The Global Genome Biodiversity Network (GGBN) Data Standard specification.

Genomic samples of non-model organisms are becoming increasingly important in a broad range of studies from developmental biology, biodiversity analyses, to conservation. Genomic sample definition, description, quality, voucher information and metadata all need to be digitized and disseminated across scientific communities. This information needs to be concise and consistent in today's ever-increasing bioinformatic era, for complementary data aggregators to easily map databases to one another. In order to facilitate exchange of information on genomic samples and their derived data, the Global Genome Biodiversity Network (GGBN) Data Standard is intended to provide a platform based on a documented agreement to promote the efficient sharing and usage of genomic sample material and associated specimen information in a consistent way. The new data standard presented here build upon existing standards commonly used within the community extending them with the capability to exchange data on tissue, environmental and DNA sample as well as sequences. The GGBN Data Standard will reveal and democratize the hidden contents of biodiversity biobanks, for the convenience of everyone in the wider biobanking community. Technical tools exist for data providers to easily map their databases to the standard.Database URL: http://terms.tdwg.org/wiki/GGBN_Data_Standard.

Identification of C-glycoside flavonoids as potential mutagenic compounds in kava.

Kava (Piper methysticum) extract products have been implicated in a number of severe hepatotoxicity cases. However, systematic toxicological studies regarding kava consumption have not been reported. In this study, 6 major kavalactones and different solvent fractions of kava roots, leaves, and stem peelings were evaluated for their mutagenic potential. None of the kavalactones was found to be positive in the experimental concentration ranges tested by the umu test (a sensitive test for point mutations). However, among the different solvent fractions, the n-butanol fraction of kava leaves was positive. Further investigations using bioassay-directed isolation and analysis indicated that 2 C-glycoside flavonoid compounds accounted for the positive mutagenic results. Two isolated compounds were identified as 2''-O-rhamnosylvitexin and schaftoside by NMR and MS techniques.

Identification of metabolites produced from N-phenylpiperazine by Mycobacterium spp.

Mycobacterium sp. 7E1B1W and seven other mycobacterial strains known to degrade hydrocarbons were investigated to determine their ability to metabolize the piperazine ring, a substructure found in many drugs. Cultures were grown at 30 degrees C in tryptic soy broth and dosed with 3.1 mM N-phenylpiperazine hydrochloride; samples were removed at intervals and extracted with ethyl acetate. Two metabolites were purified from each of the extracts by high-performance liquid chromatography; they were identified by mass spectrometry and (1)H nuclear magnetic resonance spectroscopy as N-(2-anilinoethyl)acetamide and N-acetyl-N'-phenylpiperazine. The results show that mycobacteria have the ability to acetylate piperazine rings and cleave carbon-nitrogen bonds.

[Coblation tonsillectomy. Results of a pilot study]. / Coblation-Tonsillektomie. Ergebnisse einer Pilotstudie.

BACKGROUND: The introduction of coblation tonsillectomy (CTE) may contribute to reduce the postoperative morbidity in terms of pain, delayed oral intake and bleeding. METHODS: A prospective pilot study was undertaken to evaluate the clinical course by inpatient observation (5 days) and telephone contact 6 months after CTE. The data from 61 patients (aged 44 months-69 years) were analyzed. The patients were grouped into those with surgical care of bleeding (A), non-surgical care of bleeding (B), and no bleeding event (C). RESULTS: The study was terminated early due to major bleeding complications in seven patients (A). Fifteen patients experienced minor (B) and 41 no (C) bleeding episodes. In the interview, 29 patients identified pain, lasting 16.7 (A), 11.6 (B) and 11 (C) days, as the most significant complication of surgery. CONCLUSIONS: The introduction of CTE was followed by a dramatic increase in major bleeding complications, including late bleeding episodes. Pain following tonsillectomy remains a problem to be solved by further techniques. We will continue to perform the cold dissection technique.

Selective active site inhibitors of human lactate dehydrogenases A4, B4, and C4.

Human lactate dehydrogenases (LDH-A4, -B4, and -C4) are highly homologous with 84-89% sequence similarities and 69-75% amino acid identities. Active site residues are especially conserved. Gossypol, a natural product from cotton seed, is a non-selective competitive inhibitor of NADH binding to LDH, with K(i) values of 1.9, 1.4, and 4.2 microM for LDH-A4, -B4, and -C4, respectively. However, derivatives of gossypol and structural analogs of gossypol in the substituted 2,3-dihydroxy-1-naphthoic acid family exhibited markedly greater selectivity and, in many cases, greater potency. For gossypol derivatives, greater than 35-fold selectivity was observed. For dihydroxynaphthoic acids with substituents at the 4- and 7-positions, greater than 200-fold selectivity was observed. Inhibition was consistently competitive with the binding of NADH, with dissociation constants as low as 30 nM. By comparison, a series of N-substituted oxamic acids, which are competitive inhibitors of the binding of pyruvate to LDH, exhibited very modest selectivity. These results suggest that substituted dihydroxynaphthoic acids are good lead compounds for the development of selective LDH inhibitors. Selective inhibitors of LDH-C4 targeted to the dinucleotide fold may hold promise as male antifertility drugs. Selective inhibitors of LDH-A4 and -B4 may be useful for studies of lactic acidemia associated with ischemic events. More broadly, the results raise the question of the general utility of drug design targeted at the dinucleotide binding sites of dehydrogenases/reductases.

Hospital discharge after ambulatory knee arthroscopy: A comparison of epidural 2-chloroprocaine versus lidocaine.

BACKGROUND AND OBJECTIVES: This prospective, randomized, double-blind study compares the efficacy of epidural 2-chloroprocaine and lidocaine for attaining hospital discharge criteria after ambulatory knee arthroscopy. We hypothesized that 2-chloroprocaine would facilitate earlier discharge than lidocaine. METHODS: American Society of Anesthesiologists (ASA) I and II patients were randomized to receive equipotent doses of epidural 3% 2-chloroprocaine or 1.5% lidocaine, both without epinephrine. Time to block resolution and discharge were compared between groups, along with the need for epidural reinjection, surgical times, and postoperative back pain. RESULTS: Twenty-seven patients completed the study, 13 in the 2-chloroprocaine group and 14 in the lidocaine group. The 2-chloroprocaine group was ready for discharge significantly earlier than the lidocaine group (130 +/- 17 min [range, 105 to 160] v 191 +/- 32 min [range 144 to 251]; P <.0001, 90% power). The lidocaine group required more epidural reinjections. Anesthesia-related side effects were similar in both groups. CONCLUSIONS: Epidural 3% 2-chloroprocaine without epinephrine is an advantageous choice for ambulatory knee arthroscopy. It enables readiness for discharge an hour sooner than 1.5% lidocaine, requires fewer reinjection interventions, and may reduce delayed discharge secondary to prolonged time to void. This clinical study shows the superiority of epidural 3% 2-chloroprocaine over 1.5% lidocaine for expediting hospital discharge after ambulatory surgery.

Glial swelling with eosinophilia in human post-mortem brains: a change indicative of plasma extravasation.

Swollen, intensely eosinophilic glial cells are often observed in the vicinity of hemorrhagic lesions in post-mortem human brains. We sought to determine the nature of this change. Thirty adult human brains removed at autopsy and three surgical specimens were obtained 6h to 60 days following a hemorrhagic event. They were subjected to a battery of histochemical and immunohistochemical stains. The swollen cells, which were observed in the majority of autopsy specimens in which hemorrhage had occurred within the previous 9 days, stained intensely red with Masson stain and were immunoreactive for IgG, IgM, IgA, and fibrinogen. Some were also immunoreactive for glial fibrillary acidic protein, particularly in subpial and subependymal areas, if the lesions were more than 3 days old. In white matter some of the cells were immunoreactive for CNPase. There was no labeling with markers for macrophage/microglial cells. The absence of DNA fragment detection by TUNEL suggests that the cells were not dying. Mild glial cytoplasmic eosinophilia without swelling was observed in surgical specimens. No eosinophilic swollen glia were seen in perfusion-fixed rat brains with experimental intracerebral hemorrhage, although they were seen in rat brains that were not promptly fixed. We conclude that human macroglia, including astrocytes and oligodendrocytes, ingest plasma proteins that have been released into brain parenchyma. This likely represents a homeostatic mechanism that maintains the composition of the extracellular environment. If the tissue is not promptly fixed the cells become more swollen and eosinophilic.

Evidence of widespread axonal pathology in Wolfram syndrome.

Wolfram syndrome, characterised by diabetes insipidus, diabetes mellitus, optic atrophy sensorineural deafness and acquired urinary tract abnormalities, is an hereditary neurodegenerative syndrome, the pathogenesis of which is unknown. We report the post-mortem findings on a patient with well-documented Wolfram syndrome. The brain showed severe degeneration of the optic nerves, chiasm and tracts as well as severe loss of neurons from the lateral geniculate nuclei, basis pontis, and the hypothalamic paraventricular and supraoptic nuclei. In addition, there was a widespread axonal dystrophy with axonal swellings in the pontocerebellar tracts, the optic radiations, the hippocampal fornices and the deep cerebral white matter. This widespread axonal pathology parallels the pattern of neurodegeneration and in many areas is more striking than neuronal loss.

Biotransformation of protriptyline by filamentous fungi and yeasts.

1. The potential of various fungi to metabolize protriptyline (an extensively used antidepressant) was studied to investigate similarities between mammalian and microbial metabolism. 2. Metabolites produced by each organism were isolated by high-pressure liquid chromatography and identified by nuclear magnetic resonance and mass spectrometry. The metabolites identified in one or more fungi were 2-hydroxyprotriptyline, N-desmethylprotriptyline, N-acetylprotriptyline, N-acetoxyprotriptyline, 14-oxo-N-desmethylprotriptyline, 2-hydroxy-acetoxyprotriptyline and 3-(5-hydrodibenzo[bf][7]annulen-5-yl)propanoic acid. 3. Among 27 filamentous fungi and yeast species screened, Fusarium oxysporum f. sp. pini 2380 metabolized 97% of the protriptyline added. Several other fungi screened gave significant metabolism of protriptyline, including Cunninghamella echinulata ATCC 42616 (67%), C. elegans ATCC 9245 (17%), C. elegans ATCC 36112 (22%), C. phaeospora ATCC 22110 (50%), F. moniliforme MRC-826 (33%) and F. solani 3179 (12%). 4. F. oxysporum f. sp. pini produced phase I and phase II metabolites and thus is a suitable microbial model for protriptyline metabolism.

Pseudo-subarachnoid hemorrhage: a rare neuroimaging pitfall.

OBJECTIVE: We report an unusual case of the CT appearance of diffuse subarachnoid hemorrhage in a patient with anoxic encephalopathy, a situation which neurosurgeons, neurologists, and neuroradiologists should be aware of. CLINICAL PRESENTATION: A young man collapsed unconscious in jail after abusing an unknown quantity and variety of drugs. CT scan showed a picture compatible with diffuse subarachnoid hemorrhage. INTERVENTION: As the patient had a Glasgow Coma Score of 3 no heroic intervention was undertaken. An autopsy performed 40 hours after the initial ictus and 24 hours after death revealed no evidence of subarachnoid hemorrhage but gross and microscopic evidence of anoxic encephalopathy. CONCLUSION: Anoxic encephalopathy can mimic diffuse subarachnoid hemorrhage on CT.

Structure, tumorigenicity, microsomal metabolism, and DNA binding of 7-Nitrodibenz[a,h]anthracene.

It has been previously proposed that a nitropolycyclic aromatic hydrocarbon (nitro-PAH) with its nitro functional group perpendicular or nearly perpendicular to the aromatic moiety exhibits lower tumorigenicity than the corresponding parent aromatic hydrocarbon. We also hypothesized that reduction of the nitro group is not involved, or contributed less significantly in the metabolic activation of this class of nitro-PAHs. To verify this hypothesis, we selected 7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A) for study. The X-ray crystallographic structure of 7-NDB[a,h]A was determined and indicated that the dihedral angle between the nitro functional group and the aromatic dibenz[a,h]anthracenyl moiety was 80.6 degrees, indicating the nitro group preferentially adopts a nearly perpendicular orientation. The tumorigenicity of 7-NDB[a,h]A and dibenz[a,h]anthracene (DB[a,h]A) was determined in the male B6C3F1 neonatal mouse. Mice were administered ip injections of 1/7, 2/7, and 4/7 of the total dose of 7-NDB[a,h]A (400 nmol in 35 microL of DMSO per mouse) within 24 h of birth and at 8 and 15 days of age, respectively, and sacrificed at 12 months of age. DB[a,h]A induced 78 and 96% hepatocellular adenomas and carcinomas, respectively. However, 7-NDB[a,h]A induced only 50 and 8% hepatocellular adenomas and carcinomas compared with the 8 and 4% hepatocellular adenomas and carcinomas induced by the solvent vehicle, DMSO. Aerobic metabolism of 7-NDB[a,h]A by liver microsomes of 15-day old male B6C3F1 neonatal mice resulted in trans-3,4-dihydroxy-3, 4-dihydro-7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A trans-3, 4-dihydrodiol) and trans-10,11-dihydroxy-10, 11-dihydro-7-nitrodibenz[a,h]anthracene (7-NDB[a,h]A trans-10, 11-dihydrodiol) as predominant metabolites. Under anaerobic conditions, 7-NDB[a,h]A was not metabolized (nitroreduced). The DNA adduct levels in liver and lung tissues of male B6C3F1 mice treated with 7-NDB[a,h]A and sacrificed 24 h and 6 days after final dosing were determined by 32P-postlabeling/TLC. In all cases, the DNA adducts derived from 7-NDB[a,h]A trans-3,4-dihydrodiol and 7-NDB[a, h]A trans-10,11-dihydrodiol were formed. These results suggest that both of the metabolites, 7-NDB[a,h]A trans-3,4-dihydrodiol and 7-NDB[a,h]A trans-10,11-dihydrodiol, are involved in the metabolic activation of 7-NDB[a,h]A, leading to tumor induction in the neonatal mouse. Thus, our results described in this paper support our hypotheses that a nitro-PAH with a perpendicular nitro orientation exhibits lower tumorigenicity than the corresponding parent PAH and that nitroreduction contributes less significantly in the metabolic activation.

Axonal injury and the neuropathology of shaken baby syndrome.

We examined an autopsy series of 14 children with shaken baby syndrome (SBS) who lacked skull fracture. Evidence of axonal injury was sought using immunohistochemical stains for neurofilament, 68-kDa neurofilament and beta-amyloid precursor protein (betaAPP). BetaAPP-positive axons were present in the cerebral white matter of all cases of SBS but were also present in 6 of 7 children dying of non-traumatic hypoxic ischemic encephalopathy (HIE). Swollen axons were present in 11 of 14 cases of SBS and in 6 of 7 cases of HIE. BetaAPP-positive axons were present in both groups in the midbrain and medulla. The cervical spinal cord in SBS contained betaAPP-positive axons in 7 of 11 cases; 5 of 7 contained swollen axons within the white matter tracts; in 2 immunoreactivity was localized to spinal nerve roots; in all 7 there was a predilection for staining at the glial head of the nerve root. Among cases of HIE, none showed abnormal axons or betaAPP-positive reactivity in the cervical cord white matter. We conclude that cerebral axonal injury is common in SBS, and may be due in part to hypoxic/ischemic injury. Cervical cord injury is also common, and cannot be attributed to HIE. These findings corroborate suggestions that flexion-extension injury about the cervical spinal column may be important in the pathogenesis of SBS.

Comparison of phenanthrene and pyrene degradation by different wood-decaying fungi.

The degradation of phenanthrene and pyrene was investigated by using five different wood-decaying fungi. After 63 days of incubation in liquid culture, 13.8 and 4.3% of the [ring U-14C]phenantherene and 2.4 and 1.4% of the [4,5,9,10-14C]pyrene were mineralized by Trametes versicolor and Kuehneromyces mutabilis, respectively. No 14CO2 evolution was detected in either [14C]phenanthrene or [14C]pyrene liquid cultures of Flammulina velutipes, Laetiporus sulphureus, and Agrocybe aegerita. Cultivation in straw cultures demonstrated that, in addition to T. versicolor (15.5%) and K. mutabilis (5.0%), L. sulphureus (10.7%) and A. aegerita (3.7%) were also capable of mineralizing phenanthrene in a period of 63 days. Additionally, K. mutabilis (6.7%), L. sulphureus (4.3%), and A. aegerita (3.3%) mineralized [14C]pyrene in straw cultures. The highest mineralization of [14C] pyrene was detected in straw cultures of T. versicolor (34.1%), which suggested that mineralization of both compounds by fungi may be independent of the number of aromatic rings. Phenanthrene and pyrene metabolites were purified by high-performance liquid chromatography and identified by UV absorption, mass, and 1H nuclear magnetic resonance spectrometry. Fungi capable of mineralizing phenanthrene and pyrene in liquid culture produced enriched metabolites substituted in the K region (C-9,10 position of phenanthrene and C-4,5 position of pyrene), whereas all other fungi investigated produced metabolites substituted in the C-1,2, C-3,4, and C-9,10 positions of phenanthrene and the C-1 position of pyrene.

Evidence for the role of 2-hydroxychromene-2-carboxylate isomerase in the degradation of anthracene by Sphingomonas yanoikuyae B1.

Sphingomonas yanoikuyae B1 is extremely versatile in its catabolic ability. An insertional mutant strain, S. yamoikuyae EK504, which is unable to grow on naphthalene due to the loss of 2-hydroxychromene-2-carboxylate isomerase activity, was utilized to investigate the role of this enzyme in the degradation of anthracene by S. yanoikuyae B1. Although EK504 is unable to grow on anthracene, this strain could transform anthracene to some extent. A metabolite in the degradation of anthracene by EK504 was isolated by high-pressure liquid chromatography (HPLC) and was identified as 6,7-benzocoumarin by UV-visible, gas-chromatographic, HPLC/mass-spectrometric, and 1H nuclear magnetic resonance spectral techniques. The identification of 6,7-benzocoumarin provides direct chemical and genetic evidence for the involvement of nahD in the degradation of anthracene by S. yanoikuyae B1.

Novel metabolites in phenanthrene and pyrene transformation by Aspergillus niger.

Aspergillus niger, isolated from hydrocarbon-contaminated soil, was examined for its potential to degrade phenanthrene and pyrene. Two novel metabolites, 1-methoxyphenanthrene and 1-methoxypyrene, were identified by conventional chemical techniques. Minor metabolites identified were 1- and 2-phenanthrol and 1-pyrenol. No 14CO2 evolution was observed in either [14C]phenanthrene or [14C]pyrene cultures.

Fungal transformations of antihistamines: metabolism of cyproheptadine hydrochloride by Cunninghamella elegans.

1. Metabolites formed during incubation of the antihistamine cyproheptadine hydrochloride with the zygomycete fungus Cunninghamella elegans in liquid culture were determined. The metabolites were isolated by hple and identified by mass spectrometric and proton nmr spectroscopic analysis. Two C elegans strains, ATCC 9245 and ATCC 36112, were screened and both produced essentially identical metabolites. 2. Within 72 h cyproheptadine was extensively biotransformed to at least eight oxidative phase-I metabolites primarily via aromatic hydroxylation metabolic pathways. Cyproheptadine was biotransformed predominantly to 2-hydroxycyproheptadine. Other metabolites identified were 1- and 3-hydroxycyproheptadine, cyproheptadine 10,11-epoxide, N-desmethylcyproheptadine, N-desmethyl-2-hydroxycyproheptadine, cyproheptadine N-oxide, and 2-hydroxycyproheptadine N-oxide. Although a minor fungal metabolite, cyproheptadine 10,11-epoxide represents the first stable epoxide isolated from the microbial biotransformation of drugs. 3. The enzymatic mechanism for the formation of the major fungal metabolite, 2-hydroxycyproheptadine, was investigated. The oxygen atom was derived from molecular oxygen as determined from 18O-labelling experiments. The formation of 2-hydroxycyproheptadine was inhibited 35, 70 and 97% by cytochrome P450 inhibitors metyrapone, proadifen and 1-aminobenzotriazole respectively. Cytochrome P450 was detected in the microsomal fractions of C. elegans. In addition, 2-hydroxylase activity was found in cell-free extracts of C. elegans. This activity was inhibited by proadifen and CO, and was inducible by naphthalene. These results are consistent with the fungal epoxidation and hydroxylation reactions being catalysed by cytochrome P450 monooxygenases. 4. The effects of types of media on the biotransformation of cyproheptadine were investigated. It appears that the glucose level significantly affects the biotransformation rates of cyproheptadine; however it did not change the relative ratios between metabolites produced.

Mechanism for the anti-thyroid action of minocycline.

Administration of minocycline (MN), a tetracycline antibiotic, produces a black pigment in the thyroids of humans and several species of experimental animals and antithyroid effects in rodents. We have previously shown that these effects appear to be related to interactions of MN with thyroid peroxidase (TPO), the key enzyme in thyroid hormone synthesis. In the present study, the mechanisms for inhibition of TPO-catalyzed iodination and coupling reactions by MN were investigated. MN was stable in the presence of TPO and H2O2, but adding iodide or a phenolic cosubstrate caused rapid conversion to several products. TPO-dependent product formation, characterized by on-line LC-APCI/MS and 1H-NMR, involved oxidative elimination to form the corresponding benzoquinone with subsequent dehydrogenation at the aliphatic 4-(dimethylamino) group. Addition of thiol-containing polymers (bovine serum albumin or thiol-agarose chromatographic beads) had a minimal effect on MN oxidation by TPO, but substantially reduced product formation and produced concomitant losses in free thiols. Covalent bonding through a thioether linkage of a reactive intermediate, the benzoquinone iminium ion, was inferred from these findings. Iodide- and phenolic cosubstrate-dependent oxidation of tetracycline to demethylated and dehydrogenated products was also observed, although at a slower rate than MN. The products and kinetics observed with MN were consistent with oxidation of MN by either the enzymatic iodinating species formed by reaction of TPO compound I with iodide or phenoxyl radicals/cations generated by TPO-mediated oxidation of a phenolic cosubstrate. The proposed reaction mechanism is consistent with alternate substrate inhibition of TPO-catalyzed iodination of tyrosyl residues in thyroglobulin (Tg) by MN, as previously reported. Furthermore, the observed phenoxyl radical-mediated oxidation of MN is consistent with its previously reported potent inhibition of the coupling of hormonogenic iodotyrosine residues in Tg in the reaction that forms thyroid hormones. The proposed reaction mechanism also implicates a reactive benzoquinone iminium ion intermediate that could be important in toxicity of MN.

Adipose tissue and lipid droplet embolism following periurethral injection of autologous fat: case report and review of the literature.

The authors present a case of a death associated with pulmonary adipose tissue and lipid droplet embolism following autologous fat harvesting, periurethral injection and videocystourethroscopy for the treatment of recurrent genuine stress incontinence.

Formation of mammalian metabolites of cyclobenzaprine by the fungus, Cunninghamella elegans.

The fungus, Cunninghamella elegans, was used as a microbial model of mammalian drug metabolism to biotransform a tricyclic antidepressant, cyclobenzaprine. Seventy-five percent of this drug at a concentration of 1 mM was metabolized within 72 h by C. elegans grown on Sabouraud dextrose broth. Milligram amounts of fungal metabolites were isolated by reversed-phase high performance liquid chromatography (HPLC) and their structures were characterized by 1H NMR spectroscopy, mass spectrometry, and UV spectroscopy analyses. The major fungal metabolites of cyclobenzaprine were 2-hydroxycyclobenzaprine (59%), N-desmethylcyclobenzaprine (21%), cyclobenzaprine trans-10,11-dihydrodiol (5%), N-desmethyl-2-hydroxy-cyclobenzaprine (3%), 3-hydroxycyclobenzaprine (3%), and cyclobenzaprine N-oxide (1%). These fungal metabolites were used as standards to investigate the metabolism of cyclobenzaprine by rat liver microsomes. Rat liver microsomes also biotransformed cyclobenzaprine to produce similar metabolites as the fungus. The isotope labeling of 2-hydroxycyclobenzaprine by 18O2 and the trans-configuration of the dihydrodiol suggested that these reactions were catalyzed by cytochrome P-450 monooxygenases in C. elegans. These results also demonstrated that the fungal biotransformation system could be used to predict and synthesize the mammalian drug metabolites.

Striatal dopamine, dopamine transporter, and vesicular monoamine transporter in chronic cocaine users.

Depletion of striatal dopamine (DA) has been hypothesized to explain some of the neurological and psychiatric complications of chronic use of cocaine, including increased risk for neuroleptic-precipitated movement disorders. We measured levels of DA, as well as two DA nerve terminal indices, namely, the DA transporter (DAT) and the vesicular monoamine transporter (VMAT2) in autopsied brain of 12 chronic cocaine users. Mean DA levels were normal in the putamen, the motor component of the striatum; however 4 of the 12 subjects had DA values below the lower limit of the control range. DA concentrations were significantly reduced in the caudate head (head, -33%; tail, -39%) with a trend for reduction in nucleus accumbens (-27%). Striatal DAT protein (-25 to -46%) and VMAT2 (-17 to -22%) were reduced, whereas DAT determined by [3H]WIN 35,428 binding was normal. In conclusion, our data suggest that chronic cocaine use is associated with modestly reduced levels of striatal DA and the DA transporter in some subjects and that these changes might contribute to the neurological and psychiatric effects of the drug.