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A Teramoto

Publications and source records attributed to A Teramoto.

At least 127 records · Page 7Linked to original sources

Arginine vasopressin release inhibitor RU51599 attenuates brain oedema following transient forebrain ischaemia in rats.

RU51599 is an arginine vasopressin (AVP) release inhibitor and a selective kappa opioid agonist which has a pure water diuresis effect without associated electrolyte excretion. The effect of RU51599 on brain oedema following transient forebrain ischaemia in rats was examined. Under microscopy, the visible vertebral arteries at the second vertebra could be easily electrocauterized and completely cut by microscissors to yield complete cessation of circulation of both vertebral arteries. Transient forebrain ischaemia was induced by this improved highly reproducible technique of four-vessel occlusion model. Forty-three male Wistar rats were separated into six groups; saline-treated (1 ml/kg) normal rats (n = 10), RU51599-treated (1 mg/kg) normal rats (n = 4), saline-treated (1 ml/kg) rats with complete occlusion of both vertebral arteries (n = 5), RU51599-treated (1 mg/kg) rats with complete occlusion of both vertebral arteries (n = 5), saline-treated (1 ml/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n = 11), RU51599-treated (1 mg/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n = 8). The brain water content was determined by the dry-wet weight method. Cerebral blood flow was monitored during ischaemia and reperfusion was performed by laser Doppler flowmetry to make sure to obtain reversible forebrain ischaemia. Effects of RU51599 on concentration of glutamate released from the hippocampal CA1 of rats subjected to 5 minutes four-vessel occlusion and 60 minutes of reperfusion were also investigated by the microdialysis method. This modified four-vessel occlusion method produced reversible forebrain ischaemia with a high level of success. Bilateral carotid occlusion followed by 60 minutes reperfusion caused a significant increase in brain water content (P < 0.01), which was significantly attenuated by RU51599 (P < 0.01). These findings indicate that the AVP-release inhibitor RU51599 reduced brain oedema following transient forebrain ischaemia in rats.

Animals↗

Attenuation of cryogenic induced brain oedema by arginine vasopressin release inhibitor RU51599.

Centrally released arginine vasopressin (AVP) has been implicated in the regulation of the brain water content and is elevated in the cerebrospinal fluid of patients with ischaemic and traumatic brain injuries. The protective effect of RU51599, which is a selective kappa opioid agonist as an AVP release inhibitor, on brain oedema was examined. Male Wistar rats, weighing 300 to 400 g each, were used. The cortical cryogenic injury was produced by application of a previously prepared metal probe cooled with dry ice to the dura of the right patietal region. Animals were separated into three groups. Group 1: sham operated rats without lesion production. Group 2: saline-treated rats with lesion production. Group 3: RU51599-treated rats with lesion production. In Group 3, rats were treated with RU51599 (0.1-3 mg/kg) at 30 minutes before lesion production, 1 hour, 2 hours, and 4 hours after lesion production. After 6 hours, animals were decapitated and brain water contents were measured using the dry-wet weight method. The extent of blood brain barrier (BBB) disruption was determined by assessment of Evans blue uptake based on extraction from tissue using dimethylformamide. The primary injured infarcted area was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Sodium and potassium contents in serum and brain tissue were measured using atomic absorption spectrophotometry. The antagonism of naloxone against protective effects of RU51599 on cryogenic induced brain oedema and on antinociceptive effects in acetic-acid treated animals was examined. Statistical analysis was performed using Dunnett-test and U-test following Kruskal-Wallis test. RU51599 significantly reduced the brain water contents on the injured side and the contralateral non-injured side (p < 0.01) after 4 administration of 1 and 3 mg/kg. RU51599 neither significantly inhibited BBB disruption nor reduced the primary injured infarcted area. RU51559 significantly increased brain sodium and potassium contents in the injured brain and also increased serum sodium levels (p < 0.01). Naloxone antagonized the anti-oedema effects and anti-nociceptive effects of RU51599. These findings indicate that the AVP release inhibitor, RU51599 possibly mediated by opioid receptors, has a potential protective effect on cryogenic-induced brain oedema and that centrally released AVP plays an important role in the progression of vasogenic brain oedema.

Animals↗

Immunohistochemical detection of human natural killer cell like immunoreactivity in human pituitary adenomas, using monoclonal antibody NK-1.

Natural killer (NK) cells are specialized lymphocytes which are characterized as non-T and non-B cells, as they lack classic T and B cell surface markers. Recently, NK like immunoreactivity has been identified in endocrine and neuronal tissues as well as in the tumors derived from the neuroectoderm and neuroendocrine system. We examined the expression of NK-1 like immunoreactivity in 6 normal pituitary glands and in 55 cases of neoplastic pituitaries (16 growth hormone (GH) producing adenomas, 14 prolactin (PRL) producing adenomas, 4 thyrotropin (TSH) producing adenomas, 5 adrenocortocitropin (ACTH) producing adenomas and 16 non-functioning adenomas) immunohistochemically. The expression of the S-100 protein, which is a marker for folliclo-stellate (FS) cells, which have been reported to secrete cytokines as immuno-endocrine modulators, were also examined. In normal pituitary glands, NK-1 was detected in all 6 tissues in the cytoplasm of about 5-10% of the anterior pituitary cells. By serial sectioning and double immunostaining, NK-1 immunopositivity was frequently found to be localized in ACTH cells. The colocalization with other anterior pituitary hormones such as GH. PRL, the beta-subunit of luteinizing hormone (LH beta), follicle stimulating hormone (FSH beta). TSH beta and alpha-subunit of glycoprotein (alpha SU) was not observed. The S-100 immunopositive FS cells, which were scattered among hormone producing cells, were closely associated with NK-1 immunoreactive cells in the normal pituitaries. Among the 55 cases of pituitary adenomas, NK-1 was present in all the types of pituitary tumors, and a total of 33 (60.0%) contained NK-1 positive tumor cells. The frequency of NK-1 immunoreactivity in the individual adenoma types was; 14 of 16 GH producing adenomas (87.5%), 7 of 14 PRL producing adenomas (50%). 3 of 4 TSH producing adenomas (75%), 3 of 5 ACTH producing adenomas (60%), and 5 of 16 nonfunctioning adenomas (31.3%). By double immunostaining, NK-1 was found to be frequently colocalized with ACTH in ACTH producing adenomas, and was colocalized with PRL in PRL producing adenomas, or with GH, PRL or the alpha-subunit in GH producing adenoma cells. NK-1 immunoreactive cells were observed in close association with S-100 immunopositive FS cells in the adenomas. Our results may indicate that NK-1 positive cells may have functions as a paracrine modulators of their neighboring cells, which includes S-100 positive FS cells.

Adenoma↗

Immunohistochemical expression of retinoid X receptor isoforms in human pituitaries and pituitary adenomas.

Retinoid X receptors (RXRs) are transcriptional factors that belong to the steroid/thyroid hormone receptor superfamily. There are 3 RXR isoforms-alpha, beta, gamma-known to bind 9-cis-retinoic acid as their ligand. The expression of RXRs in human pituitary glands and pituitary adenomas has not been extensively investigated. To determine whether specific RXR isoforms may play roles in the state of differentiation of pituitary adenomas, we have investigated the immunohistochemical expression of RXR alpha and RXR gamma in 6 nontumorous pituitaries and in 60 different pituitary adenomas using isoform-specific antibodies. In the nontumorous pituitaries. RXR alpha was expressed in the nuclei of almost all cells, while RXR gamma was only expressed in thyrotropin (TSH) cells and in some cells positive for growth hormone (GH) and glycoprotein alpha-subunit (alpha SU) but not in luteinizing hormone (LH) beta-subunit, follicle-stimulating hormone (FSH) beta-subunit, prolactin (PRL) or adrenocorticotropin (ACTH) cells by double immunostaining. All 60 adenomas were RXR alpha positive, and 39 of 60 adenomas (65%) were positive for RXR gamma. The incidence of RXR gamma immunoreactivity in the different adenoma types was: 13 of 16 GH-producing adenomas (81.3%), 9 of 14 PRL-secreting adenomas (64.3%), 6 of 6 TSH-secreting adenomas (100%), 2 of 5 ACTH-secreting adenomas (40%) and 9 of 19 nonfunctioning adenomas (47.4%) including immunohistochemically gonadotropin-subunit-positive adenomas. The colocalization of RXR gamma with the TSH beta subunit, GH and alpha SU in the same adenoma cells was frequently observed, and sometimes RXR gamma was colocalized with PRL, ACTH, FSH beta or LH beta as shown by double immunostaining. We conclude that RXR alpha is expressed in both human pituitaries and pituitary adenomas. In contrast, RXR gamma is expressed more broadly in pituitary adenomas than in normal pituitaries and thus may play a role in the differentiation-specific cell types in the human pituitary both under physiological and pathological conditions.

Adenoma↗

Gi3 mediates somatostatin-induced activation of an inwardly rectifying K+ current in human growth hormone-secreting adenoma cells.

SRIF activates an inwardly rectifying K+ current in human GH-secreting adenoma cells. Activation of this K+ current induces hyperpolarization of the membrane and abolishment of action potential firing. This mechanism is an essential mechanism for SRIF-induced decrease in intracellular Ca2+ concentration and inhibition of GH secretion. The activation of the inwardly rectifying K+ current is mediated by a pertussis toxin-sensitive G protein. In this article, the expression of the pertussis toxin-sensitive G protein alpha-subunits in the human GH-secreting adenoma cells were analyzed by RT-PCR, and the G protein transducing the SRIF-induced activation of this inwardly rectifying K+ current was investigated. RT-PCR of the messenger RNA from two human GH-secreting adenomas revealed that all G alpha(i1), G alpha(i2), G alpha(i3), and G alpha(o) were expressed in these adenomas. Primary cultured cells from these two adenoma cells were investigated under the voltage clamp of the whole-cell mode. Specific antibodies against the carboxyl terminus of G protein alpha-subunits were microinjected into the cells. Microinjection of antibody against the carboxyl terminal sequence of G alpha(i3) attenuated the SRIF-induced activation of the inwardly rectifying K+ current, whereas antibody against the common carboxyl terminal sequence of G alpha(i1) and G alpha(i2) did not. These data indicate that the G protein transducing the SRIF-induced activation of the inwardly rectifying K+ current is Gi3.

Adenoma↗

Inactivation of the tumor suppressor gene on 11q13 in brothers with familial acrogigantism without multiple endocrine neoplasia type 1.

Two of three brothers (the second and third brothers) and their uncle (their mother's brother) presented acrogigantism without multiple endocrine neoplasia type 1 (MEN 1). An invasive macroadenoma was found in the second brother, and it was histologically confirmed as a sparsely granulated GH cell adenoma. Two distinct microadenomas were found in the third brother, and these were histologically diagnosed as a mixed GH cell and PRL cell adenoma and a sparsely granulated GH cell adenoma, respectively. The loss of heterozygosity (LOH) was analyzed in two adenomas (GH cell adenoma from the second brother and a mixed GH cell and PRL cell adenoma from the third brother) by determining microsatellite polymorphisms of DNAs from tumors and patients' leukocytes. The LOH was found on the chromosome 11q13, whereas LOH was not detected on 1p31-36, 2p, 3p, 4, 5, 6p, 7, 8, 9p21-22, 12p, and 19q13 in both pituitary adenomas examined. The haplotype analysis showed that the same haplotype on 11q13 was found in their mother and the unaffected first brother as well as in the affected uncle and two brothers. The deleted alleles on chromosome 11q13 in the tumors of two affected brothers were, however, restricted to those transmitted from their unaffected father. These data suggest that inactivation of the MEN 1 gene or other tumor suppressor genes on chromosome 11q13 plays an important role for the development of our familial acrogigantism without MEN 1.

Adenoma↗

A growth hormone-releasing hormone-producing pancreatic islet cell tumor metastasized to the pituitary is associated with pituitary somatotroph hyperplasia and acromegaly.

The functional and morphological changes in the pituitary gland caused by a GHRH-producing pancreatic islet cell tumor that metastasized to the pituitary and caused somatotroph hyperplasia are described. A 52-yr-old woman presented with loss of visual acuity, diabetes insipidus, and acromegaly caused by a GHRH-producing endocrine carcinoma metastasized to the pituitary. The serum GHRH, GH, and insulin-like growth factor I levels of the patient were elevated. Immunohistochemical and in situ hybridization study revealed GHRH immunoreactivity and GHRH messenger RNA (mRNA) in the metastatic tumor cells. The anterior pituitary showed hyperplasia of somatotroph cells with intact acinar structure that did not contain an adenoma, determined by light microscopy using silver impregnation. Electron microscopy revealed hyperplastic characteristics of densely granulated somatotrophs. In situ hybridization documented strong signals for GH mRNA and pituitary-specific transcriptional factor Pit-1 mRNA in the hyperplastic somatotrophs. A weak signal for GHRH receptor mRNA was detected in these somatotrophs. However, using in situ RT-PCR, GHRH receptor mRNA was more conclusively observed in most of the somatotrophs. The excessive production of GHRH by metastatic tumor may have resulted in somatotroph hyperplasia by the synergistic effects of Pit-1 and GHRH receptor. It can be concluded that the pathogenesis of pituitary adenoma formation is primarily mediated by other factors than hypothalamic hormone.

Acromegaly↗

[A lateral fluid percussion model for the experimental severe brain injury and a morphological study in the rats].

Few morphological studies have been reported on fluid-percussion experimental models using mechanically induced severe brain injury have been reported. This study was initiated to evaluate microscopic and immunohistochemical findings in severe brain injury models using rats. The experimental rats and the methods used were the same as described for a fluid-percussion model. Fluid-percussion models of traumatic brain injury were produce by rapidly injecting fluid volume into the epidural space of the temporal lobe. We used 5 rats which sustained various degrees of injury by high (7.0 atm), medium (5.6 atm) and low (3.5 atm) magnitudes of impact and sham control. The rats were sacrificed and perfused transcardially with buffer solution followed by 2.5% glutaraldehyde at intervals of 24 hours, 3 days, and 7 days, and there were normal and sham control groups. In this immunohistochemical study, monoclonal antibody to 70 kilodalton neurofilament subunit was used in a standard Avidin-Biotin Complex Kit (DAKO). Microscopic findings revealed subarachnoid hemorrhage, lateral IIIrd ventricular hemorrhage, and rarefaction and petechial hemorrhage of the local contusional lesion. In the medium level injury, there was a marked petechial hemorrhage in the corpus callosum and subependymal area. In the high level injury, there was marked edema in the white matter of the ipsi- and contralateral cerebral hemisphere, and multiple petechial hemorrhage in the brain stem and cerebellum. Microscopic findings in the corpus callosum, subependyma and brain stem in the vicinity of petechial hemorrhage revealed a large number of axonal swellings, but in these specimens only a few typical axonal retraction balls were seen with Bodian and immunohistochemical stains. In conclusion, this experimental model seems to simulate local and diffuse shearing injury, showing various morphological characteristics of diffuse axonal injury.

Animals↗

[Evaluation of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral vasospasm].

We evaluated the usefulness of three-dimensional CT angiography (3D-CTA) for the diagnosis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Eleven patients with SAH who were suspected of having cerebral vasospasm on the basis of their clinical symptoms were examined by 3D-CTA with a spiral CT scanner after an intravenous bolus administration of contrast medium. 3D-CTA revealed vasospastic changes of the cerebral vessels in eight patients. Conventional angiography was performed in six patients immediately after the 3D-CTA examination, and demonstrated the cerebral vasospasm. In eight patients, a second 3D-CTA was performed with the same technique one week after the first 3D-CTA examination. The second 3D-CTA showed the cerebral vessels without vasospastic change. In conclusion, 3D-CTA is a promising, minimally invasive strategy for the assessment of cerebral vasospasm.

Cerebral Angiography↗

[Histopathological and autoradiographical studies of experimental brain tumors after continuous local chemotherapy--acute stage in rat models].

Continuous local chemotherapy has been evaluated as being an effective administration method and as a possible adjuvant therapy in the sensitivity aspect of the cell cycle for malignant glioma. However, neurotoxicity of anti-cancer agents in the normal brain and non-effective methods for the deeper part of the tumor seem to be the most serious problems. This study was initiated to evaluate histological findings, the uptake distribution, and neurotoxicity of the continuous local administration of isotope labeled anti-cancer agents in the brain tumor of rats. The experimental brain tumor of rats and the method of continuous local chemotherapy were as follows. The tumor was produced by intracerebral inoculation of cultured cells derived from rat brain tumor induced by Rous sarcoma virus (Kumanishi et al. strain). One week later Fluorouracil (5-6-3H) (17.7 Ci/m mol) and methotrexate (L-glutamyl 3-4-3H) (41.0 Ci/m mol) were administered into the brain tumors of rats utilizing a mini osmotic pump (Alzet Model 2001), respectively. We used five rats of various groups. The rats were sacrificed at various time intervals (6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs and 7 days). The tumor tissues for light microscopic autoradiography were fixed in 10% formalin for 24 hours. Sections for the light microscopic autoradiography were cut at 4 mu thick and coated with Sakura NR-M2 drips. Following exposure for one week at 4 degrees C, the sections were stained with Konidol X. Six hours after administration, slight radioactivity was distributed in the subarachnoid space and subpial brain tissue in the vicinity of the inserted tube. Twenty-four hours after administration, high radioactivity was clearly present in many tumor cells and phagocytes at the tube tip, but no radioactivity was observed in the deeper part of the tumor or normal brain tissue. In the vicinity of necrosis foci, acute toxic inflammation was also observed. In conclusion, this experimental study shows that these anti-cancer agents are capable of direct penetration into the neoplastic cells of an intracerebral tumor following continuous local administration. However, necrotic foci were small in size. The most serious side effect seemed to be the presence of acute toxic inflammation in the vicinity of the necrotic foci.

Animals↗

[Clinicopathological studies of craniocerebral gunshot injuries].

UNLABELLED: Gunshot wounds are rare in Japan because of few regulatory laws against the possession of guns. Nevertheless such wounds are increasing in prevalence these days. Reports on the microscopic findings concerning these intracerebral lesions are fewer than those on the macroscopic findings in the scalp, the skull and the intracranial cavity. In this study we evaluated computed tomographical and histopathological findings in craniocerebral gunshot injuries. CASES: Nine patients with gunshot wounds to the head were presented. All were male and the age ranged from 17 to 66 years. Four were suicides and four were attempted murders and the last one was of unknown etiology. Morphological examination was performed on 5 autopsy cases. The distance of the bullet from the cranial cavity was as follows: long distance, 4 cases; close contiguity, 5 cases. The calibers of the weapons were as follows: 38 mm in 6 cases, 45 mm in 1 case and unknown in 2 cases. RESULTS: CT scans were examined in six cases, which revealed a missile track, hemorrhagic contusion, traumatic subarachnoid hemorrhage and marked tension pneumocephalus. In some cases, CT scan also revealed bony and metallic fragments, some deep within the cranial cavity. In the histopathological study, we found marked swollen brain (brain weight over 1500 mg) and hemorrhagic contusion in the vicinity of the missile track and interhemispheric fissure, and widespread traumatic subarachnoid hemorrhage and intraventricular hematoma. We would like to emphasize especially the remote contusion seen in the distant part of the missile track as well as massive exsudation and hemorrhage around the nerve fiber bundles. Remote contusion was observed in the inferior surface of the fronto-temporal lobes, and bilateral hemorrhagic contusion was seen in the vicinity of the superior longitudinal fissure on CT scans and autopsy findings. In one case, the bullet rotated within the intracranial cavity. In conclusion, nine cases of craniocerebral gunshot injuries were examined, while we also reviewed the medical literature concerning the shearing injury produced by gunshot brain wounds. The head injuries were further delineated by the correlation between autopsy and computerized tomography findings.

Adolescent↗

[Protective effect of L-histidine (singlet oxygen scavenger) on transient forebrain ischemia in the rat].

Histidine is an efficient scavenger of highly active singlet oxygen and somewhat weaker scavenger of hydroxyl radicals. And it has been shown to protect against reperfusion injury in the heart. The effects of L-histidine were examined in the forebrain ischemia reperfusion injury of the rat hippocampus (CA-1). Male Wistar rats were treated with the free radical scavenger L-histidine for 30 minutes before transient forebrain ischemia produced by 4-vessel occlusion. The extracellular concentrations of glutamate were measured by cerebral microdialysis. The intravenous (i.v.) administration of 50 mg/kg and 100 mg/kg L-histidine protected the elevation of extracellular glutamate concentrations after transient cerebral ischemia (p < 0.01). And the administration of L-histidine prevented ischemia-reperfusion induced delayed neuronal death in the rats. Morphological changes in the CA-1 sector of the hippocampus were evaluated 7 days after 10 minutes occlusion. The average neuronal density of treated groups showed a statistically significant (p < 0.01) persistence compared with that of control groups. These results indicate that L-histidine can reduce neuronal damage after reperfusion of cerebral ischemia and further suggest that excitatory amino acid and oxygen free radicals may damage the brain by a common pathway.

Animals↗

[Postoperative three-dimensional CT angiography (3D-CTA) in evaluation of proximal clipping for ruptured vertebral aneurysms].

At present, intra-arterial angiography remains the gold standard for most cerebrovascular problems. Recently, three-dimensional computed tomographic angiography (3D-CTA) has been reported as a screening method for the diagnosis of cerebrovascular disease. This imaging modality uses the information obtained on a contrast-enhanced CT scan to generate three-dimensional images of the cerebrovascular system. We performed 3D-CTA in the preoperative and postoperative evaluation of patients undergoing proximal clipping of ruptured vertebral artery aneurysms in addition to conventional cerebral angiography. In this study, the value of 3D-CTA after proximal clipping of ruptured vertebral artery aneurysm was evaluated retrospectively. Six patients were examined with a spinal CT (HITACHI CT-W 3000) after intravenous bolus injection of 100 ml contrast material (Iohexhol 300 mgI/ml) at the rate of 2 ml/s with a 25 second pre-scanning delay. The images of 3D-CTA were reconstructed using a new 3D-volume-render (Voxel Transmission) technique. The ages of the six patients ranged from 33 to 61 years and five cases were males and one case was female. Only one patient had a saccular aneurysm and the other five had fusiform aneurysms. Two patients underwent emergency operations within 4 days, and the other four had delayed operations. The outcome was good recovery in five cases and severe disability in one case. Postoperative conventional cerebral angiography demonstrated no delineation of the aneurysms in five cases. These results correspond well to postoperative 3D-CTA. Postoperative conventional cerebral angiography could not be performed in only one patient, but the aneurysm was visualized on the third postoperative 3D-CTA. Proximal clipping is still one of the therapeutic options for ruptured vertebral aneurysms, but some reports emphasized the possibility of rebleeding after proximal clipping of vertebral artery aneurysms. The rebleeding occurred within 1 week after proximal clipping in 6 of 9 cases (66.7%), and the prognoses were extremely poor. Therefore, in patients selected for proximal clipping, it is necessary to undertake postoperative evaluation of the aneurysm within one week after proximal clipping. 3D-CTA is minimally invasive and can be easily performed repeatedly, even if the patients are in a poor condition. In conclusion, 3D-CTA is very useful especially for evaluation of ruptured vertebral artery aneurysms following proximal clipping.

Adult↗

[An unbranched-site ruptured aneurysm of callosomarginal artery].

A case of ruptured callosomarginal artery aneurysm was reported. A 47-year-old male was admitted to our hospital with disturbance of consciousness. CT scan revealed subarachnoid hemorrhage. No aneurysm was detected by initial angiography. His consciousness level deteriorated so we stopped the examination. CT scan after initial angiography showed intracerebral hematoma in the left frontal lobe. On day 15 severe vasospasm occurred and he presented with total aphasia and right hemiplegia. The third angiography disclosed a callosomarginal artery aneurysm. Neck clipping of the aneurysm was successfully performed via unilateral interhemispheric approach. Postoperative course was uneventful and the patient recovered well with mild right hemiparesis and motor aphasia. He was transferred to another hospital for rehabilitation. The incidence of distal anterior cerebral artery aneurysm has been reported as being about 5%. The location of aneurysm in this case is very rare. In the present study we review the literature on aneurysms at the distal anterior cerebral artery and discuss the clinical and radiological features.

Aneurysm, Ruptured↗

[Effect of arginine vasopressin (AVP) inhibitor in the inhibition of the peritumoral edema].

We investigated the effect of RU599 Arginine Vasopressin (AVP) inhibitor on peritumoral edema of Wistar rats implanted with C6 glioma. C6 glioma was implanted into the right caudoputamen of 3 week-old rat's brain. Five weeks after the implantation, the changes of the brain water contents were measured by the dry-weight method. RU599 (1 mg/ml/kg body weight) was administered into Wistar rats via the tail vein every one hour (total 4 times), and the same dose of saline was used as control. Rats were sacrificed 1 hour after the last administration, and the brain of each rat was divided into 3 parts such as the anterior part without a tumor, the middle part with a tumor and the posterior part without a tumor. After that each part was separated into the right and left parts. The tumor was removed from the brain. The water contents of the brain were increased in the area around the tumor and the contralateral cerebral hemisphere excluding the anterior part. RU599 could reduce the increased water contents significantly in all areas except in the tumor itself and the area surrounding the tumor. Tumor-origin brain edema includes not only localized one but also diffuse one in the brain, and this study suggests RU599 has an effect of inhibiting the diffuse brain edema.

Animals↗

Corticotropin-releasing hormone excites adrenocorticotropin-secreting human pituitary adenoma cells by activating a nonselective cation current.

The mechanisms of corticotropin-releasing hormone (CRH) induced excitation of ACTH-secreting adenoma cells were investigated using the perforated whole-cell clamp technique and intracellular Ca2+ concentration ([Ca2+]i) measurement. CRH depolarized ACTH-secreting adenoma cells by activating a nonselective cation current that showed slight inward rectification. This channel did not seem to be a member of the Ca(2+)-activated cation currents because it was activated even when the [Ca2+]i was chelated below 50 nM. The activation of the current was induced by protein kinase A-mediated pathways. By [Ca2+]i measurement, CRH increased [Ca2+]i of these cells dependently on voltage-gated Ca2+ current. This CRH-induced [Ca2+]i increase was abolished in Na(+)-free extracellular solution, but was not abolished by the addition of 5 microM tetrodotoxin to the extracellular solution. CRH-induced ACTH secretion from the cultured adenoma cells was also abolished in Na(+)-free extracellular solution, but not in tetrodotoxin-containing extracellular solution. These data indicate that a Na+ current (maybe the nonselective cation current) other than voltage-gated Na+ current plays an important role in CRH-induced [Ca2+]i increase and ACTH secretion. CRH also activated a nonselective cation current in nonadenoma human corticotrophs, suggesting that the activation of a nonselective cation current is a physiological mechanism of CRH-induced excitation in human corticotrophs.

Adenoma↗

Management of huge pituitary adenomas.

Management of huge pituitary adenoma (more than 5 cm in diameter) is one of the most important issues on the treatment of pituitary tumors. We have analyzed the therapeutic modality and the result of our cases. From 1967 to 1983, 50 patients with huge adenoma (14.1%) out of a total 354 pituitary adenomas were surgically treated. The operative mortality was 25% for radical transcranial (TC) approach (10/40), 14% (1/7) for transsphenoidal (TS) approach and 0% (0/3) for combined two stage operations. From long-term follow-up, excellent prognoses were observed in only 44% of the patients treated by radical TC operation. After 1984, we have employed partial removal by TS surgery at the first stage, followed by reoperation by TS or TC surgery with or without radiotherapy or bromocriptine in case by case. Seventeen huge pituitary adenomas out of a total 700 pituitary adenomas were operated. There was no mortality nor major complications. The two stage operation with initial TS surgery is recommended for the management of huge pituitary adenomas.

Adenoma↗