Evaluation of a Modified Version of the United Kingdom Working Party Diagnostic Criteria for Atopic Dermatitis in Tunisia.

BACKGROUND: For many years, the United Kingdom (UK) Working Party diagnostic criteria for atopic dermatitis (AD) have represented the criteria of choice for epidemiological studies. A recent study has reported a low sensitivity of these criteria among Tunisian patients, probably because of some epidemiologic characteristics of AD in our country. OBJECTIVE: Our objective was to validate a modified version of the UK Working Party criteria for AD in Tunisia by establishing their sensitivity, specificity, and positive predictive value and negative predictive value. MATERIALS AND METHODS: This case-control study was performed over a period of 18 months in our dermatology department in Tunisia. The diagnosis of AD was established clinically by 2 dermatologists who specialized in dermatoallergology. Based on the UK Working Party diagnostic criteria and respecting the epidemiological peculiarities of AD in Tunisia, we proposed a modified version of diagnostic criteria adapted to Tunisian AD. The modifications concerned the first, fourth, and fifth minor criteria of the UK Working Party diagnostic criteria list. RESULTS: We collected 156 patients and 156 controls. The mean age of AD onset was 7 years and 9 months. The inverted topography of lesions was found in 67.9% of cases. The sensitivity, specificity, positive predictive, value and negative predictive value were, respectively, 56.4%, 97.4%, 95.65%, and 69.09% for the UK Working Party diagnostic criteria and 89.1%, 95.5%, 95.1%, and 89.7% for the modified version. CONCLUSIONS: This modified version of the UK criteria seems to be a practical diagnosis tool for AD in Tunisia.

Severe childhood lichen planus pemphigoides after hepatitis A vaccination.

Background: Lichen planus (LP) pemphigoides (LPP) is a very rare autoimmune bullous disorder, that is, exceptional in children. Case Report: We report a case of LP pemphigoides with severe cutaneous and mucosal involvement in an 8-year-old girl who consulted for multiple vesicular and bullous lesions associated with shiny erythematous-purple plaques. The eruption occurred 2 months after vaccination against hepatitis A virus. The diagnosis of LP pemphigoides was confirmed by histopathology and immunofluorescence examination. The patient received oral corticosteroid therapy with rapid improvement. Conclusion: To our knowledge, this is the first report of LPP following hepatitis A vaccination, among adults and children.

Algerian propolis: between protection of normal cells and potentialisation of the anticancer effects of doxorubicin against breast cancer cells via P-glycoprotein inhibition and cell cycle arrest in the S phase.

Breast cancer is a common cancer and is the leading cause of cancer-related deaths among women worldwide. Studies have shown that breast cancer is a heterogeneous tumor with varying response to treatments. The clinical use of doxorubicin (Dox) in the treatment of cancer is limited by its cardiotoxicity which results in often fatal heart failure and the development of multidrug resistance. Therefore, new therapeutic strategies and targets are underscored. Propolis has been reported to show a broad spectrum of biological activities including anticancer activity. In this study, we investigated the role of propolis on the antitumor effects of Dox on breast cancer cells (MDA-MB-231) and its ability to provide protection against Dox-mediated damage on normal cells (MRC-5). Modifications in cell viability, apoptosis induction, cell cycle progression and permeability glycoprotein (P-gp) activity of breast cancer cells in vitro were evaluated. Propolis combined with Dox inhibited cell growth in a dose dependent manner by inducing cell cycle arrest in the S phase and caspase-dependent apoptosis. In the presence of propolis, the IC50 of Dox against MDA-MB-231 cells decreased by 10-fold. The increased sensitivity of cancer cells to the combined treatment was explained by the capacity of propolis to cause a significant increase in Dox content in MDA-MB-231. Very interestingly, Algerian propolis showed its ability to inhibit efficiently P-gp function in comparison with verapamil, reference P-gp modulator, which proves the efficacy of propolis to reverse the problem of multidrug resistance. Our results showed also that propolis could protect normal cells from deleterious effects of Dox by amelioration of cell viability. In conclusion, the obtained results indicate that Algerian propolis potentiated the antitumor effects of Dox on breast cancer cells and could reduce the problem of multidrug resistance. Therefore, Algerian propolis may be an effective agent in a combined treatment with Dox for increased therapeutic efficacy against breast cancer. Clinically, our results are relevant because with this combined therapy it may be possible to counter the problem of cancer cell resistance while reducing the problem of toxicity on normal cells.

Oxidative stress in benign prostate hyperplasia.

To assess the status of oxidative stress in benign prostate hyperplasia, a very common disease in older men which constitutes a public health problem in Jijel, prostate tissues were obtained by transvesical adenomectomy from 10 men with benign prostate hyperplasia. We measured the cytosolic levels of malondialdehyde (MDA) and glutathione (GSH) and cytosolic enzyme activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione S-transferase. The development of benign prostate hyperplasia is accompanied by impaired oxidative status by increasing levels of MDA, depletion of GSH concentrations and a decrease in the activity of all the antioxidant enzymes studied. These results have allowed us to understand a part of the aetiology of benign prostate hyperplasia related to oxidative stress.

Polyphenolic fraction of Algerian propolis protects rat kidney against acute oxidative stress induced by doxorubicin.

We evaluated the effects of propolis extract on renal oxidative stress induced by doxorubicin throughout an analytical and pharmacological study of the eastern Algerian propolis using thin layer chromatography, ultra-violet-high-performance liquid chromatography) and gas chromatography-mass spectrometry. The pharmacological study was carried out in vivo on Wistar rat pre-treated with propolis extract 100 mg/kg/day for seven days. Doxorubicin at 10 mg/kg of body weight was administered intravenously on Day 7. Serum creatinine concentration, scavenging effect of flavonoids, lipid peroxidation and glutathione concentration were measured. Chemical analysis allowed identification and quantification of the phenolic compounds including pinostrombin chalcone (38.91%), galangin (18.95%), naringenin (14.27%), tectochrysin (25.09%), methoxychrysin (1.14%) and a prenylated coumarin compound suberosin (1.65%). The total flavonoid concentration in the propolis extract was 370 mg (quercetin equivalents QE) /g dry weight (QE/g DWPE). Propolis extract restored the renal functions and reduced the toxic effect of doxorubicin. These data show a protective effect of Algerian propolis extract against doxorubicin-induced oxidative stress.

Disruption of mitochondrial membrane potential by ferulenol and restoration by propolis extract: antiapoptotic role of propolis.

This paper reports an investigation of the ability of propolis extract (a resinous substance collected by honeybees from various plant sources) to restore the collapse of mitochondrial membrane potential induced by ferulenol, a sesquiterpene prenylated coumarin derivative isolated from the plant Ferula vesceritensis . We show that ferulenol was able to induce the permeability transition pore (PTP) opening. This effect is caused by the interaction of the compound with the mitochondrial respiratory chain, more particularly by the fall of membrane potential and the inhibition of complex II. We have previously demonstrated that this inhibition results from a limitation of electron transfers involved in the respiratory chain and initiated by the reduction of ubiquinone. We hypothesized that the protective effect of propolis could be due to a direct action on mitochondrial functions. So we have investigated in vitro the mitochondrial effects of Algerian propolis using rat liver mitochondria, by analysing their effects on membrane potential, mitochondrial respiration and mitochondrial swelling. We show that propolis extract was able to restore the fall of mitochondrial membrane potential. Taken together these data reveal that propolis extract may be an interesting inhibitor of PTP and provide an additional mechanism by which the natural product propolis extract may restore the mitochondrial membrane potential and to prevent apoptotic process.

Evaluation of epirubicin-induced acute oxidative stress toxicity in rat liver cells and mitochondria, and the prevention of toxicity through quercetin administration.

Anticancer therapy with epirubicin (EPI) results in acute hepatotoxicity, likely due to the generation of free radicals. However, the oxidative status of rat liver cells and mitochondria after EPI toxicity has not been investigated. In the present study, we first investigated the pro-oxidant effect of EPI on both hepatic cells and mitochondrial function. Injection of EPI into rats at a dose of 9mg/kg (cumulative dose in human chemotherapy), induced hepatic dysfunction, as revealed by a significant increase in serum glutamate oxaloacetate transaminases (SGOT) and glutamate pyruvate transaminases (SGPT). Oxidative stress in liver cells and mitochondria was provoked by EPI because a statistically significant reduction of catalase (CAT), superoxide dismutase (SOD) and cytosolic glutathione (GSH) levels, and a significant increase in malonedialdehyde (MDA) levels - an indicator of lipid peroxidation that can perforate biological membranes - were observed. Second, the protective effect of quercetin (QE) (0.33mg/kg) against EPI-induced oxidative stress was also investigated. Indeed, the pretreatment of rats with QE protected liver cells and mitochondria from oxidative stress. This treatment prevented hepatic dysfunction by maintaining normal levels of serum transaminases following the inhibition of their hepatic leakage by preventing lipid peroxidation. Thus, QE works through the prevention of cellular membrane perforation and the antioxidant defense system of mitochondria from liver cells, which represent compartments for the permanent production of reactive oxygen species (ROS) through the respiratory chain.

Cardioprotective effects and mechanism of action of polyphenols extracted from propolis against doxorubicin toxicity.

Propolis is one of the major hive products of bees and is rich in flavonoids, which are known for antioxidant activities. It is well known that the chemical properties of phenolic acids or flavonoids, in terms of the availability of the phenolic hydrogens as hydrogen donating radical scavengers, predict their antioxidant properties. In this study, the flavonoids scavenging activity of propolis has been exploited to obtain protection against the peroxidative damage in rat heart mitochondria which was induced by the administration of an acute dose of doxorubicin (20 mg kg(-1), i.p). The peroxidative lesions were evaluated biochemically and biophysically, 24 H after DXR administration. Abnormal biochemical changes in heart mitochondria from DXR treated rats including a marked increase in both malondialdehyde (MDA) and anion superoxide production; decrease both of respiratory chain ratio (RCR= V3/V4) and P/O. Pretreatment of rats with propolis extract, given per os (100 mg/kg/day) during four days prior to DXR injection, substantially reduced the peroxidative damage in the heart mitochondria: we showed significant reducing both of mitochondrial MDA formation and production of superoxide anion, restoration of RCR and P/O and reducing of rate and the amplitude of mitochondrial swelling. The data demonstrate that antioxidants from natural sources may be useful in the protection of cardiotoxicity in patients who receive doxorubicin and as reported for its claimed beneficial effect on human health by biomedical literature.

[The flavonoids effect against vinblastine, cyclophosphamide and paracetamol toxicity by inhibition of lipid-peroxydation and increasing liver glutathione concentration]. / Effect protecteur des flavonoïdes contre la toxicité de la vinblastine, du cyclophosphamide et du paracétamol par inhibition de la peroxydation lipidique et augmentation du glutathion hépatique.

The paracetamol and cyclophosphamid are metabolized in the liver by the cytochrome P450. The formed reactive intermediates are responsible of a hepatocyte depletion of the glutathion and a lipoperoxydation. the vinblastine is also a chemotherapeutic agent hepatotoxic and hematotoxic. Otherwise, flavonoïds are polyphenols substances of plant origin having some biological and anti-oxydative properties. However no information is available on their effects on glutathion and glutathion-s-transferases. In our research, we valued the effect of oral administration of flavonoids (diosmine and quercetine) under shape of propolis extract to 60 mg/kg daily during 14 days, on hematological and hepatic toxicity of a single dose of cyclophosphamide 80 mg/kg by intravenous way, vinblastine 2 mg/kg by intravenous way and the hepatic toxicity of the paracetamol managed by oral way to 200 mg/kg corresponding to 2/3 the DL50 at the rat female albinos wistar. We did a blood numeration, an assessment of serum activities of transaminases and alkali phosphatases as well as quantification of the glutathion and the malondialdehyde (MDA) in liver homogenats of rats treated. Analyses are done at regular intervals; 1, 3, 7 and 14 days after the administration of drugs. In the group of rats treated by the cyclophosphamid paracetamol alone we observed since the 1st day, an increase of lipid peroxide (MDA) of 120% and a downfall of hepatic glutathion including the group receiving the vinblastine (until 210% of reduction). In the same way a severe leucopenia and a thrombopenia (70% of reduction) are observed between the 3rd and the 14th day at rats treated by the chemotherapeutic agents alone (cyclophosphamide and vinblastine). The combination of flavonoids with drugs have clearly reduced the effect of drugs toxicity. Indeed, the aplasic observed with the vinblastine, as well as the leucopenia and thrombopenia of the cyclophosphamide are corrected entirely. In the same way, we noted a restoration of rates of peroxide and glutathion. Flavonoïds seem to act by activation of the turn over of the glutathion and enzymes stimulating particularly glutathion-s-transferases permitting the captation of the reactive metabolites of the studied drugs.

[Hepatopathy with a progressive course after one-time administration of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-uréa (CCNU) in rats]. / Hépatopathie d'évolution progressive après une seule administration de (chloro-2-éthyl)-1-cyclohexyl-3-nitroso-1-urée (CCNU) chez le rat.

A few cases of liver involvement have been reported in patients receiving treatment with CCNU. Nitrosourea CCNU is an antitumoral agent largely used in the treatment of some types of leukemia, Hodgkin's disease, bronchial or cerebral tumors. It was shown that CCNU induced pericholangitis and intra-hepatic cholestasis in rat: moderate after 20 mg/kg CCNU, these hepatic lesions were maximal on day 8. In the present report we were interested in the evolution of hepatic alterations a long time after cessation of drug administration. So we studied hepatic ultrastructure three months after a unique 20 mg/kg or 50 mg/kg CCNU administration. Lesions were stable after 20 mg/kg CCNU and no reversibility was observed 3 months after 50 mg/kg CCNU: evolution to cholangiolysis, to adenomatous transformation of parenchyma or biliary cirrhosis were noted.

Haematotoxicity of doxorubicin and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) and of their association in rats.

Doxorubicin is an anthracycline widely used in the treatment of leukaemias, lymphomas and solid tumors. Doxorubicin cannot pass into the cerebrospinal fluid. Nitrosoureas are known to be lipophilic and to be able to penetrate the blood-brain barrier. CCNU is a nitrosourea used to treat Hodgkin's disease, brain tumors and other solid tumors. The authors have previously reported on the nephrotoxicity and hepatotoxicity of these drugs; the present paper reports their findings on haematotoxicity in female Wistar rats. In one group 40 rats received 10 mg/kg doxorubicin. In a second group 40 rats received 20 mg/kg CCNU, and a further 40 rats received 50 mg/kg CCNU. In a third group 60 rats received the association doxorubicin 10 mg/kg plus CCNU 20 mg/kg. Blood counts were performed on days 4, 8, 15, 21 and 28 after treatment. Leucopenia and severe thrombocytopenia were noted after doxorubicin administration. A biphasic decrease in the leucocyte count was observed after CCNU treatment. More severe alterations were observed when doxorubicin and CCNU were combined. Very few data on haematological abnormalities following treatment of human patients have been published. Similarities can be seen between the haematological side-effects noted in rats and those occurring in humans treated with these cytotoxic drugs. Female Wistar rats seemed to be a good model to evaluate the haematological tolerance of anthracycline, nitrosoureas or of their association. If multiple courses of these drugs have to be administered, the evolution of haematological alterations must be known: the decrease phase of blood cells is followed by a rebound phase. The drug should be avoided during this phase of granulocyte activation.

[Hepatotoxicity of (chloro-2-ethyl)-1-cyclohexyl-3-nitroso-1-urea (CCNU) in the rat]. / Hépatotoxicité du (chloro-2-éthyl)-1-cyclohexyl-3-nitroso-1-urée ou CCNU chez le rat.

Few cases of liver involvement have been reported in patients receiving treatment with CCNU. CCNU is an anti-tumoral agent used in the treatment of leukemia, Hodgkin's disease and bronchial or cerebral tumors. A single daily dose of 20 or 50 mg/kg CCNU in female Wistar rats induces an important increase of transaminases, reaching 10 times initial level between day 2 and day 6, followed by a second and moderate increase between day 21 and day 28. Three-fold increased alkaline phosphatases and conjugated hyperbilirubinemia were noted for the two doses, and was greater for the higher dose. Histological and ultrastructural studies showed two types of lesions: during the first phase of transaminase elevation, edema and inflammatory infiltration of the portal spaces; during the second phase of transaminases elevation, numerous bundles of pericanalicular microfilaments and severe dilation of the biliary tract. Hepatic cells had few alterations although some necrotic foci were observed, particularly at the higher dose. So CCNU induced an intrahepatic cholestasis with pericholangitis in the rat.