Inhibitory effect of betahistine on polysynaptic neurons in the lateral vestibular nucleus

Summary Effects of betahistine, an antivertigo drug, were examined on the lateral vestibular nucleus (LVN) neurons of cats anesthetized with -chloralose. Spike generation of monosynaptic LVN neurons elicited by vestibular nerve stimulation remained unaffected with intravenous administration of betahistine up to 5 mg/kg and with iontophoretic application of the drug up to 200 nA. In contrast, the spike generation of polysynaptic I neurons in the LVN was dose-dependently inhibited by intravenous as well as iontophoretic application of betahistine. These results suggest that small doses of betahistine more selectively interfere with synaptic transmission in the polysynaptic I neurons than in the monosynaptic neurons.     

A Case of Non-Alcoholic Pancreatitis Treated with Steroid Followed-up Using Intraductal Ultrasonography and Endoscopic Retrograde Pancreatography

A 42-year-old man with jaundice was found to have a pancreatic mass in the head by ultrasonography. Endoscopic retrograde cholangiopancreatography (ERCP) showed a segmental narrowing of the main pancreatic duct (MPD) with a mild upstream dilatation and an extrinsic stenosis of the inferior common bile duct (CBD). lntraductal ultrasonography (IDUS) showed a diffuse hypoechoic area with echogenic spots surrounding the narrowed MPD and the stenotic CBD. He was suspected of having autoimmune pancreatitis because of a characteristic pancreatogram, and 30 mg/day predniso-lone was started. Two weeks later, the narrowing of the MPD and the stenosis of the CBD improved dramatically. But the hypoechoic area remained separate from the MPD with a fine reticular pattern on the inside. It completely disappeared in the eighth week. The diachronic changes in the IDUS were characteristic in that the hypoechoic area, which initially surrounded the MPD, disappeared near the MPD, followed by a distant area. This might explain the discrepancy between the images of ERCP and IDUS in the second week of steroid therapy.     

Fibrillar beta-amyloid evokes oxidative damage in a transgenic mouse model of Alzheimer's disease.

Beta-amyloid is one of the most significant features of Alzheimer's disease, and has been considered to play a pivotal role in neurodegeneration through an unknown mechanism. However, it has been noted that beta-amyloid accumulation is associated with markers of oxidative stress including protein oxidation (Smith et al., 1997), lipid peroxidation (Mark et al., 1997; Sayre et al., 1997), advanced glycation end products (Smith et al., 1994), and oxidation of nucleic acids (Nunomura et al., 1999). Furthermore, studies from cultured cells have shown that beta-amyloid leads to an increase in hydrogen peroxide levels (Behl et al., 1994), and the production of reactive oxygen intermediates (Harris et al., 1995). Taken together, this evidence supports the idea that beta-amyloid plays a key role in oxidative stress-evoked neuropathology. In this study, we examined the induction of oxidative stress in response to amyloid load in a mouse model of Alzheimer's disease. The mice carrying mutant amyloid precursor protein and presenilins-1 (Goate et al., 1991; Hardy, 1997), develops beta-amyloid deposits at 10-12 weeks of age and show several features of the human disease (Holcomb et al., 1998; Matsuoka et al., 2001; McGowan et al., 1999; Takeuchi et al., 2000; Wong et al., 1999). Both 3-nitrotyrosine and 4-hydroxy-2-nonenal (protein and lipid oxidative stress markers, respectively) associate strongly with fibrillar beta-amyloid, but not with diffuse (thioflavine S negative) beta-amyloid, and the levels increase in relation to the age-associated increase in fibrillar amyloid load.From these data we suggest that fibrillar beta-amyloid is associated with oxidative damage which may influence disease progression in the Alzheimer's disease brain.     

Psychiatric Patients Showing Irregular β Activities in EEGs and Treatment with Antiepileptic Drugs: A Report of 15 Cases†

Abstract: Fifteen psychiatric cases are reported who were clinically diagnosed as schizophrenic, affective disorders, or neurotic, but resisted standard medication regimens, all showing irregular β activities on EEGs. The cases tended to display symptoms in common, such as dysphoria, emotional instability or frequent physical complaints. These characteristic symptoms share something mutually with the symptoms shown in some epileptic patients or psychiatric patients with epileptic EEG abnormalities without clinical seizures. Antiepileptic drugs seemed more specifically effective to the above symptoms. More than half of these cases showed improvement on EEG findings such as a decrease in irregular β activities and an increase in rhythmicity or regularity of α activities along with clinical improvement with the administration of adjunctive antiepileptic drugs. These results suggest that the adjunctive administration of antiepileptic drugs to patients with irregular β activities on EEGs is clinically useful and an EEG examination has much value in psychiatric practice to find the criteria of drug therapy.     

Subarachnoid hemorrhage from brain tumors in childhood

Six children are reported in whom subarachnoid hemorrhage was an initial symptom of brain tumor. In our neurosurgical clinics, this represented 3.6% of pediatric brain tumors and showed a frequency equal to eneurysmal rupture among nontraumatic subarachnoid hemorrhage of children. In pediatric patients, hemorrhages from brain tumors occur predominantly in the posterior fossa. The medulloblastoma, which had been believed to bleed rarely, is now realized to be a common source of tumor hemorrhages in such cases. The introduction of CT scan facilitates early recognition of hemorrhagic stroke from brain tumors and prompt management for acute intracranial hypertension and brainstem dysfunction. Although the patients achieve favorable recovery from their initial catastrophic condition, the ultimate prognosis, in the majority of cases, is still rather poor because such hemorrhages usually develop from a malignant tumor. The present and other recent reports indicate that the incidence of hemorrhagic stroke from brain tumors in pediatric patients is much higher than has been thought and is an important cause of subarachnoid hemorrhage in this age group.     

Inhibitory effect of 8-bromo cyclic GMP on an extracellular Ca2+-dependent arachidonic acid liberation in collagen-stimulated rabbit platelets

The inhibitory effect of cyclic GMP on collagen-induced platelet activation was studied using 8-bromo cyclic GMP (8brcGMP) in washed rabbit platelets. Addition of collagen (1 micrograms/ml) to platelet suspension caused shape change and aggregation associated with thromboxane (TX) A2 formation. 8brcGMP (10-1000 microM) inhibited collagen-induced platelet aggregation and TXA2 formation in a concentration-dependent manner. 8brcGMP did not affect platelet cyclooxygenase pathways, but markedly inhibited collagen-induced arachidonic acid (AA) liberation from membrane phospholipids in [3H]AA-prelabeled platelets, indicating that the inhibitory effect of 8brcGMP on collagen-induced aggregation is due to an inhibition of AA liberation. In [32P]orthophosphate-labeled platelets, collagen stimulated phosphorylation of a 20,000 dalton (20-kD) and 40-kD proteins. 8BrcGMP stimulated phosphorylation of a specific protein having molecular weight of 46-kD and inhibited collagen-induced both 20- and 40-kD protein phosphorylation. Collagen could stimulate the AA liberation without activation of phospholipase C or Na+-H+ exchange, but could not in the absence of extracellular Ca2+. These findings suggest that cyclic GMP inhibits collagen-induced AA liberation which is mediated by an extracellular Ca2+-dependent phospholipase A2. However, cyclic GMP seems to inhibit the Ca2+-activated phospholipase A2 indirectly, since 8brcGMP had no effect on Ca2+ ionophore A23187-induced platelet aggregation or AA liberation. It is therefore suggested that cyclic GMP may regulate collagen-induced increase in an availability of extracellular Ca2+ which is responsible for phospholipase A2 activation in rabbit platelets.     

Clinical significances of auditory brainstem responses (ABRS) in cases with intracranial lesion

In 47 cases with intracranial lesions, auditory brainstem responses (ABRS) were studied. From a detailed analysis of these data, the following results were concluded: In some cases, the intramedullary and extramedullary pontine tumor could be differentiated by ABR, A very small cerebello-pontine angle tumor was detected by ABR, ABR monitering was useful to evaluate brainstem function during the surgical operation, and ABRS were clinically very useful methods for predicting the outcome of a severe head injury and diagnosis of brain death. These results indicate that ABRS contribute to functional diagnosis of various diseases of the central nervous system.