Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

Under normal physiological conditions the brain primarily utilizes glucose for ATP generation. However, in situations where glucose is sparse, e.g., during prolonged fasting, ketone bodies become an important energy source for the brain. The brain’s utilization of ketones seems to depend mainly on the concentration in the blood, thus many dietary approaches such as ketogenic diets, ingestion of ketogenic medium-chain fatty acids or exogenous ketones, facilitate significant changes in the brain’s metabolism. Therefore, these approaches may ameliorate the energy crisis in neurodegenerative diseases, which are characterized by a deterioration of the brain’s glucose metabolism, providing a therapeutic advantage in these diseases. Most clinical studies examining the neuroprotective role of ketone bodies have been conducted in patients with Alzheimer’s disease, where brain imaging studies support the notion of enhancing brain energy metabolism with ketones. Likewise, a few studies show modest functional improvements in patients with Parkinson’s disease and cognitive benefits in patients with—or at risk of—Alzheimer’s disease after ketogenic interventions. Here, we summarize current knowledge on how ketogenic interventions support brain metabolism and discuss the therapeutic role of ketones in neurodegenerative disease, emphasizing clinical data.     

Sex and Depot Differences in Palmitoleic Acid Content of Human Blood and Fat

Palmitoleic acid has been classified as an insulin-sensitizing lipokine, but evidence for this from human studies has been inconsistent. We hypothesized that this is related to either the types of samples or conditions under which samples are collected. We measured plasma palmitoleic acid and total free fatty acids (FFA) using ultra-performance liquid chromatography in blood samples collected from 34 adults under a variety of conditions. We collected duplicate samples of adipose (n = 10), FFA (n = 9), and very low density lipoprotein triacylglycerol (VLDL-TAG) (n = 7) to measure the palmitoleic acid as a percentage of total fatty acids. We tested whether the percentage of palmitoleic acid was correlated with insulin resistance, as measured by homeostatic model of insulin resistance (HOMA-IR). Adipose stearoyl-coenzyme A desaturase 1 (SCD-1) protein was measured by capillary Western blotting. FFA-palmitoleic acid percentage increased as a function of total FFA and was greater (p < 0.005) in females than males. Adipose palmitoleic acid percentage was greater in females than males (p < 0.001), as was adipose SCD-1. Palmitoleic acid was greater in femoral fat than in abdominal fat in both females and males (p < 0.001), and correlated positively with HOMA-IR only in females. The test–retest reliability values for percentage palmitoleic acid were 7 ± 10% for adipose, 24 ± 26% for VLDL, and 53 ± 31% for FFA. Because FFA-palmitoleic acid percentage varies as a function of total FFA, investigators should re-evaluate how palmitoleic acid data is presented. The positive relationship between adipose palmitoleic acid and HOMA-IR in females suggests that it is not a potent insulin-sensitizing lipokine in humans.     

Biofeedback improves functional outcome after sphincteroplasty

Pax genes are expressed in specific patterns in the nervous system during development and in the adult. Recent findings suggest a link between the expression of Pax-2 and axonal guidance. Mice with a targeted deletion of Pax-2 are an excellent tool for studying axonal pathfinding at the molecular level, especially with respect to the optic chiasm. The date reviewed here suggest that Pax-2 regulates the expression of surface molecules involved in contact attraction and that the mutual regulation of the expression of Pax-2 and the Sonic hedgehog gene is of importance in the formation of the chiasm region.     

Polymorphonuclear neutrophil granulocyte chemotactic hyperresponsiveness in a case of canine acromegaly

Growth hormone (GH) has recently been shown to affect polymorphonuclear neutrophil granulocyte (PMN) function and to be secreted by mononuclear cells, indicating that the hormone may be active in an immunophysiologic network, acting as an endo- or paracrine priming agent. The purpose of the present study was to evaluate the chemotactic responsiveness of canine peripheral PMN in a dog with acromegaly, caused by spontaneous, progesterone-induced hypersecretion of GH and, secondary to this, a seven-fold increase in insulin-like growth factor I (IGF-I). The chemotactic responsiveness towards zymosan-activated serum (ZAS) and leukotriene B4 (LTB4) was evaluated at a time when the dog suffered from acromegaly and again 57 days after corrective surgery (ovariohysterectomy). The experiments showed that PMN from the patient exhibited enhanced chemotactic migration that appeared to be associated with the hypersomatotropic condition as judged from the reversibility of the phenomenon. The glucose intolerance and elevated serum alkaline phosphatase that were observed in the acromegalic dog were also shown to be reversible following surgery.     

Potassium-evoked directionally selective responses from rabbit retinal ganglion cells

Previous studies have shown that directionally selective (DS) retinal ganglion cells cannot only discriminate the direction of a moving object but they can also discriminate the sequence of two flashes of light at neighboring locations in the visual field: that is, the cells elicit a DS response to both real and apparent motion. This study examines whether a DS response can be elicited in DS ganglion cells by simply stimulating two neighboring areas of the retina with high external K+. Extracellular recordings were made from ON-OFF DS ganglion cells in superfused rabbit retinas, and the responses of these cells to focal applications of 100 mM KCl to the vitreal surface of the retina were measured. All cells produced a burst of spikes (typically lasting 50-200 ms) when a short pulse (10-50 ms duration) of KCl was ejected from the tip of a micropipette that was placed within the cell's receptive field. When KCl was ejected successively from the tips of two micropipettes that were aligned along the preferred-null axis of a cell, sequence-dependent responses were observed. The response to the second micropipette was suppressed when mimicking motion in the cell's null direction, whereas an enhancement during apparent motion in the opposite direction frequently occurred. Sequence discrimination in these cells was eliminated by the GABA antagonist picrotoxin and by the Ca(2+)-channel blocker omega-conotoxin MVIIC, two drugs that are known to abolish directional selectivity in these ganglion cells. The spatiotemporal properties of the K(+)-evoked sequence-dependent responses are described and compared with previous findings on apparent motion responses of ON-OFF DS ganglion cells.     

The Moral Dimensions of Globalization.

Responds to the comments by L. T. Hoshmand (see record 2003-08988-012) and J. Aros (see record 2003-08988-013) on the article by J. Arnett (see record 2002-18352-003) regarding the psychology of globalization. In this response, Arnett discusses the moral implications of globalization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of surface roughness on the radiative properties ofpatterned silicon wafers

The radiative properties of patterned silicon wafers have a major impact on the two critical issues in rapid thermal processing (RTP), namely wafer temperature uniformity and wafer temperature measurement. The surface topography variation of the die area caused by patterning and the roughness of the wafer backside can have a significant effect on the radiative properties, but these effects are not well characterized. We report measurements of room temperature reflectance of a memory die, logic die, and various multilayered wafer backsides. The surface roughness of the die areas and wafer backsides is characterized using atomic force microscopy (AFM). These data are subsequently used to assess the effectiveness of thin film optics in providing approximations for the radiative properties of patterned wafers for RTP applications     

A broadly cross-protective monoclonal antibody binding to Escherichia coli and Salmonella lipopolysaccharides

During the last decade, episodes of sepsis have increased and Escherichia coli has remained the most frequent clinical isolate. Lipopolysaccharides (LPS; endotoxin) are the major toxic and antigenic components of gram-negative bacteria and qualify as targets for therapeutic interventions. Molecules that neutralize the toxic effects of LPS are actively investigated. In this paper, we describe a murine monoclonal antibody (MAb; WN1 222-5), broadly cross-reactive and cross-protective for smooth (S)-form and rough (R)-form LPS. As shown in enzyme-linked immunosorbent assay and the passive hemolysis assay, WN1 222-5 binds to the five known E. coli core chemotypes, to Salmonella core, and to S-form LPS having these core structures. In immunoblots, it is shown to react with both the nonsubstituted core LPS and with LPS carrying O-side chains, indicating the exposure of the epitope in both S-form and R-form LPS. This MAb of the immunoglobulin G2a class is not lipid A reactive but binds to E. coli J5, an RcP+ mutant which carries an inner core structure common to many members of the family Enterobacteriaceae. Phosphate groups present in the inner core contribute to the epitope but are not essential for the binding of WN1 222-5 to complete core LPS. Cross-reactivity for clinical bacterial isolates is broad. WN1 222-5 binds to all E. coli clinical isolates tested so far (79 blood isolates, 80 urinary isolates, and 21 fecal isolates) and to some Citrobacter, Enterobacter, and Klebsiella isolates. This pattern of reactivity indicates that its binding epitope is widespread among members of the Enterobacteriaceae. WN1 222-5 exhibits biologically relevant activities. In vitro, it inhibits the Limulus amoebocyte lysate assay activity of S-form and R-form LPS in a dose-dependent manner and it neutralizes the LPS-induced release of clinically relevant monokines (interleukin 6 and tumor necrosis factor). In vivo, WN1 222-5 blocks endotoxin-induced pyrogenicity in rabbits and lethality in galactosamine-sensitized mice. The discovery of WN1 222-5 settles the long-lasting controversy over the existence of anti-core LPS MAbs with both cross-reactive and cross-protective activity, opening new possibilities for the immunotherapy of sepsis caused by gram-negative bacteria.