Hiatal hernia following total gastrectomy with Roux-en-Y reconstruction.

Hiatal hernias after total gastrectomy for advanced gastric cancer are very rare. We review a case of a 44-year-old male who presented with dyspnea and chest pain 2 days after total gastrectomy, lower esophagectomy, and splenectomy with retrocolic Roux-en-Y reconstruction approached by a left thoracoabdominal incision for gastric cancer at the cardia. Plain and cross-sectional imaging identified a large hiatal hernia protruding into the right thorax containing left-sided transverse colon and small intestine. Our patient underwent a laparotomy, and after hernia reduction the hiatal defect was repaired by direct suturing. He experienced anastomotic leakage and right pyothorax, but recovered. The potential cause is discussed here and the published literature on this rare complication is reviewed briefly.

Neoadjuvant chemoradiotherapy followed by esophagectomy for initially resectable squamous cell carcinoma of the esophagus with multiple lymph node metastasis.

Neoadjuvant chemoradiotherapy (CRT) was expected to improve surgical curability and prognosis for advanced esophageal cancer. However, the clinical efficacy of neoadjuvant CRT followed by esophagectomy with three-field lymphadenectomy (3FL) for initially resectable esophageal squamous cell carcinoma (SCC) remains unclear. Since 1998, we have defined the status of metastases to five or more nodes, or nodal metastases present in all three fields as multiple lymph node metastasis, which was previously shown to be associated with poor prognosis. Between 1998 and 2002, 83 patients with initially resectable esophageal SCC were prospectively allocated into two groups, according to the clinical status of nodal metastasis. Nineteen patients clinically accompanied by multiple lymph node metastasis initially underwent neoadjuvant CRT followed by curative esophagectomy with 3FL (CRT group). The other 64 patients clinically without multiple lymph node metastasis immediately received curative esophagectomy with 3FL (control group). Although the overall morbidity rate was significantly higher in the CRT group, no in-hospital death occurred in either group. Patients without pathologic multiple lymph node metastasis in the CRT group showed a significantly better disease-free survival rate than either patients pathologically with multiple lymph node metastasis in the control group or those in the CRT group. However, the differences in the overall survival rate among the groups were not significant. Thus, the significant survival benefit by neoadjuvant CRT in addition to esophagectomy with 3FL was not confirmed, although it may have been advantageous, without increase in mortality, to at least some patients who responded well to neoadjuvant CRT. Therefore, neoadjuvant CRT can be an initial treatment of choice for resectable esophageal SCC clinically with multiple lymph node metastasis. The prediction of response to CRT and the development of alternative treatment for hematogenous recurrence could achieve a further survival benefit of this trimodality treatment.

Overexpression of glucose transporter 1 in esophageal squamous cell carcinomas: a marker for poor prognosis.

SUMMARY: Recently, Glut1 (human erythrocyte glucose transporter) expression has been demonstrated in various tumors. The aim of this study is to evaluate the prognostic utility of Glut1 expression in esophageal carcinomas. We studied Glut1 expression by immunohistochemistry of paraffin sections from 63 esophageal squamous cell carcinomas. All 63 carcinomas expressed Glut1. The mean percentage of positively stained tumor cells was 77.8% (median, 84.7%). There were two staining patterns in positive cells: 'strongly positive' and 'weakly positive'. The percentage of 'strongly positive' cells (%Glut1-SP) ranged from 0% to 95.6% (mean, 32.3%; median, 27.4%). The 5-year survival rate for patients with a high %Glut1-SP (> 30%) was significantly lower than that for patients with a low %Glut1-SP (< 30%) (P < 0.01). Statistical analysis revealed that the relative risk of death for patients with high %Glut1-SP was 2.02 times that for patients with low %Glut1-SP (P = 0.064), suggesting a possible independent predictive value for %Glut1-SP.

Hemodynamics of intrahepatic cholangiocarcinoma: evaluation with single-level dynamic CT during hepatic arteriography.

BACKGROUND: We determined the radiologic characteristics of intrahepatic cholangicarcinoma (ICC) on single-level dynamic computed tomography during hepatic arteriography (CTHA) and assessed the hemodynamics of the tumor. METHODS: Eleven patients with pathologically confirmed ICC underwent single-level dynamic CTHA. After placing the catheter tip in the proper hepatic artery and running a 30-s continuous scan, scanning was performed every 15 or 30 s for 120 s. The change of contrast-enhancement pattern of the ICCs were interpreted retrospectively. RESULTS: The pattern of enhancement was classified into two types: vascular and hypovascular. In the vascular type, the contrast enhancement gradually spread from each intratum oral artery and became mottled. It changed from a mottled and hypoattenuated pattern to an even and hyperattenuated appearance in comparison with the adjacent liver approximately 120 s after the injection of contrast agent. In the hypovascular type, the tumor was barely enhanced and remained hypoattenuated compared with the adjacent liver at 120 s after the beginning of the injection. The 11 ICCs were classified into eight vascular types and three hypovascular types. Intratumoral arteries were visualized in nine tumors: eight vascular types and one hypovascular type. CONCLUSION: The contrast-enhancement pattern of ICC on single-level dynamic CTHA is related to the intratumoral artery.

Withdrawal from nicotine facilitates diazepam binding inhibitor mRNA expression in mouse cerebral cortex.

Changes in diazepam binding inhibitor (DBI) mRNA expression after withdrawal from nicotine were examined. Withdrawal from nicotine Increased DBI mRNA expression in cerebral cortices derived from nicotine-dependent mice and in the neurons continuously exposed to nicotine (0.1 microM). These results indicate that withdrawal from nicotine after its long-term exposure induces steep increase of DBI mRNA expression as reported previously in ethanol- and morphine-dependent animals.

Suppression of Ca2+ influx through L-type voltage-dependent calcium channels by hydroxyl radical in mouse cerebral cortical neurons.

In the present study, we investigated the effect of hydroxyl radical (.OH) produced by the Fenton reaction with FeSO(4) to H(2)O(2) on Ca2+ influx by measuring [(45)Ca2+] influx into mouse cerebral cortical neurons in primary culture.OH formed from 3 microM FeSO(4) and 0.01 microM H(2)O(2) significantly reduced 30 mM KCl-induced [(45)Ca2+] influx and this reduction was abolished by .OH scavengers such as N,N'-dimethylthiourea and mannitol. Nifedipine (1 microM), an inhibitor for L-type voltage-dependent Ca2+ channels (VDCCs) showed no additive effect on the reduction of the 30 mM KCl-induced [(45)Ca2+] influx, while the inhibitors for P/Q- and N-type VDCCs showed further suppression of the KCl-induced [(45)Ca2+] influx even in the presence of .OH. Bay k 8644, an activator of L-type VDCCs, dose-dependently stimulated [(45)Ca2+] influx, and this stimulation disappeared in the presence of nifedipine. Similarly, .OH also suppressed significantly [(45)Ca2+] influx induced by Bay k 8644. These inhibitory actions of .OH on the KCl- and Bay k 8644-induced [(45)Ca2+] influx were completely abolished by .OH scavengers. These results indicate that .OH has the activity to suppress Ca2+ influx through L-type VDCCs.

NMDA receptor activation enhances diazepam binding inhibitor and its mRNA expressions in mouse cerebral cortical neurons.

Effects of N-methyl-D-aspartate (NMDA) on diazepam binding inhibitor (DBI) and its mRNA expression in mouse cerebral cortical neurons were examined. A significant increase in DBI mRNA expression was observed 1 day after the exposure to 0.1 microM NMDA and the maximal expression occurred 2 days after the exposure, whereas transient exposure to 0.1 microM NMDA for 15 min, 1 and 3 h produced no changes in the expression. Similarly, no changes in the expression were found by the concomitant exposure to NMDA and MK-801, a NMDA receptor antagonist, for 72 h subsequent to the incubation with NMDA alone for 3 h. Such NMDA-induced increases in DBI mRNA expression were dose-dependently inhibited by MK-801. Moreover, neuronal DBI content significantly increased by treatment with NMDA, which was completely abolished by MK-801. These results indicate that continuous activation of NMDA receptors is an essential factor for increasing DBI expression in the neurons.

Effects of benidipine hydrochloride on cerebrovascular lesions in salt-loaded stroke-prone spontaneously hypertensive rats: evaluation by magnetic resonance imaging.

We determined possible protective effects of benidipine hydrochloride (benidipine), a dihydropyridine calcium antagonist, on cerebrovascular lesions in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). The animals were orally treated with benidipine at 1, 3 and 10 mg/kg daily for 7 weeks, and their neurological symptoms, body weight changes, systolic blood pressure and cerebrovascular lesions on magnetic resonance imaging (MRI) were determined at various time points of treatment. Moreover, the brains of the rats that showed cerebrovascular lesions on MRI in the course of treatment or completed 7-week treatment were examined histopathologically. Control rats presented such symptoms as sedation, ataxia and aggressiveness, while their MRI analysis revealed high signals over wide areas from the occipital to frontal cortex and from the corpus callosum to external capsule. These high signal areas corresponded in location to edematous or softening lesions revealed by the histopathological observation. Treatment with benidipine at 3 and 10 mg/kg ameliorated neurological symptoms, significantly suppressing cerebrovascular damages on MRI. Benidipine at 3 mg/kg significantly decreased blood pressure for the first four weeks but it did not thereafter. These findings demonstrate that benidipine can protect salt-loaded SHRSP from cerebrovascular injury as assessed by MRI.

Mechanism for increase in expression of cerebral diazepam binding inhibitor mRNA by nicotine: involvement of L-type voltage-dependent calcium channels.

We investigated the mechanisms underlying the increase in diazepam binding inhibitor (DBI) and its mRNA expression induced by nicotine (0.1 microM) exposure for 24 h using mouse cerebral cortical neurons in primary culture. Nicotine-induced (0.1 microM) increases in DBI mRNA expression were abolished by hexamethonium, a nicotinic acetylcholine (nACh) receptor antagonist. Agents that stabilize the neuronal membrane, including tetrodotoxin (TTX), procainamide (a Na(+) channel inhibitor), and local anesthetics (dibucaine and lidocaine), dose-dependently inhibited the increased expression of DBI mRNA by nicotine. The nicotine-induced increase in DBI mRNA expression was inhibited by L-type voltage-dependent Ca(2+) channel (VDCC) inhibitors such as verapamil, calmodulin antagonist (W-7), and Ca(2+)/calmodulin-dependent protein kinase II (CAM II kinase) inhibitor (KN-62), whereas P/Q- and N-type VDCC inhibitors showed no effects. In addition, nicotine exposure for 24 h induced [3H]nicotine binding to the particulate fractions of the neurons with an increased B(max) value and no changes in K(d). Under these conditions, the 30 mM KCl- and nicotine-induced 45Ca(2+) influx into the nicotine-treated neurons was significantly higher than those into non-treated neurons. These results suggest that the nicotine-stimulated increase in DBI mRNA expression is mediated by CAM II kinase activation resulting from the increase in intracellular Ca(2+) through L-type VDCCs subsequent to the neuronal membrane depolarization associated with nACh receptor activation.

Alterations in [3H]L-N(G)-nitroarginine binding in brain after transient global or transient focal ischemia in gerbils and rats.

We investigated the post-ischemic change in [3H]L-N(G)-nitroarginine binding as a marker of nitric oxide (NO) synthase in the animal brain after transient global ischemia or transient focal ischemia. Transient global ischemia in gerbils was induced for 10 min followed by 1 h to 7 days of recirculation. Transient focal ischemia in rats was induced for 45 min followed by 3 days of recirculation. Following transient global ischemia, [3H]L-N(G)-nitroarginine binding showed a significant increase in the striatum (17-18%) and hippocampal CA1 sector (24%) at 48 and 24 h after recirculation, respectively. The hippocampal CA3 sector also showed a significant elevation (32-40%) in [3H]L-N(G)-nitroarginine binding at 24 and 48 h after global ischemia. Furthermore, the dentate gyrus showed a significant increase (30-32%) in [3H]L-N(G)-nitroarginine binding at 5, 24 and 48 h after global ischemia. Thereafter, a significant reduction in [3H]L-N(G)-nitroarginine binding was observed only in the dentate gyrus 7 days after recirculation. In contrast, [3H]L-N(G)-nitroarginine binding was unchanged in the thalamus throughout the recirculation periods. Histological analysis revealed that transient global ischemia caused severe damage or cellular damage in the striatum and the hippocampal CA1 sector. The hippocampal CA3 sector and thalamus were mildly damaged, whereas the dentate gyrus was morphologically intact. Following transient focal ischemia, a marked elevation (50-52%) in [3H]L-N(G)-nitroarginine binding was found in the regions of the ipsilateral striatum in which severe infarction occurred. Our findings suggest that [3H]L-N(G)-nitroarginine binding increases in the striatum and hippocampus after transient global ischemia or transient focal ischemia. This increase in [3H]L-N(G)-nitroarginine binding may play a pivotal role not only in the pathogenesis of ischemic brain damage, but also in the restoration of injury areas after cerebral ischemia.

Post-ischemic alterations in [3H]FK506 binding in the gerbil and rat brains.

We investigated post-ischemic changes in FK506 binding protein (FKBP) in the brain after transient global ischemia in gerbils or transient focal ischemia in rats. [3H]FK506 was used to label FKBP as a immunophilin. In transient global ischemia, [3H]FK506 binding showed a transient reduction in the frontal cortex only 1 h after recirculation. In the striatum, the dorsolateral part exhibited a significant increase in [3H]FK506 binding 5, 24 and 48 h after ischemia. However, the ventromedial part showed a transient elevation in [3H]FK506 binding 24 h after ischemia. Thereafter, the ventromedial part showed no conspicuous change in [3H]FK506 binding up to 7 days after ischemia. The dorsolateral part also showed no significant change in [3H]FK506 binding 7 days after ischemia. In the hippocampus and thalamus, [3H]FK506 binding was unchanged in the stratum radiatum of the hippocampal CA1 sector, hippocampal CA3 sector, dentate gyrus and thalamus up to 7 days after ischemia. However, the stratum oriens of the hippocampal CA1 sector showed a significant reduction in [3H]FK506 binding 48 h and 7 days after ischemia. A histological study showed that transient cerebral ischemia caused a severe damage in the striatum and hippocampal CA1 sector. In a model of transient focal ischemia, a marked increase in [3H]FK506 binding was also found in the striatum and cerebral cortex where severe infarctions were observed. These results demonstrate that post-ischemic change in [3H]FK506 binding between the striatum and hippocampus may be produced by different mechanisms. Furthermore, our findings suggest that immunophilins may play some role in the pathogenesis of ischemic diseases.

Postischemic changes of

Sequential alterations of [3H]nimodipine and [3H]ryanodine binding in gerbils were investigated in selectively vulnerable regions, such as the striatum and hippocampus, 1 h to 7 days after 10 min of transient cerebral ischemia. [3H]Nimodipine binding showed no significant changes in the striatum and hippocampus up to 48 h after ischemia. Seven days after ischemia, however, a severe reduction in [3H]nimodipine binding was observed in the dorsolateral striatum, hippocampal CA1 (stratum oriens, stratum pyramidale and stratum radiatum) and hippocampal CA3 sector. On the other hand, [3H]ryanodine binding showed a significant increase in the hippocampus 1 h after ischemia. Five hours after ischemia, a significant reduction in [3H]ryanodine binding was observed only in the hippocampal CA1 sector. Thereafter, the striatum and hippocampus showed no significant alterations in [3H]ryanodine binding up to 48 h after ischemia. After 7 days, a marked reduction in [3H]ryanodine binding was observed in the striatum and hippocampus which were particularly vulnerable to ischemia. These results demonstrate that postischemic alteration in [3H]nimodipine and [3H]ryanodine binding is produced with different processes in the hippocampus. They also suggest that the mechanism for striatal cell damage caused by transient cerebral ischemia may, at least in part, differ from that for hippocampal neuronal damage. Furthermore, our findings suggest that abnormal calcium release from intracellular stores may play a pivotal role in the development of hippocampal neuronal damage. Copyright Rapid Science Ltd

Effect of NG-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, on neurotransmitter receptor systems in aged rats.

In order to examine the effect of age and nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), we studied the changes on major neurotransmitter receptor systems in 6 (adult) and 24-month-old (aged) Fischer male rats using receptor autoradiography. L-NAME was administrated intraperitoneally in aged rats once a day for 4 weeks. [3H]QNB (quinuclidinyl benzilate), [3H]HC (hemicholinium-3), [3H]muscimol, [3H]SCH 23390 ([N-methyl-3H]R[+]-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-7-ol-benzazepine), [3H]nemonapride and [3H]mazindol were used as markers of muscarinic acetylcholine receptors, high-affinity choline uptake sites, GABAA (gamma-aminobutyric acidA) receptors, dopamine D1 receptors, dopamine D2 receptors and dopamine uptake sites, respectively. The age-related change in [3H]muscimol binding in the brain was more pronounced than that in [3H]QNB, [3H]HC, [3H]SCH 23390, [3H]nemonapride and [3H]mazindol binding. Chronic treatment (4 weeks) with L-NAME caused no significant changes in [3H]QNB, [3H]muscimol, [3H]SCH 23390 and [3H]nemonapride binding in most areas of aged rat brain, as compared with vehicle-treated aged animals. However, chronic treatment with L-NAME caused a significant reduction in [3H]HC and [3H]mazindol binding in any brain regions of aged rats in comparison with the vehicle-treated aged animals. These results demonstrate that the GABAergic system is more susceptible to aging processes than cholinergic and dopaminergic systems in the brain. Furthermore, our findings suggest that nitric oxide may play some role in the regulation of choline uptake and dopamine uptake systems during aging processes. Copyright 1998 Lippincott Williams & Wilkins

[Evaluation of CTA for arterial infusion chemotherapy for liver metastasis from colorectal cancer].

To compare between the arterial blood supply of metastatic liver tumor and effects of intrahepatic arterial infusion chemotherapy (IHAC), we examined 8 patients with 27 liver metastasis from colorectal cancer. They were treated with ADM/lipiodol/5-FU/LV (19 nodules) or 5-FU/LV (8 nodules). To evaluate the arterial blood supply, CT arteriography (CTA) was performed, which classified tumors into 3 grades. Grade (Gr) 0; almost no enhancement, Gr1: less than one-third of tumor, Gr 2; less than two-thirds; Gr 3 over two-thirds (no case). As a result, 3 of NCs and 3 of PDs were Gr 0, 7 of MRs, 3 of NCs and 2 of PDs were Gr 1, and CR, PR and 7 of MRs were Gr 2. These results suggest that the arterial blood supply is necessary for a better response of IHAC and CTA is effective to forecast the response to IHAC.

Effect of NG-nitro-L-arginine on age-related changes of glutamate receptor systems and immunophilin in rats.

We investigated the effects of age and NG-nitro-L-arginine methyl ester (L-NAME) on glutamate receptor systems and immunophilin in Fischer rat brain using receptor autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent [3H]D-aspartate and [3H]FK-506 were used to label N-methyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amino acid transport sites and FK-506 binding proteins (FKBP), respectively. [3H]Glycine and sodium-dependent [3H]D-aspartate binding significantly reduced in the cerebral cortex, striatum, hippocampus, thalamus, substantia nigra and cerebellum of aged (24-month-old) rats in comparison with adult (6-month-old) animals. In contrast, [3H]MK-801 and [3H]FK-506 binding showed no significant changes in most brain regions of aged rats. Intraperitoneal chronic treatment with L-NAME (5 mg/kg, once a day for 4 weeks) showed no conspicuous changes in these binding sites in most brain areas of aged rats. In the cerebellum, however, this treatment showed a significant change in both [3H]MK-801 and sodium-dependent [3H]D-aspartate binding in aged rats. These results demonstrate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes than NMDA receptors and FKBP. Furthermore, our findings may suggest a possible role of nitric oxide in the regulation of cerebellum during aging processes.

Effect of aging on dopaminergic receptors and uptake sites in the rat brain studied by receptor autoradiography.

We studied the age-related alterations of dopaminergic receptors in the brain of Fisher 344 rats with various age (3 weeks and 6, 12, 18 and 24 months) using in vitro receptor autoradiography. [3H]SCH 23390, [3H]spiperone and [3H]nemonapride, and [3H]mazindol were used to label dopamine D1 receptors, dopamine D2 receptors and dopamine uptake sites, respectively. In immature rats (3 weeks old), [3H]SCH 23390 binding showed a significant increase in most brain regions compared to adult animals (6 months old), whereas [3H]spiperone and [3H]nemonapride bindings showed no significant alteration in any brain areas. In contrast, [3H]mazindol binding showed a significant decline in most brain regions. On the other hand, the age-related alterations in [3H]SCH 23390 binding were not observed in any brain regions. [3H]Spiperone and [3H]nemonapride bindings also showed no significant alteration in the brain during aging, except for a transient alteration in [3H]spiperone binding in the nucleus accumbens and hippocampus of 12 months old rats. However, [3H]mazindol binding showed a significant reduction in most brain areas of 12 months old rats. Thereafter, the age-related reduction in [3H]mazindol binding was observed in most brain regions of 18 and 24 months old rats. The results demonstrate that dopamine uptake sites are more susceptible to the aging process than both dopamine D1 and D2 receptors. Furthermore, our results suggest that dopaminergic receptors and dopamine uptake sites may develop with different patterns and speeds after birth. Our studies may provide valuable information concerning the effect of aging on dopaminergic systems.

Effects of vinconate on age-related alterations in [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 binding in rats.

We investigated the effects of age and (+/-)-methyl-3-ethyl-2,3,3a,4-tetrahydro-1 H-in-dolo[3,2,1-de] [1,5] naphthyridine-6-carboxylate hydrochloride (vinconate), an indolonaphthyridine derivative, on calcium channels, neurotransmitter receptor systems and immunophilin in Fischer rat brain using quantitative receptor autoradiography. [3H]MK-801, [3H]glycine, sodium-dependent D-[3H]aspartate, [3H]FK-506 and [3H]PN200-110 were used to label N-methyl-D-aspartate (NMDA) receptors, glycine receptors, excitatory amino acid transport sites, FK-506 binding proteins (FKBP) and voltage-dependent L-type calcium channels, respectively. [3H]Glycine and sodium-dependent D-[3H]aspartate binding significantly decreased in the frontal cortex, parietal cortex, striatum, nucleus accumbens, hippocampus, thalamus, substantia nigra and cerebellum of 24 month old rats in comparison with 6 month old animals. In contrast, [3H]MK-801, [3H]FK-506 and [3H]PN200-110 binding showed no significant changes in the brain of 24 month old rats. Intraperitoneal chronic treatment with vinconate (10 and 30 mg/kg, once a day for 4 weeks) dose-dependently ameliorated the significant reduction in [3H]glycine and sodium-dependent D-[3H]aspartate binding in the brain of 24 month old rats. These results demonstrate that glycine receptors and excitatory amino acid transport sites are more susceptible to aging processes than NMDA receptors, immunophilin and voltage-dependent L-type calcium channels. Furthermore, our findings suggest that vinconate may have a beneficial effect on age-related changes in glycine receptors and excitatory amino acid transport sites.

Age-related changes in [3H]nimodipine and [3H]rolipram binding in the rat brain.

Ageing is associated with changes in neurotransmission which might be correlated with abnormal calcium metabolism. Because there is evidence that nimodipine can enhance the learning abilities of ageing animals and rolipram can enhance the excitability of neurons, providing a functional basis for cognition-enhancing activity, age-related alterations in the binding of voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic adenosine monophosphate-selective phosphodiesterase (cyclic-AMP PDE) were studied in 3-week- and 6-, 12-, 18- and 24-month-old Fisher 344 rats by use of receptor autoradiography. [3H]Nimodipine and [3H]rolipram were used to label the voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP PDE, respectively. [3H]Nimodipine binding showed no obvious change in all brain areas of 12- and 18-month-old rats, as compared with 6-month-old animals. In 24-month-old rats, however, [3H]nimodipine binding increased significantly in the striatum and hippocampal CA3 sector. In contrast, [3H]rolipram binding showed no significant change in most brain areas during ageing, except for a transient change only in the hippocampal CA1 sector of 12-month-old animals. [3H]Nimodipine and [3H]rolipram binding showed a significant increase in some brain areas of 3-week-old rats compared with 6-month-old animals. The results indicate that in rats voltage-dependent L-type calcium channels are more susceptible to ageing processes than calcium/calmodulin-independent cyclic-AMP PDE. Our data also demonstrate that voltage-dependent L-type calcium channels and calcium/calmodulin-independent cyclic-AMP PDE might play roles in developmental processes. These findings might help further elucidation of the relationship between age-related neurological deficits and behavioural pharmacology including cognitive function.

Age-related changes of sodium-dependent D-[3H]aspartate and [3H]FK506 binding in rat brain.

We investigated age-related changes in excitatory amino acid transport sites and FK506 binding protein (FKBP) in 3-week-, and 6-, 12-, 18- and 24-month-old Fischer 344 rat brains using receptor autoradiography. Sodium-dependent D-[3H]aspartate and [3H]FK506 were used to label excitatory amino acid transport sites and immunophilin (FKBP), respectively. In immature rats (3-week-old), sodium-dependent D-[3H]aspartate binding was lower in the frontal cortex, parietal cortex, striatum, nucleus accumbens, whole hippocampus, thalamus and cerebellum as compared to adult animals (6-month-old), whereas [3H]FK506 binding was significantly lower in only the hippocampus, thalamus and cerebellum. 3[H]FK506 binding exhibited no significant change in the brain regions examined during aging. However, sodium-dependent D-[3H]aspartate binding showed a conspicuous reduction in the substantia nigra in 18-month-old rats. Thereafter, a significant reduction in sodium-dependent D-[3H]aspartate binding was found in the thalamus, substantia nigra and cerebellum in 24-month-old rats. Other regions also showed about 10-25% reduction in sodium-dependent D-[3H]aspartate binding. The results indicate that excitatory amino acid transport sites are more susceptible to aging process than immunophilin. Further, our findings demonstrate the conspicuous differences in the developmental pattern between excitatory amino acid transport sites and immunophilin in immature rat brain.

The significance of esophageal variceal pressure in patients with cirrhosis.

We measured the portal circulatory hemodynamic parameters in 10 cirrhotic patients with portal hypertension and esophageal varices to determine the significance of esophageal variceal pressure. In 4 patients (group I), the temporary portal vein occlusion produced significant elevations in both the esophageal variceal pressure and the portal venous pressure. The results of the portal circulatory hemodynamic assessment in this group were consistent with the predominance of the backward flow mechanism. In the remaining 6 patients (group II), however, portal vein clamping resulted in a slightly increased esophageal variceal pressure with an enormous increase in the portal pressure. The forward flow mechanism thus appeared to be predominant in group II. In other words, the results of the pressure measurements were consistent with the functional separation of the hemodynamics in the esophageal varices and portal trunk in group II and the functional hemodynamic continuity in group I. This functional separation between the esophageal varices and the portal trunk in group II might therefore have resulted from the increased blood flow in the lesser splanchnic region.