Differential effects of physostigmine and pilocarpine on the spatial memory deficits produced by two septo-hippocampal deafferentations in rats

Rats that had received two kinds of septo-hippocampal deafferentations, medial septum (MS) lesion and fimbria-fornix (FF) transection, were assayed for brain cholineacetyltransferase (ChAT) activity and spatial memory in an 8-arm radial maze task. Both lesions produced profound and long-lasting spatial memory impairments, which were characterized by a reduction in the numbers of correct arm choices and first correct choices, a reduction in the percent of correct choices and an increase in the number of errors. The degree of memory impairment was severer in FF- than in MS-lesioned rats, and paralleled that of decreases in ChAT activity in the hippocampus. MS lesion reduced ChAT activity in the hippocampus by approximately 45%, while FF lesion almost completely depleted the activity. An intraperitoneal injection of physostigmine (0.0032-0.32 mg/kg), an acetylcholinesterase (AChE) inhibitor, significantly ameliorated the spatial memory deficit induced by MS lesion, but hardly affected that by FF lesion. In contrast, intraperitoneal doses (0.032-3.2 mg/kg) of pilocarpine, a muscarinic agonist, showed a significant improvement of both types of memory deficit with bell shaped dose-response curves. The drug was more potent in the FF- than in the MS-lesioned rats. These results suggest that the septo-hippocampal cholinergic system plays a crucial role in the maintenance of spatial memory, and that the degree of septo-hippocampal deafferentation affects the efficacy of cholinergic drugs.     

The Very Low Birthweight Neonate With an Interrupted Aortic Arch and Dextrocardia

Type 1A interruption of the aortic arch complex accompanied by mirror-image dextrocardia with situs inversus was diagnosed by counter-current aortography through the radial artery. This technique is useful for aortography of the very low birthweight neonate.     

Cardiac effects of methylmethacrylate in the rat heart-lung preparation with or without volatile anesthetics

We have assessed the deleterious effects of methylmethacrylate (MMA) on cardiac function and metabolism in the isolated heart-lung preparation with or without volatile anesthetics. Wistar rats were prepared for the heart-lung model. They were randomly divided into 5 groups as follows. (1) Control (C) group. (2) Cement (M) group; they received MMA. (3) Halothane (H) group; they received MMA and 1% halothane. (4) Isoflurane (I) group; they received MMA and 1.5% isoflurane. (5) Sevoflurane (S) group; they received MMA and 2.5% sevoflurane. MMA 1000 μg/ml was administered 7 min after the start of perfusion except in the C group. At the end of the experimental period, the hearts were freeze-clamped and then myocardial high energy phosphates, lactate and glycogen were measured. Cardiac output in all groups but C group decreased significantly. PO₂ of the perfusion blood in the M, H, I and S groups was significantly lower than that in the C group. Myocardial ATP in the M, H, I and S groups was significantly lower than that in the C group. ADP and AMP in the M, H, I and S groups were higher than those in the C group. There were no significant differences in lactate and glycogen levels between the 5 groups. MMA 1000 μg/ml is much higher than the blood level (0.05–31.89 μg/ml) which was reported in clinical patients who had femoral prosthesis. Therefore, the direct contribution of MMA itself to cardiac depression may be less than the other factors such as embolism in clinical situations. Volatile anesthetics did not influence the deleterious effects of MMA on cardiac function and metabolism.     

Differential Effects of Morphine-6-glucuronide,an Active Metabolite of Morphine,and Morphine on Locomotor Activity in Mice: Involvement of the Opioid Receptor

Abstract: Subcutaneous administration of morphine (2.5 to 20 mg/kg) or an active metabolite of morphine, morphine-6-glucuronide (2.5 to 20 mg/kg), increased the locomotor activity of mice in a dose-dependent manner. Fifteen mg/kg of morphine and 20 mg/kg of morphine-6-glucuronide were almost equipotent. Subcutaneous administration of the universal opioid antagonist, naloxone, but not the δ-selective antagonist, naltrindole, significantly suppressed the hyperlocomotion induced by morphine (15 mg/kg). On the other hand the subcutaneous administration of relatively higher doses of naloxone or naltrindole significantly reduced the hyperlocomotion induced by morphine-6-glucuronide (20 mg/kg). These findings suggest that agonistic actions at the opioid receptors, especially at the δ- and μ-receptors, contribute to the morphine-6-glucuronide-induced hyperlocomotion.     

Expansion of the spectral bandwidth by spatial and chemical shift selective saturation in high-speed magnetic resonance spectroscopic imaging

A new spectral bandwidth expansion technique for highspeed magnetic resonance spectroscopic imaging (MRSI) based on an echo-planar technique is presented. This expansion can be achieved by spatial and chemical shift selective saturation without increasing the total measurement time. In addition, displacement along the slice-select direction due to chemical-shift differences between the measured compounds is also suppressed. Experimental results are shown using a phantom consisting of benzene and acetone. High spatial resolution (1 × 1 mm²) and wide spectral bandwidth (1.5–1.8 kHz; the effective spectral bandwidth has been doubled) are obtained without the displacement along the slice-select direction.     

A new synthesis of [3-C]pyruvic acid using alanine racemase

The synthesis of [3-¹¹C]pyruvic acid was attempted by two reaction systems (A: alanine racemase and -amino acid oxidase, B: alanine racemase and -alanine dehydrogenase) utilizing a new thermostable enzyme, alanine racemase. Conversion rates from , -[3-¹¹C]alanine to [3-¹¹C]pyruvic acid were almost 100% in both methods. Similar results were obtained with immobilized enzymes packed in a single column. Furthermore, the same column could be used repeatedly without a remarkable decrease of the [3-¹¹C]pyruvic acid yield. Various matrices were tested for the immobilizing enzyme, and Aminopropyl-CPG was concluded to be the most suitable since the loss of the enzyme activity was the least in the studied matrices.     

Decreased coronary flow reserve in haemodialysis patients.

BACKGROUND: Coronary flow reserve (CFR) reflects the functional capacity of microcirculation to adapt to blood demand during increased cardiac work. METHODS: Forty-one patients who had already undergone coronary angiography were studied. They consisted of 21 haemodialysis patients with no significant left anterior descending coronary artery (LAD) stenosis and 20 non-renal failure patients without LAD stenosis. We performed transthoracic Doppler recording of diastolic coronary flow velocity in the LAD at baseline and after maximal vasodilatation by adenosine triphosphate (ATP) infusion. CFR was defined as the ratio of hyperaemic to basal averaged peak flow velocity. RESULTS: Although the peak coronary velocities during hyperaemia were similar between the two groups, CFR was smaller in haemodialysis (HD) patients than in control subjects (1.96 +/- 04 versus 2.3 +/- 0.5, P = 0.001) due to the higher baseline peak coronary velocities in the former. CONCLUSIONS: The elevated baseline peak coronary velocity may be caused by cardiac hypertrophy and anaemia in HD patients.     

Minaprine improves impairment of working memory induced by scopolamine and cerebral ischemia in rats

Using a repeated acquisition procedure in a three-panel runway apparatus, the effects of minaprine on the impairment of working memory produced by scopolamine, ethylcholine aziridinium ion (AF64A) or cerebral ischemia were investigated in rats. Minaprine (3.2–32 mg/kg IP) as well as idebenone (10–100 mg/kg IP) and physostigmine (0.1–0.32 mg/kg IP) dose-dependently reduced the increase of errors (pushes made on the two incorrect panels located at each choice point) induced by 0.56 mg/kg IP scopolamine. Cerebral ischemia for 5 min caused a significant increase of errors in the runway task. Minaprine at 3.2 and 10 mg/kg administered IP immediately after blood recirculation and again 30 min before the runway test conducted 24 h after ischemia, significantly reduced increases in errors expected to occur after 5 min of ischemia. Physostigmine 0.1 mg/kg similarly attenuated the increase in errors in ischemic rats. However, minaprine at doses up to 32 mg/kg IP failed to reduce the increase of errors induced by AF64A 2.5 nmol injected into the dorsal hippocampus. These findings suggest that minaprine exerts an ameliorating effect on amnesia produced by scopolamine and cerebral ischemia, probably through mediation of its stimulant action on central cholinergic systems.     

Determination of proliferative fractions detected by immunohistochemistry with the monoclonal antibodies to bromodeoxyuridine and Ki-67 in malignant lymphomas

The stainability of proliferating cells with monoclonal antibodies to both bromodeoxyuridine (BrdU) and Ki-67 were compared in 22 malignant lymphomas and six related conditions. A significant correlation was observed (r = 0.78) between the positivities of proliferating cells determined using these two monoclonal antibodies. The growth fractions determined with the antibodies were usually related to the histologic classification, but labelling index was more varied in diffuse large cell type lymphoma. BrdU labelling was well correlated with the Working Formulation, and more useful as a prognostic indicator. On the other hand, Ki-67 was useful for broad recognition of cell proliferative ability.