[Drug abuse of pregabalin - state of the situation, risks and means of control]. / Détournement de la prégabaline à des fins toxicomaniaques - état de la situation, risques et moyens de lutte.

Pregabalin is an anticonvulsant widely used for the treatment of epilepsy and neuropathic pain. However, there is a growing concern about its misuse, particularly among drug users and patients with substance use disorders (SUD). It is often used in combination with other psychoactive molecules and at levels well above the recommended doses. Increasing cases of overdose and death associated with the misuse of pregabalin have been reported worldwide. Therefore, raising prescribers' awareness of this scourge is mandatory and the role of the pharmacist is crucial in reducing this phenomenon.

Evaluation of the reliability of human teeth matrix used as a biomarker for fluoride environmental pollution.

Environmental contamination by heavy metals has been a matter of great concern in many countries for several decades. Human exposure to such elements may cause adverse health effects and young children are particularly at risk. Many matrixes have been used for determination of metal exposure levels. Hard tissues such as teeth and bones have some advantages compared to other matrix. Dental tissues are considered to be suitable for long-term metal exposure due to their stability, resistance to physical and chemical degradation and their good preservation over time. Several studies have analyzed the teeth of animals for assessment the relationship between increased fluoride exposure and dental fluorosis, however few studies have been conducted on human teeth. Thus, the aim of the present study was to assess the reliability of human teeth matrix used as a biomarker for fluoride environmental pollution in Tunisia, and to evaluate the relationship with place of residence, age, dental caries and sex. Teeth samples (n=123) were collected from individuals living in Gafsa (fluoride-polluted area which inhabitants are to a great extent exposed to heavy metals) and Tunis (non polluted area). Samples were analyzed using a potentiometric method. The fluoride concentration was found to be significantly higher in teeth from Gafsa samples than those from Tunis. Their control levels were respectively 6793.1µg/g and 1068.8µg/g. The results indicate that there is a clear relation between fluoride concentration and residence of living. An increased level of dental fluorosis in fluoridated communities has been used to evaluate historical chronic exposure to fluoride in these communities, despite constant fluoride levels in the drinking-water. The fluoride concentration was also observed to be significantly increased in polluted area with age and in carious teeth whereas, no significant difference was observed for sex. Our study confirms well that human teeth used as a bioindicator for environmental pollution provide good chronological information on exposure, and highlighted the risks incurred by consumers living in such polluted area.

Determination of urinary trans, trans-muconic acid reference values in general Tunisian population.

We wish to determine the urinary trans,trans-muconic acid reference values in the Tunisian general population, and evaluate the impact of several factors (age, gender, tobacco...) on these reference values. Urine samples were collected from 182 healthy Tunisian subjects who had not been occupationally exposed to benzene. This determination was performed by solid phase extraction sampling technique together with high performance liquid chromatography-photodiode array detector. Trans,trans-muconic values ranged from 0.003 to 0.618 mg/g creatinine, the 95% reference interval was: 0.004-0.36, and the 90% confidence interval of the upper reference limit was: 0.24-0.62 mg/g creatinine. Urinary trans,trans-muconic levels were significantly higher among smokers. Significant differences were also observed for the < 20 and the > or = 40 age groups. As a result urinary trans,trans-muconic background levels allow the biomonitoring of workers occupationally exposed to benzene at levels as low as 0.5 ppm. Age and tobacco, but not gender may affect the trans,trans-muconic reference values.

Serum levels of ochratoxin A in healthy subjects and in nephropathic patients in Tunisia.

Ochratoxin A is a fungal toxin produced by Aspergillus and Penicillinium. These Fungi oftenly contaminate plant-derived products, and can generate deleterious toxic effects in man. In this study, ochratoxin A was determined in human serum samples collected in Tunisia, using high performance liquid chromatography (HPLC) and fluorescence detection. The samples were collected from healthy subjects (n = 105) as well as from patients with various kidney disorders. Five different kinds of kidney disorders were represented: transplanted subjects (27), patients with Chronic Interstitial Nephropathy (22) of known etiology, Chronic Vascular Nephropathy (26), Chronic Glomerular Nephropathy (26) or Chronic Interstitial Nephropathy (30) of unknown etiology. Mean concentrations of ochratoxin A in the healthy group was 0.49+/-0.79 ng/mL. The highest mean concentration of ochratoxin A was found in group of Chronic Interstitial Nephropathy of unknown etiology 1.25+/-1.22 ng/mL. Significant differences were also observed according to the geographic origin of healthy subjects and nephropthic patients within Tunisia.

Fast screening tests for the simultaneous detection of 11 drugs of abuse in urine specimens. A forensic epidemiology study of 28,298 cases in Tunisia.

Forensic investigation performed on people suspected to be drug abusers covering all Tunisian cities was conducted by monitoring an epidemiological study of human urine samples surveying positive rates of consumption for drugs of abuse. The forensic investigations were conducted on a total of 28,298 arrested individuals suspected to be drug addicts during five years (January 2010-December 2015). An immunoassay screening tests to detect elevated levels of drugs classes in urine samples was performed. These screening assays provide a preliminary qualitative test result. Only positives urine specimens were analyzed with GC-MS for confirmation. Except for cannabis, the results showed insignificant number of positive cases for cocaine, ecstasy (MDMA) and amphetamine consumptions (<1%).

Urinary levels of bisphenol A, benzophenones and parabens in Tunisian women: A pilot study.

Bisphenol A (BPA), benzophenones and parabens are commonly used in the production of polycarbonate plastics, as UV-filters and as antimicrobial preservatives, respectively, and they are thought to exhibit endocrine disrupting properties. Exposure to these compounds remains poorly characterized in developing countries, despite the fact that certain behaviors related to westernization have the potential to influence exposure. The aim of this pilot study was to measure urinary concentrations of BPA, six different benzophenones and four parabens in 34 Tunisian women. In addition, we identified some socio-demographic and dietary predictors of exposure to these compounds. Chemical analyses were carried out by dispersive liquid-liquid microextraction (DLLME) and ultra-high performance liquid chromatography with tandem mass spectrometry detection (UHPLC-MS/MS). Detection frequencies of methylparaben (MP), ethylparaben (EP) and propylparaben (PP) ranged between 67.6 and 94.1%. Butylparaben (BP) was found in 38.2% of the analyzed samples; BPA in 64.7%; and benzophenone-1 (BP-1) and benzophenone-3 (BP-3) were detected in 91.2 and 64.7% of the analyzed samples, respectively. Urinary geometric mean concentrations of MP, EP, PP, and BP were 30.1, 1.4, 2.0 and 0.5ngmL(-1), respectively. Geometric mean concentrations of BPA, BP-1, and BP-3 were 0.4, 1.3 and 1.1ngmL(-1), respectively. Our results suggest that Tunisian women are widely exposed to BPA, parabens and some benzophenones. Further studies on the general Tunisian population are needed in order to assess the levels of exposure to these compounds and to identify sources of exposure and population groups at higher risk.

Lead and cadmium concentrations in seawater and algae of the Tunisian coast.

Both lead and cadmium are toxic trace metals, even in very weak concentrations. The aim of this study was to estimate lead and cadmium pollution in various sites of the Tunisian coast and to verify the possibility of modification of the algae bioconcentration power according to water physico-chemical conditions. Our study concerned 99 samples of algae and 99 samples of seawater, taken in different sites of the Tunisian littoral. The analysis was realized by atomic absorption spectrophotometry (oven graphite). In algae, Sfax site presented the highest concentrations of lead when Sousse site showed the lowest ones. In seawater, the most amounts of lead were observed in Bizerte, Mahdia and Sfax sites, and those of cadmium in Bizerte and Medenine coasts. Bizerte's coast seems to be the most exposed zone to pollution. Indeed, the intensification of sea traffic may take place on this pollution because hydrocarbons derived from petroleum contain some tetraethylic lead characterised by its great toxicity. Sousse's region is the least polluted zone; it might be due to the development of tourism and a strict regulation of pollution in this district.

Toxic Effects of Rhamnus alaternus: A Rare Case Report.

In Tunisia, there are about 478 species of plants commonly used in folk medicine. Medicinal plants and herbal remedies used are responsible for 2% of intoxications listed by Tunisian National Poison Center. Most cases are related to confusion between edible plants and toxic plants lookalikes or to an excessive consumption of therapeutic plants. We report the case of a 58-year-old man admitted to the Emergency Department of the Regional Hospital of Zaghouan (Tunisia), with renal failure and rhabdomyolysis. The patient reported having daily consumption of a homemade tea based on Mediterranean Buckthorn roots, during the last 6 months to treat type 2 diabetes. The aim of this work was to establish an association between the consumption of the herbal remedy and the occurrence of both renal failure and rhabdomyolysis. No similar cases have been reported in recent literature.

[Zincemia, cupremia and infection in malnourished children]. / Zincémie, cuprémie et infection chez l'enfant malnutri.

BACKGROUND: Serum copper and zinc levels are decreased in malnourished and infected children. The role of either malnutrition or infection remains undetermined. POPULATION AND METHODS: Serum zinc and copper concentrations were measured by atomic absorption spectrophotometry in 31 malnourished infants aged 1 to 26 months and 28 eutrophic infants aged 3 to 22 months. Fourteen infants of the first group and 10 of the second were infected at the time of study. RESULTS: Serum zinc and copper levels were significantly decreased in infants with malnutrition (zinc: 66 +/- 32 micrograms/dl and copper: 81 +/- 51 micrograms/dl versus 108 +/- 26 and 185 +/- 21, respectively, in eutrophic infants) (p < 0.001). These levels were still lower in those malnourished infants who were infected (zinc: 49.5 +/- 18 micrograms/dl and copper: 63.5 +/- 37 micrograms/dl versus 81.56 +/- 35 and 94 +/- 56 in non infected patients) (p < 0.02). CONCLUSIONS: Infection increases the risk of low serum zinc and copper concentrations seen in malnourished children. This factor must be taken in account when treating malnutrition.

[Graded classification of acute chloralose poisoning. 509 cases]. / Classification en grades des intoxications aiguës par le chloralose. 509 cas.

OBJECTIVE: The annual incidence of chloralose poisoning has exceeded 3 cases per 100,000 inhabitants in Tunisia since 1997. The purpose of this study was to analyze clinical features of chloralose poisoning. METHODS: We reviewed patients admitted to the intensive care unit during the last 5 years to search for chloralose poisoning. The identified cases were classed into 5 grades by clinical features: depth of coma, characteristics of the myoclonia, and cerebral trunk reflex response. RESULTS: We identified 509 cases of chloralose poisoning over the last 5 years. Seventy-five patients (14.7%) were in grade 1: drowsiness alone. Four hundred ten patients (80.8%) were in grades 2 and 3: hypertonic coma and myoclonus. The clinical course was favorable after sedation, tracheal intubation and mechanical ventilation. Twenty-three patients (4.6%) were in grades 4 and 5: hypertonic coma (Glasgow coma score = 3). Three of them died. CONCLUSION: The clinical features of chloralose poisoning depend on the ingested dose. Despite the gravity of the initial clinical presentation, prognosis is excellent if symptomatic treatment is given early, even in grade 5 cases which simulate brain death.

[Acute self-induced poisoning with carbamazepine]. / Intoxication aiguë volontaire par la carbamazépine.

OBJECTIVE: We report the epidemiological, clinical, toxicological and therapeutic aspects of acute voluntary intoxication with carbamazepine. PATIENTS AND METHODS: The study included 17 cases of acute carbamazepine intoxication in patients hospitalized in our toxicology unit. RESULTS: Neurological signs predominated at admission, mainly agitation or coma associated with seizures. Mydriasis and cardiovascular signs were frequent. Blood chemistry most frequently showed hyponatremia. Mean serum carbamazepine level admission was 24 mg/l (range 4 ñ 12 mg/l). Ten patient required respiratory assistance for 28 +/- 17 hours. Symptomatic treatment and gastric lavage (+activated carbon) provided favorable outcome. CONCLUSION: Acute carbamazepine intoxication is seen with increasing frequency. Severity is related to the degree and duration of the coma, respiratory depression, seizures, cardiovascular disorders, and metabolic abnormalities. Symptomatic and specific treatment with activated carbon are required.

[Study of anti-lithogenic action of zinc sulfate in experimental lithiasis in the rat]. / Etude sur l'action anti-lithogène de sulfate de zinc vis-à-vis de la lithiase expérimentale chez le rat.

Sodium oxalate injected into young rats, via the intraperitoneal route, at a dose of 8 mg per 100 g of body weight, induced death in 50 p. cent of animals, and induced calcium oxalate crystals in renal tissue. When a zinc solution was administered prior to sodium oxalate, at the dose of 12 micrograms/100 g of body weight, the mortality rate decreased, and at the same time oxalate and calcium deposits were significant reduced (respectively P less than 0.01; P less than 0.01). The same results were found when zinc was administered at 24 micrograms/100 g of body weight, however, oxalic accumulation was found to be significantly lower in this group than in the group treated at 12 micrograms. This protection against calcium oxalate deposits was complete in the animals treated with various doses of zinc, because compared to reference animals, which received distilled water, calcium accumulation in these groups was not different and oxalate accumulation was also found to be lower (respectively P less than 0.05; P less than 0.001). Microscopic examination showed calcium crystals only in the group treated with sodium oxalate, localized preferentially in the renal papilla. All these experiments conclude on the total inhibitory effect of zinc on experimental lithiasis induced by oxalic acid, even though it was administered at a dose of only 12 micrograms/100 g of body weight.

[Comparative study between the anti-lithogenic action of zinc and copper against oxalic lithiasis in the rat]. / Etude comparative entre l'action anti-lithogène du zinc et du cuivre vis-à-vis de la lithiase oxalique chez le rat.

Intraperitoneal injection of sodium oxalate, at the dose of 8 mg/100 g of body weight, induced into rats oxalate and calcium deposits in renal tissue, compared to animals which received distilled water (respectively P less than 0.05; P less than 0.05). However, when a zinc solution was administered previously, at the dose of 24 micrograms/100 g of body weight, oxalate and calcium accumulation was found to be significantly lower than in the group treated exclusively with sodium oxalate. Similar results were found when the metal used was copper, but oxalate accumulation was found to be significantly higher in this group than in the group treated with zinc (P less than 0.01). Compared to reference animals, which received distilled water, oxalate accumulation was found to be significantly decreased in the groups treated with both zinc (P less than 0.001) and copper (P less than 0.01), whereas calcium accumulation was found to be similar. Microscopic examination showed calcium crystals only in the group treated with sodium oxalate, preferentially localized in the renal papilla. These results suggest that zinc and copper, when administered at the dose of 24 mu/100 g of body weight, completely protect against experimental lithiasis induced by oxalic acid. However, the inhibitory effect of zinc was more pronounced than that of copper, especially against oxalate accumulation.

[The effects of high-dose ascorbic acid administration on the factors of lithogenesis in the rat]. / Effets de l'administration de fortes doses d'acide ascorbique sur les facteurs de la lithogenèse chez le rat.

Administration of ascorbic acid, at 150 mg/100 ml of water intake, for one month, induced hyperoxaluria in the rats (P less than 0.001) and decreased citraturia (P less than 0.001) magnesuria (P less than 0.001) and pyrophosphaturia (P less than 0.01). The same disorders were observed when the dose administered was 300 mg/100 ml, excepted that oxaluria was considerably enhanced in this group. Despite these variations, renal deposits were not observed, even in the animals receiving 300 mg of ascorbate/100 ml of water intake. This protection was due to decreased calcium excretion (P less than 0.01 in two groups) and probably to acidification of the urine.

[Serum copper levels in obesity: a study of 32 cases]. / Le cuivre serique chez l'obese: une etude a propos de 32 cas.

Abnormalities of copper distribution in tissues and serum has been described in obese subjects. In this prospective study, we evaluated the seric level of copper by atomic absorption in a group of 32 obese (BMI > or = 30 kg/m2) compared to a group of 32 healthy subjects. We have noted an elevation of serum copper in obese with a middle level of 133 mg/dl significantly superior to the middle level of serum copper of healthy subjects, 108 mg/dl (p < 0.001). In another hand, we have noticed that the levels of serum cooper rise with the BMI. In fact, 58.3% of the obese that have a BMI > or = 40 kg/m2 show a high concentration of serum copper although only 5% of obese with BMI < 40 kg/m2 show this high concentration. This work must be completed by the determination of ceruloplasmin levels in a larger group of obese in order to establish correlations between the serum ceruloplasmin levels, the serum copper levels and the obesity.

Ochratoxin A levels in human serum and foods from nephropathy patients in Tunisia: where are you now?

Ochratoxin A is a natural mycotoxin with nephrotoxic properties that can contaminate food products. It has been detected in high amount in human serum collected from nephropathy patients, especially those categorized as having a chronic interstitial nephropathy of unknown etiology. In the present study, ochratoxin A levels were measured in commonly consumed food items and in serum samples from nephropathy and healthy subjects in Tunisia. To assess ochratoxin A, a high performance liquid chromatography method was optimized. The ochratoxin A assay showed very different scales of ochratoxin A serum and food contamination from 0.12 to 1.5 ng/mL and 0.11 to 6.1 ng/g respectively, and in healthy subjects and 0.11 to 33.8 ng/g for food and 0.12 to 3.8 ng/mL for serum in nephropathy patients suffering from chronic interstitial nephropathy of unknown etiology. The disease seems related to ochratoxin A serum levels and food contaminations, since the healthy group was significantly different from the nephropathy group (P<0.001) for both food and serum ochratoxin A contamination. Those results combined with data published already, emphasize the likely endemic aspect of ochratoxin A-related nephropathy occurring in Tunisia.

Comparative effects of the addition of meat from beef, chicken, mullet and hake to a bean seed ragout on iron metabolism and iron status in growing rats.

AIMS: The objective was to study the comparative effects of the addition of meat from beef, chicken, mullet and hake to a bean seed ragout (BSR) on iron metabolism and iron status in growing rats. METHODS: The iron metabolism and the iron status were investigated through the exploration of the total iron in the blood and the reserve of iron stored in the liver, spleen, intestine, heart and tibia. RESULTS: Our findings showed that the iron concentration in total blood significantly increased only in the BSR + beef group by 23% (p < 0.006) as compared to the control group (BSR). However, it significantly decreased in the BSR + chicken group by 19.3% (p < 0.002). The reserve of iron stored in the liver significantly increased in the BSR + beef and the BSR + hake groups by 69.5% (p < 0.003) and 160% (p < 2.5.10(-7)) respectively, as compared to the control group. The effect of hake was more pronounced than beef. However, in the BSR + chicken and the BSR + mullet groups, the reserve of iron stored in the liver did not significantly differ from the control group. The reserve of iron stored in the spleen increased significantly in all groups. The increase has reached 370% in the BSR + hake group (p < 1.10(-7)). In the intestine, the reserve of iron was significantly enhanced only in the group fed BSR + beef by 120% (p < 0.01). In contrast, this reserve was lower in the rats fed BSR + mullet than in the other groups, a reduction of 64% (p < 1.10(-5)) as compared to the control group. In the heart, iron concentration significantly increased between 36.5 and 50%, as compared to the control group. The iron stored in the tibia significantly increased only in the beef and the hake groups by 88% (p < 0.05) and 57.4% (p < 0.02) respectively. CONCLUSIONS: Our findings demonstrated that beef, chicken, mullet and hake did not have the same effect on iron metabolism and iron status in growing rats fed BSR diets. The rats fed BSR + beef have a better iron status than those fed BSR + hake, BSR + chicken or BSR + mullet in descending order.

Effect of tea on iron absorption from the typical Tunisian meal 'couscous' fed to healthy rats.

Black and green tea decoctions are popular beverages in Tunisia, especially after eating. Our study was performed to examine the effect of graded amounts of black and green tea decoction prepared under realistic Tunisian conditions on nonheme iron absorption from a typical Tunisian meal, 'couscous', by extrinsic radioiron labeling in rats. Concentrations of 300, 200 and 100 micrograms/ml of black tea decreased dramatically nonheme iron bioavailability from couscous, but 50 micrograms/ml did not influence iron absorption. The inhibition of nonheme iron from couscous varied from 36 to 61% with black tea and 30.5% with green tea. Taken together, our findings show that the tea decoction in Tunisia has a great inhibitory power and may constitute an important factor for the development of iron deficiency anemia throughout Tunisia.