Biosynthetic origin of the methoxyl extender unit in bafilomycin and concanamycin using stereospecifically labeled precursors

The microbial macrolides bafilomycin A1, B, and concanamycin A from Streptomyces spp. are potent and specific inhibitors of V-ATPases. The question of the biosynthetic origin of the two uncommon "glycolate units" of each of the macrolide structures was addressed by feeding experiments with stereospecifically 13C-labeled precursors. Our studies clearly indicate that glycerol is a source for the methoxylated C2-units and determines the orientation of the incorporation. Products from the carboxylic acid pool or TCA cycle are ruled out as key precursors. The data suggest the action of a glycerol kinase and point to phosphoglycerate as an intermediate in their biosynthesis. However, glycerate itself is not accepted as a precursor. We present the likely biosynthetic pathway and show the value of stereospecifically labeled presursors as an important tool for biosynthetic investigations.     

Regulation of hepatic blood flow: the hepatic arterial buffer response revisited

The interest in the liver dates back to ancient times when it was considered to be the seat of life processes. The liver is indeed essential to life,not only due to its complex functions in biosynthesis,metabolism and clearance,but also its dramatic role as the blood volume reservoir. Among parenchymal organs,blood flow to the liver is unique due to the dual supply from the portal vein and the hepatic artery. Knowledge of the mutual communication of both the hepatic artery and the portal vein is essential to understand hepatic physiology and pathophysiology. To distinguish the individual importance of each of these inflows in normal and abnormal states is still a challenging task and the subject of on-going research. A central mechanism that controls and allows constancy of hepatic blood flow is the hepatic arterial buffer response. The current paper reviews the relevance of this intimate hepatic blood flow regulatory system in health and disease. We exclusively focus on the endogenous interrelationship between the hepatic arterial and portal venous inflow circuits in liver resection and transplantation,as well as inflammatory and chronic liver diseases. We do not consider the hepatic microvascular anatomy,as this has been the subject of another recent review.     

Paradoxical lateralization of non-invasive electroencephalographic ictal patterns in extra-temporal epilepsies

Video-electroencephalographic (EEG) ictal recordings play an important role in the pre-surgical evaluation of patients with medically refractory focal epilepsy. Paradoxical lateralization of the scalp EEG ictal onset patterns, consistently contralateral to the side of the proven epileptogenic lesion is rare but important to recognize, with possible implications on patient management. We searched the database of the University of Munich Epilepsy Monitoring Unit for patients with extratemporal epilepsies, with scalp EEG ictal patterns consistently contralateral to the proven epileptogenic zone. All available clinical, EEG and imaging data were reviewed. Dipole source analysis of EEG seizure onset was performed where possible. Four patients were identified, who had proven paradoxical lateralization of scalp EEG ictal patterns, demonstrated by seizure freedom after epilepsy surgery, data from invasive electroencephalography, or imaging and seizure semiology. Parasagittal lesions on MRI brain scan were found in three cases. Invasive recordings with subdural electrodes were performed in one patient. Dipole source analysis of EEG seizure onset was possible in two patients, helping to correctly lateralize the ictal EEG pattern in one patient. Patients with midline or near midline neocortical seizure foci may show paradoxical lateralization of the ictal EEG, likely due to the spatial orientation of the cortical generators in the medial regions of the cerebral hemispheres. These patients may have excellent surgical outcome despite the apparently discordant EEG findings, making this an important phenomenon to be recognized in clinical practice.     

Novel Neuroimaging Findings in a Patient with Cerebral Whipple''s Disease: A Magnetic Resonance Imaging and Positron Emission Tomography Study

The authors report a 43-year-old patient with histopathologically proven cerebral Whipple's disease. Magnetic resonance imaging (MRI) revealed a multilayered left frontal lesion without mass effect, no perifocal brain edema, no contrast enhancement, and a thin shell of fluid signal that presented as an incomplete, open ring. An [11C]methionine positron emission tomography (PET) study showed low uptake below the threshold that is characteristic for brain tumors. In precise co-registration to the MR images, the PET data showed that increased uptake was mainly located in the direct adjacent part of the MRI lesion. The fluid signal on MRI corresponded to the extensive outflow of fluid from the lesion, which was observed during neurosurgical resection, and also to the neuropathological findings. The authors conclude that this cerebral manifestation of Whipple's disease made a unique and hitherto undescribed appearance on MRI; uptake pattern of PET amino acid tracer may help in the preoperative distinction of inflammatory from neoplastic lesions.