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The most common side effects of iodinated contrast media are hypersensitivity reactions and kidney failure. Aseptic sialadenitis or iodide mumps is a rare complication. Herein we report a case of “iodide mumps” that occurred in a patient without renal failure following administration of an iodinated contrast medium for a thoracic-abdominal scan. The outcome was favorable after 2 to 3 days. The pathogenesis of this side effect remains unclear but it consists of non-allergic reactions, making allergological exploration unnecessary, and subsequent use of contrast media is not contraindicated.

Introduction Pulmonary toxicity causally related to Imatinib (IM) therapy is uncommon in patients with chronic myeloid leukemia. Case report A 61-year-old patient with chronic myeloid leukemia was treated with IM at 400 mg daily dose. One month within IM, he developed skin lesions and then acute dyspnea and non-productive cough. Chest radiograph and high-resolution lung computed tomography (CT) revealed bilateral reticulonodular infiltration in both lungs. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 7. The pharmacovigilance investigation was carried out and implicated IM Management & outcome: IM was discontinued and started steroid therapy (Prednisolone®) at 1 mg/kg daily. Two weeks after, the dyspnea, and abnormal X-ray and CT findings are improved. Discussion The early diagnosis of pulmonary toxicity related to IM therapy is needed to avoid further determinal effects of the drug.

A high-fat diet (HFD) promotes oxidative stress, which contributes to the development of kidney dysfunction. We examined the protective effects of an ethanol extract of artichoke leaves (EEA) compa...

Introduction Nilotinib, as the second generation of tyrosine kinase inhibitor, has significant efficacy in patients with chronic myeloid leukemia resistant or intolerant to Imatinib. Aplastic anemia induced by tyrosine kinase inhibitors is an uncommon complication. Case report A 34-year-old female case with CML in the chronic phase was treated with Imatinib in first-line therapy. Nilotinib was switched because of failure to achieve complete cytogenetic response at 6 months following Imatinib. Three years with Nilotinib, the patient developed a persistent pancytopenia grade 4 while a major molecular response was achieved. Management & Outcome Nilotinib was discontinued. However, the hematologic finding of the patient had not recovered after three months. A bone marrow biopsy showed marked hypocellularity and fatty tissue without evidence of myelofibrosis. Immunosuppressive therapy was started. Unfortunately, the patient died due to septic and hemorrhagic shock nine months after Nilotinib interruption. According to Naranjo's algorithm, the causality relationship with the drug is probable with a score of 5. Discussion Aplastic anemia is an uncommon adverse event of tyrosine kinase inhibitors but it can be a fatal complication. The early diagnosis of aplastic anemia related to Nilotinib therapy is needed to avoid further detrimental effects of the drug.

Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purp...

Therapies - In Press.Proof corrected by the author Available online since lundi 17 septembre 2018

The effects of cefuroxime on reproductive system were investigated in male rats. Doses of 0, 30, 60 or 120 mg/kg of cefuroxime were intraperitoneally injected daily, for 7 days. Half of the rats were euthanized 24 h after the last dose and other half were induced to death 70 days after the last treatment. After 8 days of the experiment, results showed that cefuroxime induced a significant reduction in the weights of testes, epididymis and accessory sex organs. In addition, it decreased sperm quality, plasma testosterone level, and antioxidant enzyme activities while increasing the level of malondialdehyde. After a complete cycle of spermatogenesis and epididymal maturation, the results indicated complete reversibility of the adverse effects previously mentioned. In conclusion, cefuroxime induced reversible dose-dependent adverse effects on testicular and epididymal functions of rats.

Background: Lawsonia inermis-extracted oil is known for therapeutic properties, especially wound healing. This study assesses the potential of this oil for wound healing in a rat model. Methodology: To assess the potential of L. inermis-extracted oil for wound healing, phytochemical, antibacterial, and antioxidant analyses were conducted. Uniform wound excision was induced on the dorsum of randomly selected rats divided into 3 groups cleaned and treated with saline solution (control), Cicaflora (reference), and L. inermisoil. Biopsies performed after healing were histologically assessed. Conclusions: The quality and content of the fatty acids in the oil were determined. Results showed a high content of bioactive components inducing an efficient wound healing effect determined by an in vivo study. Histological and chromatic assessment findings revealed healing in the oil-treated group but not in the untreated group, a full reepithelialization with reappearance of skin appendages and well-organized collagen fibers without any inflammatory cells. This might be due to a synergistic effect of the phytoconstituents present in the oil.

Background people suffering from substance use disorders (SUD) often die by suicide, so that the prevention of suicide attempts (SA) remains a top priority in this population. SA recurrence is common and is associated with suicide death, but this phenotype has been overlooked in SUD populations. Thus, we aimed at identifying the risk factors of SA recurrence in SUD, controlling for both gender and levels of exposure to addictive substances, including tobacco. Methods we consecutively recruited 433 treatment-seeking outpatients with either opiate or cocaine use disorder and assessed their lifetime history of addictive and suicidal symptoms by standardized questionnaires. They were reliably classified as never, single or recurrent (≥ 2) suicide attempters, whose characteristics were identified by multinomial regression, stratified by gender; and compared to our previous work on serious SA in order to identify common or different risk profiles. Results 86/140 (61%) suicide attempters reported recurrence. The mean number of SA was 3.1. Recurrence was independently associated with psychiatric hospitalization in both genders, with nicotine dependence in men and with sedative use disorders in women. Limitations psychiatric diagnoses were derived from the current medication regimen. Conclusion specific and possibly avoidable/treatable risk factors for the recurrence of SA in SUD have been identified for the first time, opening new avenues for research and prevention in this high-risk population. Apart from nicotine dependence, these risk factors were very similar to those of serious SA. Although this comparison is indirect for now, it suggests a common liability towards suicidal behavior.

Aim Hyperuricemia is defined by the European Rheumatology Society as a uric acid level greater than 6 mg/dl (60 mg/l or 360 μmol/l). Our goal was to evaluate the hypouricemic effect of nettle. For this reason, we have first of all try to create an hyperuricemic animal model which is very suitable because at the level of literature there is not an exact model, there are many models and our objective is to set an adequate model. Materials and methods An attempt has been made to test acute and chronic hyperuricemia by varying the duration and method of induction of potassium oxonate. Similarly, attempts have been made to induce chronic hyperuricemia through an animal and vegetable diet. The reversibility of hyperuricemia was tested with a maintenance protocol. Key findings For the creation of the hyperuricemia model, it has been shown that acute hyperuricemia cannot be induced by short administration of potassium oxonate and persistent chronic hyperuricemia can be induced only after daily administration of oxonate of potassium by intraperitoneal injection for 15 days. Indeed, hyperuricemia was reversible after stopping the administration of potassium oxonate. The high-purine diet is also capable of inducing chronic hyperuricemia but to a less extent. Significance After creating an adequate model of hyperuricemia while setting the dose of potassium oxonate, route of administration and duration. A maintenance protocol was followed which subsequently made it possible to deduce that the daily administration of potassium oxonate must be continued to maintain the hyperuricemia.

Supplemental material, sj-pdf-1-opp-10.1177_1078155220984239 for Hypersensitivity pneumonitis related to imatinib mesylate therapy in a patient with chronic myeloid leukemia by Faten Kallel, Olfa Kassar, Imen Maaloul, Maha Charfi, Kamilia Ksouda and Moez Elloumi in Journal of Oncology Pharmacy Practice

International audience; Rationale Behavioral disturbances (BD) are prevalent in patients with substance use disorders (SUD). Objectives To test the hypothesis that chronic exposure to cocaine could favor the acquisition of BD that were not present in childhood. Methods We used child and adult ADHD self-report screening scales (WURS-25 and ASRS-6, respectively, with their usual threshold) as assessment tools for significant BD. In a cross-sectional assessment of 382 patients with multiple SUD, we investigated BD and then "de novo" BD (i.e., by restricting the sample to patients below the threshold for childhood BD) (N = 214). We also tested for a gradient effect between patients' lifetime DSM IV cocaine and opioid dependence status and the prevalence of BD. Results BD were found in 188/382 (42.9%) subjects and in 74/214 (34.6%) subjects. Three clinical factors were associated with BD in the whole sample: the number of cocaine dependence criteria (OR = 1.36 [1.14-1.64], p = 0.001), the number of opioid dependence criteria (OR = 0.69 [0.52-0.91], p = 0.010), and a personal history of using cocaine through rapid routes of administration (OR = 0.41 [0.19-0.88], p = 0.022). The same three factors were associated with "de novo" BD in the restricted sample: OR = 1.35 ([1.11-1.63], p = 0.002), OR = 0.83 ([0.70-0.99], p = 0.046), and OR 0.37 ([0.16-0.86], p = 0.022), respectively. There were significant gradients for BD according to the cocaine exposure categories in the whole (Mantel-Haenszel, p < 0.001) and in the restricted sample (Mantel-Haenszel, p = 0.002). Conclusions Cocaine exposure was positively associated with behavioral disturbances in a dose-dependent manner in this clinical sample, whilst opioid exposure showed a negative association.

Purpose Drug rash with eosinophilia and systemic symptoms (DRESS) is a serious adverse drug reaction. Carbamazepine is the most common causes of this syndrome. The HLA-A*31:01 allele has been shown to be strongly correlated with carbamazepine-induced DRESS syndrome in European, Japanese, Han Chinese and other asian population but not in African populations. So, our purpose is to study there is a correlation between HLA-A*31:01 and carbamazepine-induced DRESS syndrome in africain population? Methods HLA class I (A and B) typing was performed on 7 subjects with carbamazepine-DRESS syndrome and 25 tolerants controls subjects. DNA typing HLA class I (A) alleles was checked by the polymerase chain reaction amplification Sequence Specific Oligonucleotide Probes (SSO) (reverse-SSO assay). High resolution HLA DNA Kit based on the Luminex technology (One Lambda ® ) was used according to the manufacturer's protocol. Results The HLA-A*31:01 allele, which has a prevalence of 1% in Tunisian population, was significantly associated with DRESS syndrome. It was detected in 57.14% of cases (4/7) and only 4% of controls subjects (1/25). Thus, the carrier frequency of HLA-A*31:01 allele in the cases group was also significantly higher than in the controls group (57, 14% vs 4% P = 0,004). Odds ratio is estimated 32 (OR = 32 [2.6; 389.2]) Conclusion Similarly to other ethnicities, the presence of the HLA-A*31:01 allele was associated with carbamazepine-DRESS syndrome in a sample of North African population. Future study must be conducted on a larger sample in order to confirm these results.

Background and purpose Chronic exposure to potassium bromate (KBrO3), a toxic halogen in the environment, has become a global problem of public health. The current study aims to elucidate for the first time the effect of Urtica dioica (UD) on behavioural changes, oxidative stress, and histopathological changes induced by KBrO3 in the cerebellum, kidney, liver and other organs of adult rats. Study design and methods The rats were divided into four groups: group 1 served as a control received physiological serum, Group 2 received KBrO3 (2 g/L of drinking water), group 3 received KBrO3 and Urtica dioica (100 mg/kg), and group 4 received KBrO3 and Urtica dioica (400 mg/kg). We then measured behavioural changes, oxidative stress, and biochemical and histological changes in the cerebellum, liver, kidney and others organs in these rats. After 30 days of treatment, the animals were sacrificed. Results We observed significant behavioural changes in KBrO3-exposed rats. When investigating redox homeostasis in the cerebellum, we found that mice treated with KBrO3 had increased lipid peroxidation and protein oxidation in the cerebellum. In addition, it inhibits hepatic and lipid peroxidation (malondialdehyde), advanced oxidation protein product (AOPP), attenuates KBrO3-mediated enzyme depletion, catalase, superoxide dismutase, glutathione peroxidase enzymatic and antioxidant activities in the liver and kidney. Rats that were co-managed with Urtica dioica at the high portion of 400 mg/kg indicated a higher effect than that treated with the low dose of 100 mg/kg practically in all the tests carried out. Conclusion Our results demonstrate that Urtica dioica is a potential therapeutic agent for oxidative stress associated with neurodegenerative diseases.

Low-molecular-weight heparins may cause adverse skin reactions, especially eczematous eruptions. A 60-year-old woman with a history of mitral valve replacement and frontal hemorrhagic stroke, who had been treated with carbamazepine and enoxaparin for 2 months, consulted our department for a sudden onset of generalized pruritic rash. There was facial edema, cheilitis, and a rash of eczematous lesions electively localized to the site of enoxaparin injections. Blood analysis showed eosinophilia= 2500 e/mm3, gamma GT = 526 and lipasemia= 126. Initially we suspected the diagnosis of carbamazepine induced DRESS syndrome. Then the final diagnosis was generalized eczema on heparin in view of the exclusive localization of the lesions at the sites of enoxaparin injections, the rapid resolution of the eruption and the result of biopsy and allergological investigation. Dermatologic effects of heparins commonly used in medical and surgical practice are numerous, and clinical pictures can be misleading, as in our case.

Imipenem is a carbapenem antibiotic largely used to treat infection diseases. The present study was designed to investigate the effects of imipenem/cilastatin (IMP) on oxidative stress, antioxidant levels, testicular structure and sperm parameters in rats. Adult Wistar rats (84days old; N=8/group) were treated intraperitoneally with physiological serum containing 0mg/kg, 30mg/kg, 50mg/kg and 80mg/kg of IMP for one week. The results revealed that exposure to IMP especially at high doses, significantly decreased sexual organs weights (testis, epididymis, seminal vesicle and prostate), sperm characteristics (motility, viability and count) and plasma testosterone level while increased sperm abnormality. In addition, the testicular tissue level of lipid peroxidation (LPO) was significantly increased while the level of activities of superoxide dismutase (SOD), catalase (CAT) and glutathion peroxidase (GPx) decreased compared to the control group. Severe testicular lesions were recorded in the seminiferous tubules as well as a significant impairment in sperm characteristics. In conclusion, IMP induced an oxidative stress-status and histopathological changes in the testis and altered spermatogenesis in particular at both 50 and 80mg/kg dose-levels (p

Diabetes mellitus (DM) is associated with hyperglycemia, inflammatory disorders and abnormal lipid profiles, currently the extracts from leaves of cynara scolymus has been discovered to treat metabolic disorders and has been stated by multitudinous scientists according to a good source of polyphenols compounds. The present study aimed to evaluate the protective effect of the ethanol leaves extract of C. scolymus in alloxan induced stress oxidant, hepatic-kidney dysfunction and histological changes in liver, kidney and pancreas of different experimental groups of rats. We determinate the antioxidant activity by ABTS .+ and antioxidant total capacity (TAC) of all extracts of C. scolymus leaves, the inhibition of α-amylase activity in vitro was also investigated. Forty male Wistar rats were induced to diabetes with a single dose intraperitoneal injection (i.p.) of alloxan (150 mg/kg body weight (b.w.)). Diabetic rats were orally and daily administrated of ethanol extract from C. scolymus at two doses (200-400 mg/kg, b.w) or (12 mg/kg, b.w) with anti-diabetic reference drug, Acarbose for one month. Ethanol extract of C. scolymus effect was confirmed by biochemical analysis, antioxidant activity and histological study. The results indicated that the ethanol extract from leaves of C. scolymus showed the highest antioxidant activity by ABTS .+ (499.43g± 39.72 Trolox/g dry extract) and (128.75 ± 8.45 mg VC /g dry extract) for TAC and endowed the powerful inhibition in vitro of α-amylase activity with IC50=72,22 ug/uL. In vivo, the results showed that ethanol extract from the leaves of C. scolymus (200-400 mg/kg) decreased significantly (p < 0.001) the α-amylase levels in serum of diabetic rats, respectively associated with significant reduction (p < 0.001) in blood glucose rate of 42,84% and 37,91% compared to diabetic groups after 28 days of treatment, a significant lowered of plasma total cholesterol (T-Ch) by 18,11% and triglyceride (TG) by 60,47%, significantly and low-density lipoproteins (LDL-C) by 37,77%, compared to diabetic rats, moreover, the administration of ethanol extract appears to exert anti-oxidative activity demonstrated by the increase of CAT, SOD and GSH activities in liver, kidney and pancreas of diabetic rats. This positive effect of the ethanol extract from C. scolymus was confirmed by histological study. These observed strongly suggest that ethanol extract from the leaves of C. scolymus has anti-hyperglycemic properties, at least partly mediated by antioxidant and hypolipidemic effects.

Obesity plays a pivotal role in the insulin resistance disease, which is related to hypertension, hyperlipidemia, type 2 diabetes mellitus, and an increased risk of cardiovascular disease. The purpose of the present study was done to evaluate the effect of artichoke leaves extract (ALE) in the high-fat diet (HFD)-induced cellular obesity and cardiac damage in Wistar rats. Body and organ weights, serum lipid profile, cardiac markers, and antioxidants enzymes were measured. Oral administration of ALE at two doses 200 and 400 mg/kg for a period of 60 days showed a significant decrease in body and organ weights, serum total cholesterol, triglycerides, LDH, ALT accompanied by decreasing in oxidative stress biomarker (MDA, and AOPP) and increasing antioxidant enzymes (SOD, CAT, and GPx) levels as compared to HFD groups. The histological findings showed a cardioprotective effect of ALE. These findings suggest that ALE exert anti-oxidant cardiac effects in HFD- induced obese rats.

Background Natural products, whether pure compounds or standardized plant extracts, offer unlimited opportunities for other drug sources due to the unequaled availability of chemical diversity. Stinging Nettle (Urtica dioica) is a unique herbaceous perennial flowering plant with stinging hairs. The leaf extract of nettle was one of the herbal remedies which the experimental, clinical and trials have complemented each other. It is a very well-known plant with a wide historical background use of stems, leaves and roots. It has a long history of use as power sources such as soup or curry, and also used as fiber and a medicinal plant. Urtica dioica has traditionally been used in the control of cardiovascular disorders especially hypertension. The leaf extract of Urtica dioica has been reported to improve glucose homeostasis in vivo. Nettle root could prevent some of the effects of prostatic hyperplasia. Extracts of nettle leaf are used as anti-inflammatory remedies for rheumatoid arthritis. Urtica dioica extract significantly increased the sensitivity of breast cancer cells to paclitaxel. This article aims to review the very wide ranging of pharmacological effects of Urtica dioica extract. Methods Articles on PuBmed between 1980 and 2019. Results Description and critical review of the pharmacological effects of Urtica dioica and other uses. Conclusion The nettle is actually a plant with many qualities and uses. The interest in it is deserved and it is given by other studies and investigations.

Lawsonia inermis-extracted oil is known for therapeutic properties, especially wound healing. This study assesses the potential of this oil for wound healing in a rat model.To assess the potential of L. inermis-extracted oil for wound healing, phytochemical, antibacterial, and antioxidant analyses were conducted. Uniform wound excision was induced on the dorsum of randomly selected rats divided into 3 groups cleaned and treated with saline solution (control), Cicaflora (reference), and L. inermisoil. Biopsies performed after healing were histologically assessed.The quality and content of the fatty acids in the oil were determined. Results showed a high content of bioactive components inducing an efficient wound healing effect determined by an in vivo study. Histological and chromatic assessment findings revealed healing in the oil-treated group but not in the untreated group, a full reepithelialization with reappearance of skin appendages and well-organized collagen fibers without any inflammatory cells. This might be due to a synergistic effect of the phytoconstituents present in the oil.

Cynara scolymusL. (Artichoke) has been used for the treatment of metabolic disorders. The purpose of the present study was to investigate the hepatoprotective effect ofCynara scolymusleaves extract against a high fat diet (HFD) induced rats. This study investigated the most abundant phenolic compounds richCynara scolymusleaves extract and it is antihypercholesterolemic and antioxidative effectsin vivo. The hypercaloric high fat diet (HFD) was treated with 200 mg/kg and 400 mg/kg of ethanol extract (EEA) from leaves ofCynaraand atorvastatin (ATOR) (10 mg/kg/day) during an 8-week period. Lipid profile was measured and oxidative stress systematic in hepatic tissue was determined. Our data revealed that HFD-induced hepatic dysfunction manifested by significant abnormal levels of AST, ALT, ALP, LDH, and OCT was accompanied by increasing levels of oxidative stress biomarker (ROS, MDA, and AOPP) while decreasing in antioxidant status. Coadministration of EEA significantly reduced serum lipid profile and hepatic disorders which was confirmed to be histological by reducing the fatty liver deposition in hepatic lobule. These findings suggest thatCynaraleaves exert antiobesity and antioxidant liver effects in HFD-induced obese rats.

Background:Inflammatory response is a common physiological response that protects the host of many harmful stimuli such as toxins, local injuries and pathogens. Today, non-steroidal anti-inflammatory drugs are the most commonly prescribed for the treatment of many inflammatory treatments. However, long term administration of these NSAIDs causes many adverse effects, including gastrointestinal ulcers and bleeding and kidney damage. Therefore, the need for new anti-inflammatory drugs with fewer side effects is required.Objectives:The aim of our study was to evaluate the anti-inflammatory activity of Cinnamomum verum (C. Verum) on rats while testing the dose effect and the typical effect of the solvent.Methods:The edema was induced by injection of carrageenan solution (CARR) in paw of rats according to the method of Winter et al, 1963. The measurements of volumes of right hind paw of each rat were taken before induction of edema and each 1 h, 2 h, 3 h, 4 h and 5 h after the injection of carrageenan. 7 groups of 6 rats received, one hour before the injection of the carrageenan, different treatment: G1= witness, G2=CARR + saline solution, G3= CARR+ Acetylsalicylic acid, G4= CARR + C. verum- MeOH 100, G5= CARR + C. verum- MeOH 300, G6= CARR + CARR + C. verum- EtOH 100 and G7= CARR + C.verum- EtOH 300.Results:For this test, the volume of edema increases with time, this increase is greater in the group treated with saline solution than with the extracts of C.Verum and with Acetylsalicylic acid. The extracts of C. Verum administered intraperitoneally one hour before the injection of the carrageenan, reduced the edema in the third hour after.Conclusion:The interesting anti-inflammatory activity of Cinnamomum verum recorded in this work may at least in part support its popular use in traditional medicine [1, 2].References:[1]Mirza Muhammad Fahd Qadir, Attya Bhatti, Muhammad Usman Ashraf, Mansur Abdullah Sandhu, Sidrah Anjum, Peter John. Immunomodulatory and therapeutic role of Cinnamomum verum extracts in collagen-induced arthritic BALB/c mice. Inflammopharmacology 2018 Feb;26(1):157-170.[2]Heping Cao, Joseph F Urban Jr, Richard A Anderson. Cinnamon polyphenol extract affects immune responses by regulating anti- and proinflammatory and glucose transporter gene expression in mouse macrophages. J Nutr 2008 May;138(5):833-40.Disclosure of Interests:None declared

Background:Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the leading causes of hypersensitivity reactions to drugs. The pathogenesis may be immunological mechanisms (allergic reactions) or non specific immunological reactions often incriminated in cross reactivity independently of chemical structure of these molecules. Understanding of the underlying mechanism is necessary for prevention and choice of safe alternatives [1, 2].Objectives:Analyze all cases of non-steroidal anti-inflammatory drugs cutaneous eruption reported to sfax pharmacovigilance service since January 2015 to December 2020 and evaluate the possibility of cross-reactions between different molecules in this class.Methods:We conducted a retrospective study of all cases reported to sfax pharmacovigilance department. An enquiry of pharmacovigilance was performed in patients who presented side effects to AINS. The imputability study was carried out by the French method of Imputability. Medical history specifies if there is a re-administration to assess tolerance and cross-reactivity.Results:Our study included 87 patients whose average age was 45, 8 years. The sex ratio (F/M) was 1.18. lysine salicylate acetyl is the most incriminated (31%), then mefenamic acid (19.5%), diclofenac (19.5 %), ketoprofen in (9.2%), piroxicam in (6.9 %), ibuprofen in (5.4%), celocoxib in (3.4%), tiaprofenic acid in (1.1%) and naproxen in 1.1% of cases. The most common skin injury was urticaria in 29 cases (33.3%). Fixed drug eruption was observed in 17 cases. Maculopapular rash was observed in 19 cases, anaphylaxis in 5 cases and 4 cases of photosensitivity were observed. In our study we found cross-reactivity between (NSAIDs) in 8 patients.Conclusion:The diagnostic approach is often based on the controlled administration of the drug to assess tolerance and to identify safe alternatives. In cases of intolerance to COX 1 inhibitors, cross-reactions to selective cox 2 inhibitors are very rare [3].References:[1]Inmaculada Dona, Maria Salas, James R Perkins and al. Hypersensitivity Reactions to Non-Steroidal Anti-Inflammatory Drugs. Curr Pharm Des 2016; 22(45):6784-6802.[2]Flavia Angeletti, Franziska Meier, Nadja Zöller, Markus Meissner, Roland Kaufmann, Eva Maria Valesky. Hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAIDs) - a retrospective study. J Dtsch Dermatol Ges 2020 Dec; 18(12):1405-1414.[3]N Blanca-López, J A Cornejo-García, M C Plaza-Serón, and al. Hypersensitivity to Nonsteroidal Anti-inflammatory Drugs in Children and Adolescents: Cross-Intolerance Reactions. J Investig Allergol Clin Immunol 2015; 25(4):259-69.Disclosure of Interests:None declared

Introduction L’urticaire aigue est une pathologie frequente et de causes multiples. L’origine medicamenteuse intervient dans 10 a 30 % des cas selon les etudes. L’objectif de notre travail etait de colliger tous les cas d’urticaire aigue suspectes d’etre liees aux medicaments et qui ont ete notifies au Service Regional de Pharmacovigilance de Sfax durant la periode allant du mois de janvier 2010 au mois de decembre 2015 et d’etudier les particularites de l’urticaire superficielle commune associee a un angiœdeme en les comparant avec celles de l’urticaire superficielle commune. Methodes Notre etude est de type retrospectif. Une enquete de pharmacovigilance a ete realisee chez les patients presentant une urticaire aigue. L’etude d’imputabilite a ete faite selon la Methode Francaise d’Imputabilite de Begaud. Resultats Notre population d’etude a comporte 160 patients qui sont repartis en 2 groupes : un groupe de 104 patients ayant une urticaire superficielle commune isolee (soit 65 %) et un groupe de 56 patients ayant une urticaire superficielle commune associee a un angiœdeme (soit 35 %). La tranche d’âge la plus touchee dans les 2 groupes d’etudes est celle des adultes âges entre 40 et 65 ans. Une predominance feminine a ete notee dans les 2 groupes mais elle a ete plus marquee chez les patients ayant un angiœdeme associe. L’atopie etait frequente dans les 2 groupes de l’etude mais plus prononcee chez les patients presentant une urticaire superficielle commune isolee. Dans les 2 groupes d’etude, les beta-lactamines etaient la classe therapeutique la plus pourvoyeuse d’urticaire, suivi par les anti-inflammatoires non steroidiens et le paracetamol. L’etude d’imputabilite a conclu a un role medicamenteux possible ou vraisemblable dans 73 % des cas d’urticaire superficielle commune et dans 76,8 % des cas de l’autre groupe. Conclusion Au terme de cette etude, nous avons conclu que les caracteristiques de l’urticaire associee a l’angiœdeme sont comparables a celles de l’urticaire superficielle commune sauf que les antecedents d’atopie ont ete plus prononces avec ce dernier et que la predominance feminine a ete plus marquee dans l’urticaire associee a un angiœdeme.

Artichoke (Cynara scolymus) leaf extract was one of the few herbal remedies which the clinical and experimental trials have complemented each other. Both experimental and clinical effects have been verified through extensive biomedical herbal remedy research. Specifically, antioxidant, choleretic, hepatoprotective, bile-enhancing and lipid-lowering effects have been demonstrated, which corresponded with its historical use. Ongoing research seems to indicate that artichoke indeed have medicinal qualities. Most significant appears to be its beneficial effect on the liver. In animal studies, liquid extracts of the roots and leaves of artichoke have demonstrated an ability to protect the liver, with possibly even to help liver cells regenerate. Although research is not yet conclusive, scientists were optimistic that its long-standing use in humans for digestive and bowel problems was indeed justified. It may also play a role in lowering cholesterol and thus help to prevent heart disease. Boiled wild artichoke reduced postprandial glycemic and insulinemic responses in normal subjects but has no effect on metabolic syndrome patients. This article intended to review the wide ranging pharmacological effects of artichoke leaf extract.

Aims Methadone is characterized by wide intersubject variability regarding the dose needed to obtain full therapeutic response. We assessed the influence of sociodemographic, ethnic, clinical, metabolic and genotypic variables on methadone maintenance dose requirement in opioid-dependent responder patients.

The present study was aimed to evaluate the analgesic properties of Urtica dioica (UD) and to profile phytochemicals by gas chromatography-mass spectrometry (GC-MS). The ethanolic extracts were prepared by maceration method and extraction using rotary evaporator. The analgesic activity was analysed by hot plate method, formalin test, acetic acid-induced writhing test and the tail-flick test with different doses of the ethanolic extract. In all tests, the leaf's ethanolic extract exhibited significant analgesic activity (p

Objective. Artichoke (Cynara scolymusL.) was one of the plant remedies for primary health care. The present study was focused on the determination of chemical composition, antioxidant activities, and anti-inflammatory activity and on analyzing its major bioactive polyphenols by HPLC.Methods. Artichoke Leaves Extracts (ALE) were analyzed for proximate analysis and phytochemical and antioxidant activity by several methods such as DDPH, ABTS, FRAP, and beta-carotene bleaching test. The carrageenan (Carr) model induced paw oedema in order to investigate the anti-inflammatory activity. Identification and quantification of bioactive polyphenols compounds were done by HPLC method. The oxidative stress parameters were determined; CAT, SOD, GSH, MDA, and AOPP activities and the histopathological examination were also performed.Results. It was noted that EtOH extract of ALE contained the highest phenolic, flavonoid, and tannin contents and the strongest antioxidants activities including DDPH (94.23%), ABTS (538.75 mmol), FRAP assay (542.62 umol), andβ-carotene bleaching (70.74%) compared to the other extracts of ALE. Administration of EtOH extract at dose 400 mg/kg/bw exhibited a maximum inhibition of inflammation induced by Carr for 3 and 5 hours compared to reference group Indomethacin (Indo).Conclusion. ALE displayed high potential as natural source of minerals and phytochemicals compounds with antioxidant and anti-inflammatory properties.

Olive tree leaves (Olea europaea L.) have been widely used in traditional remedies as extracts, herbal teas and powder in European and Mediterranean countries. Bioactivities of olive tree were obtained by product extracts. They were attributing to antioxidant and phenolic components such as oleuropein, hydroxytyrosol, tyrosol and ligstroside. Studies were indicating that biologically active compounds in olive leaves products were effective in treating different disorders. Several studies have been showing that oleuropein (up to 6–9% of dry matter in the leaves) possesses a wide range of pharmacological and health-promoting properties including antiarrhythmic, spasmolytic, immune stimulant, cardioprotective, hypotensive, antioxidant and anti-inflammatory effects. Practical Applications Olea europaea preparations have been widely used in folk medicine in different countries. The medicinal parts of the olive tree were the leaf extracts. Many researchers have been searching for olive leaves subproducts that could have beneficial effects on human health. In the present review, compounds obtained from olive leaf extracts had been subject to numerous investigations of their therapeutic properties.

Background Many drugs increase the duration of the QT interval of patients, potentially leading to harmful effects such as polymorphic ventricular arrhythmias. Most of these drugs do so by inhibiting the rapid component IKr of the delayed rectifier potassium current IK. Methadone is the most prescribed heroin maintenance treatment and is known to inhibit the cardiac potassium channel hERG, which recapitulates IKr. In order to evaluate if any polymorphism of potassium channels’ genes could explain some of the “idiosyncratic” QT prolongations observed in patients treated with methadone, we tested the association between KCNE1 , KCNE2 , and KCNH2 polymorphism and the QT interval prolongation in those patients, controlling for other variables associated with a decrease of the repolarizing reserve. Methods A cohort of 82 patients treated with stable dosage of methadone (mean dosage 65 mg/d) for at least three months was genotyped for five polymorphisms in KCNE1 , KCNE2 and KCNH2 genes and had their corrected QT (QTc) assessed. Results The mean QTc interval was 415 ± 34 ms. In a linear regression model, longer QTc interval was associated with methadone dosage and with one genetic factor. Each copy of a Lys allele at codon 897 of KCNH2 , the gene that encodes the cardiac potassium voltage-gated channel hERG, was associated with a 15.4 ms longer QTc (95% CI [4.6–26.2]; p = 0.001). Conclusion KCNH2 genotyping may be relevant in the analysis of cumulative risk factors for QT prolongation in patients on methadone maintenance treatment.

Although rare, anaphylactic reactions induced by PPIs have been reported. The presence of cross-reactivity between different members of the group is not clear. We analyzed all cases of allergic skin reactions to PPIs notified in regional pharmacovigilance center of Sfax during a 12 years period and assessed the possibility of cross-reactions between different molecules of this class. An enquiry of pharmacovigilance was conducted for each case according to the French imputation method. We called then, all patients who developed an allergic reaction to a PPI with a plausible or credible imputation. A patch test to all the molecules was carried out to study the possibility of cross-reactivity between PPIs. Thirty-seven patients have developed skin disease, with a total of 1 172 cutaneous adverse effects (3%) notified in our regional pharmacovigilance center. The skin disease most frequently observed was maculopapular rash (19 cases or 51%), followed by urticaria in 9 cases (24%). The omeprazole was the most implicated in the genesis of these adverse events (in 31 cases: 83.78%). Lansoprazole was administered to 5 patients having allergy to omeprazole with good tolerance. Patch tests were realized for6 patients having allergy to omeprazole. They were positive with omeprazole at 72 h in all cases and negative with lansoprazole in 5 cases. In one third of cases, lansoprazole was a good alternative at patients developing allergy to omeprazole, esomeprazole or pantoprazole. In one case we have contraindicated all PPIs. In the other cases we have preconized surveillance for the use of lansoprazole.

Sulfasalazine is widely used in the treatment of chronic inflammatory bowel disease (IBD) and certain rheumatic diseases. However, its use is associated with a high rate of adverse effects (AEs) which can be cutaneous, hematological, renal, hepatic, gastrointestinal or neurological. The aim of our study was to collect all cases of AEs suspected to be associated with the use of sulfasalazine in patients hospitalized in the department of Gastroenterology from the Hospital Hedi Chaker of Sfax (Tunisia) for a period of 5 years and to search the incriminated fraction (sulfonamide or salicylate). Our study population included 69 patients who received sulfasalazine for the treatment of IBD. We collected, in 23 patients (33%), 25 AEs suspected to be related to sulfasalazine. Cutaneous and hematological reactions are the most common. The subsequent administration of mesalazine was performed in 15 patients. It was well tolerated in 14 patients. So we were suspecting probably the responsibility of sulfonamide fraction in these cases. The mechanism of sulfasalazine induced AEs may be toxic or immunoallergic with the possibility of a cross-reaction with the other antimicroacterial sulfonamides.

Summary Background Methadone is prescribed in France as a maintenance treatment for heroin dependence since 1969. Nevertheless, the optimal duration of methadone maintenance treatment and how detoxification from methadone at the end of the treatment should be performed is still discussed. Objective To conduct a literature review on when and how detoxify clients from methadone maintenance treatment and to collect the opinion of experts in the field. Documentary sources We searched the PubMed, Embase, Cochrane Library and PsycINFO databases on the 1966–2011 period using the keywords “methadone”, “maintenance”, “detoxification”, “tapering”, “cessation”, “withdrawal”. We also searched data in other addictive journals in French that are not available in those databases. We also collected the opinion of the physician in charge of the oldest methadone program in France (1969). Studies selection We excluded studies that used methadone as short time treatment of heroin withdrawal and thus selected 23 articles. Results There is a consensus on when methadone maintenance treatment should be stopped, defined by the client's will to stop , the judgement from the physician that the client has been stable for a period of time that is long enough , but also the client's motivation to live his life without maintenance treatment . There is also a majority, among articles on how methadone treatment should be stopped, recommending ambulatory, practical approaches using slow tapering of the dose , with the ability to go back to the previous dose if needed, namely in case of relapse to heroin use, heavy withdrawal or psychiatric symptoms. Limits There are few articles addressing the subject, especially comparing prospectively different cessation strategies. Conclusion Methadone maintenance treatment should not necessarily be maintained all life long and can be stopped within its prescription setting, including medical, psychological and social evaluation.

The risk of cardiovascular disease in elderly is significantly higher than in young subjects; paradoxically some treatments that have proven their efficacy in reducing cardiovascular risk are often under prescribed in this age group. The benefits of statins in secondary cardiovascular prevention are well established in patients

Background. Medicinal plants have proved at all times to be a powerful remedy for health care. Accordingly, grape seed, sesame, and fenugreek extracted oils with pharmacological properties are investigated as wound treatments. This study assesses the potential of our oils for healing wounds induced on rats.Methods. Phytochemical analyses of oils have involved: quality value, polyphenol, chlorophylls, carotene, and fatty acids. Antibacterial activity was carried out. Antioxidant activity was evaluated: the scavenging effect on DPPH radicals, the reducing power, andβ-carotene discoloration. Uniform wound excision was induced on rats dorsum randomly divided into five groups: groups treated with “CICAFLORA®” and tested oils and untreated one. The posthealing biopsies were histologically assessed.Results. Wound biopsies treated with oils showed the best tissue regeneration compared to control groups. Groups treated with our oils and “CICAFLORA” had higher wound contraction percentage. Polyunsaturated fatty acids in oils act as inflammatory mediators increasing neovascularization, extracellular remodeling, migration, and cell differentiation. Wound healing effect was attributed to antibacterial and antioxidant synergy.Conclusion. According to findings, oils showed better activity in wound healing compared to “CICAFLORA” due to a phytoconstituents synergy. However, clinical trials on humans are necessary to confirm efficacy on human pathology.

Les inhibiteurs de la pompe a protons (IPP) sont largement utilises en pathologie gastro-œsophagienne et gastroduodenale. Ils sont bien toleres avec tres peu d’effets secondaires. Cependant, ils peuvent engendrer une pancreatite aigue qui est un effet tres rare mais peut etre grave et mortelle dans certains cas. Nous rapportons un cas de pancreatite aigue liee au premier inhibiteur de la pompe a protons, l’omeprazole, notifie au service de pharmacovigilance de Sfax. Une elevation des enzymes pancreatiques et des signes radiologiques tomodensitometriques ont confirme le diagnostic d’une pancreatite aigue. Une etiologie biliaire, infectieuse, ainsi que tumorale ont ete ecartees. Ainsi, une origine medicamenteuse a ete suspectee et le score d’imputabilite a ete cote plausible. Le mecanisme exact de cet effet indesirable est discute, il parait lie indirectement a une augmentation du taux de gastrine secondaire a une suppression de la secretion acide.

Prescription of generic products is a way to reduce health expense. Bioequivalence is the most appropriate procedure to evaluate the quality and therapeutic efficacy of a generic product. Generic prescriptions are a strategic choice in Tunisia.We expose in this work, a bioequivalence study witch compare a generic (test) product: DIABENIL* manufactured by a Tunisian pharmaceutical industry Dar Essaidaly to the innovative (reference) product: DAONIL* of Aventis pharma laboratories.The bioequivalence of two glibenclamide 5-mg tablets was determined in healthy human, adult volunteers after a single dose in a randomized cross-over in double blind study. Test and reference were administered to twenty-four healthy volunteers of both sexes after overnight fasting. In total, 15 Blood samples were collected before and following the administration of the drug. Serum concentrations of glibenclamide were determined by validated HPLC method. The pharmacokinetic parameters AUC0t, AUC0 , Cmax and tmax were tested for bioequivalence.All parameters showed bioequivalence between both formulations as their confidence intervals were within the bioequivalence acceptable range of 0.80-1.25 limits.We conclude that the two formulations exhibited comparable pharmacokinetic profiles and that the two products can be considered interchangeable in medical practice.

Early onset of heroin use is a severity marker of heroin use disorder. We studied the interaction between early onset and rapid transition to heroin dependence recorded with retrospective interviews in 213 patients with severe heroin dependence and history of methadone maintenance treatment. General linear models were used to identify independent factors associated with early onset, factors associated with rapid transition to dependence, and a multivariate model was used to study the interaction of those two dimensions. Lifetime history of anxiety disorders and age at onset of cannabis use are shared common risk factors and are associated with the interaction.

The risk of cardiovascular disease in elderly is significantly higher than in young subjects; paradoxically some treatments that have proven their efficacy in reducing cardiovascular risk are often under prescribed in this age group. The benefits of statins in secondary cardiovascular prevention are well established in patients80 years. In primary prevention, these drugs reduce the risk of myocardial infarction and stroke, but their effects on cardiovascular mortality remain uncertain. In very elderly patients, there are no randomized trials relative to the impact of statins on morbi-mortality in primary prevention as well in secondary prevention. Adverse effects in the elderly seem to be statistically similar to those occurring in young people , but the prescription in very old people should be individualized, taking into account the life expectancy, the life quality, the comorbidities, and especially the risk of drug interactions.