Synaptic mechanisms of excitatory amino acids and NMDA receptor mediated brain excitability

L-Glutamate and related excitatory amino acids (EAA) are firmly established as major excitatory synaptic transmitter substances in the vertebrate central nervous system. Questions which have been addressed include: How many receptors are there for the EAAs?; What ion channels and/or 'second-messenger' systems are regulated by these receptors?; What are the roles of EAAs in higher neural functions?; Are they involved in neurological disorders? EAA receptors appear not only to mediate normal synaptic transmission along excitatory pathways but also to participate in the modification of synaptic connections during development. However, overaction of receptors can also mediate neuronal degeneration and even cell death. NMDA receptor antagonists markedly attenuate neuronal necrosis. Therefore, it appears that ischemia- and hypoglycemia-associated brain damage results not from a lack of energy substrates but rather via the mediation of NMDA receptors and 'excitotoxic' mechanisms. The action of ketamine anesthesia is closely associated with a block of the NMDA receptor. Ketamine binds to a site within the lumen of the NMDA-activated channel and can become trapped there when the channel closes. Current evidence indicated that NMDA receptor antagonists will be of value for the treatment of delayed neuronal death. NMDA receptor will lead to understanding the mechanisms underlying learning and memory, the control of neuronal excitability and neuronal death.     

gamma-Aminobutyric acid enhances the tone of human internal anal sphincter.

The effect of gamma-aminobutyric acid (GABA) on the human internal anal sphincter was investigated. Cumulative applications of GABA produced concentration-dependent contractions (10(-8)-10(-5) M) of the isolated human sphincter. Pretreatment with bicuculline (GABAA antagonist) turned them to relaxation. Muscimol, a GABAA agonist, induced concentration-dependent contractions (10(-8)-10(-5) M); however, baclofen (GABAB agonist, 10(-8)-10(-5) M) promoted concentration-dependent relaxation of the strips. These results suggested that both excitatory GABAA receptors and inhibitory GABAB receptors exist in the internal anal sphincter. Oral administration of sodium valproate (1600 mg/day), a GABA transaminase inhibitor, enhanced the anal canal resting pressure in 10 normal volunteers. Anal manometry showed a significant elevation in tonus without affecting amplitudes or frequencies. These results indicated that endogenous GABA, which was increased by sodium valproate, produced elevations in the anal canal resting pressure through its specific receptors in the human internal anal sphincter.     

Leukocyte Apheresis Using a Centrifugal Cell Separator in Refractory Ulcerative Colitis: A Multicenter Open Label Trial

Abstract: Recently, successful results of ulcerative colitis (UC) treatments with leukocyte apheresis have been reported by several institutes. To certify the efficacy of leukocyte apheresis in refractory UC patients, a multicenter open label trial was conducted, and results were analyzed. Fifty patients diagnosed with active steroid‐resistant UC were enrolled in this study from 14 medical centers. Using a centrifugal cell separator (Component Collection System, Haemonetics), leukocyte apheresis was performed once a week for 5 weeks. General conditions and abdominal symptoms were recorded daily, and laboratory tests were followed weekly. Changes of colonoscopic and histological manifestations of luminal activity through the study period were evaluated. At the end of the study period, stool frequency was decreased to less than 4 times a day in 68.4% (26 of 38) and serum C‐reactive protein (CRP) concentration was normalized in 56.7% (17 of 30) of the patients. Colonoscopic remission was achieved in 57.7% (26 of 45), and histological improvement was noted in 54.1% (20 of 37) of the patients tested. Improved disease activity was demonstrated in 74% (37 of 50) of the patients by general assessment criteria. Analysis of the trial data confirmed the valid clinical efficacy of leukocyte apheresis by centrifugal cell separator in refractory UC patients.     

Different origin of leiomyoblastoma by immunohistochemical study.

Leiomyoblastoma has been regarded as a neoplasm of smooth muscle origin. With recent progress in immunohistostaining techniques, many clinicopathological discrepancies have been pointed out about the origin of leiomyoblastoma. It has been claimed that gastrointestinal non-epithelial tumors should be regarded as stromal tumors in order to study their origin. In the present study, we performed various forms of immunohistostaining in seven cases of leiomyoblastoma to determine their origin. One case expressed desmine and muscle specific actin and was considered to be derived from smooth muscle. Four neoplasms expressed X-100 protein (two cases were also NSE positive) and were thought to be derived from the nerve. Two cases were of unknown derivation. These results suggest that the cells of leiomyoblastoma may arise from a primitive to totipotential cell of neural lineages that may anomalously express smooth muscle filaments.     

Muscarinic receptor-mediated hydrolysis of phosphatidylinositols in human neuroblastoma (SH-SY5Y) cells is sensitive to pertussis toxin

Effects of pertussis toxin or cholera toxin on carbachol-stimulated inositol-1-phosphate ([3H]IP1) accumulation were studied using the human neuroblastoma cell line (SH-SY5Y). The maximal carbachol-stimulated [3H]IP1 accumulation in the SH-SY5Y cells was decreased from 51.4 fmol/10(6) cells to 42.4 fmol/10(6) cells (P less than 0.05) and 22.1 fmol/10(6) cells (P less than 0.01) in the absence and presence of 1 microgram/ml and 10 micrograms/ml pertussis toxin, respectively while the EC50 values did not change. Cholera toxin (1 mg/ml) did not alter carbachol-stimulated [3H]IP1 accumulation in these cells. These results suggest that a pertussis toxin sensitive G-protein may be involved in muscarinic receptor-phosphatidylinositol hydrolysis coupling in SH-SY5Y cells.     

Gorham massive osteolysis

Gorham syndrome (massive osteolysis) is a very rare tumour-like lesion characterized by progressive osteolysis. The diagnosis must be confirmed by the microscopic finding of intramedullary angioma-like vascular structures. We report a case of a 15-year-old boy with a pathological fracture in his left humerus. Imaging modalities such as magnetic resonance imaging, computed tomography, angiography and bone scintigraphy failed to disclose to tumorous lesion that filled a cavity in the left humerus. After observing the boy's progress for 6 months, a temporary diagnosis of Gorham syndrome was made, and surgical treatment was chosen. After resection of the left humeral head and the proximal one-quarter of the humerus, thorough curettage was performed in the distal humerus and an intramedullary artificial humeral head fixed with adequate success. Pathological examination of the specimen revealed intramedullary haemangioma of the humerus.