Flunarizine induces a transient loss of tyrosine hydroxylase immunoreactivity in nigrostriatal neurons

Neurotoxic effects of flunarizine (Fz), a selective calcium channel blocker, on the nigrostriatal dopamine system was investigated. Systemic injections of Fz to mice resulted in a transient loss of tyrosine hydroxylase (TH) immunoreactive nigrostriatal neurons without cell loss. TH immunoreactivity in these neurons was greatly reduced as rapidly as one day after drug administration (regardless of dosage used) and thereafter recovered in both dose- and time-dependent manners. Such a novel neurotoxic action of Fz may constitute a morphological substrate for reversible drug-induced parkinsonian signs described in recent clinical case reports.     

Quantitative analysis of sodium fast and slow component in in vivo human brain tissue using MR Na image]

In vivo sodium concentrations in the normal brain tissue and a tumorous tissue were analyzed using MR Na image. The nuclear magnetic resonance enabled us to divide the signal from sodium in the living tissue into 2 parts based on the differences of T2 value. Those are fast component having the T2 value of less than 5 msec and slow component of 15-40 msec. We investigated the effect of macromolecules on T2 value of sodium image using polyvinyl alcohol (PVA) powder. MR Na image was taken with the parameters of TR/TD, 110 ms/1.9 ms (FID image) and TR/TE, 110 ms/20 ms (SE image). Saline solution showed high intensity on both FID image and SE image. Saline solution added PVA (PVA phantom) also showed high intensity on FID image, whereas the signal intensity of PVA phantom in SE image extinguished. To know the relation between the signal intensity and sodium concentration, sodium concentration--signal intensity curve was obtained using phantoms with various sodium concentrations (0.05-1.0%). This curve showed a direct proportion between sodium concentration and signal intensity on Na image. We measured further the sodium concentrations of the human brain tissue. Sodium phantoms were arranged around the heads and the MR Na images of the normal brains from 3 volunteers and a patient with a brain tumor (meningioma) were taken. The sodium concentrations of occipital lobe, basal ganglia and the tumorous tissue were calculated using the sodium concentration--signal intensity curve obtained from the phantoms arranged around the heads.(ABSTRACT TRUNCATED AT 250 WORDS)     

A clinical study of cerebral perfusion during pulsatile and nonpulsatile cardiopulmonary bypass

The purpose of this study was to determine the effect of pulsatile flow on cerebral perfusion under cardiopulmonary bypass (CPB). Twenty-three patients who underwent cardiac operations were divided into two comparable groups: Group A (N = 11) had standard nonpulsatile flow, while in Group B (N = 12), a pulsatile pump was used. The blood flow of left common carotid artery and radial arterial pressure were continuously monitored during cardiac operation in both groups and cerebral vascular resistance was calculated. In Group B, the perfusion pressure of left common carotid artery was monitored and compared with that of radial artery. Arterial and internal jugular venous blood were sampled and the difference of cerebral A.V O2 contents and cerebral oxygen consumption was calculated. Cerebral vascular resistance in Group B (54.0 +/- 11.2% of the value of before-CPB) significantly decreased compared to that in Group A (72.2 +/- 11%) at the end of CPB (p less than 0.05). Pulse pressure following pulsatile CPB flow was 15.1 +/- 5.8 mmHg monitored in radial artery and it reduced to 8.5 +/- 5 mmHg in left common carotid artery. Although there was no significant difference in cerebral oxygen consumption of both groups during and just after CPB, the difference of cerebral A-V O2 contents of Group B was greater than Group A just after CPB. These data suggest that pulsatile flow may minimize the cerebral microcirculatory shunt during CPB, resulting from the reduction of cerebral vascular resistance.     

Differential expression of the beta I- and beta II-PKC subspecies in the postnatal developing rat brain; an immunocytochemical study.

Differential expression of protein kinase C subspecies, beta I- and beta II-PKC, derived from a single gene by alternative splicing was evidenced in the postnatal developing rat brain. Immunoblot analysis of the PKC subspecies in the whole developing brain showed that beta I-PKC was present at birth and then gradually increased, while beta II-PKC was not present at birth or on postnatal day 3, then increased rapidly from day 7 to the maximum value seen in the adult brain. Under light microscopy, beta I-PKC immunoreactivities seen at birth were the most intense in the brainstem and intense in the diagonal bundle and globus pallidus. beta I-PKC immunoreactivities in these neurons weakened from day 7 and disappeared in the adult brain, while in the cerebral cortex, triangular septal nucleus and pontine nucleus beta I-PKC immunoreactivities were week at birth and then gradually increased. beta II-PKC immunoreactivities were first visible in neurons on day 7 and increased progressively. beta I- and beta II-PKCs were not co-localized in a neuron, as far as examined. The immunoreactivities of beta I-PKC at birth were localized in growth cone-like structures as well as in the dendrites and perikarya. Similarly, alpha-PKC was also present at birth in the growth cone-like structure. Immunoblot analysis revealed that beta I-PKC was present at birth in the growth cone-rich fraction from the hindbrain but not in that from the forebrain, while alpha-PKC was found in the growth cone-rich fraction from both the forebrain and the hindbrain. beta II- and gamma-PKC were not detected in the growth cone-rich fraction from either forebrain or hindbrain. These findings suggest that beta I- and beta II-PKC play a role in different stages of development and in different neurons; both beta-subspecies may be involved in postnatal developing neuronal functions while only beta I-PKC plays functional roles in the growth cone, in the prenatal developmental stage.     

Time-course changes of regional cerebral blood flow by SPECT with N-isopropyl-p-[123I]-iodoamphetamine in childhood partial seizures]

Single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]-iodoamphetamine was performed twice at different times in 18 children suffering from partial seizures to evaluate the time-course changes of the hemodynamics in the focal region. Comparison of the 2 SPECT images revealed that a decreased regional cerebral blood flow (CBF) in the first was normalized in 4 cases (22.2%) and contracted in 7 cases (38.9%). The region of decreased blood flow in the second was contralateral to that in the first in 1 case (5.6%) and unchanged in 6 cases (33.3%). Most of the normalized and contracted cases were those in which clinical seizures disappeared and the EEG findings were normalized. In these cases which responded to treatment, the decreased regional CBF was also found to be improved. Repeated SPECT appears to be useful for evaluating the therapeutic efficacy. On the other hand, most of the unchanged cases were those in which clinical seizures were frequent or uncontrolled, or which persistently showed the abnormalities in their EEG. SPECT was considered to reflect well the conditions of the epileptic foci. These results indicate that repeated SPECT for observing the time-course changes of the regional CBF represents a useful technique with can be applied in evaluating the therapeutic efficacy or deciding the time to discontinue treatment and for pathogenetic elucidation of the epileptic foci.     

Risk of gallstones following gastrectomy in Japanese men

The risk of gallstones developing after gastrectomy in middle-aged Japanese men was investigated in a study of 2,738 men aged between 48 and 56 years who underwent both gallbladder ultrasonography (US) and a barium study of the upper digestive tract. It was revealed that 61 men had gallstones, 37 had had their gallbladder removed previously, and 55 had a history of gastrectomy. The prevalence of gallstones was 3.5 times higher in the men who had previously undergone gastrectomy (7.7%) than in those who had not (2.2%) (P=0.03). Moreover, gallstones tended to be more prevalent in those who had undergone Billroth II gastrectomy (12.5%) compared with those who had undergone Billroth I gastrectomy (5.6%); however, the difference was not significant. These results indicate that gastrectomy using either Billroth I or Billroth II reconstruction predisposes to gallstone formation. Nevertheless, it was estimated that prior gastrectomy was responsible for no more than 5% of gallstones in the study population.