Easy Identification of Optimal Coronal Slice on Brain Magnetic Resonance Imaging to Measure Hippocampal Area in Alzheimer's Disease Patients.

INTRODUCTION: Measurement of an- hippocampal area or volume is useful in clinical practice as a supportive aid for diagnosis of Alzheimer's disease. Since it is time-consuming and not simple, it is not being used very often. We present a simplified protocol for hippocampal atrophy evaluation based on a single optimal slice in Alzheimer's disease. METHODS: We defined a single optimal slice for hippocampal measurement on brain magnetic resonance imaging (MRI) at the plane where the amygdala disappears and only the hippocampus is present. We compared an absolute area and volume of the hippocampus on this optimal slice between 40 patients with Alzheimer disease and 40 age-, education- and gender-mateched elderly controls. Furthermore, we compared these results with those relative to the size of the brain or the skull: the area of the optimal slice normalized to the area of the brain at anterior commissure and the volume of the hippocampus normalized to the total intracranial volume. RESULTS: Hippocampal areas on the single optimal slice and hippocampal volumes on the left and right in the control group were significantly higher than those in the AD group. Normalized hippocampal areas and volumes on the left and right in the control group were significantly higher compared to the AD group. Absolute hippocampal areas and volumes did not significantly differ from corresponding normalized hippocampal areas as well as normalized hippocampal volumes using comparisons of areas under the receiver operating characteristic curves. CONCLUSION: The hippocampal area on the well-defined optimal slice of brain MRI can reliably substitute a complicated measurement of the hippocampal volume. Surprisingly, brain or skull normalization of these variables does not add any incremental differentiation between Alzheimer disease patients and controls or give better results.

Two novel microbial conversion products of progesterone derivatives.

Two novel microbial steroid hydroxylations were found in a screening of 131 microorganisms under aerobic conditions. 17 alpha-Hydroxyprogesterone was hydroxylated in the 8 beta-position by Corynespora melonis CBS 16260, and fermentation of 17 alpha-acetoxyprogesterone with Pycnosporium species ATCC 12231 yielded 11 beta-hydroxy- and 11 beta, 12 beta-dihydroxy-17 alpha-acetoxyprogesterone. The known 11 beta-hydroxy compound could be obtained as a single product with Trichothecium roseum ATCC 12519.

Aspects for the future of biotransformations.

Biotransformations have gained extensive importance in practical use as a support for chemical synthesis or in the conversion of natural products. Biotransformations may present an enlargement, a sequential degradation or a specific modification of synthetic or natural compounds. The tools for biotransformations are principally mammalian, plant or microbial cells and their cell-free enzymes. In technical practice the biocatalysts are so far limited to the use of microorganisms and some cell-free enzymes of low cost. Although numerous microbial or enzymatical reactions were already developed for industrial processes, the capacities of biotransformations offer a broad field of inexhaustible possibilities for the future.

Production of drugs by microbial biosynthesis and biotransformation. Possibilities, limits and future developments (1st communication).

Before the advent of alchemy the therapeutic aids for man and animals consisted exclusively of using natural products in many different forms. Chemical syntheses have been used for little more than 100 years as a means of obtaining drugs. The discovery of penicillin and the first industrial production of this compound in 1941/42 opened the door to a third way for the preparation of drugs by exploitation of the manifold biosynthetic capabilities of microorganisms to produce antibiotics or more recently other pharmacologically active substances. The selective use of individual enzymatic transformation stages with microorganisms in chemical production pathways in particular by biotransformations of steroids in 1950 expanded the field of biotechnological production of pharmaceuticals. The increasing knowledge in the regulation of the biosynthesis of primary and secondary metabolites, the growing experience in the use of microorganisms as biocatalysts and source of valuable enzymes and the development of new economical technical procedures raised the number and volume of drugs prepared by microbial biosynthesis and biotransformation. The modern method of the genetic engineering supported by the chemical DNA-synthesis enabled the preparation of important proteohormones and physiologically active peptides in microorganisms. Finally, the development of monoclonal antibodies, although at present still formed in mammalian cells, will lead to new ways of therapy in future. A review is given on the present state of biotechnological productions of antibiotics, vitamins, steroids, alkaloids, amino acids and pharmaceutical enzymes combined with new developments in the preparation of blood factors, enzyme inhibitors, hormones and physiologically active peptides and the possible future use of monoclonal antibodies.

Microbial side-chain degradation of sterols.

Apart from the broadly used diosgenin and some further natural compounds sterols gained an increasing importance as raw material for the synthesis of steroid drugs. Parallel to the elucidation of the pathways of the enzymatic degradation of sterols technical processes were developed for a specific degradation of the side-chain to useful primary products. A review is given on the present state of this field and the trends to further improvements.

Microbial transformations of some monoterpenoids and sesquiterpenoids.

The absolute configurations of fragrances, flavours and drugs are often important for their special properties. The growing interest of organic chemists in chiral synthons has stimulated work on biotransformations, for which readily available and inexpensive compounds can be used as substrates. Microbial transformations of 1-menthenes like gamma-terpinene, alpha-terpinene, limonene and alpha-phellandrene give the corresponding 1,2-trans-diols with high stereospecificity. Because of the volatility and toxicity of these substrates, and their low solubility in aqueous solutions, a special fermentation technique has been developed in which the terpenes are fed continuously to extended cultures of Corynespora cassiicola or Diplodia gossypina. (4R)-Limonene is transformed by Gibberella cyanea to (1S,2S,4R)-p-menth-8-en-1,2-diol, but 3,3,5,5-tetramethyl-limonene yields a 6-monohydroxylated product and a 6,10-dihydroxylated product with a 6-hydroxy-8,10-epoxy structure as the main metabolite. Vicinal diols are also formed from aliphatic terpenes, by reaction at the terminal isoprenoid groups. Some oxirane structures are found as intermediates. Acyclic sesquiterpenes often form complex mixtures when they are metabolized further. The products of the transformation of trans-nerolidol by several fungi are given as examples. Cyclic sesquiterpenes, with less flexible structures, are oxidized more specifically. Whereas longifolene is a very poor substrate for Corynespora cassiicola, isolongifolene is always hydroxylated at one of the methyl groups attached to C-7. The 14- or 15-hydroxy compounds are further oxidized, very fast, in the 3 position or 4 position.

Preparation and ultraviolet light-induced transformation of an antifungal mixture of heptaene antibiotics of Streptomyces surinam.

Conditions for the production and isolation of an antifungal antibiotic mixture (DJ400) were investigated. Different preparations of DJ400 may contain at least 12 different heptaenes, which were characterized by partition chromatography (peak number) and ultraviolet (UV) spectra (types A, B, C). Irradiation with UV light transformed the predominant UV spectrum of type B into A. Comparison of untreated and UV-irradiated products indicated that the main components may exist in two forms with identical structures except for an all trans-heptaene system in A compounds and one internal cis double bond in B compounds. The ratio of the major components 6B and 8B depended on the media composition. Component 4B is probably a precursor of 6B; 10B and 12 may be precursors of 8B.