Titanate nanotubes as an efficient oral detoxifying agent against drug overdose: application in rat acetaminophen poisoning.

Voluntary drug intoxication is mainly due to drug overdose or the interaction of several drugs. Coma and its associated complications such as hypoventilation, aspiration pneumopathy, and heart rhythm disorders are the main hallmarks of drug intoxication. Conventional detoxification treatments, including gastric lavage or vomiting, administration of ipecac or activated charcoal (CH), and the use of antidotes, have proven to be inefficient and are generally associated with severe adverse effects. To overcome these limitations, titanate nanotubes (TiNTs) are proposed as an efficient emerging detoxifying agent because of their tubular shape and high adsorption capacity. In the present study, the detoxifying ability of TiNTs was evaluated on paracetamol (PR)-intoxicated rats. Results indicate that the loading ability of PR into TiNTs (70%) was significantly higher than that recorded for CH (38.6%). In simulated intestinal medium, TiNTs showed a controlled drug release of less than 10% after 72 h of incubation. In PR-intoxicated rats, TiNTs treatment resulted in a 64% decrease of PR after 4 h of poisoning versus 40% for CH. Concomitantly, TiNTs efficiently reduced PR absorption by 90% after 24 h of poisoning, attenuated the elevated levels of biochemical markers (i.e., alanine aminotransferase, aspartate aminotransferase, creatinine, and TNF-α) and mitigated oxidative stress by increasing the activity of superoxide dismutase and reducing the oxidized glutathione/total glutathione ratio, suggesting a histoprotective effect of TiNTs against paracetamol-induced toxicity in rats. In addition to their safety and high stability in the entire gastro-intestinal tract, biodistribution analysis revealed that TiNTs exhibited low intestinal absorption owing to their large cluster size of compact aggregate nanomaterials across the intestinal villi hindering the absorption of paracetamol. Collectively, these data provide a new and promising solution for in vivo detoxification. TiNTs are expected to have great potential for the treatment of voluntary and accidental intoxication in emergency care.

The status of chemical elements in the blood plasma of children with autism spectrum disorder in Tunisia: a case-control study.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders defined by a deficit in social interactions and the presence of restricted and stereotypical behaviors or interests. The etiologies of autism remain mostly unknown. Many genetic and environmental factors have been suspected. Among these environmental factors, exposure to several chemical elements has been previously studied. The purpose of this study was to compare the levels of trace elements in the blood plasma of children with ASD with typically developed children (TDC). The participants in this study consisted of 89 children with ASD (14 girls and 74 boys) and 70 TD children (29 girls and 41 boys). The levels of 33 chemical elements have been analyzed by inductively coupled plasma spectrometry (ICP-MS). We detected significant differences in the levels of eight elements between the two groups, among which there were three rare earth elements (REEs): Eu, Pr, and Sc (p = 0.000, p = 0.023, and p < 0.001 respectively); four heavy metals: Bi, Tl, Ti, and V (p = 0.004, p < 0.001, p = 0.001, and p = 0.001 respectively); and one essential element: Cu (p = 0.043). Children with ASD had higher levels of Er, Pr, Sc, Bi, Tl, Ti, and V, and lower levels of Cu in comparison with the TD group. The children exposed to passive smoking had lower levels of lead (Pb) compared with children without exposure (p = 0.018). Four elements (Cr, Er, Dy, and Pr) were negatively correlated to the severity of ASD. The level of Cu was significantly associated with autistic children's behavior (p = 0.014). These results suggest that children with ASD might have abnormal plasma levels of certain chemical elements (including Er, Pr, Sc, Bi, Tl, Ti, and V, and Cu), and some of these elements might be associated with certain clinical features.

Reduced peripheral availability of tryptophan and increased activation of the kynurenine pathway and cortisol correlate with major depression and suicide.

Objectives: Patients affected by major depression (MDD) are at high risk of suicide. The metabolism of tryptophan (Trp) along the serotonin (5-HT) and kynurenine (Kyn) pathways was found dysfunctional in MDD and in suicide. However, a clear biological framework linking dysfunctions in Trp metabolism via 5-HT and Kyn, cortisol, and the activities of tryptophan and indoleamino 2,3-dioxygenase (TDO, IDO) enzymes has not been yet clarified in MDD with or without suicidal behaviours.Methods: We analysed peripheral markers of Trp via 5-HT and Kyn pathways, Kyn/Trp ratio as a measure of TDO/IDO activities, cortisol, and psychopathology in 73 non-suicidal and 56 suicidal MDD patients, and in 40 healthy controls.Results: Plasma Trp levels were lower and the ratio Kyn/Trp higher in suicidal MDD than in non-suicidal MDD patients and controls. Trp levels and the ratio Kyn/Trp correlated with suicidal ideation, and cortisol with the Kyn/Trp ratio. Finally, Trp levels discriminated controls from non-suicidal and suicidal MDD patients, and also non-suicidal from suicidal MDD patients.Conclusions: Reduced availability of Trp for 5-HT synthesis and increased activation of the Kyn pathway and cortisol correlate with depression and suicide. Low plasma Trp levels may be a biomarker of MDD and suicide in MDD.

Lipid profile in schizophrenia: case control study.

INTRODUCTION: Cardiovascular diseases are common co morbidities of schizophrenia and constitute the main factors of high mortality in this pathology. Cardiovascular damages are favored by some risk factors, of which one of the most important is dyslipidemia. In this context, a study of lipid profile in schizophrenia is interesting.  The aims of this study were to compare the lipid profile of patients with schizophrenia to healthy controls and to investigate the associations between lipid parameters and demographics, clinical and treatment characteristics of the patients. METHODS: We conducted a case-control study between April 2013 and March 2014 on 78 patients with schizophrenia and 68 healthy subjects who benefited from the dosage of four serum lipid parameters: total cholesterol (TC), triglycerides (TG), High-density lipoprotein Cholesterol (HDL-C) and Low-density lipoprotein cholesterol (LDL-C). For the socio-demographic and clinical assessments, we used an information sheet and the following psychometric scales: PANSS (Positive And Negative Syndrome Scale), CGI (Clinical Global Impressions), GAF (Global Assessment Functionning) and the Calgary scale for depression. RESULTS: The comparative study showed that serum concentrations of TC and LDL-C were significantly higher for patients compared to healthy controls respectively with (t=2,83 ; p=0,008) and             (t=9,35; p<0,001), the cholesterol ratio (TC / HDL-C) was also significantly higher for patients           (t=2,23; p=0,033). The patients had significantly higher prevalence of hypercholesterolemia              (OR = 2.96) and low density hyperlipoproteinemia (OR = 18.79). The analytical study in the population of patients showed that the age ≥35 year-old, male gender and alcohol consumption were associated with disturbances in lipid parameters. Cannabis consumption was associated with significantly lower concentrations in TG. Concerning clinical features, paranoid schizophrenia was associated with less dyslipidemia unlike the depressive dimension assessed by the Calgary scale. There was a negative correlation between plasmatic TG concentrations and doses of antipsychotics. CONCLUSION: The vast majority of the literature confirms that patients with schizophrenia are at greater risk of dyslipidemia. This high risk appears to be more important with the consumption of alcohol and tobacco. It seems also that age and masculine gender are dyslipidemia risk factors for schizophrenic patients. The paranoid type of schizophrenia and positive symptoms seem to be associated with less dyslipidemia while depressive symptoms worsen lipid parameters. It then follows that, clinical and regular monitoring of lipid profile, lifestyle recommendations (smoking cessation, exercise and balanced diet) and appropriate therapeutic choices could help reduce morbidity and mortality among patients with schizophrenia. A special focus should be accorded to patients with high negative and depression symptoms.

Comparison of Mineral Contents in Three Different Tobacco Formulations.

We identified and quantified a variety of mineral elements in 18 tobacco samples purchased from a Tunisian market. In total, 25 mineral elements have been measured in cigarettes, water pipe tobacco, and smokeless tobacco using inductively coupled plasma-optical emission spectroscopy following microwave-assisted digestion. Statistical analyses were performed using SPSSTM, version 18.0. The lowest concentrations of all studied elements were observed in water pipe tobacco. Significantly higher concentrations of Al, Fe, Mg, Na, Ca, Cr, and Co were found in smokeless tobacco, while cigarettes brands contained the highest concentrations of K, Mn, Ni, Ba, and Sr. There was no significant difference between the mineral contents of local and foreign cigarettes and conventional and light cigarettes. Our findings demonstrated that local smokeless tobacco appears to be the most hazardous tobacco type. The concentration of minerals in light cigarettes was not significantly different from the concentration in conventional cigarettes.

ABCB1 and SLCO1B3 Gene Polymorphisms and Their Impact on Digoxin Pharmacokinetics in Atrial Fibrillation Patients among the Tunisian Population.

BACKGROUND: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. METHODS: ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0.5 mg) without (group I, n = 58) or with the co-administration of P-gp inhibitors (group II, n = 44). SDCs were determined at 6 h following the oral dose. RESULTS: SDCs levels were significantly higher in patients who were co-administered P-gp inhibitors. No influence was noted in ABCB1 and SLCO1B3 polymorphisms on SDC in group I patients. However, SDCs values were significantly different among ABCB1 single nucleotide polymorphisms (SNPs) genotypes of 2677G>T/A (TT, GG>GT, p < 0.05) and 3435C>T (TT, CC>CT, p < 0.05) only in group II with no effect of 1236C>T and SLCO1B3 SNPs. CONCLUSION: Results suggest that P-gp inhibitors and ABCB1 gene polymorphisms may affect digoxin pharmacokinetics.

Paraoxonase 1 polymorphisms (L55M and Q192R) as a genetic marker of diabetic nephropathy in youth with type 1 diabetes.

INTRODUCTION: Paraoxonase 1 (PON1) polymorphisms have been largely involved in diabetes complications. The aim of the study is to evaluate the effects of PON1 polymorphisms (L55M and Q192R) on diabetic nephropathy (DN). MATERIAL AND METHODS: The study involved 116 children and adolescents with type 1 diabetes (T1D) and 91 healthy subjects. Albumin excretion rate (AER) was determined by immunoturbidimetry. PON1 activity was measured by a spectrophotometric method, and genotyping of PON1 gene was assessed by multiplex PCR followed by RFLP. RESULTS: PON1 activity was inversely correlated to AER (r = -0.245, p = 0.008). A significant decrease (p = 0.037) in PON1 activity was shown between patients with nephropathy and those without (162 [57-618] vs. 316 [37-788] IU/L, respectively). The distribution of AER was, for L55M polymorphism MM > LM > LL (p = 0.002), and for Q192R polymorphism QQ > QR > RR (p < 0.001). The opposite distribution was noted for PON 1 activity (p < 0.001). LMQQ and MMQQ haplotypes seem to increase AER (p = 0.004, p = 0.003, respectively) and to reduce PON1 activity (p = 0.011, p = 0.052, respectively) in youths with T1D. However, LLRR haplotype seems to have the opposite effect. CONCLUSIONS: This study demonstrated that PON1 polymorphisms L55M and Q192R seem to be genetic markers involved in the development of DN in T1D. (Endokrynol Pol 2017; 68 (1): 35-41).

The association between altered lipid profile and suicide attempt among Tunisian patients with schizophrenia.

BACKGROUND: There have been many studies on psychiatric disorders, but very little is known about the biology of suicide with schizophrenia. In the present study, we are looking for a possible connection between altered lipid profile and suicidal behavior in schizophrenic Tunisian patients. METHODS: Assay of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) has been done for 126 schizophrenic patients with and without suicide attempts and 131 healthy controls recruited in the University Hospital of Monastir. RESULTS: TC and LDL-c levels were significantly higher in schizophrenic patients compared to controls. TC was significantly lower in schizophrenic patients with suicide attempt compared to those without suicide attempt. Depending to the sonority of suicide attempt, TC was significantly lower in patients with recent suicide attempt compared to those with lifetime suicide attempt and without suicide attempt (p < 0.001), and no significant differences between TG, LDL-c, and HDL-c were noted. CONCLUSIONS: Results of this study showed that TC levels in schizophrenic patients after a recent suicide attempt are significantly lower than in patients without suicide attempt and with lifetime suicide attempts. TC can be one of biological markers defined suicidal risk for schizophrenic patients.

CT genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism is protector factor of major depressive disorder in the Tunisian population: a case control study.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric disorder with considerable mortality. Death from unnatural causes, largely suicidal or quasi-suicidal, has a particularly high risk for the functional disorders, especially depression and schizophrenia. One of the prospective risk factors for this disease is hyperhomocysteinemia and folate deficiency. The methylenetetrahydrofolate reductase (MTHFR) gene encodes for a 5-methylenetetrahydrofolate reductase involved in folate metabolism and neurotransmitter synthesis. The aim of this research is to study the association between the C677T polymorphism of MTHFR gene and depression in Tunisian population, to explore their relationship with clinical and therapeutic characteristics of this disease. And it may lead to discover a novel marker to identify a patient with a higher risk of development of depressive disorder to be. This marker can be used for better therapeutic management and prevent disease installation. METHODS: Our study included 208 depressive patients, 187 controls aged between 44.1 ± 13.5 and 38.9 ± 13.2 years, respectively. MTHFR gene polymorphisms were determined by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism). RESULTS: No significant difference was detected in the distribution of the genotype frequencies of MTHFR C677T polymorphisms (χ (2) = 5.443, df = 2, p = 0.066) between patients and controls. But when we study the risk of these genotypes, CT genotype is significantly more frequent in controls compared to patients, it may be a protection from depression (OR = 0.655, CI 95 % = 0.432-0.995, p = 0.047, OR* = 0.638, CI 95 %* = 0.415-0.983, p* = 0.04, before and after adjustment). Women, TT Genotype can increase four times the risk to be depressive. Addictive behavior seems to be associated with CT genotype and there was no significant association between clinical and therapeutic characteristics and this polymorphism. CONCLUSION: This paper is the first study to prove that CT genotype of MTHFR C677T polymorphism may protect from depression and TT genotype seems to be associated with women's depression. Further studies are required with other polymorphisms and biochemical factors that must be investigated to clarify the implication of MTHFR C677T polymorphism in the pathophysiology of depression.

Toxic effects of methamidophos on paraoxonase 1 activity and on rat kidney and liver and ameliorating effects of alpha-tocopherol.

The role of alpha-tocopherol on nephrotoxicity and hepatotoxicity induced by methamidophos (MT) was investigated in wistar rats. Animals were given via gavage, for four weeks, a low dose of MT (MT1), a high dose of MT (MT2), vitamin E (200 mg/kg of bw) or both MT2 plus vitamin E (Vit E) and control group was given distillate water. MT treatment resulted in a significant decrease in the body weight of MT2-treated group. Moreover, MT-treated groups had significantly lower butyrylcholinesterase (p < 0.01) and paraoxonase 1 (PON1) activities compared with the control group (p < 0.05). However, MT2-treated group had significantly higher alkaline phosphatase activity compared with untreated rats (p < 0.05). Both MT-treated groups had significantly higher urea (p < 0.01) and uric acid levels (p < 0.05) compared with the control group. However, significant low uric acid level (p < 0.05) was noted in MT2 plus vit E-treated rats compared with MT2-treated group. Histopathological changes in organ tissues were observed in both MT-treated groups and MT2 plus vit E-treated rats. However, the damage was reduced in MT2 plus vit E-treated rats. Therefore, this study deduces that alpha-tocopherol administration may ameliorate the adverse effects of subacute exposure to MT on rat liver and kidney and this antioxidant can protect PON1 from oxidative stress induced by this organophosphorus pesticide. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 842-854, 2016.

C3 Polymorphism Influences Circulating Levels of C3, ASP and Lipids in Schizophrenic Patients.

Excessive activation of complement is associated with many diseases including schizophrenia. Investigation of C3 polymorphisms, circulating C3, cleavage product ASP/C3adesArg, and lipid metabolism. Cross-sectional analysis. C3 genotyping (CC vs GG for R102L) was performed on 434 Tunisian people consisting of 272 schizophrenic (SZ) patients and 162 control subjects. In a age- and gender-matched subgroups of the three genotypes (131 SZ and 112 NOR), plasma triglycerides, total cholesterol (C), LDL-C, HDL-C, ASP, and complement C3 were measured. C3 gene polymorphism influences BMI and plasma C3, ASP, triglyceride, total cholesterol, LDL-C and HDL-C among SZ patients (p < 0.05-0.0001), with increasing values demonstrated from CC (common form) to CG (heterozygote form) to GG (rare homozygote) forms. Significant correlations between plasma C3 and BMI, triglyceride, HDL-C and ASP (p < 0.05-0.0001) were observed, while ASP correlated with BMI and LDL-C (p = 0.005, p = 0.001, respectively) in SZ patients. Further, proportional conversion of C3 to ASP (%ASP/C3) also increased (p < 0.0001, GG>CG>CC). C3 polymorphisms and plasma C3, ASP and %ASP/C3 correlated with lipid parameters in this SZ population, suggesting that factors predisposing patients to schizophrenia are permissive for complement pathway activation and dyslipidemic influences.

Paraoxonase 1 activity and lipid profile in schizophrenic patients.

OBJECTIVE: This study aimed to investigate the variations of paraoxonase 1 (PON1) activity and lipid profile in patients with schizophrenia and the association of this activity with the sociodemographic, clinical and therapeutical characteristics of this population. PATIENTS AND METHODS: Our cross-sectional study included 140 schizophrenic patients and 119 control subjects aged respectively 37.3±10.4 and 41.4±10 years. PON1 activity was determined using Konelab 30™ equipment (Thermo Electron Corporation). Plasma total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (c-HDL) and low-density lipoprotein cholesterol (c-LDL) concentrations were determined using Cobas 6000™ (Roche Diagnostics), apolipoproteins (ApoA1, ApoB) and lipoprotein (a) (Lp(a)) were determined using Integra 400 plus (Roche Diagnostics). RESULTS: Compared to controls, patients had no significant decrease of PON1 activity and significantly lower ApoA1, c-HDL levels, and significantly higher levels of TG, ApoB, Lp(a) and TC/c-HDL and ApoB/ApoA1 ratios. Furthermore, PON1 activity was correlated with TG/c-HDL ratio. The lowest PON1 activity was noted in obese patients, in paranoid sub-type and in patients treated with combination of typical and atypical antipsychotics without significant difference. Moreover, it was associated with gender and cigarette smoking but not with alcohol consumption status. CONCLUSION: Schizophrenic patients had a decrease in PON1 activity and perturbations in their lipid profiles that contribute to increase the risk of cardiovascular diseases. In addition, our results revealed that there was no association between the decrease of PON1 activity and any demographic or clinical characteristics. Therefore, such patients require specific care, particularly with regard to their lipid profile.

Association between serum cystatin C levels and cardiovascular disease in type 2 diabetic patients.

Serum cystatin C concentration was recently reported as a marker of cardiovascular disease (CVD). In the present study, we evaluated the association between the increase of serum cystatin C levels and the risk of CVD in type 2 diabetes. 42 patients with type 2 diabetes were included in the present study; 27 of them have CVD. The control group consisted of 30 healthy adults. Cystatin C, creatinine, microalbuminuria and CRP were measured on Cobas 6000(TM). Cystatine C level was significantly higher in patients with CVD. A significant difference in serum cystatin C was found in patients with and without CVD among albuminuria. No difference in serum cystatin C levels was found according to number of affected vessels. A cystatin C level above 1.10 mg/L was associated with increase of risk of CVD with significant difference (OR = 42.52; IC 95% 1.455 to 1242.827 and p = 0.029). Our results suggested that the increase of serum cystatin C concentrations is a potential marker for CVD in diabetes.

[Plasma cholinesterase activity in hepatic diseases]. / Étude de l'activité de la cholinestérase plasmatique au cours des atteintes hépatiques.

Plasma cholinesterase activity (ChE) may vary in some pathological circumstances. We studied the changes in activity of this enzyme according to the type of liver injury, to assess the interest of this parameter in the diagnosis of liver diseases. Our study was performed on 102 patients with different liver diseases and 53 healthy controls. The ChE activity was lower in patients compared to control group (p < 0.0001), and more pronounced in cirrhotic patients compared to those suffering from hepatitis. Elevated activities of AST, ALT, GGT and ALP and bilirubinemia, and decreased albuminemia were noted in patients compared to controls (p < 0.001). Hypoalbuminemia was significantly important in cirrhotic patients compared to those suffering from cholestasis or hepatitis. A correlation between ChE and bilirubin, albumin and serum protein was found in patients with cirrhosis or those with chronic hepatitis. A significantly lower activity of ChE was found in patients with hepatic insufficiency (HI). In case of suspicion of HI, the prescription of ChE activity could guide or confirm the diagnosis of the impairment.

Association of PON1 and PON2 polymorphisms with PON1 activity and significant coronary stenosis in a Tunisian population.

PON1 and PON2 have attracted considerable attention as candidate genes for coronary heart disease because their enzymes function as key factors in lipoprotein catabolism pathways. We studied the distribution of PON1 and PON2 polymorphisms, including genotyping, lipid profile, and PON1 activity, and their association with PON1 activity and significant coronary stenosis (SCS) in a Tunisian population. PON1 activity was lower in patients with SCS than in controls. It increased with the R allele (QQ < QR < RR) in PON1-192 genotypes and with the L allele (MM < ML < LL) in PON1-55 genotypes. In the presence of metabolic syndrome and diabetes, PON1-192RR and PON2-311CC were associated with an increased risk of SCS and PON1-55MM seems to have lower risk. This association was evident among nonsmokers for PON1-55MM and among smokers for PON1-192RR and PON2-311CC. The GTGC haplotype seemed to increase the risk of SCS compared with the wild haplotype in a Tunisian population.

LC-ESI-MS quali-quantitative determination of phenolic constituents in different parts of wild and cultivated Astragalus gombiformis.

High-performance liquid chromatography electrospray ionization mass spectrometry (LC-ESI-MS) profiling of the MeOH extract of Astragalus gombiformis Pomel (Fabaceae) aerial parts guided the isolation of seven phenolic compounds among which 7-methylquercetin 3-O-α-l-rhamnopyranosyl-(1→2)-ß-D-galactopyranoside (2) and 7-methylquercetin 3-O-α-L-rhamnopyranosyl-(1→2)-[6-O-(3-hydroxy-3-methylglutaryl)-ß-D-galactopyranoside] (7) whose structures were elucidated by NMR and ESI-MS experiments. The radical scavenging activities of isolated compounds were investigated, by using the TEAC assay. Furthermore quantitative analyses were performed by LC-ESI-MS and applied to the comparative profiling of different parts (aerial parts, leaves and stems) of cultivated and wild A. gombiformis samples, confirming the interest of these compounds as markers of the species. Finally, a Principal Component Analysis was carried out in order to highlight the differences between different parts of cultivated and wild plants.

Biological and chemical study of Astragalus gombiformis.

Extracts of aerial parts and roots of wild Astragalus gombiformis Pomel were tested for their antibacterial, antioxidant, and insecticidal activities and contents of phenolic compounds. Antibacterial activity was tested by the paper disk agar diffusion method and determination of the minimal inhibitor concentration. Among the tested extracts, three extracts (methanol, chloroform, and ethyl acetate) from aerial parts and two extracts (water, methanol) from roots exhibited diameters of inhibition zone equal or above 12 mm (at 150 microg/ disk) and minimal inhibitor concentrations ranging between 233 and 1250 microg/ml. Spectrophotometric and HPLC analyses showed that contents of both total polyphenols and flavonoids, as well as antioxidant activity were higher in the methanolic extract of aerial parts as compared to roots. No insecticidal activity of the extracts of the aerial parts was found against Culex pipiens.

In vitro effects of three antidepressant drugs on plasma paraoxonase activity.

BACKGROUND: Paraoxonase 1 (PON1) is important in organophosphates and xenobiotic metabolism and as an antioxidant bio-scavenger. PON1 activity was shown to significantly decrease in depressed patients after antidepressant treatment instauration. Our aim was to investigate the in vitro inhibitory effects of three antidepressants (imipramine, amitriptyline and fluoxetine) on PON1 activity. METHODS: Plasma from healthy volunteers was spiked with antidepressant drugs. The working solutions were then diluted with plasma to obtain concentrations that covered the therapeutic margin. PON1 was tested by a kinetic method in triplicate after incubation at 37°C for 2 h. RESULTS: Tricyclic antidepressants significantly inhibited PON1. Fluoxetine had no effect. The inhibition percentage for imipramine was 15.6% at 100 µg/L after incubation for 1 h (131±1 vs. 155±2 IU/L; p<0.01). At 350 µg/L, the inhibition percentage for imipramine 19.2% after 1 h and 20.2% after 2 h. Amitriptyline was a stronger inhibitor: 26% after 30 min at 125 µg/L. At 250 µg/L, the inhibition percentage for amitriptyline was 36.5% after 30 min (100±4 vs. 159±2 IU/L; p<0.01). CONCLUSIONS: The tested tricyclic antidepressants significantly inhibit PON1 activity in a concentration-dependent manner. Amitriptyline had a higher inhibition potency than imipramine.

Interference of tobacco smoke with immunochromatography assay for urinary drug detection.

BACKGROUND: This study aimed to evaluate the interference of tobacco smoke on immunochromatography assay of urinary drug detection. METHODS: Our study included 256 voluntary subjects (143 passive smokers and 113 current smokers). Cotinine was measured by immunoenzymatic method and thiocyanates (SCN(-)) by selective electrode. Urinary drug was detected by immunochromatography assay. A positive result is completed by an analytical method with an immunometric assay. RESULTS: False positive results for benzodiazepines are significantly more frequent in smokers compared with passive smokers (90.2% Vs 22.4%; χ(2) = 116.62, p < 10(-3)). For smokers, the number of cigarettes was significantly higher in subjects with falsely positive results for benzodiazepines compared with subjects with negative results (32 ± 11 Vs 20 ± 10; p = 0.04). Between these two groups, we established a significant difference for urinary cotinine (345 ± 211 Vs 117 ± 54 µg/µmol; p < 10(-3)) and for plasma SCN(-) (101.6 ± 3.4 Vs 98.8 ± 2.1 µmol/L; p = 10(-3)). Urinary cotinine and consumption duration present the highest values of areas under curves (AUC) of the receiver-operating-characteristic (ROC) curves. The cut-off of 167.6 µg/µmol and 10.5 years were found as predictive factors of false positive results. CONCLUSION: Tobacco smoke interferes with immunochromatography assay of urinary drug detection; therefore, all subjects must be questioned about their smoking status to avoid such false results during results interpretation.