Diastereomeric quinolinone alkaloids from the marine-derived fungus Penicillium janczewskii

From Penicillium janczewskii, obtained from a marine sample, two new diastereomeric quinolinones, 3S,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (1) and 3R,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (2), were identified, along with two known alkaloids, peniprequinolone (3) and 3-methoxy-4-hydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (4). Cytotoxicity testing on eight tumor cell lines revealed a moderate specificity of 2 on SKOV-3 cells.     

New aromatic compounds from the marine mangrove Bruguiera gymnorrhiza

The phytochemical investigation of the stem of Bruguiera gymnorrhiza yielded five new aromatic compounds (1-5), of which the bruguierols A - C (1-3) represent a new structural skeleton in natural product chemistry. All structures have been determined by NMR spectroscopic studies. Among them, 3 showed moderate activity against Gram-positive and Gram-negative bacteria including mycobacteria and resistant strains (MICs 12.5 microg/mL).     

Weekly vinblastine in pediatric low-grade glioma patients with carboplatin allergic reaction

BACKGROUND: Carboplatin-based regimens have demonstrated activity in unresectable low-grade glioma (LGG) in children. Despite an interesting toxicity profile, the use of these regimens has been limited by the development of carboplatin hypersensitivity reaction (HSR) in up to 30% of patients. Desensitization has been the recommended approach for HSR. However, no guidelines have existed to aid physicians when carboplatin desensitization techniques fail. METHODS: A pilot study of monotherapy with weekly vinblastine for LGG in 9 children who developed carboplatin HSR on a carboplatin and vincristine regimen was performed. RESULTS: Vinblastine toxicity was moderate and readily manageable. None of the 9 patients had disease progression on therapy. Magnetic resonance imaging evaluation of tumor size from diagnosis to the end of vinblastine treatment showed 1 complete response (CR), 1 partial response (PR), 5 objective effects (OE), and 2 stable diseases (SD). CONCLUSIONS: This experience suggested that weekly vinblastine has a good efficacy to toxicity ratio in the treatment of LGG and can be a valuable option for children who develop severe HSR.     

Plasma kinetics of lutein, zeaxanthin, and 3-dehydro-lutein after multiple oral doses of a lutein supplement

BACKGROUND: Adequate intake of lutein is postulated to reduce the risk of age-related macular degeneration, but kinetic information for developing a dosing regimen is sparse. OBJECTIVE: The objective was to characterize lutein plasma kinetics in a multiple dosing design and to assess the effects of lutein intake on concentrations of other plasma carotenoids. DESIGN: After a run-in period of 7 d, 19 healthy volunteers were assigned to receive daily oral doses of 4.1 mg lutein (n = 8; group 1) or 20.5 mg lutein (n = 8; group 2) for 42 d or no lutein (n = 3; control group). The supplement contained 8.3% zeaxanthin relative to lutein (100%). The time profiles of plasma xanthophyll concentrations were monitored over the dosing phase, and samples were collected frequently on day 42 and for 24 d after dosing. RESULTS: Average plasma all-E-lutein concentrations increased from 0.14 to 0.52 +/- 0.13 and 1.45 +/- 0.69 micromol/L in groups 1 and 2, respectively. Dose-normalized lutein bioavailability in group 2 was approximately 60% of that in group 1. Kinetic disposition half-life did not differ significantly between groups. On average, dosing for 18 d was required to reach a >90% fraction of the steady state concentration, which is consistent with an effective half-life for accumulation of approximately 5.6 d. Plasma kinetics of all-E-lutein were paralleled by those of all-E-3-dehydro-lutein. Kinetic analysis indicated formation of all-E-3-dehydro-lutein from lutein. Lutein was well tolerated and did not affect the concentrations of other carotenoids. CONCLUSION: Long-term supplementation with 4.1 and 20.5 mg lutein as beadlets increased plasma lutein concentrations approximately 3.5- and 10-fold, respectively.     

Chronic myeloid leukemia: a model for oncology

Leukemias have traditionally served as model systems for research on neoplasia because of the easy availability of cell material from blood and marrow for diagnosis, monitoring and studies on pathophysiology. Beyond these more technical aspects, chronic myeloid leukemia (CML) became the first neoplasia in which the elucidation of the genotype led to a rationally designed therapy of the phenotype. Targeting of the pathogenetically relevant BCR-ABL tyrosine kinase with the selective kinase inhibitor imatinib has induced remissions with almost complete disappearance of any signs and symptoms of CML. This therapeutic success has triggered an intensive search for target structures in other cancers and has led to the development of numerous inhibitors of potential targets, which are being studied in preclinical and clinical trials worldwide. This review deals with some of the recent developments that have evolved since our last review in this journal in 2000 (Hehlmann R, Hochhaus A, Berger U, Reiter A (2000) Current trends in the management of chronic myelogenous leukemia. Ann Hematol 79:345–354).     

Does contextual information influence positive and negative schizotypy scores in healthy individuals? The answer is maybe

Defensive responding in schizotypy questionnaires might depend on context. Students completed a schizotypy questionnaire in a "psychiatric" context or a "creativity" context. Positive, but not negative, schizotypy scores were lower in the psychiatry than in the creativity group, but findings applied mainly to male participants. The implications of these findings are critically discussed.     

Cortical distinction between the neural encoding of objects that appear to glow and those that do not

Objects that appear to glow appear very different from those that do not. However, the neural representation of glow has not been investigated. We present data from an fMRI study which suggest that an extra-striate visual area is involved in the encoding of glowing stimuli, and that this activation does not arise from luminance or contrast factors. Possible functional reasons for the existence of such an area are discussed.     

Health service aspects of psychosomatic inpatient treatment in a general hospital

The study objective is to outline basic aspects of medical care service structure in the fields of psychosomatic medicine in a clinical acute-care setting. A total of 216 inpatients in a psychosomatic ward of a general hospital were investigated during a 32 months period using a retrospective study design. Referring physicians and clinics along with referral procedures, the waiting period, teamwork with other clinics, as well as patient and therapy characteristics are described. According to provisions of outpatient psychosocial care, general practitioners refer the majority of the inpatients (55 %), followed by other clinics (25 %) and psychosomatic and psychiatric outpatient specialists (20 %). An outpatient department along with a psychosomatic C-L service are key elements for a psychosomatic department to ensure coordination of the referral procedure. The average waiting period lasts 21 days, the average length of stay is 48 days. 60 % of the inpatients show somatic and psychiatric co morbidity. A psychopharmacological treatment has to be taken into consideration along with multi-modal psychotherapy in a third of all patients.     

An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene

Mutations of the protein O-mannosyltransferase (POMT1) gene affect glycosylation of alpha-dystroglycan, leading to Walker-Warburg syndrome, a lethal disorder in early life with severe congenital muscular dystrophy, and brain and eye malformations. Recently, we described a novel form of recessive limb girdle muscular dystrophy with mild mental retardation, associated with an abnormal alpha-dystroglycan pattern in the muscle, suggesting a glycosylation defect. Here, we present evidence that this distinct phenotype results from a common mutation (A200P) in the POMT1 gene. Our findings further expand the phenotype of glycosylation disorders linked to POMT1 mutations. Furthermore, the A200P mutation is part of a conserved core haplotype, indicating an ancestral founder mutation.