Potentiality of benthic dinoflagellate cultures and screening of their bioactivities in Jeju Island, Korea

Eleven strains of benthic dinoflagellates (Amphidinium carterae (D1), Prorocentrum rhathymum (D2),Symbiodinium sp. (D3), Coolia malayensis 1 (D4), Ostreopsis ovata 1 (D5), Ostreopsis ovata 2 (D6),Coolia malayensis 2 (D7), Amphidinium operculatum 1 (D8), Heterocapsa psammophila (D9), Cooliamalayensis 3 (D10) and Amphidinium operculatum 2 (D11)) were collected in Jeju Island, Korea and cultured in 20 L carboys after establishing unialgal cultures. Their growth potential and biomass productivity were evaluated using two different culture media (IMK and f/2 medium); it was found thatIMK medium has the potential to culture benthic dinoflagellates compared to commonly used f/2 medium. Among the benthic dinoflagellates, A. carterae (D1) had the maximum cell density (148.6 × 103 cells mL-1), growth rate (0.317 ± 0.01 divisions day-1) and biomass (0.260 ± 0.03 g L-1 dry weight) in IMK medium at 20 days of culture. Also, screened bioactivities among the methanolic extracts of cultured dinoflagellates showed A. carterae (D1) to have the highest antioxidant and  anti-inflammatory effect and O. ovata 1 (D5) had the highest anticancer activity compared to the other strains. Taken together, this is the first report on the growth potential and biomass production of benthic dinoflagellate strains isolated from Jeju Island in appropriate culture medium as well as their importance in potential pharmacological applications.Key words: Amphidinium carterae, benthic dinoflagellates, biomass, bioactivities, culture conditions, Jeju Island

Alpha-Synuclein in bio fluids and tissues as a potential biomarker for Parkinson’s disease

Background: Parkinson's disease (PD) is a chronic neurological disorder that impairs normal motor function and has no cure at present. Diagnosis of PD is clinical only; biopsies confirming the presence of the disease can only be done post-mortem. Furthermore, similarities in the manifestation of PD symptoms to other diseases such as Multiple System Atrophy (MSA), make early diagnosis difficult and ambiguous. As a result, there is a high demand for research investigating biomarkers for timely diagnosis of PD. Alpha-synuclein (α-SYN) is a protein found misfolded in the brain and other body tissues of PD patients. Its relevance and association to PD make it a prime biomarker candidate. However, reports in the literature suggest that the structural form and location of α-SYN are key to yield a reliable diagnosis. The aim of this Minireview is to highlight efforts made in studying α-SYN as a biomarker over the past decade. Key Findings: Based on the literature surveyed, α-SYN was indeed the most widely studied candidate biomarker for PD. Cerebrospinal fluid (CSF) and skin were promising sites for assessing α-SYN effectiveness in differentiating PD from MSA. Furthermore, gastro-intestinal α-SYN was suitable for early diagnosis of PD. A combination of total α-SYN and other forms including but not limited to phosphorylated α-SYN were the best predictors of the disease. Conclusion: Misdiagnosis of patients enrolled in clinical trials is a confounding factor for PD drug development. A robust biomarker for PD will help eradicate this problem. Identifying an accurate biomarker for PD will also ensure timely therapeutic intervention to manage symptoms better and improve the quality of life of patients. The promise α-SYN and its phosphorylated form show in different tissues is a step forward in this direction.published_or_final_versio

The novel mTOR inhibitor RAD001 (Everolimus) induces antiproliferative effects in human pancreatic neuroendocrine tumor cells

Background/Aim: Tumors exhibiting constitutively activated PI(3) K/Akt/mTOR signaling are hypersensitive to mTOR inhibitors such as RAD001 (everolimus) which is presently being investigated in clinical phase II trials in various tumor entities, including neuroendocrine tumors (NETs). However, no preclinical data about the effects of RAD001 on NET cells have been published. In this study, we aimed to evaluate the effects of RAD001 on BON cells, a human pancreatic NET cell line that exhibits constitutively activated PI(3) K/Akt/mTOR signaling. Methods: BON cells were treated with different concentrations of RAD001 to analyze its effect on cell growth using proliferation assays. Apoptosis was examined by Western blot analysis of caspase-3/PARP cleavage and by FACS analysis of DNA fragmentation. Results: RAD001 potently inhibited BON cell growth in a dose-dependent manner which was dependent on the serum concentration in the medium. RAD001-induced growth inhibition involved G0/G1-phase arrest as well as induction of apoptosis. Conclusion: In summary, our data demonstrate antiproliferative and apoptotic effects of RAD001 in NET cells in vitro supporting its clinical use in current phase II trials in NET patients. Copyright (c) 2007 S. Karger AG, Basel

Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

Eradication of chronic myeloid leukemia stem cells: a novel mathematical model predicts no therapeutic benefit of adding G-CSF to imatinib

Imatinib mesylate induces complete cytogenetic responses in patients with chronic myeloid leukemia (CML), yet many patients have detectable BCR-ABL transcripts in peripheral blood even after prolonged therapy. Bone marrow studies have shown that this residual disease resides within the stem cell compartment. Quiescence of leukemic stem cells has been suggested as a mechanism conferring insensitivity to imatinib, and exposure to the Granulocyte-Colony Stimulating Factor (G-CSF), together with imatinib, has led to a significant reduction in leukemic stem cells in vitro. In this paper, we design a novel mathematical model of stem cell quiescence to investigate the treatment response to imatinib and G-CSF. We find that the addition of G-CSF to an imatinib treatment protocol leads to observable effects only if the majority of leukemic stem cells are quiescent; otherwise it does not modulate the leukemic cell burden. The latter scenario is in agreement with clinical findings in a pilot study administering imatinib continuously or intermittently, with or without G-CSF (GIMI trial). Furthermore, our model predicts that the addition of G-CSF leads to a higher risk of resistance since it increases the production of cycling leukemic stem cells. Although the pilot study did not include enough patients to draw any conclusion with statistical significance, there were more cases of progression in the experimental arms as compared to continuous imatinib. Our results suggest that the additional use of G-CSF may be detrimental to patients in the clinic

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

Neither MRI, CT nor US is superior to diagnose tumors in the salivary glands – an extended case study

OBJECTIVES: Ultrasonography (US), computed tomography (CT) and magnetic resonance imaging (MRI) are the most common radiological procedures for the diagnosis of tumor-like lesions of the salivary glands. The aim of the present study was to determine whether MRI or CT provide additional information besides that delivered by US. STUDY DESIGN/METHODS: 109 patients with a tumor-like lesion of the salivary glands underwent surgery. MRI and CT were arranged in 73 and in 40 patients respectively, whereas all 109 patients were prospectively diagnosed by US. The results of CT, MRI and US were compared with the histological outcome. Furthermore, the recent rise in the number of CT and MRI studies was investigated. RESULTS: On CT and MRI, there was no rise in the percentage of malignant tumors or advanced surgical procedures. In respect of the radiological assessment of the lesion (benign/malignant) and the correct diagnosis, CT, MRI and US were comparable in terms of sensitivity, specificity and accuracy. No significant difference was found in the Chi-square test (p > 0.05). CONCLUSION: The evaluation of the preoperative results of CT, MRI and US revealed no advantage for CT or MRI; these procedures are only required in specific cases. An update or revision of the current preoperative diagnostic management is deemed necessary