Monoaminergic neurotransmitter alterations in postmortem brain regions of depressed and aggressive patients with Alzheimer's disease

Depression and aggression in Alzheimer's disease (AD) are 2 of the most severe and prominent neuropsychiatric symptoms (NPS). Altered monoaminergic neurotransmitter system functioning has been implicated in both NPS, although their neurochemical etiology remains to be elucidated. Left frozen hemispheres of 40 neuropathologically confirmed AD patients were regionally dissected. Dichotomization based on depression and aggression scores resulted in depressed/nondepressed (AD + D/AD − D) and aggressive/nonaggressive (AD + Agr/AD − Agr) groups. Concentrations of dopamine, serotonin (5-HT), (nor)epinephrine ((N)E), and respective metabolites were determined using reversed-phase high-performance liquid chromatography. Significantly lower 3-methoxy-4-hydroxyphenylglycol (MHPG) and higher homovanillic acid levels were observed in Brodmann area (BA) 9 and 10 of AD + D compared with AD − D. In AD + Agr, 5-hydroxy-3-indoleacetic acid (5-HIAA) levels in BA9, 5-HIAA to 5-HT ratios in BA11, and MHPG, NE, and 5-HIAA levels in the hippocampus were significantly decreased compared with AD − Agr. These findings indicate that brain region-specific altered monoamines and metabolites may contribute to the occurrence of depression and aggression in AD.     

Combining different assays and chemical analysis to characterize the genotoxicity of waters impacted by textile discharges

Waters receiving textile discharges can exhibit genotoxic and mutagenic activity, which has been related to the presence of dyes and aromatic amines as synthesis precursors or byproducts. The aim of this study was to identify dyes and aromatic amines in water samples impacted by textile discharges, and to evaluate the genotoxic responses of these samples using the Salmonella/microsome assay in strains TA98 and YG1041, and the Fpg‐modified comet assay in the RTL‐W1 fish cell line. The genotoxicity of river samples downstream of the discharge was greater than the upstream samples in both of the Ames tests. The Fpg‐modified comet assay detected similar levels of DNA damage in the upstream and downstream samples. Mutagenicity was not detected with TA98, except for the Quilombo River samples, but when YG1041 was used as the tester strain mutagenicity was detected for all sites with a very different profile in upstream sites relative to the other sites. The mutagenic response strongly indicated that aromatic amines or dyes were contributing to the mutagenic activity downstream. The impact of textile discharges was also confirmed by chemical analysis, because the highest concentrations of azo dyes and aromatic amines were detected in the river downstream. This study shows the value of combining assays measuring complementary endpoints to better characterize the mutagenicity of environmental samples, with the advantage that this approach provides an indication of what classes of compounds are responsible for the effect. Environ. Mol. Mutagen. 57:559–571, 2016. © 2016 Wiley Periodicals, Inc.     

Histochemical study of mast cells from the thymus of mice receiving ACTH<Subscript>1–24</Subscript>

Synthetic ACTH_1–24 analogue administered in a daily dose of 0.01 mg/kg decreased the number and size of mast cells and increased intracellular serotonin concentration. ACTH_1–24 induced degranulation of young mast cells and release of undersulfated heparin. Correlation analysis showed that hormonal imbalance produced by ACTH_1–24 was accompanied by redistribution of bioamines. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 138, No. 7, pp. 107–110, July, 2004     

Evidence for ras gene mutation in 2-amino-3-methylimidazo[4,5-f]quinoline–induced colonic aberrant crypts in the rat

Aberrant crypt foci (ACF) are putative peneoplastic lesions that develop after treatment of animals with colon carcinogens, including cooked-meat heterocyclic amines such as 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Male F344 rats given IQ by gavage on alternating days for 2 wk (130 mg/kg body weight) and killed 12 wk after the final carcinogen dose had an average of 4.4 ACF/colon and an average of 3.2 crypts/focus. The DNA from these ACF was amplified by the polymerase chain reaction and analyzed by 3′-primer mismatch and direct sequencing methods for mutations in the Ki-ras proto-oncogene. Of the 37 IQ-induced ACF screened, three contained a GGT→GAT mutation in codon 12 and one contained a GGC→GCC mutation in codon 13. The approximately 11% frequency of mutation in IQ-induced ACF is within the range of previous ACF studies of azoxymethane, which reported a 7–37% incidence of Ki-ras mutaion. These findings suggest that for both compounds, ras mutations occur during early stages of colorectal tumorigenesis. However, while ras mutations can be detected with increasing frequency in azoxymethane-induced adenomas and carcinomas, they are reportedly absent in IQ-induced colon tumors. Thus, for IQ and related compounds additional factors (possibly increased cell proliferation) may be important in the later stages of colorectal tumorigenesis. © 1995 Wiley-Liss Inc.     

Amino acids and biogenic amines during spontaneous malolactic fermentation in Tempranillo red wines

This paper examines the changes undergone by the nitrogenated fraction of wine during malolactic fermentation (MLF) produced by the indigenous microbiota in 16 industrial-scale vinifications at technologically well-equipped wineries. Statistically significant increases (between 5% and 35%) were found in 15 of the 24 amino acids analyzed; decreases (between 4% and 29%) were found only in four. The biogenic amines histamine, tyramine and putrescine increased by between 106% and 174%, but histamine final concentrations in wine were not too high, under the limit of 10 mg/L established by Switzerland. There was a non-significant increase of 2.0–2.3 μg/L in ethyl carbamate.     

Biomonitoring of aromatic amines V: acetylation and deacetylation in the metabolic activation of aromatic amines as determined by haemoglobin binding

Aromatic amines are metabolically activated by N-oxidation of either the amine or the acetamide as a first step and esterification of the resulting N-hydroxyl derivatives as a second step. Both pathways may lead to DNA-adducts and subsequently to DNA lesions and mutations. Since the accumulation of non-acetylated adducts has been associated with tumour initiating properties, the balance between acetylation and deacetylation may greatly influence the biological effect. Hydrolysable haemoglobin adducts representing the bioavailability of N-hydroxylamines and the corresponding nitroso-derivatives were analysed following oral administration to female Wistar rats of two arylamine-acetamide couples: 4-aminobiphenyl and 2-aminofluorene, and two arylamine-acetamide-diacetamide triples: benzidine and 3,3′-dichlorobenzidine. The results show that the mono-acetamides are readily deacetylated in vivo whereas the diacetamides are not. A dynamic equilibrium is indicated to exist between acetylation and deacetylation, which depends on substrate specificity, and the role of deacetylation is emphasised. In addition, acetylation polymorphism was studied with 4-chloroaniline and 3,3′-dichlorobenzidine in slow acetylating A/J and rapid acetylating C57BL/6J mice. The slow acetylator genotype was associated with significantly higher haemoglobin-adduct levels for both arylamines. The results provide additional support for the use of haemoglobin adducts in biomonitoring as a dosimeter for the biologically active dose of arylamines/arylacetamides. Moreover, biomonitoring of haemoglobin adducts may provide information about an individual's susceptibility to the toxic and carcinogenic effects of these chemicals. Received: 19 January 1998 / Accepted: 7 April 1998     

Occupational exposure and urological cancer

Occupational exposure is definitely a major cause of cancer. In the field of urology, the urinary bladder is the most important target. A classical cause of bladder cancer is exposure to carcinogenic aromatic amines, especially benzidine and beta-naphthylamine. Such exposures were related to work places in the chemical industry, implying production and processing of classical aromatic amines, and in the rubber industry. Occupational bladder cancer has also been observed in dyers, painters and hairdressers. Even some occupations with much lower exposures to carcinogenic aromatic amines, like coke oven workers or workers in the rubber industry after the ban on beta-naphthylamine, are at risk. In these occupations, exposure to complex mixtures of substances containing combustion products (e.g. polycyclic aromatic hydrocarbons) or nitrosamines is common. Renal cell cancer has been observed as an occupational disease in cases of very high exposure to trichloroethylene having led to narcotic or prenarcotic symptoms. Occupationally related cancers of the prostate or the testes appear currently not relevant.     

Neuromodulation of the locomotor network by dopamine in the isolated spinal cord of newborn rat

We have analysed the action of the neuromodulatory catecholamine, dopamine (DA), on the lumbar locomotor network using an isolated in vitro newborn rat spinal cord preparation. We have also attempted to determine the respective contribution of the D1- and D2-like receptors on the dopamine-mediated effects. Bath application of DA-induced slow locomotor-like rhythmic activity (cycle-period 20-30 s) in ventral motor roots. Bursts were alternating between segmental right and left side and between ipsilateral flexor and extensor units. This rhythm was blocked by D1 (SCH-23390) and D2 (raclopride, sulpiride) receptor antagonists, but was unaffected by the dopamine-beta-hydroxylase blocker, fusaric acid, thereby ruling out indirect noradrenaline-mediated effects. The D1 agonist, SKF-81297 induced prolonged slow rhythmic bursting, while the selective D2 agonists, quinpirole and quinelorane, had no effect. DA and the D1 agonist, SKF-81297 also increased the period and burst amplitude of N-methyl-d-l-aspartate-induced locomotor activity. The effects of dopamine and SKF-81297 on the N-methyl-d-l-aspartate-induced rhythm were long-lasting; persisting for 1 hour after washout. The DA action was blocked by MDL-12 330 A, an inhibitor of adenylate cyclase, suggesting the involvement of cAMP. Together these results indicate that dopamine can exert neuromodulatory actions on mammalian motor networks via short-lasting permissive influences and a newly reported, long-lasting modulation of motor network activity.     

GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population

Tobacco smoking and occupation are major risk factors of bladder cancer via exposure to polycyclic aromatic hydrocarbons (PAHs) and aromatic amines. Glutathione S-transferase (GST) M1, T1 and P1 are involved in the detoxification of PAH reactive metabolites. Two N-acetyltransferase isozymes, NAT2 and NAT1, have major roles in catalyzing the N-acetylation and O-acetylation of aromatic amines. Cytochrome p450 1B1 (CYP1B1) and sulfotransferase 1A1 (SULT1A1) are also involved in the metabolism of PAHs and aromatic amines. It is hypothesized that the genetic polymorphisms of these metabolic enzymes have an effect on the individual susceptibility to bladder cancer in particular by interacting with relevant environmental exposures. A hospital-based case-control study among men in Brescia, Northern Italy recruited 201 incidence cases and 214 controls from 1997-2000. Occupational exposures were blindly coded by occupational physicians. Genotyping of polymorphisms were carried out with PCR-RFLP method. Unconditional multivariate logistic regression was applied to model the association between genetic polymorphisms and bladder cancer risk. Effect modifications by age of onset, smoking and occupational exposures to PAHs and aromatic amines were evaluated. We also conducted an analysis of interaction between genetic factors. GSTM1 and GSTT1 null genotype were associated with an increased risk of bladder cancer with an odds ratio (OR) of 1.69 (95% confidence interval [CI] = 1.11-2.56) and 1.74 (95% CI = 1.02-2.95), respectively. The effect of GSTM1 null was seen particularly in heavy smokers, and there was a combined effect with occupational exposure of aromatic amines (OR = 2.77, 95% CI = 1.08-7.10). We observed a trend (p-value < 0.01) of increasing cancer risk comparing subjects with normal GSTM1 and T1 activity to subjects with one (OR = 1.82, 95% CI = 1.16-2.85) or both null genotypes (OR = 2.58, 95% CI = 1.27-5.23). NAT2 slow acetylator was associated with marginally increased risk of bladder cancer (OR = 1.50, 95% CI = 0.99-2.27), and the OR for the joint effect with occupational exposure of aromatic amines was 3.26 (95% CI = 1.06-9.95). SULT1A1 Arg213His polymorphism showed a marginal protective effect. These findings suggest that individual susceptibility to bladder cancer may be modulated by GSTM1, GSTT1 and NAT2 polymorphisms.     

Food safety evaluation of broccoli and radish sprouts.

Three cultivars of broccoli seeds (Brassica oleracea var. italica), cv. Tiburon, cv. Belstar and cv. Lucky, and two cultivars of radish seeds (Raphanus sativus), cv. Rebel and cv. Bolide, were germinated for three and five days and safety aspects such as microbiological counts and biogenic amines were investigated. Cytotoxicity evaluation was also carried out. Broccoli and radish sprouts contained numbers of mesophilic, psychrotrophic, total and faecal coliform bacteria which are the usual counts for minimally processed germinated seeds. Putrescine, cadaverine, histamine, tyramine, spermidine and spermine increased during sprout production although these levels were below those permitted by legislation (5 mg/100 g of edible food). Broccoli and radish sprouts demonstrated no toxic effects on proliferation and viability of HL-60 cells and should be included in our diets as healthy and safe fresh foods.