Tacrolimus trough level and oxidative stress in Tunisian kidney transplanted patients.

BACKGROUND: The effect of tacrolimus (TAC) on oxidative stress after kidney transplantation (KT) is unclear. This study aimed to evaluate the influence of TAC trough levels of oxidative stress status in Tunisian KT patients during the post-transplantation period (PTP). METHODS: A prospective study including 90 KT patients was performed. TAC whole-blood concentrations were measured by the microparticle enzyme immunoassay method and adjusted according to the target range. Plasma levels of oxidants (malondialdehyde (MDA) and advanced oxidation protein products (AOPP)) and antioxidants (ascorbic acid, glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD)) were measured using spectrophotometry. The subjects were subdivided according to PTP into three groups: patients with early, intermediate, and late PT. According to the TAC level, they were subdivided into LL-TAC, NL-TAC, and HL-TAC groups. RESULTS: A decrease in MDA levels, SOD activity, and an increase in GSH levels and GPx activity were observed in patients with late PT compared to those with early and intermediate PT (p < 0.05). Patients with LL-TAC had lower MDA levels and higher GSH levels and GPx activity compared with the NL-TAC and HL-TAC groups (p < 0.05). CONCLUSION: Our results have shown that in KT patients, despite the recovery of kidney function, the TAC reduced but did not normalize oxidative stress levels in long-term therapy, and the TAC effect significantly depends on the concentration used.

Melatonin Ingestion Prevents Liver Damage and Improves Biomarkers of Renal Function Following a Maximal Exercise.

Background: While the promotion of the beneficial effects of melatonin (MEL) ingestion on the modulation of oxidative stress is widespread, less attention is given to the biological influence that it could exert on the results of hematology and clinical chemistry parameters. This study was undertaken to assess the effects of acute MEL ingestion on these parameters during a maximal running exercise. Methods: In double blind randomized design, 12 professional soccer players [age: 17.54 ± 0.78 yrs, body mass: 70.31 ± 3.86 kg, body height: 1.8 ± 0.08 m; maximal aerobic speed (MAS): 16.85 ± 0.63 km/h; mean ± standard deviation], all males, performed a diurnal (17:00 h ± 30 h) running exercise test (RET) at 100% of their MAS following either MEL or placebo ingestion. Blood samples were obtained at rest and following the RET. Results: Compared to placebo, MEL intake decreased post-exercise biomarkers of liver damage (aspartate aminotransferase, p<0.001; alanine aminotransferase, p<0.001; gamma-glutamyltransferase; p<0.05) and improved post-exercise renal function markers (i.e., creatinine, p<0.001). However, lipid profile, glucose, lactate and leukocyte were not affected by MEL ingestion. Regarding the time to exhaustion, no difference was found between MEL (362.46 ± 42.06 s) and PLA (374.54 ± 57.97 s) conditions. Conclusion: The results of this investigation clearly attest that MEL ingestion before a maximal running exercise might protect athletes from liver damage and perturbation in renal function biomarkers. However, this study comprises an acute MEL supplementation and no assessment on chronic effects or circadian rhythm the day before was done.

Melatonin supplementation alleviates cellular damage and physical performance decline induced by an intensive training period in professional soccer players.

Melatonin has been proved to have positive effects on cellular damage and metabolic regulation. The aim of the study was to determine the effect of melatonin supplementation during an intensive training period on physical performance decline, oxidative stress and cellular damage state. The investigation was conducted on 20 soccer players who participated in an exhaustive six-day training schedule associated with daily 5 mg oral melatonin or placebo ingestion. Resting blood samples and physical performance were measured before and after the training period. The mixed 2-way ANOVA (group x training camp) showed that compared to placebo, melatonin intake prevented an increase in advanced oxidation protein products (p>0.05) and increased the antioxidant enzyme activity (i.e., superoxide dismutase; p<0.001). In addition, melatonin prevented an increase of biomarkers of renal function (e.g., creatinine; p>0.05) and biomarkers of muscle (e.g., creatine kinase; p>0.05) and liver (e.g., gamma-glutamyltransferase; p>0.05) damage. Furthermore, melatonin alleviated the deterioration in physical performance (countermovement jump, five-jump test and 20-m sprint; p>0.05). In conclusion, the obtained data showed increased oxidative stress and renal, muscle and liver damage in professional soccer players during an exhaustive training schedule. Melatonin intake during the training period exerts beneficial effects on physical performance and protects tissues against the deleterious effects of reactive oxygen species and cellular damage.

Oxidative stress in patients with asthma and its relation to uncontrolled asthma.

This study aims to evaluate markers of oxidative stress in Tunisian asthmatic patients and investigate whether their markers are correlated with uncontrolled asthma. This prospective cohort study was conducted on 48 healthy subjects and 60 patients with asthma (34 patients with controlled asthma and 26 patients with uncontrolled asthma). The levels of malondialdehyde (MDA), advanced oxidation protein products (AOPP), and glutathione (GSH), as well as the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), were estimated in plasma by spectrophotometry. Asthmatic patients have significantly higher plasmatic levels of MDA and AOPP than healthy controls (p < 0.001). Lower GSH level and GPx activity were found in patients with asthma compared to controls (p < 0.001). In contrast, higher SOD activity was noted in asthmatic patients (p < 0.001). The comparison among the patients with controlled asthma and uncontrolled asthma revealed increased MDA and AOPP levels and SOD activity (p < 0.001) as well as a decreased GSH level and GPx activity (p = 0.004, p = 0.019) in patients with uncontrolled asthma. Spirometry level was significantly correlated with SOD activity (r = 0.447; p = 0.010), whereas no significant correlations were found with the other parameters (MDA, AOPP, GSH, and GPx). Asthmatic patients, especially those with uncontrolled asthma, suffer a high degree of reactive oxygen species (ROS) formation causing considerable oxidative stress. Increased MDA level and SOD activity and reduced GPx activity were predictors of poorly controlled asthma.

[Multiple drug hypersensitivity in patients with an allergy to antibiotics]. / Hypersensibilité médicamenteuse multiple chez des patients ayant une allergie aux antibiotiques.

INTRODUCTION: Multiple drug hypersensitivity (MDHS) is defined as confirmed drug hypersensitivity (DHS) to 2 or more drugs that are not chemically related. The objective of our study is to describe the cases of MDHS with antibiotics notified to the regional pharmacovigilance service (SRPV) of Sfax (Tunisia). METHODS: Our study is of a descriptive cross-sectional type, focusing on patients who consulted at the SRPV in Sfax during the period between 2013 and 2020 and who presented at least two episodes of DHS occurring at different times (at least one month apart). RESULTS: In our study, we included 29 patients (18 women and 11 men with a mean age of 59 years) who presented 69 sequential MDHS reactions documented either by a positive re-administration in 29 cases or by allergological exploration in 20 case, or by a highly suggestive clinical history in 20 cases. The frequency of MDHS was 1.13%. The drugs involved in the occurrence of these 69 DHS reactions were antibiotics in 55 cases (80%), antiepileptics in 6 cases (9%), NSAIDs in 4 cases (6%) and other drugs in 4 cases (6%) (one case with allopurinol, one case with strontium ranelate and two cases with gliclazide). CONCLUSION: MDHS pose a real problem of therapeutic management. Indeed, these reactions can lead to a difficult choice of drugs with the impossibility of prescribing optimal first-line therapies.

Primary ciliary dyskinesia associated with multiple drug intolerance syndrome: a case report.

INTRODUCTION: The term multiple drug intolerance syndrome is used for patients who express adverse drug reactions to three or more drugs without a known immunological mechanism. It is a distinct clinical entity, different from cross-reactivity. The symptoms can range from a benign rash to life threatening syndromes like drug reaction with eosinophilia and systemic symptoms. CASE REPORT: We report the case of an 8-year-old child with primary ciliary dyskinesia complicated by bronchiectasis who presented multiple drug intolerance syndrome.Through this observation; we discuss the diagnostic elements of this syndrome. CONCLUSION: In the absence of validated criteria for diagnosing multiple drug intolerance syndrome, a detailed history is essential, especially to identify the warning signs and the risk factors.

Overexpression of P-glycoprotein and resistance to Imatinib in chronic myeloid leukemia patients.

BACKGROUND: The P-glycoprotein (P-gp) is one of the mechanisms of Imatinib (IM) resistance in chronic myeloid leukemia (CML). P-gp has been identified as an efflux pump involved in releasing of IM outside CML cells. To date, the P-gp involvement in the IM resistance development was not completely understood. Therefore, the present study aimed at measuring the P-gp expression level on lymphocytes from Tunisian patients with CML and correlating this level with a molecular response to IM. METHOD: The expression of P-gp on peripheral blood lymphocytes from 59 Tunisian patients with CML (27 IM responder patients vs 32 IM non-responder patients) was evaluated by flow cytometry. RESULT: Our finding showed significantly positive expression of P-gp in the lymphocytes from the IM non-responder group when compared to the IM-responder group (P = .001). In IM non-responder CML patients, the comparison between CCyR achievers and non-achievers showed a high mean fluorescence intensity (MFI) of P-gp expression in patients who did not achieve their CCyR (P = .001). The comparison between patients with primary and secondary resistance to IM showed an increasing MFI value in patients with primary resistance to IM (P = .001). Besides, the comparison between nilotinib-treated and dasatinib-treated patients proved a high value of MFI in nilotinib-treated patients (P = .001). CONCLUSION: The overexpression of P-gp on lymphocytes has significantly correlated with the failed molecular response to IM in patients with CML.

Effect of Different Running Exercise Modalities on Post-Exercise Oxidative Stress Markers in Trained Athletes.

The aim of this study was to examine the effect of running exercise modality on oxidative stress. Thirteen endurance athletes (age: 21.46 ± 0.66 years) performed three different running exercise modalities (Continuous running exercise (CR): continuous running exercise at 75% of VO2max for 25 min; intermittent running exercise #1 (15/15): intermittent running protocol, 15 s running at 75% of VO2max, 15 s passive recovery, performed for 50 min; intermittent running exercise #2 (30/30): intermittent running protocol, 30 s running at 75% of VO2max, 30 s passive recovery, performed for 50 min) in a randomized order. Blood samples were drawn at rest and immediately after each running exercise and assessed for malondialdehyde (MDA), advanced oxidation protein products (AOPP), superoxide dismutase(SOD), and glutathione peroxidase (GPX) activities. MDA increased by 55% following 30/30 exercise (p < 0.01), while it remained unchanged with CR and15/15 exercise. SOD increased after CR (+13.9%, p < 0.05), and also remained unchanged after 15/15 (p > 0.05) and decreased after 30/30 (-19.7% p < 0.05). GPX and AOPP did not change after exercise in all experimental sessions (p > 0.05). In conclusion, 30/30 intermittent running induced higher lipid damages than the 15/15 and CR exercise. 15/15 intermittent exercise promoted a better balance between free radicals production and antioxidant defense compared to continuous exercise and intermittent 30/30 exercise.

Effect of nocturnal melatonin intake on cellular damage and recovery from repeated sprint performance during an intensive training schedule.

An optimal recovery between training sessions is of similar if not greater importance as the training content and program of the training, itself. One of the most used strategies for improving recovery is the ingestion of supplements. The present study aimed to evaluate the effect of 5 mg oral melatonin supplementation on the recovery from repeated sprint (RSA) of performance and biochemical responses (i.e. oxidative stress, leukocytosis cellular damage) after an intensive training camp (TC). Twenty soccer players performed an RSA test before and after an intensive six-day TC associated with nocturnal melatonin (n = 10) or placebo (n = 10) ingestion. Resting and post-RSA test blood samples were obtained before and after the TC. Compared to placebo, melatonin intake decreased resting oxidative stress markers (i.e, advanced oxidation protein products), leukocytosis (i.e. white blood cells (WBC), neutrophils (NE)) and biomarkers of cellular damage (i.e. creatine kinase (CK)). It also lowered post-exercise leukocytosis (i.e. WBC, NE, lymphocytes (LY), monocytes (MO)) and biomarkers of cellular damage (i.e. CK, aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT)) and raised the activity of the main antioxidant enzymes (i.e. glutathione peroxidase (GPx), glutathione reductase (GR)). In addition, compared to placebo, melatonin reduced the deterioration of the best and total time during the RSA test after the TC. In conclusion, nocturnal melatonin supplementation during an intensive TC alleviated oxidative stress, leukocytosis and cellular damage and improved recovery of RSA performance in soccer players.

Relationship of oxidative stress in the resistance to imatinib in Tunisian patients with chronic myeloid leukemia: A retrospective study.

BACKGROUND: This work aimed to evaluate oxidative stress in chronic myeloid leukemia (CML) patients treated with tunisian (IM) vs controls and in CML patients with resistance to IM vs patients without resistance to IM. METHODS: The study included 40 CML patients and 34 controls. Of 40 patients with CML, 26 patients were developed in resistance to IM. The oxidant/antioxidant markers were evaluated by spectrophotometric methods for all used samples. RESULTS: For CML patients, increased malondialdehyde (MDA) and advanced oxidation protein products (AOPP) levels were found compared to controls (P < .001; P = .01). Higher catalase (CAT) activity (P = .048) and lower superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, reduced Glutathione (GSH) and vitamin C levels were found in CML patients (P < .001). The comparison between the resistant vs no-resistant CML patients revealed higher MDA level (P = .02) and CAT and SOD activities in IM-resistant patients (P = .04, P = .03). GPx activity was reduced (P = .04). Furthermore, increased mean ratio of MDA/GSH, MDA/GPx, and SOD/(GPx + CAT) was found in IM-resistant patients as compared with no-resistant (P = .01, P = .01, P = .035). The mean ratio of GPx/GSH in the IM-resistant CML patients was lower than in IM no-resistant one (P = .039). For IM-resistant patients, we found negative correlation between MDA level and the ratio SOD/(CAT + GPx) (r = -0.46, P = .002); and positive correlation between SOD and (CAT + GPx) activities (r = 0.38, P = .06) and between GSH level and GPx activity (r = 0.53, P = .01). CONCLUSIONS: Our results have shown a highly disturbed oxidative profile in IM-resistant CML patients as compared to no-resistant. The H2 O2 has a key role in the resistance to IM treatment.

Polysaccharides extraction from Opuntia stricta and their protective effect against HepG2 cell death and hypolipidaemic effects on hyperlipidaemia rats induced by high-fat diet.

The aim of this study was to analyse cytoprotective effect of polysaccharides compound from Opuntia stricta (O. stricta) cladode (POS) in vitro including its radical scavenging activities and protective effects against hypercholesterolaemia. Our results showed that glucose was the dominant monosaccharides (30.35%). Arabinose, pyranose, fructose, galactose, glucose, sorbitol, S-inositol, M-inositol, trehalose and saccharose found in this species. O. stricta polysaccharides did not cause any cytotoxic effect on HepG2 cells within the range of concentrations tested (0-400 µgml-1). Pre-treatment of HepG2 cells with POS (100 µgml-1) significantly (p < .05) protected against cytotoxicity induced by DPPH and ABTS radicals. The POS showed strong antioxidant potential in vitro. The results indicated also that POS significantly prevented hypercholesterolaemia-induced elevation of serum biomarkers and induced increase in serum lipid profile. Moreover, the hypercholesterolaemia characterised by elevated lipid peroxidation (MDA) and reduced antioxidant enzyme defences (SOD, CAT and GPx) was restored by POS treatment.

[Epicutaneous patch testing in delayed drug hypersensitivity reactions induced by antiepileptic drugs]. / Place du patch-test dans le diagnostic des réactions d'hypersensibilités retardées induites par les antiépileptiques.

INTRODUCTION: Antiepileptic drugs are widely used and are associated with numerous side effects including skin eruptions. Epicutaneous tests have been used with variable success in skin drug reactions. The purpose of this study was to evaluate the profitability of epicutaneous tests in delayed hypersensitivity reactions induced by antiepileptic drugs. METHODS: We analyzed all cases of allergic skin reactions to antiepileptic drugs notified in regional pharmacovigilance center of Sfax (Tunisia) between June 1, 2014 and April 30, 2016. The imputation score, determined using the French imputation method, should be at least doubtful. Patch-tests were performed in accordance with the general Europen network on Drug Allergy/European Academy of Allergy and Clinical Immunology (ENDA/EAACI) guidelines. Patch-tests were read according to the generally accepted criteria of the International contact dermatitis research group (ICDRG). RESULTS: In our study, 20 patients were included, among which 23 events were observed. The drug involved in delayed hypersensitivity reactions was carbamazepine in 11 cases, phenobarbital in 10 cases and valproic acid in 4 cases. The clinical reactions caused by the drug were classified as maculopapular exanthema (11 cases), DRESS syndrome (6 cases), Stevens-Johnson syndrome (2 cases), fixed drug eruption (2 cases) and erythroderma (2 cases). Patch-tests were positive in 19 patients (95 %). Cross-reactivity between antiepileptic drugs was observed in 4 cases: between valproic acid and carbamazepine in 2 cases between valproic acid and phenobarbital in 1 case and between phenobarbital and carbamazepine in 1 case. CONCLUSION: In this study, patch testing was a safe and useful method in confirming the culprit drug in delayed hypersensitivity reactions induced by antiepileptic drugs.

Oxidative Stress in Tunisian Patients With Acute Lymphoblastic Leukemia and Its Involvement in Leukemic Relapse.

The aim of the present study was to evaluate in patients with acute lymphoblastic leukemia (ALL), the oxidative status and antioxidant defense and its involvement in the relapse of ALL. The plasmatic levels of malondialdehyde, advanced oxidation of protein products and reduced glutathione (GSH), and the plasmatic activities of catalase, superoxide dismutase (SOD), and glutathione peroxidase were determined in 34 patients who were newly diagnosed with ALL and compared with 92 healthy individuals. The plasmatic concentrations of malondialdehyde and advanced oxidation of protein products were higher in ALL patients than in controls and increased during chemotherapy. A decrease in glutathione peroxidase activity and an increase in catalase and SOD activities and GSH plasma levels were observed in ALL patients, as compared with sex-matched controls. Moreover, SOD activity and GSH levels were significantly correlated with the relapse of ALL patients. These data suggest the involvement of oxidative stress in acute lymphoid leukemias and leukemic relapse.

Ciprofloxacin-induced crystal nephropathy.

Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug.

[Prospective observational study of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with chronic renal failure]. / Étude prospective observationnelle des hyperkaliémies secondaires aux inhibiteurs de l'enzyme de conversion chez des patients ayant une maladie rénale chronique hospitalisés.

OBJECTIVE: To study the incidence and risk factors of angiotensin converting enzyme inhibitors-induced hyperkalemia in hospitalized patients with hypertension and preexisting chronic renal failure. METHODOLOGY: Two-months prospective observational study was used including all hospitalized patients older than 18 years with a history of hypertension, non-dialyzed chronic renal failure and who had angiotensin converting enzyme prescription at the time of the admission. Hyperkalemia greater than or equal to 5 mmol/L was detected in these patients. The studied variables were demographic, clinical, biological and therapeutic. RESULTS: Eight patients, among 27 included, had a hyperkalemia (2963%). They were 73±15 years old. Factors that predispose to hyperkalemia were present in all patients. Hyperkalemia was associated in six cases with decompensation of renal function. The age was associated with hyperkalaemia in patients treated with angiotensin converting enzyme inhibitors (RC=1.21; IC95 1,11-1,46; P=0,021). Diabetes is a possible risk factor (OR=59 021 et, 95 0.93 to 2410, P=0.053). Compared with patients who did not develop hyperkalemia, the occurrence of hyperkalemia in patients included was associated with a longer duration of hospitalization (OR=130, 95 112 to 160, P=0. 022). CONCLUSION: The prescription of angiotensin converting enzyme inhibitors in the elderly with chronic renal failure and diabetes requires careful monitoring of serum potassium.

Helicobacter pylori associated with chronic urticaria.

Chronic urticaria is one of the most frequent skin diseases in medical practice. Urticaria is defined as acute if the whealing persists for less than six weeks and as chronic if it persists for longer. Chronic urticaria that lasts for several years to decades significantly impairs the quality of life. There is evidence that Helicobacter pylori has a critical role in different extragastric diseases such as chronic urticaria. We present a case of chronic urticaria in an adult patient with H. pylori infection and disease regression after triple anti-H. pylori therapy. In contrast to the autoimmune mechanisms involved in chronic urticaria against which no specific treatment strategy has been developed, infections with H. pylori could be treated with triple therapy. It is suggested that laboratory tests for the detection of this pathogen should be performed in patients with chronic urticaria.