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This study aimed to assess the efficacy of Nitraria retusa extract (NRE) in reducing weight, body mass index (BMI), body fat composition (BF), and anthropometric parameters among overweight/obese women, comparing the results with those of a placebo group. Overweight/obese individuals participated in a 12-week, double-blind, randomized, placebo-controlled trial. Body weight, BMI, body composition, and anthropometric parameters were assessed. Additionally, lipid profile and safety evaluation parameters were evaluated. Compared to the placebo group, the NRE group exhibited a mean weight loss difference of 2.27 kg (p < 0.001) at the trial's conclusion. Interestingly, the most significant weight reduction, amounting to 3.34 kg ± 0.93, was observed in younger participants with a BMI > 30.0. Similarly, BMI and BF% significantly decreased in the NRE group, contrary to the placebo group (p = 0.008 and p = 0.005, respectively). The percentage of body water (BW) (p = 0.006) as well as the ratio of LBM/BF (p = 0.039) showed a significant increase after the NRE intervention compared to the placebo. After age adjustment, all variables, except LBM/BF, retained statistical significance. Additionally, all anthropometric parameters were significantly reduced only in the NRE group. Most importantly, a significant reduction in Triglyceride (TG) levels in the NRE group was revealed, in contrast to the placebo group (p = 0.011), and the significance was still observed after age adjustment (p = 0.016). No side effects or adverse changes in kidney and liver function tests were observed in both groups. In conclusion, NRE demonstrated potent antiobesity effects, suggesting that NRE supplementation may represent an effective alternative for treating obesity compared to antiobesity synthetic drugs.
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Fármacos Antiobesidad , Magnoliopsida , Obesidad , Extractos Vegetales , Femenino , Humanos , Fármacos Antiobesidad/uso terapéutico , Composición Corporal , Índice de Masa Corporal , Método Doble Ciego , Obesidad/tratamiento farmacológico , Sobrepeso/tratamiento farmacológico , Proyectos Piloto , Extractos Vegetales/uso terapéutico , FitoterapiaRESUMEN
In the present study, we aimed to explore the feasibility, compliance, and potential benefits of Nitraria retusa extract (NRE) intervention in both healthy (BMI ≤ 24.9 Kg/m2) and overweight/obese adults (BMI > 25 Kg/m2). A total of 98 participants, including 37 healthy individuals and 61 overweight/obese adults, were randomly assigned to either a low-dose (500 mg/day) or a high-dose (2000 mg/day) NRE intervention group. Plasma lipid biomarkers, liver and kidney functions, general hematology, and blood glucose levels were measured at the baseline and 10 days after intervention. While the lipid profile of the healthy participants did not show any statistically significant changes, the obese participants in the high-dose group experienced a significant decrease in triglyceride levels (within-group difference p value = 0.004) and an increase in HDL levels (within-group p value < 0.001). No significant differences were observed in other parameters, indicating that NRE at the given doses was safe. Furthermore, the study had impressive compliance and acceptability, with over 90% of participants completing the intervention and diligently following the study protocol. This pilot study represents the first investigation into the feasibility, acceptability, and potential benefits of NRE intervention on lipid profiles in human volunteers.
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Magnoliopsida , Sobrepeso , Adulto , Humanos , Proyectos Piloto , Obesidad , Lípidos , TéRESUMEN
Background: Rosmarinus officinalis L.is traditionally used as an infusion in the treatment of several diseases and in particular against neuropsychiatric disorders, such as anxiety and depression. It was established that rosemary extracts show an antidepressant effect on animal models. However, to the best of our knowledge, there is no scientific data that highlights the therapeutic effects of rosemary intake on human mental health.Aim: This study investigated whether rosemary tea consumption affects the plasma levels of anxiety and depression biomarkers in healthy volunteers.Methods: Twenty-two healthy volunteers aged between 20 and 50 years old consumed rosemary tea prepared from 5 g of dried rosemary in 100 mL boiled water once a day for 10 days. Plasma concentrations of Brain-Derived Neurotrophic Factor (BDNF), Interleukine-6 (IL-6), Interleukine-4 (IL-4), Tumor Necrosis Factor- alpha (TNF-α), Interferon-gamma (IFNÏ), and cortisol were measured by enzyme-linked immunosorbent assay using commercial ELISA kits (R&D systems) before rosemary consumption and at the end of the experiment.Results: Rosemary tea consumption significantly increased the concentration of BDNF([BDNF]D0 = 22363.86 ± 12987.66 pg/mL, [BDNF]D10 = 41803.64 ± 28109.19, p = 0.006) and TNF-α([TNF-α] D0 = 39.49 ± 14.44 pg/mL, [TNF-α] D10 = 56.24 ± 39.01, p = 0.016). However, a slight variation that was statistically non-significant in INFÏ, cortisol, IL-4, IL-6 levels and in the ratio IL-4/INFÏ was observed (p > 0.05).Conclusion: Our findings highlight the promising anxiolytic and/or antidepressant effects of rosemary tea consumption in healthy volunteers since it increases the level of the most reliable depression biomarker BDNF. However, more powerful studies with larger sample size, carefully-chosen target population and, an extended intervention period are required.
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Rosmarinus , Animales , Antidepresivos/uso terapéutico , Ansiedad/tratamiento farmacológico , Biomarcadores , Factor Neurotrófico Derivado del Encéfalo , Depresión/tratamiento farmacológico , Voluntarios Sanos , Humanos , Hidrocortisona , Interleucina-4 , Interleucina-6 , Proyectos Piloto , Té , Factor de Necrosis Tumoral alfaRESUMEN
INTRODUCTION: GST non-functional genotypes can lead to the accumulation of toxic intermediates, resulting in liver damage and increasing susceptibility to ATDH. AIM: To investigate the impact of GST Mu (GSTM1), GST Theta (GSTT1) null genotypes, and GST Pi (GSTP1; adenosine (A) > guanine (G), rs1695) variant allele on the development of ATDH in Tunisian patients treated with anti-tuberculosis therapy. METHODS: This was a case-control study including patients receiving anti-tuberculosis regimen. Cases (n = 23) were tuberculosis patients presenting ATDH during two months of anti-tuberculosis drug therapy. Controls (n = 30) were patients treated for tuberculosis, but presenting no ATDH. Genotyping was performed using a polymerase chain reaction-restriction fragment length polymorphism. RESULTS: No statistically significant association was observed between GSTM1 and GSTT1 homozygous null genotypes, and the risk of ATDH. A statistically significant association between GSTM1 and GSTT1 double null genotypes, and the risk of ATDH was found (p = 0.033) between cases and controls. For GSTP1, the distribution of GG homozygous mutant genotype was significantly associated with ATDH compared with the wild and the transition A to G (AA + AG) genotypes. CONCLUSION: Double deletion of GSTM1 and GSTT1 may predispose to ATDH in a Tunisian population. Moreover, GSTP1 rs1695 (A > G) genotyping can predict susceptibility to developing ATDH.
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Antituberculosos/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Gutatión-S-Transferasa pi/genética , Glutatión Transferasa/genética , Adulto , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Variantes Farmacogenómicas , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , TúnezRESUMEN
INTRODUCTION: neffa, a form of air-dried smokeless tobacco used in North Africa, is spuriously perceived as a lower risk alternative to smoking. The objective of this study was to provide information on some harmful constituents of neffa and to use them for cancer risk assessment. METHODS: a high-performance liquid chromatography method coupled with fluorescence detector was used to determine polycyclic aromatic hydrocarbons (PAHs) in one sample of neffa. An atomic absorption spectrometry was performed to determine the concentrations of lead and cadmium in three samples of neffa. The levels of toxicants found in neffa were used to assess for lifetime cancer risk as advocated by the US Environment Protection Agency. RESULTS: the determination of PAHs in neffa allowed the identification of phenanthrene and anthracene. However, the higher molecular weight PAHs such as Benzo(a)Pyrene B(a)P were not detected. The concentrations of cadmium and lead varied between 1.3 to 2.8µg/g and 1.7 to 4.6µg/g respectively. Cancer risk for cadmium and lead varied between 4.2E-03 to 9.3E-03 and 2.5E-06 to 6.4E-06 respectively. Cancer risk for Cd exceeded the range of 10E-04 to 10E-06 of an acceptable risk. CONCLUSION: neffa is not a healthy alternative for overcoming smoking addiction. It contains mineral and organic pulmonary toxicants. This study could serve as a scientific basis to inform consumers about the products´ toxicity and help them to quit smokeless tobacco (SLT) use.
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Neoplasias/etiología , Hidrocarburos Policíclicos Aromáticos/análisis , Tabaco sin Humo/análisis , Cadmio/análisis , Carcinógenos/análisis , Carcinógenos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Humanos , Plomo/análisis , Hidrocarburos Policíclicos Aromáticos/aislamiento & purificación , Medición de Riesgo , Espectrofotometría Atómica , Uso de Tabaco/efectos adversos , Tabaco sin Humo/efectos adversos , TúnezRESUMEN
Rosmarinus officinalis L. is a widespread aromatic plant commonly consumed as a tea in traditional cuisine and in folk medicine to treat various illnesses due to its therapeutic properties. To the best of our knowledge, there are no reports on the bioavailability and metabolism of R. officinalis tea polyphenols in humans. This study was aimed at assessing the bioavailability and nutrikinetics of R. officinalis phenolic compounds in healthy humans for the first time. Forty-eight compounds were identified in plasma and urine. Few un-metabolized compounds were detected since rosemary polyphenols were extensively metabolized into phase II conjugates, with rapid appearance and clearance in plasma, pointing to small intestinal absorption. Phase II derivatives of caffeic acid showed kinetics compatible with both intestinal and colonic hydrolysis of rosmarinic acid yielding free caffeic and 3,4-dihydroxyphenyl-lactic acids, which were absorbed and metabolized into phase II derivatives. These metabolites, along with reduced forms of caffeic acid and their phase II metabolites, and those of hydroxyphenylpropionic, hydroxylphenylacetic, benzoic and hippuric acids, highlight the importance of colonic absorption. Total urinary excretion of the phenols added up to 235 µmol, corresponding to 22.3% of the ingested amount (1055 µM). In conclusion, rosemary tea polyphenols are partially bioavailable and extensively metabolized, mainly by the colonic microbiota.
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Rosmarinus , Disponibilidad Biológica , Humanos , Fenoles , Polifenoles , TéRESUMEN
BACKGROUND: Thyroid metabolism involves iodine, which allows us to use radioactive iodine for diagnostic and therapy purposes. The efficiency of radioiodine therapy depends on several parameters; the ability of thyroid tissue to uptake radioactive iodine is one of them. OBJECTIVE: The objective of this work is to quantify the radioactive iodine uptake on thyroid tissue. METHODS: In this work, we developed a method to quantify the in vivo uptake of iodine-131 on sections of thyroid glands removed by thyroidectomies. We performed an analysis of histological sections of the thyroid tissue by beta imaging. We had the opportunity to quantify the fixed radioactivity and to analyze its distribution in the thyroid gland, thanks to the good spatial resolution available with the type of detector used. RESULTS: The results gave a high image resolution showing the heterogeneity of iodine-131 fixation by the thyroid tissue. We were able to quantify the tissue radioactivity in mega Becquerel (MBq) per volume unit. CONCLUSION: This work has shown that the direct quantification of the thyroid tissue uptake is possible using the beta imaging system.
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Yodo , Neoplasias de la Tiroides , Humanos , Yoduros , Radioisótopos de YodoRESUMEN
AIM AND OBJECTIVE: Parkinson's disease (PD) is the second most common neurodegenerative disease. It is a multifactorial disorder (caused by aging, environmental, and genetic factors). Metabolomics can help explore the biomarker profiles for aging. Recent studies showed an association between the glutathione S-transferases (GSTs) polymorphisms and PD risk. The purpose of this study was to evaluate the association of this genetic polymorphism and the metabolomic profile in PD Tunisian patients, in order to identify effective biomarkers in the genetic differentiation. MATERIALS AND METHODS: In this study, the metabolomic profile changes related to GSTs polymorphism were searched in 54 Tunisian PD patients treated with L-dopa, using a gas chromatography-mass spectrometry (GC-MS) technique. RESULTS: The study results showed that mannose, methyl stearate, and three other unknown metabolites, increased in patients with GSTM1 positive genotype, while glycolic acid, porphine, monomethyl phosphate, fumaric acid, and three other unknown metabolites decreased in patients with GSTM1 positive genotype. Subsequently, the levels of glycolic acid, erythronic acid, lactic acid, citric acid, fructose, stearic acid, 2-amino-2-methyl-1,3-propanediol and three other unknown metabolites increased in patients with GSTM1 positive genotype, while the levels of proline, valine and two unknown metabolites decreased with GSTT1 positive genotype. CONCLUSION: All these altered metabolites are related to energy metabolism and it can be concluded that GSTs polymorphism based the shifting in energy metabolism and led to oxidative stress.
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Glutatión Transferasa/metabolismo , Metabolómica , Enfermedad de Parkinson/metabolismo , Anciano , Biomarcadores/análisis , Biomarcadores/metabolismo , Femenino , Cromatografía de Gases y Espectrometría de Masas , Glutatión Transferasa/genética , Humanos , Masculino , Enfermedad de Parkinson/genética , Polimorfismo Genético/genética , TúnezRESUMEN
Introduction:Laurus nobilis is known in the field of herbal medicine and in vitro studies that it has beneficial effects such as antibacterial, antifungal, antidiabetes, and anti-inflammatory properties.Objective: We investigated whether L. nobilis tea consumption affects the plasma levels of lipid biomarkers in healthy volunteers.Methods: Thirty healthy Tunisian volunteers aged between 20 and 57 years old consumed L. nobilis infusion, prepared from 5 g of dried L. nobilis leaves in 100 ml boiled water, once a day during 10 days. Plasma concentrations of serum low-density lipoprotein (LDL) cholesterol, triglycerides and HDL (high-density lipoprotein) cholesterol were measured by Beckman Coulter D × 600 analyzer before L. nobilis consumption and at the end of the experiment.Results:L. nobilis tea consumption significantly increased the concentration of HDL cholesterol ([HDL cholesterol] D0 = 1.34 ± 0.25 pg/mL, D11=1.42 ± 0.29, p = 0.01). However, a slight decrease that was statistically non-significant in LDL cholesterol and triglycerides levels was observed (p < 0.05).Conclusions: These findings highlight the improving blood lipidic profiles, which means a possible positive effect on reducing the risk of cardiovascular disease of L. nobilis tea consumption in healthy volunteers. However, more powerful studies with an extended treatment period are required.
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HDL-Colesterol/sangre , LDL-Colesterol/sangre , Laurus , Tés de Hierbas , Triglicéridos/sangre , Adulto , Biomarcadores/sangre , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Hojas de la Planta , TúnezRESUMEN
Poisoning and accidental oral intoxication are major health problems worldwide. Considering the insufficient efficacy of the currently available detoxification treatments, a pioneering oral detoxifying adsorbent agent based on a single biocompatible metal-organic framework (MOF) is here proposed for the efficient decontamination of drugs commonly implicated in accidental or voluntary poisoning. Furthermore, the in vivo toxicity and biodistribution of a MOF via oral administration have been investigated for the first time. Orally administered upon a salicylate overdose, this MOF is able to reduce the salicylate gastrointestinal absorption and toxicity more than 40-fold (avoiding histological damage) while exhibiting exceptional gastrointestinal stability (<9% degradation), poor intestinal permeation, and safety.
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Antídotos/uso terapéutico , Aspirina/envenenamiento , Sobredosis de Droga/prevención & control , Estructuras Metalorgánicas/uso terapéutico , Administración Oral , Adsorción , Animales , Antídotos/administración & dosificación , Antídotos/metabolismo , Antídotos/toxicidad , Aspirina/sangre , Aspirina/química , Aspirina/orina , Femenino , Absorción Gastrointestinal/efectos de los fármacos , Yeyuno/patología , Hígado/patología , Estructuras Metalorgánicas/administración & dosificación , Estructuras Metalorgánicas/metabolismo , Estructuras Metalorgánicas/toxicidad , Ratas Wistar , Estómago/patología , Distribución TisularRESUMEN
BACKGROUND: The aim of this study was to evaluate whether the glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) null alleles may contribute to carbamazepine-induced hepatotoxicity. METHODS: A cross-sectional prospective study was conducted to identify the frequency distribution of GSTM1 and GSTT1 alleles in 129 Tunisian epileptic patients treated with carbamazepine. Null alleles were determined using a Polymerase Chain Reaction. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured by standard methods. RESULTS: Our results showed that the frequencies of GSTM1 (-) null allele and GSTT1 null (-) allele were 74.4 and 17.8% respectively. The ALT and AST levels were elevated in 46 (35.7%) and 33 (25.6%) cases. The mean values of ALT and AST were approximately 1.32 and 3.61 times higher than the upper limit of normal levels, respectively. The values of ALT and AST were significantly higher in GSTM1 (-) allele than in GSTM1 (+) (p = 10-3.and 0.004, respectively). The level of ALT was significantly higher in combination of GSTM1 (-)/T1(-) than in combined GSTM1(-)/T1(+) and combined GSTM1(+)/T1(+) (p = 0.2 and 0.03, respectively), and that of AST was significantly higher in combination of GSTM1(-)/T1(-) and in combination of GSTM1(+)/T1(-) than in combination of GSTM1(+)/T1(+) (p = 10-3 and 10-3, respectively). CONCLUSIONS: Our findings suggest that the GSTM1 (-) allele may be considered as a key factor for the development of carbamazepine-induced hepatotoxicity. Results related to GSTT (-) allele and elevation in AST levels should be considered with caution as AST may be elevated in other pathophysiological conditions.
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Carbamazepina/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Predisposición Genética a la Enfermedad/genética , Glutatión Transferasa/genética , Adulto , Alelos , Estudios Transversales , Epilepsia/tratamiento farmacológico , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Estudios Prospectivos , Factores de Riesgo , Túnez , Adulto JovenRESUMEN
BACKGROUND: Rosmarinus officinalis is an aromatic plant used in folk medicine as a result of the therapeutic properties associated with its phenolic composition, being rich in rosmarinic acid (RA) and caffeic acid (CA). To better understand the bioactivity of these compounds, their absorption and metabolism were assessed in human Caco-2 and HepG2 cells, as small intestine and liver models, respectively, using RA and CA standards, as well as a rosemary infusion and ferulic acid (FA). RESULTS: Test compounds were partially up-taken and metabolized by Caco-2 and HepG2 cells, although a higher metabolization rate was observed after hepatic incubation compared to intestinal incubation. CA was the compound best absorbed followed by RA and FA, showing metabolites percentages of 30.4%, 11.8% and 4.4% in Caco-2 and 34.3%, 10.3% and 3.2% in HepG2 cells, respectively. RA in the rosemary infusion showed improved bioavailability compared to pure RA. Methyl derivatives were the main metabolites detected for CA and RA after intestinal and hepatic metabolism, followed by methyl-glucuronidates and glucuronidates. RA was also minimally hydrolyzed into CA, whereas FA only was glucuronidated. Rosemary polyphenols followed the same biotransformation pathways as the standards. In addition, phase II derivatives of luteolin were observed. CONCLUSION: Rosemary polyphenols are partially metabolized in both the intestine and liver. © 2018 Society of Chemical Industry.
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Extractos Vegetales/metabolismo , Polifenoles/metabolismo , Rosmarinus/química , Células CACO-2 , Células Hep G2 , Humanos , Mucosa Intestinal/metabolismo , Intestinos/química , Hígado/química , Hígado/metabolismo , Modelos Biológicos , Extractos Vegetales/química , Polifenoles/química , Rosmarinus/metabolismoRESUMEN
INTRODUCTION: Rosemary (Rosmarinus officinalis L.) is an aromatic plant common in Tunisia and it is widely consumed as a tea in traditional cuisine and in folk medicine to treat various illnesses. Currently, most research efforts have been focused on rosemary essential oil, alcoholic and aqueous extracts, however, little is reported on rosemary infusion composition. OBJECTIVE: To investigate compounds present in rosemary tea obtained from Rosmarinus officinalis L. collected in a sub-humid area of Tunisia in order to assess whether the traditional rosemary tea preparation method could be considered as a reference method for rosemary's compounds extraction. METHODOLOGY: Qualitative characterisation of Rosmarinus officinalis tea obtained after rosemary infusion in boiled water was determined by high performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry (HPLC-ESI-QTOF-MS). Quantitative analysis relies on high performance liquid chromatography with diode array detector (HPLC-DAD). RESULTS: Forty-nine compounds belonging to six families, namely flavonoids, phenolic acids, phenolic terpenes, jasmonate, phenolic glycosides, and lignans were identified. To the best of the authors' knowledge eucommin A is characterised for the first time in rosemary. Rosmarinic acid (158.13 µg/g dried rosemary) was the main compound followed then by feruloylnepitrin (100.87 µg/g) and luteolin-3'-O-(2â³-O-acetyl)-ß-d-glucuronide (44.04 µg/g). Among quantified compounds, luteolin-7-O-rutinoside was the compound with the lowest concentration. CONCLUSION: The infusion method allows several polyphenols present in rosemary tea to be extracted, therefore it could be a reference method for rosemary's compounds extraction. Moreover, traditional Tunisian Rosmarinus officinalis tea consumption is of interest for its rich phenolic content. Copyright © 2017 John Wiley & Sons, Ltd.
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Bebidas/análisis , Rosmarinus/química , Clima , Glicósidos/química , Hidroxibenzoatos/química , Lignanos/química , Estructura Molecular , Polifenoles/química , TúnezRESUMEN
INTRODUCTION: The prescribed dose and carbamazepine plasma concentration to achieve the optimal therapeutic efficacy are highly variable from one patient to the other. Our study aimed to determine whether biological parameters may be used as plasma markers that can individually adjust the carbamazepine dose necessary to optimize therapeutic efficacy. MATERIAL AND METHODS: Ninety-four epileptic patients under carbamazepine monotherapy and who have never used combination therapy were recruited from the consecutive admissions at the Department of Neurology "CHU Sahloul" of Sousse Central Hospital in Tunisia from February 2010 to April 2011. The patients were monitored for epilepsy for three years on average. Carbamazepine and 10,11-epoxide-carbamazepine concentrations were analyzed through high-performance liquid chromatography. Simultaneously, therapeutic efficacy was assessed through the annual number of seizures in each patient. RESULTS: Our results showed the absence of any significant correlations between specific dose (mg/kg/day), carbamazepine plasma concentrations and therapeutic efficacy (r = 0.0025, p = 0.30; r = 0.1584, p = 0.38 respectively), whereas both plasma 10,11-epoxide-carbamazepine concentration and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with therapeutic efficacy (r = 0.34, p = 0.03; r = 0.45, p = 0.008 respectively). The optimum therapeutic response was observed among patients who simultaneously had a plasma concentration of 0.8 µg/ml of metabolite and 5.5 µg/ml of carbamazepine. CONCLUSIONS: The results suggest that plasma levels of both carbamazepine and of 10,11-epoxide-carbamazepine must be set to achieve an optimum therapeutic response.
RESUMEN
Glutathione S-transferases (GSTs) enzymes are involved in the detoxification of several endogenous and exogenous substances. In this study, we evaluated the effects of two glutathione S-transferase polymorphisms, (GSTM1 and GSTT1) on bipolar disorder (BPD) risk susceptibility in a Tunisian population. These polymorphisms were analyzed in 229 healthy subjects and 109 patients with BPD, using a polymerase chain reaction. Statistical analysis was performed using SPSS 18.0. The relative associations between the GSTs genotypes and BPD were assessed by calculating odds ratios (ORs) and 95% confidence intervals (CLs). The study results demonstrated that individuals with GSTM1 [OR=1.51, 95% CI: 0.93-2.45, p=0.081] or GSTT1 [OR=1.65, 95% CI: 0.95-2.88, p=0.060] were not associated with the risk of BPD, whereas a significant association was found between individuals with both GSTM1/T1 null genotype and BPD risk [OR=2.96, 95% CI (1.26-7.03), p=0.005]. These genotyping finding revealed that the absence of both GSTM1 and GSTT1 activity could be a contributor factor for the development of BPD.
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Trastorno Bipolar/genética , Glutatión Transferasa/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Túnez , Adulto JovenRESUMEN
The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.
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Anticonvulsivantes/metabolismo , Carbamazepina/metabolismo , Citocromo P-450 CYP3A/genética , Resistencia a Medicamentos/genética , Epilepsia/tratamiento farmacológico , Epóxido Hidrolasas/genética , Adulto , Anticonvulsivantes/uso terapéutico , Carbamazepina/uso terapéutico , Epilepsia/genética , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , TúnezRESUMEN
This study aimed to assess the relationship between plasma levels of carbamazepine and its active metabolite 10,11-epoxide-carbamazepine, and the therapeutic response in patients with bipolar disease. Thirteen patients were kept on a fixed individual dose of carbamazepine for 19 weeks under psychiatric care. Steady-state plasma concentrations of carbamazepine and its metabolite 10,11-epoxide-carbamazepine were measured at weeks 4, 12, and 20 by HPLC essay. Simultaneously, the psychopathologic state was assessed using the Brief Psychiatric rating scale (BPRS). Upon correlational analysis, mean BPRS scores did not correlate with the plasma levels of carbamazepine, whereas both mean plasma levels of 10, 11-epoxide-carbamazepine concentrations and 10,11-epoxide-carbamazepine to plasma carbamazepine ratio were closely correlated with mean values of BPRS scores (r = 0.80, p =10(-4), r= -0.89, p =10(-3) respectively). Optimum therapeutic response was observed among patients who had a plasma metabolite level of 1.4 µg/mL and a plasma carbamazepine concentrations of 7 µg/mL simultaneously. These results suggest that both plasma carbamazepine and 10,11-epoxide-carbamazepine levels must be fixed to achieve optimum therapeutic response. In order to reach these conditions, inhibitor drugs (such as valproic acid) or inductor drugs (such as phenobarbital) of epoxyde-hydrolase might be coadministered with the carbamazepine in order to adapt the plasma level of 10,11-epoxide-carbamazepine.
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Antimaníacos/farmacocinética , Antimaníacos/uso terapéutico , Trastorno Bipolar/tratamiento farmacológico , Carbamazepina/farmacocinética , Carbamazepina/uso terapéutico , Adulto , Antimaníacos/sangre , Trastorno Bipolar/sangre , Carbamazepina/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Glutathione-S-transferases enzymes are involved in the detoxification of several endogenous and exogenous substances. In this present study, we evaluated the effects of two glutathione-S-transferase polymorphisms, (GSTM1 and GSTT1) on epilepsy risk susceptibility in a Tunisian population. These polymorphisms were analyzed in 229 healthy subjects and 98 patients with epilepsy, using a polymerase chain reaction (PCR). Odds ratio (ORs) was used for analyzing results. The study results demonstrated that individuals with the GSTM1 null genotype were at an increased risk of developing epilepsy [OR=3.80, 95% confidence interval (CI) (2.15-4.78)], whereas no significant effects were observed between individuals with GSTT1 null genotype and epilepsy risk [OR=1.15, 95% CI (0.62-2.12)]. These genotyping finding revealed that the absence of GSTM1 activity could be contributor factor for the development of epilepsy disease.
Asunto(s)
Epilepsia/genética , Predisposición Genética a la Enfermedad/genética , Glutatión Transferasa/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Femenino , Glutatión Transferasa/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Túnez/epidemiología , Adulto JovenRESUMEN
Professional exposures to respirable dusts from phosphate mines are associated with the development of an inflammatory response and airways diseases. This study was performed on 12 phosphate workers versus 8 unexposed controls, including smokers and non-smokers. It consisted of assessing the incidence of phosphate dusts exposure associated or not with smoking on the plasmatic inflammatory status of phosphate mine workers versus controls. The following parameters were studied: hematological profile and plasma level of seven cytokines (IL-1ß, IL-6, IL-8, IL-10, IL-12, tumor necrosis Factor (TNF-α), macrophage inflammatory protein (MIP-1ß)) and two eicosanoids (leucotriene B-4 (LTB-4) and 15(S)-hydroxyeicosatetraenoic acid (15(S)-HETE)) measured by a multiplexed flow cytometric method (CBA: Cytometric Bead Array) or ELISA. In phosphate workers, mainly smokers, the level of white blood cells (WBCs) and lymphocytes (LYM) was significantly higher as compared with controls. This was associated with enhanced levels of IL-1ß, IL-6, IL-8, MIP-1ß, and LTB-4. In smokers (including phosphate mine workers and controls), the level of LYM was also significantly higher than in controls. Based on a logistic regression analysis, smoker phosphate mine workers have a higher relative risk than controls to have an increase concentration of some cytokines, especially IL-1ß, IL-6, IL-8, TNF-α, and MIP-1ß. Moreover, the combined effect of smoking and phosphate dusts exposure increases the level of leucocytes as well as the concentration of IL-1ß, IL-6, IL-8, MIP1-ß, and LTB-4. The present study demonstrates that phosphate dusts are able to trigger a systemic inflammatory reaction characterized by enhanced levels of circulating immunocompetent cells, plasmatic cytokines and eicosanoids, and it establishes that these side effects are enhanced by smoking.