New macrolides from the sponge Chondrosia corticata

Three new oxazole-containing metabolites, neohalichondramide (5), (19Z)-halichondramide (6), and secohalichondramide (7), along with four previously reported compounds of the same structural class were isolated from the marine sponge Chondrosia corticata collected from Guam. The structures of novel compounds were determined on the basis of combined spectroscopic analyses. These compounds exhibited significant cytotoxicity and antifungal activity toward the human leukemia cell-line K562 and Candida albicans, respectively.     

A cDNA microarray analysis of gene expression profiles in rat hippocampus following a ketogenic diet

The ketogenic diet (KD) is an effective therapy for medically intractable epilepsy, but its anticonvulsant mechanisms are unknown. Few studies to date have addressed the molecular changes following treatment with a KD. In the present study, we fed juvenile rats either a standard diet or a KD for 1 month, and then determined changes in hippocampal gene expression using cDNA microarray analysis (Clontech). To validate the microarray expression results, we also performed Northern blot and RT-PCR analysis on a small subset of affected genes. Among a total of 1176 cDNAs, 42 genes were strongly up- or down-regulated (>2-fold change over controls) by a KD. We found that the expression of mitochondrial ATP synthase beta subunit, mitochondrial ATP synthase D subunit (ATP5H) and mitochondrial ATP synthase beta subunit precursor (ATP5F) were especially increased in KD-treated group, whereas the KD down-regulated protein kinase C (PKC) beta and epsilon isoforms. Thus, the most prominent changes were seen in genes encoding proteins involved in mitochondrial metabolic and intracellular signal transduction pathways. Our data provide some insights into the complex cascade of cellular changes in the hippocampus induced by a KD, some of which may contribute to its anticonvulsant effects.     

Therapeutic effects of gemcitabine on cutaneous manifestations in an Adamantiades-Behçet's disease-like mouse model

Abstract: The aim of this work was to study the effects and side effects of gemcitabine (2′,2′‐difluorodeoxycytidine, dFdC), a pyrimidine synthesis inhibitor, on skin lesions of a herpes simplex virus (HSV)‐induced Adamantiades–Behçet's disease (ABD)‐like mouse model. For the dose‐escalation study, ICR mice were treated intraperitoneally with dFdC over 5 days. For the efficacy study, ICR mice were inoculated with HSV and classified as having ABD according to a revised Japanese classification, and then 18 ABD mice were randomly assigned to placebo, 0.06 or 0.12 µg of dFdC/day over 5 days. Serum levels of interleukin‐4 (IL‐4), IL‐6, IL‐10, interferon‐γ (IFN‐γ), and tumor necrosis factor‐α (TNF‐α) were determined using enzyme‐linked immunosorbent assay. After application of 3 µg of dFdC over 5 days, alanine aminotransferase increased (P = 0.032), but all other kidney and liver parameters were unchanged. In ABD mice, 5 days of dFdC treatment with 0.06 or 0.12 µg of dFdC/day resulted in a dose‐dependent improvement of cutaneous manifestations by more than 60% (P = 0.017). There was no significant change in cytokine levels, and none of the cytokine levels correlated with response to treatment. Moreover, dFdC shows promising effects to improve cutaneous lesions in the HSV‐induced ABD‐like mouse model. In this animal model, effects of dFdC on the cytokine profile remained inconclusive.     

Metronidazole-induced encephalopathy

We report the clinical, neuropsychological, and neuroimaging findings of two patients of diffuse encephalopathy associated with the use of metronidazole. Both patients showed characteristic abnormalities on magnetic resonance imaging (MRI) with diffusion weighted imaging (DWI) and recovered incompletely after the discontinuation of metronidazole. We also suggest that MRI with DWI may be useful in the diagnosis of metronidazole-induced encephalopathy, and that they have a role in the prediction of prognosis.     

Depiction and local staging of rectal tumors: comparison of transrectal US before and after water instillation

PURPOSE: To determine whether transrectal ultrasonography (US) with intrarectal water instillation can improve the depiction and accuracy of US in local staging of rectal tumors. MATERIALS AND METHODS: Between October 1999 and February 2002, 63 patients (mean age, 56 years; age range, 23-91 years) with 63 rectal tumors were evaluated with transrectal US before and after intrarectal water instillation. Transrectal US examinations were performed with a 7-10-MHz radial transducer. Immediately after the first transrectal US examination, the rectal lumen was filled with 50-150 mL of degassed water, and a second US examination was performed. All patients underwent surgery within 1 month after transrectal US. Depiction of the tumor was compared between the two methods. The McNemar test was used to compare the accuracy between the two techniques in local staging of the tumor by using pathologic findings in the resected specimen as the standard. RESULTS: The tumors ranged from 0.5 to 8.0 cm (mean, 2.8 cm) as measured at pathologic evaluation. All 63 tumors were clearly depicted at transrectal US after water instillation, while only 42 (67%) of the tumors were depicted at transrectal US before water instillation. In the 42 tumors clearly depicted at transrectal US examinations both before and after water instillation, the accuracy of transrectal US in local tumor staging was significantly higher after water instillation (85.7% [36 of 42]) than before water instillation (57.1% [24 of 42]; P <.001). CONCLUSION: Water instillation during transrectal US examination of rectal tumors improves the depiction and local staging of the tumors.