1. Effect of High-Caloric Nutrition on Survival in Amyotrophic Lateral Sclerosis
Albert C Ludolph, Johannes Dorst, Jens Dreyhaupt, et al. Ann Neurol. 2020 Feb;87(2):206-216.doi: 10.1002/ana.25661.Epub 2020 Jan 6.
Objective:Weight loss has been identified as a negative prognostic factor in amyotrophic lateral sclerosis, but there is no evidence regarding whether a high-caloric diet increases survival. Therefore, we sought to evaluate the efficacy of a high-caloric fatty diet (HCFD) for increasing survival. Methods:A 1:1 randomized, placebo-controlled, parallel-group, double-blinded trial (LIPCAL-ALS study) was conducted between February 2015 and September 2018. Patients were followed up at 3, 6, 9, 12, 15, and 18 months after randomization. The study was performed at 12 sites of the clinical and scientific network of German motor neuron disease centers (ALS/MND-NET). Eligible patients were randomly assigned (1:1) to receive either HCFD (405kcal/day, 100% fat) or placebo in addition to riluzole (100mg/day). The primary endpoint was survival time, defined as time to death or time to study cutoff date. Results:Two hundred one patients (80 female, 121 male, age = 62.4 ± 10.8 years) were included. The confirmatory analysis of the primary outcome survival showed a survival probability of 0.39 (95% confidence interval [CI] = 0.27-0.51) in the placebo group and 0.37 (95% CI = 0.25-0.49) in the HCFD group, both after 28 months (point in time of the last event). The hazard ratio was 0.97, 1-sided 97.5% CI = -∞ to 1.44, p = 0.44.Interpretation:The results provide no evidence for a life-prolonging effect of HCFD for the whole amyotrophic lateral sclerosis population. However, post hoc analysis revealed a significant survival benefit for the subgroup of fast-progressing patients. ANN NEUROL 2020;87:206-216.
2. Possible biosynthetic pathways for all cis-3,6,9,12,15,19,22, 25,28-hentriacontanonaene in bacteria
Shinji Sugihara, Ryuji Hori, Hitomi Nakanowatari, Yasuhiro Takada, Isao Yumoto, Naoki Morita, Yutaka Yano, Kazuo Watanabe, Hidetoshi Okuyama Lipids. 2010 Feb;45(2):167-77.doi: 10.1007/s11745-009-3380-9.
A very long chain polyunsaturated hydrocarbon, hentriacontanonaene (C31:9), was detected in an eicosapentaenoic acid (EPA)-producing marine bacterium, which was isolated from the mid-latitude seashore of Hokkaido, Japan, and was tentatively identified as mesophilic Shewanella sp. strain osh08 from 16S rRNA gene sequencing. The geometry and position of the double bonds in this compound were determined physicochemically to be all cis at positions 3, 6, 9, 12, 15, 19, 22, 25, and 28. Although C31:9 was detected in all of the seven EPA- or/and docosahexaenoic acid-producing bacteria tested, an EPA-deficient mutant (strain IK-1Delta8) of one of these bacteria had no C31:9. Strain IK-1Delta8 had defects in the pfaD gene, one of the five pfa genes responsible for the biosynthesis of EPA. Although Escherichia coli DH5alpha does not produce EPA or DHA inherently, cells transformed with the pfa genes responsible for the biosynthesis of EPA and DHA produced EPA and DHA, respectively, but not C31:9. These results suggest that the Pfa protein complex is involved in the biosynthesis of C31:9 and that pfa genes must not be the only genes responsible for the formation of C31:9. In this report, we determined for the first time the molecular structure of the C31:9 and discuss the possible biosynthetic pathways of this compound.
3. Stereoselective synthesis of (all-Z)-hentriaconta-3,6,9,12,15,19,22,25,28-nonaene
Liudmila Filippova, Ida Aarum, Martine Ringdal, Martin Kirkhus Dahl, Trond Vidar Hansen, Yngve Stenstrøm Org Biomol Chem. 2015 Apr 28;13(16):4680-5.doi: 10.1039/c5ob00313j.
Several microorganisms produce small quantities of polyunsaturated hydrocarbons and such natural products are of interest. Starting from the ethyl ester of eicosapentaenoic acid, the total synthesis of the natural product (all-Z)-hentriaconta-3,6,9,12,15,19,22,25,28-nonaene has been achieved in eight steps and 15% overall yield. The synthesis is based on a stereoselective Wittig reaction and confirms the all-Z-configuration of the nine double bonds in this highly unsaturated natural product.
