Cytotoxic chalcones and flavonoids from the leaves of Muntingia calabura

Two new dihydrochalcones, 2',4'-dihydroxy-3'-methoxydihydrochalcone, (-)-3'-methoxy-2',4',beta-trihydroxydihydrochalcone, a new flavanone, (2 S)-(-)-5'-hydroxy-7,3',4'-trimethoxyflavanone, and a new flavonol derivative, muntingone, along with sixteen known compounds, were isolated from the leaves of Muntingia calabura. The structures of these new compounds were determined using spectral analyses including extensive 2D NMR data. Among the isolates, (2 S)-5'-hydroxy-7,3',4'-trimethoxyflavanone, 4'-hydroxy-7-methoxyflavanone, 2',4'-dihydroxychalcone, and 2',4'-dihydroxy-3'-methoxychalcone exhibited cytotoxicity (IC (50) values < 4 microg/mL) against P-388 and/or HT-29 cell lines in vitro.     

New cytotoxic cyclobutanoid amides, a new furanoid lignan and anti-platelet aggregation constituents from Piper arborescens

Three new cyclobutanoid amides with trans-trans-trans configurations, piperarborenine C, piperarborenine D and piperarborenine E, and a new furanoid lignan, (+)-arborone, together with twelve known compounds, were isolated from the stems of Piper arborescens. The structures of these new compounds were determined by means of spectral analyses. Piperarborenine C, (+)-diayangambin, piplartine, piperolactam B, piperolactam C, aristolactam BIII, goniothalactam, and methyl trans-3,4,5-trimethoxycinnamate possessed anti-platelet aggregation activity in vitro. Among them, piplartine showed the most potent anti-platelet aggregation activity induced by collagen and showed an IC50 value of 21.5 microM. Piperarborenines A - E, piperarborenine, aristololactam BIII and goniothalactam showed significant cytotoxic activity (IC50 values < 4 microg/mL) against P-388, HT-29 and A549 cell lines in vitro.     

Cervids as Babesiae hosts, Slovenia

We describe cervids as potential reservoir hosts of Babesia EU1 and B. divergens. Both babesial parasites were found in roe deer. Sequence analysis of 18S rRNA showed 99.7% identity of roe deer Babesia EU1 with the human EU1 strain. B. divergens detected in cervids was 99.6% identical to bovine B. divergens.     

Ferromagnetic materials in patients: detection before MR imaging

A number of surgical clips and other metallic materials embedded within patients have ferromagnetic properties that present a potential hazard when in the strong fields associated with magnetic resonance imaging. Several types of magnetometers and metal detectors were investigated as possible pre-imaging screening devices. The sensitivities and costs of these devices are given.     

Epidural haematoma after evacuation of contralateral subdural haematoma

Background Sequentially evolving intracranial bilateral haematomas, where the second haematoma develops after the surgical removal of the first one is rarely reported. Aim To report a patient who developed an epidural haematoma after evacuation of a contralateral subdural haematoma. Methods A 49-year-old male was admitted to our department after head injury. A brain computerized tomography (CT) scan revealed an acute subdural haematoma in the right temporal area which was evacuated. During his stay in the intensive care unit, he was submitted to intracranial pressure monitoring, which soon rose. Results A new CT scan showed an acute epidural haematoma in the contralateral parietal area that was also evacuated. Conclusions While rising intracranial pressure after the evacuation of a traumatic haematoma is usually attributed to brain oedema or recurrent haematoma at the craniotomy site, the development of a contralateral epidural haematoma requiring surgical treatment should not be overlooked.     

Cytotoxic xanthones and biphenyls from the root of Garcinia linii

Three new xanthones, linixanthones A-C, two new biphenyls, garcibiphenyls A and B, and a new benzopyran, garcibenzopyran, together with twelve known xanthones and a known biphenyl have been isolated from the root of Garcinia linii. The structures of these new compounds were determined through spectral analyses. Among the isolates, five compounds exhibited cytotoxicities (ED50 values < 4 microg/mL) against P-388 and HT-29 cell lines in vitro.     

Emerging roles of targeted small molecule protein-tyrosine kinase inhibitors in cancer therapy

Targeted protein-tyrosine kinase inhibitors (PTKIs) comprise a new, rapidly evolving class of low molecular weight anticancer drugs. Two members of this class, imatinib (Gleevec) and gefitinib (Iressa), are currently approved for market use in the United States. This review discusses the scientific history behind these two PTKI drugs, including the role of the targeted kinase in cancer etiology, the biochemistry of selective inhibition, the evaluation of clinical efficacy, and the mechanisms whereby drug resistance has emerged. Other PTKIs undergoing clinical evaluation are also described, including epidermal growth factor receptor kinase inhibitors (erlotinib, PKI166, and CI-1033) and PTKIs designed to disrupt tumor vascularization (SU5416, SU6668, SU11248, PTK787, and ZD6474). How might one apply current knowledge to the efficient development of new agents that would target as-yet-unexploited oncogenic PTKs such as chimeric anaplastic leukemia kinases or Janus kinases? Ideally, the targets should contain structurally distinct drug interaction epitopes, although it is not necessary that these epitopes be unique to a single target, because effective drugs may inhibit multiple kinases involved in an oncogenic process. Oral availability is a highly desirable feature because daily oral administration can maintain a sustained efficacious plasma concentration, whereas intermittent parenteral administration may not. Perhaps most importantly, one must verify the presence of an appropriate molecular target on a case-by-case basis before selecting a patient for PTKI therapy. Thus, the development of molecularly targeted diagnostic tools will be crucial to the ultimate success of molecularly targeted PTKI therapy.