Effects of naftidrofuryl oxalate, a 5HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus

We investigated the effects of age and naftidrofuryl oxalate (Naftidrofuryl), a 5-HT₂ antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [³H]Quinuclidinyl benzilate (QNB), [³H]cyclohexyl-adenosine (CHA), [³H]MK-801, and [³H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-d-aspartate (NMDA), and γ-aminobutyric acid-A (GABA_A) receptors, respectively. [³H]PN200-110 labeled L-type Ca²⁺ channels. [³H]Forskolin, [³H]cyclic adenosine monophosphate (cAMP), [³H]phorbol 12,13-dibutyrate (PDBu), and [³H]inositol 1,4,5-triphosphate (IP₃) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP₃ receptors, respectively. Approximately 20% reductions in [³H]QNB, [³H]forskolin, and [³H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [³H]CHA, [³H]MK-801, [³H]muscimol, [³H]PN200-110, [³H]cAMP, and [³H]IP₃ binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications.     

Immunohistochemical study of collagen type III in adenomyosis]

To clarify the mechanism of the origin of adenomyosis, we investigated the immunohistochemical distribution of collagen type III in the human endometrium and the adenomyosis throughout the menstrual cycle. 1) Collagen type III was localized in the stroma of normal endometrium and ectopic endometrium, and in the myometrium. No staining of collagen type III was observed in the endometrial gland. 2) The intensity of staining for collagen type III in the basal layer of normal endometrium was stronger than those in the functional layer. The staining in the proliferative phase was stronger than that in the secretory phase. 3) The intensity of staining of collagen type III in ectopic endometrium paralleled that in the basal layer of normal endometrium. 4) The intensity of staining of collagen type III in the myometrium did not change throughout the menstrual cycle. These results suggest that close similarities exist between stromal cells in normal endometrium and in ectopic endometrium from the viewpoint of the extracellular matrix.     

Experimental models of reflex contractile activity in the rabbit bladder

We were able to produce two highly reproducible experimental models (in the rabbit) that demonstrated a high degree of reflex bladder contractile activity. In one model, a somatovesical reflex was induced by touching or pinching the perineal area. This reflex may be organized through a neurogenic reflex at the spinal level. In another model, rhythmic bladder contractions were produced by distal urethral constriction in the absence of bladder distension. These rhythmic contractions were thought to be due to a supraspinal reflex. In both types of contractile reflexes, intravenous administration of hexamethonium inhibited the reflex contractile activity virtually completely, intravenous atropine inhibited over 90% of the induced contractile activity, thus suggesting that these contractions were mediated reflexly through cholinergic stimulation. These two models of reflex bladder contractions should be useful for the study of hyperreflexic bladders.     

Tumor vascularity under angiotensin II-induced hypertension--angiographic observations

The selective increase in tumor blood flow under angiotensin II-induced hypertension was observed to be the result of passive vascular beds irresponsive to angiotensin II. We investigated whether or not increased tumor blood flow resulting from angiotensin II-induced hypertension could be recognized on angiographic findings. Angiography under angiotensin II-induced hypertension was performed in 51 patients with various cancers, and angiographic findings indicating increased tumor vascularity were recognized in 40 (78.4%) of them. Based on the assumption that the increase in tumor oxygen tension was brought about by increased tumor blood flow, the possibility of utilizing this phenomenon in hyperbaric oxygenation radiotherapy was suggested.     

A case-control study of breast cancer among Japanese women: with special reference to family history and reproductive and dietary factors

Summary To study the effects of family history and reproductive, anthropometric, and dietary factors on the risk of breast cancer among low risk populations, we conducted a hospital-based case-control study involving 908 patients with breast cancer and their matched controls, in Japan. A positive family history of breast cancer significantly increased the risk of breast cancer (odds ratio = 1.52, 95% confidence interval: 1.14–2.03). The risk further increased with increasing number of family members affected. Obesity, single marital status, fewer births, a late childbirth, and less consumption of green-yellow vegetables and dairy products were also associated with an increased risk of breast cancer. These associations were independent in multivariate analyses. There was no increase in risk associated with consumption of high fat foods. When analyzed by menopausal status, the association with family history of breast cancer, especially in the first degree of relatives, was more evident for premenopausal breast cancer. The associations with obesity and lower consumption of dairy products were more pronounced for postmenopausal breast cancer, while those with lower parity and single marital status were stronger for premenopausal breast cancer.     

3 cases of müllerian duct cyst]

We report 3 cases of müllerian duct cyst. Percutaneous puncture, aspiration and instillation of a sclerosing agent under ultrasound guidance was performed in each case. Ultrasound is valuable in the diagnosis is of cysts in the region of the prostate and seminal vesicles. Aspiration under ultrasound guidance would also be of therapeutic value.     

Effects of a new histamine H2-receptor antagonist, Z-300, on gastric secretion and gastro-duodenal lesions in rats: comparison with roxatidine.

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1- thio)acetamido.2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at less than 10(-5) M did not affect the contraction of guinea pig ileum in response to carbachol. Z-300, administered either orally or parenterally, significantly inhibited the basal and histamine-stimulated gastric acid secretion in rats. Gastric acid secretion stimulated by histamine, pentagastrin or carbachol in Heidenhain pouch dogs was also significantly inhibited by the compound. The effect persisted for greater than 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl.ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.     

The local hyperthermochemotherapy for pleural carcinomatosis]

Local hyperthermochemotherapy was performed in 17 cases to control malignant effusion and intrathoracic disseminated lesions. Of these 15 patients, 11 cases primary lung cancer, 4 cases metastatic lung cancer had pleural carcinomatosis and 2 cases were malignant diffuse mesotheliomas. The procedure was radiofrequency hyperthermia (13.56 MHz) maintaining the peripleural temperature at 42-43 degrees C for 45-60 minutes, combined simultaneously with the intrathoracic administration of cisplatin (1-2 mg/m2, bolus) through a thoracic double lumen trocar tube. The treatment was repeated from 2 to 4 times at 7-day intervals. In 14 cases (87.5%) complete or partial response according to the criteria of the Japan Lung Cancer Society were obtained. There were 2 cases of no change and one case that was impossible to evaluate. In one lung cancer case, the disappearance of pleural disseminated lesions was confirmed by flexible thoracoscopy after the procedure. In 12 cases, there were abdominal complaints due to side effects of the hyperthermochemotherapy, such as vomiting and nausea, but these symptoms were milder than those caused by intravenous injection of anti-cancer agents, for example cisplatin, in conventional chemotherapy treatment. The median survival time and 2 years survival of the patients with the present procedure were 15 months and 41.7% respectively. Although distant metastases appeared in most cases, none had local recurrence and particularly noteworthy pleural effusion was well controlled. The above experience suggested that the local hyperthermochemotherapy is useful to control pleural effusion and can improve the quality of life of patients with pleural carcinomatosis.     

Long-term changes in gerbil brain neurotransmitter receptors following transient cerebral ischaemia.

1. Receptor autoradiographic and histological techniques were used to investigate long-term changes in the gerbil brain following transient cerebral ischaemia. 2. Transient ischaemia was induced for 3 min and 10 min, and the animals were allowed to survive for 8 months. 3. Histological examination revealed that 3 min ischaemia caused neuronal damage and mild shrinkage only in the hippocampal CA1 sector. Ten minutes of ischaemia produced severe neuronal damage in the striatum and the hippocampal CA1 and CA3 sectors. Considerable shrinkage was seen in the hippocampus; the dentate gyrus, however, was not damaged. 4. Three minutes of ischaemia produced changes in the binding of [3H]-quinuclidinylbenzilate ([3H]-QNB), [3H]-muscimol, and [3H]-MK-801 in various brain regions, as determined autoradiographically. In contrast, [3H]-cyclohexladenosine ([3H]-CHA) and [3H]-PN200-110 ([3H]-isradipine) binding in the brain was unaltered. 5. Ten minutes of ischaemia resulted in a major loss of neurotransmitter receptors, especially in the hippocampus. The substantia nigra showed a significant reduction in [3H]-CHA binding, whereas the striatum, which was morphologically damaged, showed no significant changes in any of the neurotransmitter receptors examined. 6. The results demonstrated that long-term survival after transient cerebral ischaemia produced alterations in neurotransmitter receptors, especially in the hippocampal formation, where considerable shrinkage was noted. These results also suggest that the hippocampal damage was not static, but progressive.