Influence of histamine depletion on learning and memory recollection in rats

To clarify the role of endogenous histamine in learning and memory, the effect of -fluoromethylhistidine on active avoidance response in rats was studied. -Fluoromethylhistidine (20–100 mg/kg or 10–50 µg) significantly (P<0.05 orP<0.01) prolonged the response latency in active avoidance response when administered by either intraperitoneal or intracerebroventricular injection. These effects were dose-related and long lasting. A prolongation of the response latency induced by an intraperitoneal injection of -fluoromethylhistidine (100 mg/kg) was antagonized by intracerebroventricular injection of histamine (10 and 20 ng) in a dose-dependent manner. In addition, the acquisition of this response was retarded by a consecutive intracerebroventricular injection of -fluoromethylhistidine (50 µg), whereas histamine (100 ng) facilitated the response acquisition when administered by the same route. Both intraperitoneal (100 mg/kg) and intracerebroventricular injection of -fluoromethylhistidine (50 µg) significantly (P<0.05 orP<0.01) decreased the brain histamine content, especially in the hippocampus and hypothalamus. When -fluoromethylhistidine (50 µg) was injected intracerebroventricularly, there is a high correlation between a prolongation of the response latency and a decrease in histamine content of these brain areas. Based on these findings, it was concluded that an intimate relation may exist between a prolongation of response latency in the active avoidance response and a decrease in the brain histamine content; endogenous histamine may play an important role in learning and memory recollection in rats.     

Contribution of Monoamine Oxidase(MAO) to the Binding of Tertiary Basic Drugs in Isolated Perfused Rat Lung

The effect of tertiary basic drugs on mitochondrial MAO activity and the effect of MAO inhibitors (MAOIs) on basic drug accumulation in the isolated perfused rat lung were studied to clarify the role of MAO in drug binding to lung tissue. In the perfused lung preparation, the inhibition of MAO by basic drugs correlated well with their lipid solubilities and followed competitive kinetics. The inhibitory rank order (imipramine diphenhydramine > quinine > metoclopramide > procainamide) also correlated with their accumulation in the perfused lung. Moreover, MAOI treatment decreased the accumulation of basic drugs in the lung, and the potency of MAOIs to inhibit drug accumulation in the lung correlated with their MAO inhibitory activity. These results indicate that lung MAO has specific binding sites for basic drugs and may function as a drug reservoir.     

The protective effect of thromboxane A2 synthetase inhibitor against ischemic liver injury

To evaluate the role of thromboxane A₂ (TXA₂) in ischemic liver injury, the serum changes in thromboxane B₂ (TXB₂) and 6-keto-prostaglandin F₁ alpha (6-K-PGF₁) following warm ischemia of the total canine liver were examined, and the protective effect of a TXA₂ synthetase inhibitor was assessed. Total liver ischemia was performed for 60 min on two groups of dogs: a control group, in which ischemia alone was performed, and an OKY-046 group, which received a TXA₂ synthetase inhibitor. A temporary active portacaval shunt was used to eliminate the effects of splanchnic venous stasis during clamping of the hepatic pedicle. Postoperative changes in liver function, assessed by the transaminase enzyme levels, and in prostaglandins were recorded and the histologic liver findings of both groups 1 week after ischemia were compared. The levels of 6-K-PGF₁ increased after reperfusion in both groups, while those of TXB₂ increased in the control group but maintained low levels in the OKY-046 group. Liver function was better and histologic changes less marked in the OKY-046 group than in the control group, suggesting the important role of TXA₂ in ischemic liver injury and the usefulness of a TXA₂ synthetase inhibitor for protecting the liver against ischemic injury.     

Intracisternal injection of TRH antibody blocks gastric emptying stimulated by 2-deoxy-d-glucose in rats

We evaluated the effect of 2-deoxy-d-glucose (2-DG) on gastric emptying of a non nutrient solution in conscious rats using a Phenol red method. Intravenous injection of 2-deoxy-d-glucose dose-dependently increased the rate of gastric emptying. This stimulatory action of 2-DG was abolished by subdiaphragmatic vagotomy. Intracisternal injection of thyrotropin-releasing hormone (TRH) antibody blocked intracisternal TRH and intravenous 2-DG-induced enhancement of gastric empyting but not the stimulation of gastric emptying induced by intracisternal pancreatic polypeptide. The TRH antibody injected intraperitoneally had no effect. These results suggest that endogenous TRH in the brain is involved in vagal-dependent stimulation of gastric emptying by 2-DG.     

Preservation of hypervascularity in hepatocellular carcinoma after effective proton-beam radiotherapy--CT observation

AIM: The aim of this study was to describe persistence of hypervascularity in proton treated hepatocellular carcinoma at serial follow-up computed tomography (CT). METHODS: Four patients with unresectable solitary hypervascular hepatocellular carcinoma underwent 55-82 Gy proton-beam irradiation for a period of 15-47 days. Follow-up CT including plain, enhanced and dynamic imaging was performed for a period of 9-36 months. RESULTS: Good preservation of arterial blood supply while gradual decrease in tumour size was clearly depicted by dynamic CT. CONCLUSION: We believe that preservation of hypervascularity as judged by enhancement at CT and magnetic resonance imaging, does not necessarily mean that radiotherapy in hypervascular malignant tumours has been unsuccessful.     

Adjuvant immunotherapy using fibroblasts genetically engineered to secrete interleukin 12 prevents recurrence after surgical resection of established tumors in a murine adenocarcinoma model

BACKGROUND: To explore effective therapeutic strategy against cancer of the gastrointestinal tract, tumor vaccination using fibroblasts secreting interleukin-12 (IL-12) was developed as an adjuvant therapy against murine tumor after surgical resection. METHODS: Initially, IL-12 was genetically engineered into fibroblasts (IL-12/3T3 cells), and then we evaluated in vivo and in vitro antitumor effects. In the vaccination model, irradiated C-26 tumor mass was reinoculated intradermally with IL-12/3T3 cells in mice as a tumor vaccine to examine how much it suppresses tumor recurrence. RESULTS: IL-12/3T3 cells producing 7.2 ng/10(6) cells/24 h murine IL-12 in vitro exerted dose-dependent potent tumor suppression when coinoculated with C-26 cells in vivo. Specific immunity was also acquired in 63% of mice in vivo. In the vaccination model, protective immunity was developed in 70% of mice that were inoculated with irradiated tumor mass and IL-12/3T3 cells. In addition, local recurrence was not observed in vaccinated mice, although 44% of control mice had recurrence. CONCLUSIONS: Coinoculation of genetically engineered fibroblasts secreting IL-12 with irradiated tumor mass was proved to be an effective tumor vaccine. This system of vaccination is easily applicable to clinical situations, particularly to human gastrointestinal tract cancers.     

Severe stenosis of the internal carotid artery and intracerebral hematoma associated with neurofibromatosis type 1: a case report

Neurofibromatosis Type 1 produces a broad spectrum of clinical manifestations as a result of widespread dysplasia of mesodermal and neuroectodermal tissues. One of the most serious aspects of the disease relates to the arterial involvement that may occur. We report a case of severe stenosis of the internal carotid artery and intracerebral hemorrhage associated with neurofibromatosis Type 1. A 49-year-old female was admitted to our hospital after she had suddenly become comatose. On admission, she demonstrated a decerebrate posture in response to painful stimuli, and was assessed as grade 200 according to the Japan Coma Scale. Physical examination disclosed widespread cutaneous neurofibromas and cafe-au-lait spots. Computed tomography of the head revealed a right putaminal extensive hematoma, with a maximum diameter of 7 cm. The hematoma was removed. After this surgical treatment, cerebral angiography was performed. It showed severe stenosis of the terminal portion of the right internal carotid artery associated with a fine telangiectatic network, indicating the presence of moyamoya vessels in the basal ganglia. Although intracranial hemorrhage associated with neurofibromatosis type 1 is a rare condition, fine telangiectatic collateral vessels caused by occlusive cerebrovascular disease, intracranial aneurysms, brain tumors, or hypertension caused by pheochromocytoma or stenosis of the renal artery should be considered as the cause of hemorrhage.     

Effects of activation of renal adenosine A2 receptor on renal function and renin release in dogs.

Direct effects of adenosine A2 receptor activation on renal function were examined in dogs. When renal perfusion pressure was maintained constant at 100 mmHg, renal administration of a selective A2 receptor agonist, CGS 21680C (sodium salt of CGS 21680, 2-[p-(2-carboxyethyl) phenethylamino]-5'-N-ethylcarboxamido adenosine) (1 microg x kg(-) x min (-1)), although it decreased blood pressure by 20 mmHg, increased renal blood flow and renin release, whereas glomerular filtration rate and urine flow were unaffected. These results suggest that stimulation of renal A2 receptor led to both afferent and efferent arteriolar dilatation, whereas renal A2 receptor plays a minor role in urine formation. CGS 21680C induced renin release and tachycardia that were blocked by propranolol, indicating these effects of A2 receptor stimulation appeared to be indirect.