N-Acetylglycyl-D-glutamic acid

[Polysialic Acid for Immunomodulation in an Animal Model for Wet Age-Related Macular Degeneration (AMD)].[Pubmed:28380648]

Klin Monbl Augenheilkd. 2017 May;234(5):657-661.

Background Chronic activation of the innate immune system is a hallmark of retinal degenerative diseases, including age-related macular degeneration (AMD). Overt microglia and macrophage reactivity, as well as dysregulation of the alternative complement system, trigger and sustain retinal degeneration. It is now accepted that there exists a vicious cycle of mononuclear phagocyte reactivity, abnormal intrinsic complement activation, damage of Bruch's membrane, dysfunction of the retinal pigment epithelium, photoreceptor degeneration and choroidal neovascularization (CNV). Targeting the innate immune system may, therefore, be a complementary approach to anti-angiogenic therapy. This article presents data from polysialic acid treatment experiments in the laser-induced mouse model of wet AMD. Material and Methods The laser-CNV mouse model was used to simulate events of neovascular AMD. Polysialic acid was applied by intravitreal injection and microglia activity was assessed with Iba1 staining of retinal and RPE/choroidal flat mounts. Neovascular leakage was determined by fluorescein angiography. Results Intravitreal injection of polysialic acid reduced retinal and RPE/choroidal lesion-associated microglia activity in the laser-induced mouse model of AMD. Polysialic acid treatment also diminished vascular leakage at laser spots in this model. Conclusion Local retinal immunomodulation with polysialic acid presents a novel concept for treatment of inflammatory conditions related to neovascular AMD.

Performance, intestinal microflora, and amino acid digestibility altered by exogenous enzymes in broilers fed wheat- or sorghum-based diets.[Pubmed:28380608]

J Anim Sci. 2017 Feb;95(2):740-751.

The objective of the current study was to compare the effects of dietary enzymes and nutrient restriction on performance and bone mineralization in birds fed wheat- or sorghum-based diets. A total of 720 d-old male broiler chicks were randomly allocated to 8 treatments, with 6 replicates per treatment and 15 birds per replicate. Birds were reared in floor pens from 0 to 35 d. The study used a 2 x 4 factorial arrangement with 2 grains (sorghum or wheat) and 4 diets: positive control (no enzyme and ME, digestible Lys, Ca, and P sufficient, negative control (NC; no enzyme and reduced ME [-100 kcal/kg], digestible AA [-2%], Ca [-0.12 percentage points], and available P [-0.18 percentage points in the starter phase and -0.22 percentage points in the grower phase]), NC + nonstarch polysaccharide-degrading enzymes + phytase (500 phytase units [FTU]; NCCP), and NC + phytase (1,000 FTU; NCP). From 0 to 35 d, birds fed wheat-based diets had greater G:F (4.5%), BW gain (9.2%), breast meat yield (6.8%), and tibia ash (2.0%) compared with birds fed sorghum-based diets. Across grain types, the NCCP treatment improved BW gain ( < 0.001), feed intake ( < 0.001), G:F ( < 0.05), and livability ( < 0.001) compared with the NC treatment. Birds fed NCP had greater BW gain ( < 0.001), feed intake ( < 0.001), G:F ( < 0.001), and livability ( < 0.001) compared with birds fed NC. Birds fed the NCP diet had greater BW gain ( < 0.001), toe ash ( < 0.01), and tibia ash ( < 0.001) compared with birds fed the NCCP diet. There was a grain x diet interaction for feed intake ( < 0.01), BW gain ( < 0.001), tibia ash ( < 0.01), and tibia breaking strength ( < 0.05). The influence of enzymes was more pronounced in sorghum-based diets than in wheat-based diets. Birds fed wheat-based diets had greater ileal digestibility of His, Met, Val, Phe, Ile, Leu, Trp, Glu, Pro, Ala, Tyr, and Cys compared with those fed sorghum-based diets ( < 0.05). Across grain types, NCP had greater apparent ileal digestibility of Met, Lys, Ser, Pro, Gly, and Cys than NC ( < 0.05). The results suggest that wheat is superior to sorghum for broilers, as expected, but that enzyme supplementation has the capability to restore the compromised bird performance due to feeding sorghum. In addition, compared with nonstarch polysaccharide-degrading enzymes and phytase (500 FTU/kg feed) added in concert, phytase supplemented at 1,000 FTU/kg resulted in a further improvement of some of the performance and bone mineralization parameters in male broilers fed sorghum-based diets.

Influence of wet heating and autoclaving on chemical composition and standardized ileal crude protein and amino acid digestibility in full-fat soybeans for pigs.[Pubmed:28380613]

J Anim Sci. 2017 Feb;95(2):779-788.

One batch each of eight full-fat soybeans (FFSB) was used to determine the effect of different heat treatments including wet heating (WH) and autoclaving (AC) on chemical composition and standardized ileal digestibility (SID) of CP and AA in growing pigs. The raw FFSB (K0) were either treated by WH at 80 degrees C for 1 min (K1), at 100 degrees C for 6 min (K2), or at 100 degrees C for 16 min (K3). Thereafter, these batches were expanded at 125 degrees C for 15 s. A further heat treatment included AC at 110 degrees C for 15 (Z1), 30 (Z2), 45 (Z3), or 60 (Z4) min of FFSB that were subjected to the same WH treatment as K3. Diets were formulated to contain the respective FFSB as the sole source of CP and AA. A N-free diet was used to measure basal endogenous losses of CP and AA in an additional period at the end of the experiment. Eight ileally cannulated pigs (28 +/- 1 kg) were allocated to a row-column design with 8 diets and 6 periods of 7 d each. An increase in the duration of WH had no effect on contents of AA (% of CP) and NDF, but NDIN contents linearly increased ( < 0.05) with increasing time for WH. Autoclaving resulted in a linear decrease ( < 0.05) of trypsin inhibitor activity (TIA), contents of Arg, Leu, Ala, Asp, Cys, and Gly as well as Lys to CP ratio (Lys:CP), reactive Lys to CP ratio (rLys:CP), and in an increase ( < 0.05) in contents of NDF and NDIN. There was a quadratic response ( < 0.05) of SID of CP and AA as time for WH at 100 degrees C increased from 0 (K0) to 6 (K2) up to 16 (K3) min. Moreover, a quadratic response ( < 0.05) to increasing time of AC was observed for SID of Arg, Phe, and Pro. The SID of CP and all indispensable AA showed a quadratic response ( < 0.05) to decreasing TIA, urease activity, protein solubility in 0.2% potassium hydroxide, protein dispersibility index, Lys:CP, (lightness), and to increasing NDIN and (redness). In addition, there was a linear increase ( < 0.05) in SID values with decreasing rLys:CP and increasing NDF contents. In conclusion, WH proved to be suitable for increasing SID values. Further improvement of SID of most AA could be achieved on additional AC treatment from Z1 to Z3, however, it needs to be considered, if the observed increase due to AC is cost effective in view of the additional production costs. Several chemical and physical parameters can be used in the feed industry for quality control purposes to predict the extent of heat damage on SID of CP and indispensable AA in FFSB.

Neutron scattering shows a droplet of oleic acid at the center of the BAMLET complex.[Pubmed:28380660]

Proteins. 2017 Jul;85(7):1371-1378.

The anti-cancer complex, Bovine Alpha-lactalbumin Made LEthal to Tumors (BAMLET), has intriguing broad-spectrum anti-cancer activity. Although aspects of BAMLET's anti-cancer mechanism are still not known, it is understood that it involves the oleic acid or oleate component of BAMLET being preferentially released into cancer cell membranes leading to increased membrane permeability and lysis. The structure of the protein component of BAMLET has previously been elucidated by small angle X-ray scattering (SAXS) to be partially unfolded and dramatically enlarged. However, the structure of the oleic acid component of BAMLET and its disposition with respect to the protein component was not revealed as oleic acid has the same X-ray scattering length density (SLD) as water. Employing the difference in the neutron SLDs of hydrogen and deuterium, we carried out solvent contrast variation small angle neutron scattering (SANS) experiments of hydrogenated BAMLET in deuterated water buffers, to reveal the size, shape, and disposition of the oleic acid component of BAMLET. Our resulting analysis and models generated from SANS and SAXS data indicate that oleic acid forms a spherical droplet of oil incompletely encapsulated by the partially unfolded protein component. This model provides insight into the anti-cancer mechanism of this cache of lipid. The model also reveals a protein component "tail" not associated with the oleic acid component that is able to interact with the tail of other BAMLET molecules, providing a plausible explanation of how BAMLET readily forms aggregates. Proteins 2017; 85:1371-1378. (c) 2017 Wiley Periodicals, Inc.

Excitatory action of some aspartate- and glutamate-containing dipeptides after intracerebroventricular injection in mice.[Pubmed:1655472]

Eur J Pharmacol. 1991 May 17;197(2-3):157-60.

The effects of some dipeptides, analogues of N-acetyl-alpha-L-aspartyl-L-glutamate, were studied after i.c.v. administration into mice in acute experiments. N-Acetyl-alpha-L-aspartyl-L-glutamate itself did not induce seizures in animals, but prevented glutamate-induced convulsions. All other dipeptides possessed excitatory glutamate-like actions. Some structural requirements for the excitatory effects of the dipeptides are discussed.