The extract of Mucuna pruriens possesses histamine activity

ObjectiveTo investigate the activity of the active principle in the spines of the seed pods of Mucuna pruriens using contraction of guinea pig ileum as index of pharmacological activity.MethodsThe active principle was extracted with 0.0015 M NaCl. Muscle strips of guinea pig ileum were prepared and contractile responses were measured using a Kymograph. Two sets of experiment were conducted: (1). The contraction of the ileum in presence of different concentrations of histamine, 2-methylhistamine and the extract of Mucuna pruriens. (2). The contractile response of the ileum in presence of different concentrations of the extract and antagonists including diphenhydramine, atropine and methysergide.Results(1) The extract of Mucuna pruriens hair, 2-methylhistamine and histamine produced dose dependent contraction of guinea pig ileum (Extract ED₅₀ = 13.0 μg/mL, 2-methylhistamine ED₅₀ = 8.5 μg/mL and histamine ED₅₀ = 10.0 μg/mL). (2) Diphenhydramine, an H₁ antagonist competitively blocked the contractile response of the Mucuna pruriens extract. (3) Coadminstration of the Mucuna pruriens extract either with different doses of antimuscarinic agent atropine or 5-hydroxytryptamine blocking agent methysergide did not alter the extract induced contractile response of the guinea pig ileum.ConclusionThese results demonstrate that the spines of Mucuna pruriens possess histamine activity which may contribute to its itching and painful irritation effects.     

Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors

BRAF and NRAS are commonly mutated in cancer and represent the most frequent genetic events in malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, about 10% of the cases lack mutations in these genes. It is our hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild-type GIST pathogenesis. Alterations in RAS/MEK/ERK pathway may also be involved in development of imatinib resistance in GIST, particularly in tumors lacking secondary KIT or PDGFRA mutations. Imatinib-naive wild-type GISTs from 61 patients, including 15 children and 28 imatinib-resistant tumors without secondary KIT mutations were analyzed. Screening for hot spots mutations in BRAF (exons 11 and 15) and NRAS (exons 2 and 3) was performed. A BRAF exon 15 V600E was identified in 3 of 61 GIST patients, who shared similar clinical features, being 49- to 55-years-old females and having their tumors located in the small bowel. The tumors were strongly KIT immunoreactive and had a high risk of malignancy. An identical V600E BRAF mutation was also identified in one of 28 imatinib resistant GIST lacking a defined mechanism of drug resistance. In conclusion, we identified a primary BRAF V600E mutations in 7% of adult GIST patients, lacking KIT/PDGFRA mutations. The BRAF-mutated GISTs show predilection for small bowel location and high risk of malignancy. A secondary V600E BRAF mutation could represent an alternative mechanism of imatinib resistance. Kinase inhibitors targeting BRAF may be effective therapeutic options in this molecular GIST subset.