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.     

Primary (granulomatous) angiitis of the central nervous system with multiple aneurysms of spinal arteries. Case report

A 55-year-old woman with primary (granulomatous) angiitis of the central nervous system in association with non-Hodgkin's lymphoma (mucosa-associated lymphoid tissue type) presented with an acute spinal subdural hemorrhage secondary to rupture of one of several fusiform inflammatory aneurysms of the spinal cord radicular arteries. The literature on hemorrhagic complications, aneurysms, and spinal cord involvement in granulomatous angiitis is reviewed. Recognition of granulomatous angiitis is important, as the condition may be responsive to immunosuppressive therapy.     

Carcinoembryonic antigen in diagnosis and monitoring of colorectal cancer]

Female SJL mice are more susceptible than male mice to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP)-specific T lymphocytes. In the present study, we examined mechanisms involved in this gender-related difference in disease susceptibility. MBP-specific T lymphocytes derived from spleens of males during the effector phase of adoptive EAE produced significantly higher levels of IL-10, an anti-inflammatory cytokine in EAE. A protective effect of testosterone was then shown. Females implanted with dihydrotestosterone pellets demonstrated a significantly less severe course of EAE as compared with females implanted with placebo pellets. Finally, MBP-specific T lymphocytes derived from dihydrotestosterone-implanted females produced significantly higher levels of IL-10 than those from placebo. Together these data indicate that testosterone exerts a protective effect in EAE that is mediated at least in part by enhanced production of IL-10 by autoantigen-specific T lymphocytes.     

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.     

Secobarbital in humans discriminating triazolam under two-response and novel-response procedures

The percentage of long-term survivors after intensive chemotherapy and the outcome of MDS patients who achieve partial remission (PR) with intensive chemotherapy (IC) are not known. Between 1981 and 1996 we treated 99 patients with de novo MDS who had high-risk MDS or progression to AML, with IC. 41 (41%) achieved CR, 16 (16%) achieved partial remission (PR), 26 (26%) had failure, and 16 (16%) died in aplasia. Eight of the patients who achieved CR were autografted, three were allografted and the remaining cases received moderate consolidation chemotherapy. After IC, the 16 PR patients fulfilled the criteria for RA in 15 cases and CMML in one case. Median PR duration was 17 months, and three PR were > 3 years (39, 50+, 82+ months). Median actuarial survival of patients who achieved PR and CR was 18 months and 20 months from the onset of IC, respectively (difference not significant). Of the 71 patients treated before 1993, with sufficient follow-up, 10 (14%) had survived > 4 years (long-term survivors). Four of them were alive in first CR after 49+ to 110+ months and probably cured, two were alive in PR after 50+ and 82+ months and four had died after 49-78 months. Long-term survivors were characterized by a significantly higher incidence of RAEB-T at diagnosis, and with normal or favourable cytogenetic findings. In patients with RAEB-T at diagnosis included before 1993, 8/23 (35%) cases who had no unfavourable karyotype had survived > 4 years. Our findings suggest that MDS patients who achieve PR with IC, and not only those who achieve CR, can benefit from this type of treatment. The percentage of long-term survivors remains low, however, and is almost restricted to patients with RAEB-T at diagnosis and no unfavourable karyotype.     

Temporal specialization and generalization

A standard relation has two dimensions: attributes and tuples. A temporal relation contains two additional orthogonal time dimensions: valid time records when facts are true in the modeled reality, and transaction time records when facts are stored in the temporal relation. Although there are no restrictions between the valid time and transaction time associated with each fact, in many practical applications the valid and transaction times exhibit restricted interrelationships that define several types of specialized temporal relations. This paper examines areas where different specialized temporal relations are present. In application systems with multiple, interconnected temporal relations, multiple time dimensions may be associated with facts as they flow from one temporal relation to another. The paper investigates several aspects of the resulting generalized temporal relations, including the ability to query a predecessor relation from a successor relation. The presented framework for generalization and specialization allows one to precisely characterize and compare temporal relations and the application systems in which they are embedded. The framework's comprehensiveness and its use in understanding temporal relations are demonstrated by placing previously proposed temporal data models within the framework. The practical relevance of the defined specializations and generalizations is illustrated by sample realistic applications in which they occur. The additional semantics of specialized relations are especially useful for improving the performance of query processing     

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.