ABSTRACT
Objective Acute brain injury (ABI) is a catastrophic event, leading to disruption of the normal cerebral metabolic pathways and a subsequent cerebral energy deficit. Ketones (beta-hydroxybutyrate (BHB) and acetoacetate) may represent an alternative metabolic substrate with the potential to improve cerebral energy supply and decrease injury. The purpose of this study was to evaluate baseline ketone concentrations in the ABI population. Methods Thirty-eight patients with ABI were enrolled into the study and followed for up to 7 days. We collected arterial blood samples immediately after admission and daily to measure the levels of BHB and acetoacetate. Where possible, matching cerebrospinal fluid (CSF) specimens were also collected. Results During the study period, plasma BHB levels were increased initially but normalized by day 3 while acetoacetate levels remained within the normal range. The change in BHB was significant. There were 30 observations in 10 patients where BHB could be measured in both blood and CSF. When the data were averaged over patients there was a weak correlation between blood and CSF BHB (Spearman's ρ = 0.62, p = 0.054). Conclusion Blood ketone concentrations remain low within the ABI population. An external source of ketones will be required to increase blood concentrations to clinically relevant levels.
Subject(s)
3-Hydroxybutyric Acid/blood , Acetoacetates/blood , Brain Injuries/blood , 3-Hydroxybutyric Acid/cerebrospinal fluid , Acetoacetates/cerebrospinal fluid , Adult , Aged , Brain Injuries/cerebrospinal fluid , Female , Glasgow Coma Scale , Humans , Intensive Care Units , Male , Middle Aged , Prospective Studies , Statistics as Topic , Time FactorsABSTRACT
Two families of dogs (Australian cattle dogs and Shetland sheepdogs) with an inherited "spongiform leukoencephalomyelopathy" were identified, with widespread vacuolation of white matter of the brain and spinal cord. Affected dogs of both breeds developed tremors at 2-9 weeks of age followed by progressive neurological worsening with ataxia, paresis, paralysis, spasticity, and cranial nerve dysfunction. The modes of inheritance of both families were most likely maternal. The cerebrospinal fluid (CSF) analysis showed elevated ratio of 3-OH butyrate to acetoacetic acid. Mitochondrial DNA sequencing showed a G to A transition at 14,474 nt (G14474A, GenBank accession no. NC002008 ) that results in an amino acid change of valine-98 to methionine (V98M) of mitochondrial encoded cytochrome b. Western blot analysis showed increased levels of core I and core II but decreased level of cytochrome c1 of the complex III and cytochrome c oxidase of the complex IV of the respiratory chain.
Subject(s)
Canavan Disease/genetics , Cytochromes b/genetics , Dog Diseases/genetics , Heredodegenerative Disorders, Nervous System/genetics , Mutation, Missense , 3-Hydroxybutyric Acid/cerebrospinal fluid , Acetoacetates/cerebrospinal fluid , Animals , Blotting, Western , Canavan Disease/cerebrospinal fluid , Canavan Disease/pathology , Cytochromes c1/metabolism , DNA, Mitochondrial/genetics , Dog Diseases/cerebrospinal fluid , Dog Diseases/pathology , Dogs , Electron Transport Complex III/metabolism , Electron Transport Complex IV/metabolism , Female , Heredodegenerative Disorders, Nervous System/cerebrospinal fluid , Heredodegenerative Disorders, Nervous System/pathology , Male , Molecular Sequence Data , Nerve Fibers, Myelinated/pathology , PedigreeABSTRACT
In order to obtain information about blood and cerebrospinal fluid (CSF) concentrations, and CSF/blood ratio data of fuel related substrates at the end of a prolonged fast in children, we have selected biochemical data from fasting test procedures in 11 control children aged 3-5 yr, fasted 24 h, and 58 control children aged 6-15 yr, fasted 40 h. There was a good correlation between blood and CSF concentrations for glucose, acetoacetate and beta-hydroxybutyrate. The relation with age and sex has been analyzed only in the older children. CSF and blood values for glucose are positively related with age, and both ketones are negatively related with age. Lactate, pyruvate and alanine concentrations in blood and CSF are not related with age, except for CSF pyruvate. With respect to the CSF/blood ratio for the above mentioned components, only the value for acetoacetate is sex and age related. The calculated median caloric values for the sum of glucose, lactate, pyruvate and ketones in CSF are independent of age at the end of a 40-h fast. The diminished glucose contribution on the CSF caloric homeostasis in younger children is fully compensated by the ketone bodies.
Subject(s)
Acetoacetates/metabolism , Blood Glucose/metabolism , Energy Metabolism , Fasting , Hydroxybutyrates/metabolism , Acetoacetates/blood , Acetoacetates/cerebrospinal fluid , Adolescent , Aging/metabolism , Blood Glucose/cerebrospinal fluid , Child , Child, Preschool , Female , Homeostasis , Humans , Hydroxybutyrates/blood , Hydroxybutyrates/cerebrospinal fluid , Male , Sex FactorsABSTRACT
L-1- Methylheptyl -gamma- bromoacetoacetate was found to be a competitive inhibitor of the acetylcholinesterases (electric eel, Ki = 17.2 microM; rat brain, Ki = 32.6 microM) and of butyrylcholinesterase (horse serum, Ki = 1.2 microM). The L-isomer was a more effective inhibitor than the D-isomer. The bromine atom at the gamma-position of the acidic moiety, the specific length of the carbon chain constituting the secondary alcohol moiety, and the presence of the ketone radical at the acidic moiety of the ester were necessary for the anticholinesterase action. 1- Methylheptyl -gamma- bromoacetoacetate formed a complex with acetylcholinesterase or butyrylcholinesterase without hydrolysis of its own molecule.
