La verità visibile nella natura e nella scrittura. Sul baco da seta di Khamis bar Qardahe (fine del XIII secolo)

Khamis bar Qardaḥe was an East Syrian author active in the last decades of the 13th century, probably a representative member of the East-Syrian community at the court camp of the Il-Khans, and somehow connected with the town of Arbela. In the present article, his poetic work is presented in the broader context of the so-called ‘Syriac Renaissance’, as an example of late East-Syriac literature profoundly influenced by Persian poetry. The poem On the Silk-Worm is here critically edited and translated for the first time into a European language. Its complicated imagery turns out to be an interesting mélange of philosophical concepts, meta-literary reflection – poetry as a way to knowledge and salvation –, Christian themes – including the virginal conception of Mary –, and Persian, possibly Sufic, motifs. The monorhyme poem is rich with sound figures such as alliteration and etymological play

Steroid therapy for a case of severe drug-induced cholestasis.

OBJECTIVE: To report a severe case of cholestatic liver disease successfully treated with corticosteroids following combined therapy with clarithromycin and nimesulide. CASE SUMMARY: A 15-year-old girl was admitted with cholestasis probably related to treatment with clarithromycin and nimesulide for an upper respiratory tract infection. Other causes of liver disease (infections, metabolic liver disorders, genetic cholestatic syndromes, autoimmune diseases, primary biliary tract disorders) were excluded. Liver biopsy showed a severe canalicular cholestasis with bile plugs in dilated bile canaliculi, giant cell transformation, and portal and lobular infiltrate. An objective causality assessment suggested that cholestasis was probably related to clarithromycin and/or nimesulide use. No benefit was derived from a course of ursodeoxycholic acid therapy. Since the patient experienced a progressive worsening in cholestasis, prednisone was started after 20 days. This therapy was promptly followed by improvement in clinical and laboratory test results. After 2 months of prednisone treatment, the patient became symptom-free with normal liver function tests. DISCUSSION: The manifestations of drug-induced hepatotoxicity are highly variable, ranging from asymptomatic hypertransaminemia to fulminant hepatic failure. No specific treatment for drug-induced hepatotoxicity exists. Early recognition and drug withdrawal are the keys to management of hepatotoxicity, but in some cases, liver disease may persist despite discontinuation of the drug. Possible advantages of corticosteroid therapy have not been well demonstrated. CONCLUSIONS: Application of the Naranjo probability scale indicates a probable relationship between cholestasis and nimesulide plus clarithromycin use. This case draws attention to a possible therapeutic option for some cases of drug-induced hepatotoxicity that show a severe course without any sign of improvement

La verit\ue0 visibile nella natura e nella scrittura: Sul baco da seta di Khamis bar Qarda\u1e25e (fine del XIII secolo)

Khamis bar Qarda\u1e25e was an East Syrian author active in the last decades of the 13th century, probably a representative member of the East-Syrian community at the court camp of the Il-Khans, and somehow connected with the town of Arbela. In the present article, his poetic work is presented in the broader context of the so-called \u2018Syriac Renaissance\u2019, as an example of late East-Syriac literature profoundly influenced by Persian poetry. The poem On the Silk-Worm is here critically edited and translated for the first time into a European language. Its complicated imagery turns out to be an interesting m\ue9lange of philosophical concepts, meta-literary reflection \u2013 poetry as a way to knowledge and salvation \u2013, Christian themes \u2013 including the virginal conception of Mary \u2013, and Persian, possibly Sufic, motifs. The monorhyme poem is rich with sound figures such as alliteration and etymological play

Ruta graveolens L. induces death of glioblastoma cells and neural progenitors, but not of neurons, via ERK 1/2 and AKT activation

Glioblastoma multiforme is a highly aggressive brain tumor whose prognosis is very poor. Due to early invasion of brain parenchyma, its complete surgical removal is nearly impossible, and even after aggressive combined treatment (association of surgery and chemo- and radio-therapy) five-year survival is only about 10%. Natural products are sources of novel compounds endowed with therapeutic properties in many human diseases, including cancer. Here, we report that the water extract of Ruta graveolens L., commonly known as rue, induces death in different glioblastoma cell lines (U87MG, C6 and U138) widely used to test novel drugs in preclinical studies. Ruta graveolens' effect was mediated by ERK1/2 and AKT activation, and the inhibition of these pathways, via PD98058 and wortmannin, reverted its antiproliferative activity. Rue extract also affects survival of neural precursor cells (A1) obtained from embryonic mouse CNS. As in the case of glioma cells, rue stimulates the activation of ERK1/2 and AKT in A1 cells, whereas their blockade by pharmacological inhibitors prevents cell death. Interestingly, upon induction of differentiation and cell cycle exit, A1 cells become resistant to rue's noxious effects but not to those of temozolomide and cisplatin, two alkylating agents widely used in glioblastoma therapy. Finally, rutin, a major component of the Ruta graveolens water extract, failed to cause cell death, suggesting that rutin by itself is not responsible for the observed effects. In conclusion, we report that rue extracts induce glioma cell death, discriminating between proliferating/undifferentiated and non-proliferating/differentiated neurons. Thus, it can be a promising tool to isolate novel drugs and also to discover targets for therapeutic intervention

<i>R</i>. <i>graveolens</i> a.e. is able to induce ERK1/2 phosphorylation in glioma and in A1 proliferating neural cells.

<p>Western blotting detection of p-ERK1/2 and ERK1/2 proteins in C6 glioma cells (A), in U138 glioma cells (B), in A1 cells (C) and in U87MG (D) treated with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. for 5, 10, 30 and 60 minutes. Two specific bands are observed respectively at 44 and 42 kDa. Each blot is representative of three separate experiments. The graphs show the relative quantitation of p-ERK1/2 and ERK1/2 in the different cell lines. Data are expressed as ratios of p-ERK/ERK. Asterisks represent p<0.05 <i>vs</i> controls. (G-H) MTT assay in U87MG cells (E), A1 cells (F), C6 glioma cells (G) and U138 cells (H) treated for 48 hours with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. (R48), 10μM PD98059 (PD) or in combination (PD+R48); *p<0.01 <i>vs</i> control conditions.°p<0.05 <i>vs</i> R48.</p

<i>R</i>. <i>graveolens</i> a.e. induces cell death in proliferating but not in differentiated A1 cells.

<p>(A) Microphotographs of the mouse mesencephalic embryonic cell line A1 mes c-myc (A1). They are proliferating/undifferentiated in the presence of serum (left panel) but acquire a neuronal phenotype upon serum withdrawal and stimulation with cAMP (right panel). (B) MTT assay on proliferating A1 cells in control conditions (♦) or treated with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. (■) for 24, 48, 72 and 96 hours. *p<0.01 <i>vs</i> controls. (C) MTT assay on differentiated A1 cells in control conditions (♦) or treated with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. (■) for 48 and 72 hours *p<0.01 <i>vs</i> controls. (D) Trypan blue exclusion test on proliferating A1 cells treated (light grey) or not (dark grey) with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. for 24, 48 and 72h; *p<0.01 <i>vs</i> controls. (E) Trypan blue exclusion test on differentiated A1 cells treated (light gray) or not (dark gray) with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. for 48 and 72h; *p<0.01 <i>vs</i> controls.</p

<i>R</i>. <i>graveolens</i> extract induces cell death of U87MG human glioma cells.

<p>(A) MTT assay on proliferating U87MG human glioma cells treated with vehicle (♦) or with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. (■) for 24, 48, 72, 96h, *p<0,01 vs control conditions. (B) Trypan blue exclusion test on U87MG glioma cells treated (light gray) or not (dark gray) with 1mg/ml <i>R</i>. <i>graveolens</i> a.e. for 24, 48 and 72h; *<0,01 <i>vs</i> control conditions.</p

Rutin does not influence proliferating A1 cells viability.

<p>Trypan blue exclusion test on proliferating A1 cells treated with or without (control) increasing concentrations of rutin (3μg/ml, 30μg/ml and 300μg/ml) for 24, 48 and 72h.</p

<i>R</i>. <i>graveolens</i> a.e. induces apoptosis in A1 cells.

<p>(A) Cell cycle was analyzed by means of Tali image-based cytometry on proliferating A1 cells in control conditions (dark grey) and 48h after 1mg/ml <i>R</i>. <i>graveolens</i> a.e. treatment (light grey) *p<0.01 <i>vs</i> controls (B) Number of apoptotic nuclei/100 cells treated (R48) or not (CTRL) with 1 mg/ml <i>R</i>. <i>graveolens</i> a.e. for 48 hours. *p<0.01 <i>vs</i> controls. (C-E) Caspase 3 activity expressed as absorbance at 400 nm in A1 cells (C), U87MG cells (D) and C6 cells (E) treated with vehicle (CTRL), 1mg/ml <i>R</i>. <i>graveolens</i> a.e. for 24 (R24) or 48 (R48) hours, 10μM PD98059 in combination with ml <i>R</i>. <i>graveolens</i> a.e. for 48 hours (PD+R48), 1μM wortmannin in combination with ml <i>R</i>. <i>graveolens</i> a.e. for 48 hours (W+R48) or the combination of the two inhibitors (PD+W+R48) for 48 hours. *p<0.01 <i>vs</i> control conditions.</p