Biochemical studies on the epileptic cerebral cortex

Within the range of our investigations the most important biochemical characteristics in the brain of idiopathic epileptic patients seem to be defect in the production of and the attendant decrease in free amino acids of the brain. On account of these phenomena there seem to occur the acceleration of the ChE activity and a poor utilization of glucose. Of the free amino acids in the brain the combined amount of glutamic acid, glutamine and &#947;-aminobutyric acid (GABA) will occupy the major portion of the total free amino acids found in brain, and thus diminution in the contents of glutamic acid and GABA in the brain of idopathic epileptic patients has quite an important meaning. At the present stage it is not yet possible to give any definitive answer to the question why such decrease occurs but it is believed that the most urgent problem facing us today is the amino acid metabolism that is associated with glutamic acid and the comparative studies of the amino acid metabolism in the epileptic brain to that in the non-epileptic brain are required. The fact that &#947;-amino-&#946;-hydroxybutyric acid (GABOB), the substance that suppresses the central excitation, is decreased seems to indicate biochemically the existence of a defect in the processes of excitation in the brain of idiopathic epleptic patients.</p

Hypoglycemic activity of Momordica charantia (bitter melon)

Diabetes mellitus (DM) represents a global health and economical problem. Many patients with DM in Asia, South America, India and East Africa have traditionally used the water extract of unripe fruits of Momordica charantia (bitter melon) as some form of complementary and alternative medicine. Studies of laboratory animals have shown the beneficial blood-glucose lowering and anti-diabetic effects of this remedy. Some oral components that bring lower blood glucose level have been isolated : charantin (sterol glycosides), charantin (polypeptide) and cucurbine-type triterpenes. Part of their actions are related to AMP-activated kinase and repression of the oxidative stress that is increased in DM. Most clinical reports are not fully convincing due to the lack of randomized control studies. The present article reviews the pharmacological and clinical effects of bitter melon with special emphasis on the anti-diabetic effects, and some effects that would require caution in the context of human trials

Clinical Applica­tion of Sialic Acid I. On Serum Sialic Acid Contents in Patients

1) The contents of sialic acid in patients of various diseases sera were determined and increases of it were noticed in several diseases. 2) Sialic acid contents ranged between 50 and 100 mg./dl. in the normal serum. 3) But in the pathological serum, it ranged between 90 and 170 mg./dl. in cancer patients, between 80 and 110 mg./dl. in peptic ulcer, between 75 and 135 mg./dl. in arachnoiditis, and between 90 and 120 mg./dl. in epilepsy. 4) In other several diseases, sialic acid contents were determined.</p

Inhibitory Effect of Fermented Papaya Preparation on Hydroxyl Radical Generation from Methylguanidine

We have previously shown that extremely high level of guanidino compounds such as methylguanidine (MG), known as a neurotoxin and also a nephrotoxin, generate reactive oxygen species (ROS) using an electron spin resonance (ESR) technique with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In this in vitro study, the inhibitory effect of fermented papaya preparation (SAIDO-PS501:PS-501) on hydroxyl radical (·OH) generation from MG was examined using an ESR spectrometry, and it was found that PS-501 suppressed ·OH generation from MG in a dose-dependent manner. The ID50 value of PS-501 was 8 mg/ml. On the contrary, glucose itself did not suppress ·OH generation from MG up to100 mg/ml, whereas PS-501 almost completely suppressed ·OH generation from MG at a dose of 100 mg/ml. These results imply that PS-501 itself may have a beneficial effect of preventing ROS- and MG-related diseases

Natural antioxidants may prevent posttraumatic epilepsy: a proposal based on experimental animal studies.

Head injury or hemorrhagic cortical infarction results in extravasation of blood and breakdown of red blood cells and hemoglobin. Iron liberated from hemoglobin, and hemoglobin itself, are associated with the generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS have been demonstrated to be involved in the mechanism of seizures induced by iron ions in the rat brain, an experimental animal model for posttraumatic epilepsy (PTE). ROS are responsible for the induction for peroxidation of neural lipids, i.e., an injury of neuronal membranes, and also could induce disorders in the excitatory and inhibitory neurotransmitters. Antioxidants, such as a phosphate diester of vitamin E and C (EPC-K1) and antiepileptic zonisamide, have been known to prevent the epileptogenic focus formation, or to attenuate seizure activities in the iron-injected rat brain. Natural antioxidants, such as alpha-tocopherol, and condensed tannins, including (-)-epigallocatechin and (-)-epigallocatechin-3-O-gallate, adenosine and its derivative, melatonin, uyaku (Lindera Strychnifolia), fermented papaya preparations, Gastrodia elata BI., and Guilingji, have been demonstrated to scavenge ROS and/or RNS and to be prophylactic for the occurrence of epileptic discharge in the iron-injected rat brain.</p

Superoxide Dismutase Activity in Cerebrospinal Fluid and Its Relation to Compression of the Lumbosacral Nerve Root

In the pathophysiology of lumbosacral radiculopathy, inflammation of the nerve root is of critical importance. Additionally, free radicals have been shown to be associated with some inflammatory process. This study was designed to investigate whether free radicals participate in the pathophysiology of nerve root involvement. We measured superoxide dismutase (SOD) activity in cerebrospinal fluid (CSF) of 31 patients with unilateral lumbosacral radiculopathy caused by a herniated disc using electron spin resonance (ESR) spectrometry. Then SOD activity was compared with the type of nerve root compression as seen on preoperative myelography. SOD activity in the normal control group was 7U/ml, while that in the hernia group remarkably decreased. The concentration gradient of SOD activity was different between central herniation and centrolateral herniation. Our findings indicate that free radicals are generated after nerve root compression. Under severe deficiency of SOD activity in CSF, serum SOD penetrates into CSF after further compression. In addition, SOD in CSF may play an important role in protecting against nerve root involvement.</p

The Anticonvulsant Zonisamide Inhibits Hydroxyl Radical Generated from Methylguanidine

Methylguanidine (MG) is a known nephrotoxin and neurotoxin, and an intracisternal injection of MG can induce convulsions in experimental animals. In this in vitro study, we examined the inhibitory effects of the antiepileptic agent zonisamide (ZNS) on hydroxyl radicals (•OH) generated from MG by using an electron spin resonance (ESR) technique. ZNS scavenged •OH generated from MG in a dose-dependent manner through direct scavenging during the auto-oxidation of MG. The rate constant of ZNS reacting with the •OH was at a near diffusion-controlled rate. These findings indicate that ZNS might detoxify MG and could thus protect against convulsive disorders

Effects of Guilingji on brain monoamines and their metabolites in mice.

Guillingji powder, a complex prescription of traditional Chinese medicines, has been pharmacologically shown to be a possible anti-aging agent, and also used for the treatment of male hypogonadism and female dysgenesis. Since the levels of numerous brain monoamines and their metabolites such as norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) have been correlated with aging, we examined the effects of Guilingji powder and its extract on such monoamines and metabolites in the cerebrum and the cerebellum of mice using HPLC-ECD. The results showed that dietary intake of Guilingji powder had the effect of increasing the NE level and the DOPAC/DA ratio, and decreasing the 5-HT level and 5-HT/NE ratio in the cerebrum. In the cerebellum, the powder did not produce any changes in the levels of the compounds investigated. The extract of Guilingji, on the other hand, not only increased the NE level and the DOPAC/DA ratio but also the 5-HIAA/5-HT ratio in the cerebrum. However, the extract did not decrease the 5-HT in the cerebrum, although it decreased the 5-HT/NE. Unlike the powder, the extract had an effect in the cerebellum, which increased the DOPAC/DA ratio. These results suggest that Guilingji may have the action of modulating the levels and the metabolism of monoamines.</p

A Novel Animal Model of Nonalcoholic Steatohepatitis (NASH): Hypoxemia Enhances the Development of NASH

Recent reports described a high incidence of nonalcoholic steatohepatitis (NASH) in patients with obstructive sleep apnea. Accordingly, we hypothesized that recurrent and intermittent hypoxemia plays an important role in the pathogenesis of NASH. Our objective was construction of a practical and accurate experimental model to reproduce the key features of NASH in humans. Chemical hypoxemia through methemoglobinemia was induced by daily intraperitoneal injection of sodium nitrite (40 mg/kg) for 4 weeks in rats with fatty liver. The later was induced by 4-week feeding a choline-deficient high-fat diet (CDHF). Besides, the normal chow diets feeding groups were prepared with in the same manner except for CDHF feeding. The animal experiment was performed in four groups; Normal control, Hypoxemia, CDHF, and CDHF + hypoxemia. Nitrite was given for the later 4 weeks to each rat of Hypoxemia and CDHF + hypoxemia. CDHF + hypoxemia rats were confirmed to develop histological changes that resemble those of patients with NASH, together with biochemical liver dysfunction, while CDHF group was limited in mild steatosis, and Hypoxemia group liver was normal. Present study established a reproducible and useful NASH model resembling the main features of NASH in humans, and showed first that recurrent and intermittent hypoxemia aggravate fatty liver to steatohepatitis and liver fibrosis