Effects of caffeine, nicotine, ethanol and sodium selenite on pancreatic carcinogenesis in hamsters after initiation with N-nitrosobis(2-oxopropyl)amine.

The modulating effects of caffeine, nicotine, ethanol and sodium selenite on development of N-nitrosobis(2-oxopropyl)-amine (BOP)-initiated pancreatic tumors were investigated. Female Syrian golden hamsters were given s.c. injections of BOP (10 mg/kg body weight) or saline alone once a week for 3 weeks and then administered 2000 p.p.m. caffeine, 25 p.p.m. nicotine, 20% ethanol or 4 p.p.m. sodium selenite in their drinking water for the next 37 weeks. Control animals were given tap water alone after BOP initiation. Only the BOP-treated groups developed pancreatic adenocarcinomas and dysplasias. The multiplicity of pancreatic carcinomas was significantly higher (P less than 0.05) in animals receiving caffeine than in the controls. In addition, caffeine treatment slightly increased the incidence of carcinomas. Nicotine and ethanol also showed tendencies to enhance pancreatic carcinogenesis, although there were statistically no significant differences regarding lesion development. In contrast, sodium selenite administration was associated with a tendency for a decrease in the number of carcinomas and dysplasias. Thus, among these chemicals of obvious significance to human life-style, caffeine enhanced the development of pancreatic tumors when administered during the post-initiation phase in this hamster model.     

The effect of dietary safflower phospholipid on steroids in gastrointestinal tract of rats fed a hypercholesterolemic diet.

The effect of dietary safflower phospholipid (Saf-PL) on the postprandial changes of steroids in the small intestinal and cecal contents was examined in rats fed a hypercholesterolemic diet. The triglyceride mixture (SP-Oil) containing a comparable amount of linoleic acid to Saf-PL was used as a reference fat source. Saf-PL suppressed the elevation of plasma cholesterol levels at all times after meal intake, when compared to SP-Oil. The reduction of plasma cholesterol in rats fed the Saf-PL diet was exclusively observed both in chylomicron plus very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions. The rate of gastric emptying was not modified by the Saf-PL diet. The level of neutral steroids in the small intestinal contents was almost comparable in both groups, but in the cecal contents and feces it was significantly higher in rats fed the Saf-PL diet. On the other hand, the level of acidic steroids in the small intestinal contents tended to be higher in rats fed the Saf-PL diet than in those fed the SP-Oil diet, whereas in the cecal contents and feces it was comparable in the two diets. These results suggest that Saf-PL causes the accumulation of neutral steroids in the cecum due to the rapid transit through the small intestine.     

7-Nitroindazole, a selective inhibitor of neuronal nitric oxide synthase: effect on sevoflurane MAC and cerebellar cyclic GMP in mice

Purpose Considerable evidence suggests that nitric oxide (NO) plays a role in synaptic transmission in the central and peripheral nervous systems. However, whether inhibition of NO synthesis decreases minimum alveolar concentration (MAC) of inhalational anesthetics is controversial. We examined the effects of 7-nitroindazole (7-NI), a selective inhibitor of neuronal NOS (nNOS), on the MAC of sevoflurane and cerebellar cyclic guanosine monophosphate (cGMP) levels in mice. Methods Sevoflurane MAC and cerebellar cGMP levels were determined in mice after acute intraperitoneal or weeklong gavage feeding of 7-NI. Sevoflurane MAC and cerebellar cGMP levels after chronic treatment were measured on days 1, 4, and 7 and were repeated after an acute intraperitoneal dose of nitro ^g -l-arginine methylester (l-NAME). Results Acute and chronic treatment with 7-NI decreased the sevoflurane MAC by 20%–30%. Reduction of cerebellar cGMP levels was greater after intraperitoneal administration of NOS inhibitors than after gavage feeding of 7-NI. Conclusion Acute or chronic selective inhibition of neuronal NOS decreases the sevoflurane MAC and cerebellar cGMP levels in mice. 7-NI permitted probing of the role of NO in perception of noxious stimuli.     

Slow-adapting responses of the Pacinian corpuscles of cat planta

Slow-adapting impulses were recorded from the single nerve fiber innervating the Pacinian corpuscle of the cat planta, which was stimulated by constant pressure. Slow-adapting Pacinian corpuscles responded to both low-frequency (0.1-0.01 Hz) and high-frequency (400–800 Hz) vibrations. Simultaneously performed electron microscopy showed that there were no definite ultrastructural differences between slow- and fast-adapting Pacinian corpuscles.     

Functional change in the rat spinal cord by chronic spinal transection and possible roles of monoamine neurons

Two types of spinal reflex responses, extensor reflex and ventral root potential, were compared physiologically and pharmacologically in acute and chronic spinal cord transected rats. The recovery curve of the extensor reflex, recorded as evoked electromyogram, in chronic spinal rats was strikingly different from that in acute spinal rats. Namely, shortening of the reflex amplitude suppression period (stimulus interval: 20 msec) and appearance of the supernormal period (30-60 msec) were observed in chronic spinal rats. The recovery curves of ventral root potential (monosynaptic reflex) and M wave were almost the same in both preparations. In the frequency depression curve, the amplitude of the extensor reflex in chronic spinal rats was higher at high frequency stimulation than that in acute spinal rats. 5-Hydroxytryptophan, 5-methoxy-N,N-dimethyltryptamine and quipazine enhanced the extensor reflex in chronic spinal rats with a potency of 200-400, 8 and 4 times stronger than that in acute spinal rats, respectively. These drugs did not show consistent effects on the monosynaptic reflex of ventral root potential in chronic spinal rats. These results strongly suggest that the spinal interneurons where descending serotonergic fibers terminate become supersensitive and functionally modified in chronic spinal rats. It is speculated that the supersensitivity of these interneurons may play an important role in spasticity.     

The epidemiological study of hepatolithiasis in the Kamigoto district, Nagasaki where hepatolithiasis is high incidence

Regional distribution, age, sex, type of disease and history of surgery of the biliary tract were examined in 134 patients with hepatolithiasis in the Kamigoto district. The ratio of patient to population was 1:126 in the region showing the highest incidence. When classified by age at establishment of the diagnosis, patient in their sixties comprised the largest portion in both sexes. The ratio of men to women was 1:1.2. When classified in accordance with the draft by Research Group for the Study of Hepatolithiasis, 103 cases (76.9%) were of the intrahepatic type, and 31 cases (23.1%) were of the intra-extrahepatic type. The stones were found in the right lobe in 58 patients (43.3%), the left lobe in 59 patients (44.0%) and the both lobes in 17 patients (12.7%). Forty-four patients (32.8%) had a history of surgery of the biliary tract. Ultrasonographic examination of the abdomen in junior high school students revealed hepatolithiasis in one. As a result, the intrahepatic type and the right lobe type are high frequency in this district, and epidemiological survey of the family history and the food habit in this district is necessary.