found in large amounts in the urine of patients with phenylketonuria by gas chromatography mass spectrometry selected ion monitoring. Using deuterated o-hydroxymandelic acid as an internal standard, five patients were found to excrete 150-340 ng mg-1 creatinine. This may be compared with the excretion of 4-16 ng mg-1 creatine by normal subjects. Neither o-octopamine nor o-synephrine were found in urine under conditions by which 1 ng mg-1 creatinine would have been detected.

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o-Hydroxymandelic acid and m-hydroxymandelic acid have been identified in human urine by gas chromatography mass spectrometry selected ion monitoring. After solvent extraction the urinary acids were converted to their O-trifluoroacetoxy methyl ester derivatives which were identified by comparison of the retention times and relative intensities of the characteristic m/z 374 and m/z 315 ions with those from authentic samples. 4,6-[2H3]-o-hydroxymandelic acid and 2,4,6-[2H3]-m-hydroxymandelic acid were synthesized for use as internal standards in the quantitative estimation of the isomeric hydroxymandelic acids excreted in urine. In ten normal adults the following results were obtained: o-hydroxymandelic acid 4--16 ng mg-1 creatinine and m-hydroxymandelic acid 11--71 ng mg-1 creatinine. Acid hydrolysis of the urine or ingestion of a diet of known composition did not affect these results, indicating that these compounds are excreted as the free acids and probably arise by metabolism of the corresponding phenylethanolamine(s).

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