Saburo Ogasahara

Treatment of Kearns‐Sayre syndrome with coenzyme Q10

We studied the metabolism of coenzyme Q10 (CoQ) and the effects of CoQ therapy in five patients with Kearns-Sayre syndrome (KSS). Although the mitochondrial fraction was increased in muscles from KSS patients, CoQ content was slightly low. CoQ synthesis was normal in fibroblasts from KSS patients. Administration of 120 to 150 mg/d of CoQ improved abnormal metabolism of pyruvate and NADH oxidation in skeletal muscle. CoQ therapy decreased CSF protein concentration and CSF lactate/pyruvate ratio. ECG abnormalities and neurologic symptoms also improved.

Improvement of abnormal pyruvate metabolism and cardiac conduction defect with coenzyme Ql0 in Kearns‐Sayre syndrome

In a patient with Kearns-Sayre syndrome, concentration of coenzyme Ql0, a component of the mito-chondrial electron transport system, was decreased in serum and in the mitochondrial fraction of skeletal muscle. Serum concentrations of lactate and pyruvate were abnormally high, especially after exercise or oral glucose loading. Levels of folic acid in plasma and CSF were decreased. ECG showed a first-degree atrioventricular block. After administration of coenzyme Ql0 60 to 120 mg daily for 3 months, serum levels of lactate and pyruvate became normal, with improvement of atrioventricular block and ocular movements.

Dopamine metabolism in the central nervous system after discontinuation of l-dopa therapy in patients with Parkinson disease

The dopamine turnover rate in the central nervous system (CNS) of parkinsonian patients was studied by means of the intravenous probenecid test during drug holiday (DH) and alternate day L-dopa therapy (ADDT). After L-dopa therapy was stopped, the dopamine turnover rate decreased more rapidly in patients with the marked wearing-off phenomenon than that in patients without fluctuation of symptoms. The lumbar CSF concentrations of L-dopa and 3-O-methyldopa of patients with and without wearing-off phenomenon were similar during L-dopa therapy. DH improved the effect of L-dopa on parkinsonian symptoms; it did not affect, however, the metabolism of exogenous L-dopa. The dopamine turnover rate in the CNS before L-dopa therapy or on on-days did not differ between patients tolerating and those not tolerating ADDT. However, it was significantly lower on off-days in patients not tolerating ADDT than in those tolerating ADDT. The relationship between dopamine storage in the CNS and the response to L-dopa therapy is discussed.

Decreased activities in mitochondrial inner membrane electron transport system in muscle from patients with Kearns-Sayre syndrome.

The present study shows biochemical data on skeletal muscle from 5 patients with Kearns-Sayre syndrome (KSS). Enzyme activities per muscle wet weight in the electron transport system of inner mitochondrial membrane were not significantly different in KSS from those in normal subjects except one patient with long duration of symptoms. On the other hand, mitochondrial contents were increased and enzyme activities per mitochondrial protein in the electron transport system were markedly decreased in the muscle of all cases. These results suggest that the decreased enzyme activity of the mitochondrial electron transport system in each mitochondrion may result in a compensatory increase in mitochondrial contents in the muscle of KSS.

Simple method for the simultaneous determination of noradrenaline, dopamine and serotonin by stepwise elution from a short column of weak cation-exchange resin

A simple method for the simultaneous determination of noradrenaline, dopamine and serotonin using a short column of Amberlite CG-50 is described. Noradrenaline and dopamine were eluted from the column with phosphate buffers containing 1.5 and 4.0% boric acid, respectively, and then serotonin was eluted with 1.0 N HCl. Catecholamines were determined by a modification of the ethylenediamine condensation method using potassium ferricyanide as oxidant and isobutanol for extraction of the fluorophores. Serotonin was measured by the acidic o-phthalaldehyde method. The method was applied to the simultaneous determination of noradrenaline, dopamine and serotonin in discrete regions of rat brain.

Trophic effect of iron-bound transferrin on acetylcholine receptors in rat skeletal muscle in vivo ☆

Trophic effect of iron-bound transferrin (FeTf) on the total content of acetylcholine receptors (AChRs) and the specific activity of AChRs in innervated and denervated skeletal muscle was investigated in vivo. The right ischiadic nerves of 15 rats weighing 160 g were transected. FeTf (1.2 mg/ml) was injected daily into bilateral crural muscles of rats for the following 11 days. Control groups received injections of saline or no treatment. FeTf significantly increased the total content of AChRs and the specific activity of AChRs in innervated and denervated muscle compared with control groups (P less than 0.001). This result shows that intramuscular injections of FeTf may be useful for the treatment of disorders of neuromuscular transmission.

Focal luxury perfusion with an early-filling vein in relation to neurological symptoms evoked by heat

SummaryA 50-year-old man with a 1-year history of transient attacks of left total hemiparesis was admitted to hospital with a complaint of increasing frequency of attacks. Minimal or moderate left hemiparesis was elicited by elevation of environmental temperature when taking a hot bath or a hot shower. Right carotid angiography revealed an early-filling vein near the right central sulcus. An increase of focal luxury perfusion by elevation of body temperature seemed to cause relative ischaemia in this paracentral gyrus.

Elevation of Rat Brain Histamine Content by Microwave Irradiation

ABSTRACT The brain histamine level of rats sacrificed by focused microwave irradiation was approximately six times higher than that of rats sacrificed by decapitation when assayed with a sensitive and specific high performance liquid chromatography fluorometric method. Repeated microwave irradiation resulted in further increases not only in histamine but also in some of the free amino acids, indicating that proteins are hydrolyzed under these conditions. We, thus, believe it is unlikely that free histidine alone is responsible for the observed increase in histamine content. It is suggested that proteins are directly hydrolyzed by the heat produced from repetitive microwave irradiation, and that histamine is formed from the histidine residues of some peptide chains.

Changes in the Levels of Cyclic Nucleotides and Monoamines in Rat Brain During the Sleep-Wakefulness Cycle: Application of the Microwave Fixation Method to Sleep Research

ABSTRACT The levels of cyclic nucleotides, serotonin, 5-hydroxyindoleacetic acid, noradrenaline, and dopamine in the brain of rats were determined during the sleep-wake-fulness cycle using the microwave fixation method. Rats were restrained in specially designed frames in which they could move their heads and limbs freely and take food and water ad libitum . They were acclimatized to the microwave applicator for 1 hour a day for 5-7 days. They were then sacrificed by microwave irradiation of the heads during polygraphic monitoring of various periods of the sleep-wakefulness cycle. This procedure made it possible to obtain brain tissue during the sleep-wakefulness cycle for the analysis of labile substances. The content of cyclic AMP decreased during sleep in all brain regions except the cerebellum. In the hippocampus, midbrain, pons-medulla and cerebellum, the level of cyclic GMP was highest during wakefulness, whereas in the striatum it was highest during paradoxical sleep. The content of cyclic GMP in the midbrain and pons-medulla was higher during paradoxical sleep than during slow-wave sleep. The content of serotonin increased in the cerebral cortex and midbrain during sleep. The level of 5-hydroxyindoleacetic acid increased during slow-wave sleep in the hippocampus and decreased in various brain regions during paradoxical sleep. The content of noradrenaline and dopamine were not changed during the sleep-wakefulness cycle. These changes in the metabolism of first and second messengers during the sleep-wakefulness cycle suggest that these substances may play some roles in the regulation of sleep and wakefulness. The microwave fixation method is suitable to fix the metabolism of the brain during the sleep-wakefulness cycle because of rapid heat denaturation of the enzymes in vivo .

Urinary Catecholamine Response to Glucagon in Young and Elderly Patients with Essential Hypertension

本態性高血圧症, 血圧維持機構における交感神経系の関与が注目されている. しかし, 多種の要因が複雑に関与しているため現在のところ明確な結論は得られていない. 今回, 本態性高血圧症における加齢による交感神経系の関与の差異を検索するため, グルカゴン負荷時の尿中カテコールアミン反応性 (尿中アドレナリンおよびノルアドレナリン排泄値) を指標とすることにより, 老年性および若年性本態性高血圧症の交感神経系機能を比較検討した. その結果, 1) 若年性本態性高血圧症患者において, 交感神経系の反応性亢進をみたが, 2) 老年性本態性高血圧症患者においては, 交感神経系の反応性亢進は認められなかった. また, 3) 若年性および老年性の正血圧者群においては, 交感神経系反応性に有意な差異が認められず, 今回の実験に関する限り, 正血圧者群における加齢による交感神経系の反応性変化は認められなかった. 以上の結果より, 本態性高血圧症における病因としての交感神経系の関与は, 若年性本態性高血圧症では強く疑われたが, 老年性本態性高血圧症においては認める事ができなかった.