New cadinene sesquiterpenoids from the Formosan soft coral Xenia puerto-galerae

Six new cadinene sesquiterpenoids, xenitorins A-F (1-6), were isolated from the methylene chloride solubles of the Formosan soft coral Xenia puerto-galerae. The structures were elucidated by 1D and 2D NMR spectral analysis, and their cytotoxicity against selected cancer cells was measured in vitro.     

A new experimental model for secondary hyperparathyroidism

We have developed an animal model to study the pathogenesis of secondary hyperparathyroidism by inducing stable uremia in Sprague-Dawley rats by selective microligation of terminal branches of the left renal artery, followed by right nephrectomy. After 4 weeks the animals were killed, the parathyroid glands were removed and weighed, and blood samples were obtained. Of 30 rats, uremia developed in 22 (73%; uremic group) and eight (27%) died or did not become uremic. A sham-operated group of 15 rats served as control (control group). Creatinine levels were 1.8 +/- 0.5 mg/dl in the uremic group versus 0.5 +/- 0.1 mg/dl in the control group (p less than 0.0001). Parathyroid glands were hyperplastic in all rats with uremia and were heavier than parathyroid glands of control animals (70.3 +/- 26 vs 19.1 +/- 8 micrograms; p less than 0.0001). In the group with uremia, parathyroid hormone levels were increased over those of the control group (112.6 +/- 13 vs 28.9 +/- 6.2 pg/ml; p less than 0.0001), whereas osteocalcin levels were similar (36.6 +/- 11 vs 37.5 +/- 1 ng/ml). Serum calcium, phosphate, and alkaline phosphatase levels were similar in both groups. Our model can be used to test hypotheses concerning the treatment of secondary hyperparathyroidism and the relative pathogenetic relevance of vitamin D deficiency and phosphate retention.     

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.     

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.     

Differing histologic findings after bilateral and focused parathyroidectomy

BACKGROUND: Minimally invasive parathyroid surgery with intraoperative parathyroid hormone testing has been reported to be as successful as a bilateral operation. This study aimed to determine whether the histologic findings and outcomes differ in patients with primary sporadic hyperparathyroidism treated by a focal or a bilateral parathyroid exploration with intraoperative parathyroid hormone testing. To make the two groups comparable all patients had a solitary parathyroid adenoma identified preoperatively. STUDY DESIGN: Eighty unselected patients with primary hyperparathyroidism and a single abnormal parathyroid gland identified preoperatively by sestamibi scanning or ultrasonography were included in this study. All patients had intraoperative parathyroid hormone testing. RESULTS: Forty-five patients had standard bilateral neck explorations and 35 patients had focal neck explorations. In the bilateral neck exploration group a single adenoma was found in 38 patients (84%), a double adenoma in 3 patients (7%), hyperplasia in 3 patients (7%), and carcinoma in 1 patient (2%). In contrast, a single adenoma was identified in all patients in the focal neck exploration group. Sestamibi scanning and intraoperative parathyroid hormone assay were accurate in 87% and 84%, respectively, in the bilateral neck exploration group and in 96.9% and 94.3%, respectively, in the focal neck exploration group. All patients were normocalcemic (mean followup 17 months). CONCLUSIONS: Patients with primary hyperparathyroidism having a bilateral exploration had about a 15% higher rate of multiple parathyroid tumors than did patient having a focal approach. Despite this observation all patients were normocalcemic postoperatively. This suggests that either some histologically abnormal parathyroid glands do not function or there will be recurrences in patients treated by a focused approach. Longterm followup will be necessary to determine whether patients treated by focal neck exploration will develop recurrent primary hyperparathyroidism.