Therapeutic potential of AMPA receptor antagonist perampanel against cerebral ischemia: beyond epileptic disorder

<正>Stroke is a leading cause of mortality and severe neurological disability worldwide; however, curative therapeutic options are limited. Although recanalization therapy using endovascular thrombectomy has demonstrated great benefits in the functional outcome of patients with acute ischemic stroke, the rate of excellent clinical outcomes remains limited. Therefore, the current recanalization     

Experimental studies of photo radiation therapy on neuroblastoma

A combination of Photo Radiation Therapy (PRT) using Argon-Dye Laser with hematoporphyrin derivatives (HpD) was used experimentally on a cytogenetically highly malignant neuroblastoma xenograft, which exhibited a homogeneously staining region and caused DNA amplifications in chromosomes. The tumor tissue was treated with 500 joules/cm2 of laser. The dosage of HpD was 50 mg per kg body weight. Necrosis of over 50% of the tumor was observed in half the specimens. Swollen cytoplasmic organelles and ruptured cell and nuclear membranes were observed by electron microscopy after PRT. PRT may be used with other treatment modalities for the removal of residual and metastatic tumors.     

Pharmacological properties of MO-8282, a novel antidepressant

The pharmacological properties of MO-8282 (1,2,3,4-tetrahydro-2-methyl-9H-dibenzo [3,4: 6,7]cyclohepta [1,2-c]pyridine maleate) as an antidepressant were investigated. At doses 10 times less than those of amitriptyline, MO-8282 showed similar potencies in reducing the duration of immobility during forced swimming in rats and in potentiating stereotype induced by L-DOPA. Intermediate doses of MO-8282 reduced the duration of immobility during forced swimming, in mice as well, suppressed muricide behavior of olfactory-bulbectomized rats and antagonized clonidine-induced suppression of exploratory activity in mice. MO-8282 moderately antagonized the ptosis but not the hypothermia induced by reserpine in mice. MO-8282 exhibited weak antagonism against the tremor, lacrimation and diarrhea induced by tremorine, but its activity was milder than that of amitriptyline. The uptake of noradrenaline into rat hypothalamic synaptosomes was inhibited by MO-8282 at concentrations 20 times less than equally effective doses of amitriptyline, but the uptake of dopamine or serotonin was unaffected by MO-8282. A single oral administration of MO-8282 at a dose of 30 mg/kg accelerated noradrenaline turnover, but did not affect dopamine and serotonin turnover in the rat brain. MO-8282 strongly inhibited noradrenaline-, histamine- or adenosine-sensitive adenylate cyclase activity of guinea pig brain. Its mode of action differed from that of imipramine, rather resembling that of mianserin. MO-8282 did not affect monoamine oxidase activity of rat liver. These results suggest that the pharmacological characteristics of MO-8282 are different from those of tricyclic antidepressants and rather similar to those of mianserin, but more potent. The results, therefore, indicate that MO-8282 is possibly a novel antidepressant.     

Effect of the free radical scavenger MCI-186 on spinal cord reperfusion after transient ischemia in the rabbit

Objective: Paraplegia remains a serious complication of aortic operations. The production of free radicals during reperfusion after transient ischemia is believed to induce secondary spinal neuronal injury, resulting in paraplegia. The aim of the present study was to clarify the protective effect and method of administration of antioxidants on the neurological and histological outcome in the animal model for reperfusion injury after transient spinal cord ischemia. Methods: New Zealand white rabbits underwent surgical exposure of the abdominal aorta that was clamped for 15 minutes to achieve spinal cord ischemia. Group A animals received two 10 mg/kg doses of 3-methyl-l-phenyl-2-pyrazolin-5-one (MCI-186) at the time of release of the aortic clamp and 30 minutes later. In group B, MCI-186, 5 mg/kg, was given three times, at the time of aorta clamp release, 30 minutes and 12 hours later. In group C (control group), one dose of vehicle was administered. Neurological status was assessed using modified Tarlov’s score until 168 hours after operation. Spinal cord sections were examined microscopically to determine the extent of ischemic neuronal damage. Results: Groups A and B animals had better neurological function than group C (p(0.001). In contrast, group C animals exhibited paraplegia or paraparesis with marked neuronal necrosis. The number of surviving neurons within examined sections of the spinal cord was significantly greater in group B than in group C (p(0.001). Conclusion: In a 15-minute ischemia-reperfusion model using rabbits, systemic repetitious administration of MCI-186, a free radical scavenger, was found to have a protective effect on the spinal cord neurons both neurologically and histologically. We postulate that the drug minimizes the delayed neuronal cell death for reperfusion injury after transient ischemia by reducing the free radical molecules. Moreover, it was thought that we could protect delayed neuronal cell death more effectively by administering MCI-18612 hours later.     

A new operational approach for the piriform sinus fistula

It has been well documented that piriform sinus fistulae often cause suppurative thyroditis; however, when a piriform sinus fistula does not present this symptom, making a correct diagnosis is very difficult. We have experienced 11 cases of a piriform sinus fistula. The conventional operational approach was performed in the initial eight patients, among which there were four recurrences in two patients. Therefore, a new operational approach was introduced for the three most recent cases and one recurrent case. First, the existence of the internal orifice of the fistula is confirmed with a laryngoscope, after which a transverse incision on the neck is made and the abscess dissected. The side wall of the piriform sinus is then opened with the help of a laryngoscope and the bottom part of the mucosa of the sinus transected with the internal orifice of the fistula, after which the fistula is removed en bloc with the bottom part of the sinus and abscess cavity. Using this operation, we experienced no complications and there has been no recurrence so far.This paper was presented at the 23rd Annual Meeting of Pacific Association of Pediatric Surgeons, June 1990 in Kona, Hawaii.     

Immunotherapy for lung cancer by streptococcal preparation OK-432

To evaluate the clinical efficacy of OK-432 immunotherapy, patients admitted between 1975 and 1982 were randomized into two groups: An immunochemotherapy (IM-C) group and a chemotherapy (control) group. For each group, a fixed chemotherapy was administered using a combination of three drugs. The survival rates of cases with non-small cell carcinoma were evaluated at the end of 1987. One hundred and fifty-seven cases in the IM-C group and 148 in the control group were eligible for evaluation of long-term survival rates. Statistically significant improvement of the survival rates in the IM-G group were noted in the following items: All cases, resected cases, non-resected cases, resected stage I + II cases, resected stage III cases, completely resected cases, incompletely resected cases, and cases with epidermoid carcinoma. However, in comparison of adenocarcinoma there was no significant difference between the two groups. SU-polysaccharide skin test and natural killer activity were the best immunological parameters during the OK-432 therapy. To intensify the effects of immunotherapy, a possibility of regional immunotherapy was studied following some experimental works. Regional infusion of LAK cells (induced by incubation of patient's lymphocytes with rIL-2) through bronchial artery after regional infusion of OK-432 and chemotherapeutics showed favorable effect for advanced lung cancer. Future prospect of these regional adoptive immunotherapy was discussed.     

Closure of a large bronchial fistula with a latissimus dorsi myocutaneous flap

We describe a case of a large bronchial fistula and empyema after right upper lobectomy that was treated successfully with open window thoracostomy followed by a latissimus dorsi myocutaneous flap and limited thoracoplasty. A latissimus dorsi myocutaneous flap can provide immediate airtight closure of a large bronchial fistula, allowing lavage and curettage of the empyema cavity to reduce the chance of postoperative infection. An important aspect of this technique is that the deepithelialized skin side rather than muscle is sutured to an opening of the bronchus. As compared with other techniques, a latissimus dorsi myocutaneous flap is superior in that it requires a single incision and does not require an intraop-erative change of position. In addition, the technique causes little dysfunction of the chest and shoulder and preserves the vascular supply to ensure the viability of the flap even if it was divided in a previous operation.     

Antiulcer effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl] carbamoyl]methyl]-amino-N-methylbenzamide in experimental gastric and duodenal ulcers

Effects of 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl] methyl]-amino-N-methylbenzamide (DQ-2511), a newly synthesized compound, were evaluated using various types of experimental gastric and duodenal ulcers in rats. Pretreatment with DQ-2511, over the dose range 30-300 mg/kg p.o., resulted in a dose-related inhibition of water-immersion stress-, serotonin-, acetylsalicylic acid (ASA)-, indometacin-, ethanol-, and 2-deoxy-D-glucose(2DG) plus indometacin-induced gastric ulcers as well as cysteamine-induced duodenal ulcers. The antiulcer potencies of DQ-2511 were equal to or greater than those of H2-receptor antagonist cimetidine in these ulcer models except for ASA- and 2DG plus indometacin-induced ulcers. The rate of healing of chronic gastric ulcers induced by acetic acid was significantly accelerated by DQ-2511 (100 and 300 mg/kg p.o.) but not by the same doses of cimetidine. DQ-2511, at doses of 30 mg/kg p.o. and above, produced a significant decrease in gastric acid and pepsin output in pylorus-ligated rats. In anesthetized rats with acute gastric fistulae, 30 mg/kg i.v. of DQ-2511 significantly inhibited gastric acid secretion stimulated by 2DG, whereas it did not affect gastric hyperacidity evoked by either carbachol, histamine or pentagastrin. At effective antiulcer doses, this compound produced a sustained increase in gastric mucosal blood flow in conscious, restrained rats. Based on these observations, DQ-2511 is characterized as a new antiulcer compound with beneficial effects on both gastric aggressive and defensive factors. Furthermore, these results indicate a possible superiority of DQ2511 over cimetidine in regard to its antiulcer potency and spectrum.     

Percutaneous radiofrequency neurotomy of lumbar medial branch (facet rhizotomy)--a report of 6 cases

We performed radiofrequency neurotomy of lumbar medial branch as a treatment of facet syndrome. Our six cases had no indication for surgical therapy, such as neuralgia, spinal canal stenosis without neurological deficit except for pain and deformed spines. Facet joint injection with regional anesthetics and steroids could not prevent their recurrent back pain. By facet rhizotomy, they could obtain relief of back pain for several months to a year. We conclude that facet rhizotomy is a more effective method for facet syndrome when a proper indication is present.