Antibacterial activity and virtual screening by molecular docking of lycorine from Pancratium foetidum Pom (Moroccan endemic Amaryllidaceae).

Lycorine is an alkaloid isolated from bulbs of Pancratium foetidum Pom Amaryllidaceae of the genus Lycoris. It has very strong pharmacodynamics properties and biological effects, among others, antimalarial, antiviral, antitumor, and anti-inflammatory. Lycorine has been identified and characterized by thin layer chromatography, IR and NMR (1H and 13C NMR, COZY, HMBC, HSQC and NOESY). The antibacterial activity of lycorine has been evaluated. Lycorine has a moderate antibacterial activity on the majority of strains studied, nevertheless it is more effective than Streptomycin and Ampicillin against bacteria: P. aeruginosa, En. cloacae. To confirm these results, it is necessary to use qualitative techniques and methods, etc… We performed a virtual docking ligand-lycorine protein screening study to predict and characterize their mode of interaction with the LpxC receptor. Docking results have shown that lycorine can interact with target amino residues studied by hydrogen and metal-ion bonds. In addition, the ADME-Tox profile study has shown that lycorine is all in agreement, either with Lipinski's critics or with the toxicity standards.

Essential oil composition and antifungal activity of Melissa officinalis originating from north-Est Morocco, against postharvest phytopathogenic fungi in apples.

To investigate biological control methods against post-harvest phytopathogenic fungi in apples, tests on the antifungal activity of essential oil of Melissa officinalis were carried out. The essential oil, obtained by hydrodistillation, was analyzed by gas chromatography coupled with mass spectrometry (GC-MS). Analysis of the essential oil was able to detect 88.7% of the components. The main components are P-mentha-1,2,3-triol (13.1%), P-menth-3-en-8-ol (8.8%), pulegone (8.8%), piperitynone oxide (8.4%) and 2-piperitone oxide (7.3%). The determination of the antifungal activity of the essential oil of M. officinalisis carried out in vitro using the technique of poison food (PF) and the volatile activity test (VA). To carry out these two tests, three phytopathogens that cause the deterioration of apples have been selected: Botrytis cinerea, Penicillium expansum and Rhizopus stolonifer. The overall results of this study suggest that M. officinalis essential oil has potential as a bio-antifungal preservative for the control of post-harvest diseases of apple.

Are infundibular dilatations at risk of further transformation? Ten-year progression of a prior documented infundibulum into a saccular aneurysm and rupture: Case report and a review of the literature.

Infundibular dilatations (IFDs) are conical, triangular, or funnel-shaped enlargements at the origin of cerebral arteries, and they are primarily located (7-25%) on the posterior communicating artery (PComA). Progression over time into a saccular aneurysm with a risk of rupture of a previously demonstrated IFD has rarely been reported. We report the case of a 60-year-old female who presented 10 years earlier with a subarachnoid hemorrhage caused by a left internal carotid artery aneurysm rupture. At that time, the carotid angiography showed the left internal carotid artery aneurysm and a right posterior communicating artery infundibular dilatation. Neck clipping for the left internal carotid artery aneurysm was performed and the patient was discharged with no neurological deficit. Ten years later, the patient suffered a second fatal subarachnoid hemorrhage; carotid angiography revealed a right posterior communicating artery aneurysm developed from the previously documented infundibular dilatation with a de novo right anterior choroidal artery aneurysm. This case is another proof of the small but growing number of examples of infundibular transformation over time, as well as their risk of progression into saccular aneurysms and subsequent rupture.

A rare localization of meningioma: meningioma of the foramen of Monro.

Intraventricular meningiomas (IVM) are rare tumors, constituting only 0.5 to 2% of all intracranial meningiomas, and meningiomas localized within the foramen of Monro are exceptional, with only a very few cases reported in the literature. We report the case of a 41-year-old man, admitted to our department for headaches. MRI found a mass tissular well enhanced after gadolinium injection, arising in the region of the foramens of Monro, and extended to the lateral and the third ventricles. Histological examination revealed a meningioma.

[Xeroderma pigmentosum associated with intracerebral tumor: a case report]. / Xeroderma pigmentosum compliqué d'une tumeur intracérébrale : à propos d'un cas.

Patients with the genetic disease xeroderma pigmentosum (XP) lack the ability to carry out a specific type of DNA repair process called nucleotide excision repair (NER). The NER pathway plays a critical role in the repair of DNA damage resulting from ultraviolet (UV) radiation. We report a case of a patient presenting a cutaneous form of XP. She presented acute paralysis of the third cranial nerve with cutaneous anesthesia. Nuclear magnetic resonance imaging revealed an intracranial tumor. She underwent surgery with incomplete tumor resection; anatomopathological study showed a schwannoma. Complementary radiosurgery was performed. The association between XP and neurological cancer is rare but not impossible. A priori, it would be assumed that the major medical outcome of hereditary deficiencies in DNA repair processes would be an increased risk of cancer. Indeed, there is an increased risk of cancer in several known DNA repair deficiencies including XP.

Intracranial meningioma in children: different from adult forms? A series of 21 cases.

OBJECTIVE: Intracranial meningiomas are very rare in children, comprising only 0.4 to 4.1% of pediatric tumors and only 1.5 to 1.8% to all intracranial meningiomas. The goal of this study of pediatric meningiomas was to establish their epidemiological profile as well as their clinical and radiological features, to assess the long-term outcome, and compare this result with adult meningioma. PATIENT AND METHODS: We conducted a retrospective study from June 1983 to June 2007; during this period 521 patients underwent surgery for primary meningioma at the Rabat Hospital, Department of Neurosurgery. Twenty-one patients were under 16 years of age (4%). The clinical charts and imaging data were reviewed. RESULTS: The mean age was 10.3 years (range: 2 to 16 years), with 13 boys and eight girls. In one patient a neurofibromatosis was associated. The mean delay to diagnosis was 4.6 months (range: 1 to 12 months). The most common clinical sign was raised intracranial pressure (90%). Of the meningiomas diagnosed, 47% were convexity meningiomas while 24% were parasagittal and 19% were skull-base meningiomas; in two cases (9.5%) the location was intraventricular. The mean tumor diameter was 6.6 cm (range: 3 to 10 cm). A large cystic component was found in 24% of the cases. Surgery achieved a Simpson grade I resection in 47%; 62% of the tumors were grade I and 24% were grade II based on World Health Organization pathological classification. The mean follow-up period was 33 months (range: 6 to 120 months). The recurrence rate was 33%. CONCLUSION: Pediatric meningiomas are larger than those found in the adult population; there is a male predominance with high incidence of a cystic component and high-grade meningiomas, thus explaining the increased recurrence rate despite the multimodal treatment.

[Sub occipital Pott's disease: report of 8 cases]. / Tuberculose de la jonction caranio-rachidienne. A propos de 8 observations.

Craniocervical Pott's disease remains exceptional, and may cause spinal instability and severe cervicomedullary complications. We report eight cases of tuberculous spondylodiscitis at the craniocervical junction revealed by signs of spinal cord compression, torticollis and dysphagia. The value of CT and MR imaging is discussed.

Cytotoxic effect and electrophysiologic activity of (R)-bgugaine, an alkylpyrrolidine alkaloid against MRC-5 fibroblasts.

The cytotoxicity and the electrophysiological effects against MRC-5 fibroblasts of 2-alkylpyrrolidine, (-)-R-bgugaine [1], a natural alkaloid, extracted from Arisarum vulgare Targ., (Araceae) were studied. This compound showed a cytotoxic potential against MRC-5 fibroblasts at 10 microg/ml. The electrophysiological study of this molecule on MRC-5 cells was carried out using the technique of patch-clamp and showed that (-)-R-bgugaine [1] has a sub-maximum effect on the outward potassium (current) at the concentration of 1 microM (0.281 microg/ml). In this study we show that R-bgugaine [1] activates the outwards potassium (current) activated by intracellular calcium.

Cytotoxic effect and electrophysiological activity of (S)-bgugaine, an alkylpyrrolidine alkaloid against MRC-5 fibroblasts.

(+)-S-bgugaine [1], is an alkaloid prepared by enantioselective synthesis. This alkaloid is an isomer of R-bgugaine [2], an alkaloid isolated from Arisarum vulgare, an Araceae toxic plant of Morocco. The cytotoxic effect and the electrophysiological activity of (+)-S-bgugaine [1] against MRC-5 fibroblasts of (+)-S-bgugaine 1, were studied. (+)-S-bgugaine [1] showed a cytotoxic potential at 40 microg/ml against these MRC-5 cells. The electrophysiological study on MRC-5 cells was carried out using the technique of patch-clamp and showed that the activity of compound 1 involved a reduction of outward potassic current at the concentration of 100 microM (28.1 microg/ml) and was accentuated by 200 microM (56.2 microg/ml). In this study we show that S-bgugaine [1], decreases the outward potassic current.

Irniine, a pyrrolidine alkaloid, isolated from Arisarum vulgare can induce apoptosis and/or necrosis in rat hepatocyte cultures.

The effects of irniine, a pyrrolidine alkaloid extracted from the tubers of Arisarum vulgare, on rat hepatocyte primary cultures and rat liver epithelial cell line (RLEC) were studied. Cytotoxicity was first evaluated by LDH release, MTT and NR tests and MDA production, while cellular alterations were visualized by electron microscopy and DNA gel-electrophoresis. In hepatocyte and RLEC cultures, a major toxicity appeared at 40 microM of irniine and was demonstrated by an increase in LDH release and decreases in MTT reduction and NR uptake while concentrations lower than 40 microM did not induce significant changes in these parameters. However, we observed an increase in MDA production at 30 microM. Important alterations of the nuclei and mitochondria were also visualized by electron microscopy in cells treated with 50 microM. Using DNA gel-electrophoresis, we demonstrated that irniine at 40 and 50 microM induced DNA damage. All together these results demonstrate that: (1) Irniine induces a significant hepatotoxicity. (2) Irniine toxicity is not mediated by a metabolic derivative since RLEC, which do not contain a monooxygenase system, were also affected by this compound. (3) Irniine induces a significant DNA damage and oxidative stress which leads to cell death by necrosis and/or by apoptosis. Moreover, our data suggest that the alkaloid irniine contained in A. vulgare may be involved in the toxic symptoms observed after medicinal use or consumption of the plant tubers as food both by humans and animals.

Bgugaine, a pyrrolidine alkaloid from Arisarum vulgare, is a strong hepatotoxin in rat and human liver cell cultures.

Toxicity of bgugaine, a pyrrolidine alkaloid extracted from the tubers of Arisarum vulgare, was studied in three different liver cell culture models: (1) the rat hepatocyte primary culture; (2) a liver epithelial cell line; and (3) the human hepatoblastoma cell line HepG2. Cytotoxicity was evaluated by LDH release, MTT reduction and MDA production. DNA fragmentation was analysed by flow cytometry or DNA gel-electrophoresis. In hepatocyte and epithelial cell cultures, drug toxicity appeared at 30 microM and was evaluated by an increase in LDH release, a decrease in MTT reduction and a higher level of MDA production. Bgugaine concentrations lower than 30 microM did not induce changes in these parameters. In HepG2 cells, bgugaine treatment also induced LDH release at concentrations of 40 and 50 microM. DNA fragmentation, analysed in the HepG2 cell line by flow cytometry, was observed in cultures exposed to 50 microM bgugaine. However, using DNA gel-electrophoresis, we demonstrated that lower bgugaine concentrations (10, 20 and 30 microM) also induced DNA damage. Our results show that: (1) bgugaine induces an important hepatotoxicity; (2) bgugaine toxicity is not mediated by a metabolic derivative; and (3) bgugaine induces a significant DNA damage. Therefore, our data suggest that the alkaloid bgugaine contained in Arisarum vulgarae may be involved in the toxicologic symptoms observed after consumption of this plant tubers by humans and animals.

DNA affinity of active alkaloids from Arisarum vulgare Targ.

Some 2-alkylpyrrolidine and 2-alkylpiperidine alkaloids isolated from Arisarum vulgare Targ. demonstrated activity in a high-performance liquid chromatographic system designed to detect compounds capable of interacting with DNA. (-)-R-Bgugaine (N-H), an alkaloid prepared by synthesis, exhibited an important positive response, with total inhibition of DNA absorption at 254 nm. The concentration-dependence of these compounds was determined.

A new toxic alkylpyrrolidine alkaloid from Arisarum vulgare.

From the tubers of Arisarum vulgare Targ. (Araceae), a new toxic alkylpyrrolidine alkaloid has been purified and characterized. By 2D COSY NMR spectroscopic methods, its structure was elucidated as: (-)- R- N-methyl-2-[9'-(2''-methoxyphenyl)nonyl]pyrrolidine.

The immunomodulator OM-89 induces ACTH and glucocorticoid secretion in rats through an IL-1 dependent pathway.

The immunomodulator OM-89 (bacterial extract from E. coli), known to act on the immune system by modulating both humoral and cellular responses, significantly increases ACTH and glucocorticoids secretion in normal Wistar rats. A comparative administration of IL-1 displays a similar pattern of release. Moreover, OM-89-induced responses are blocked by IL-1ra, the soluble receptor antagonist of IL-1. The effect of OM-89 can thus be explained, at least in part, via IL-1 which directly enhances the secretion of both stress hormones. Finally, a comparative experiment between control and stressed rats (by immobilization) shows that the responses to OM-89 measured in this study (ACTH and corticosterone secretion) are stress-modulated.