Cardiovascular Responses to Somatosensory Stimulation and Their Modulation by Baroreflex Mechanisms

Exposure of experimental animals to noxious somatic stimulations sometimes induces sustained hypertension. Information regarding the medullary projections of somatic afferents and the neurotransmitters involved in them is incomplete. The present investigation in urethane-anesthetized, artificially ventilated, adult male Wistar rats was undertaken to clarify some of these issues. It was observed that the inhibition of contralateral, ipsilateral, or bilateral rostral ventrolateral medullary pressor area (RVLM) with muscimol attenuated the pressor and tachycardic responses to sciatic nerve stimulation. Similar inhibition of the medial subnucleus of the solitary tract (mNTS) exaggerated the cardiovascular responses to sciatic nerve stimulation. Interruption of the baroreflex by microinjections of ionotropic glutamate receptor antagonists into the mNTS or barodenervation also exaggerated the responses to sciatic nerve stimulation. Unilateral stimulation of the aortic nerve blocked the cardiovascular responses to the sciatic nerve stimulation. These results indicated that in the rat, the ascending afferents in the sciatic nerve project bilaterally to the RVLM as well as mNTS; an excitatory amino acid, probably glutamate, is released in the mNTS in response to the sciatic nerve stimulation; and barodenervation or blockade of baroreflex in the mNTS exaggerates, while baroreceptor stimulation inhibits, cardiovascular responses to somatosensory stimulation.     

Audiovisual temporal capture underlies flash fusion

When sequential visual flashes are accompanied by a lower number of sequential auditory pulses, the perceived number of visual flashes is lower than the actual number, an illusion termed ‘flash fusion’. We examined whether temporal capture of flashes by pulses underlay flash fusion. One of the visual flashes was given a luminance increment, and observers reported which flash had the luminance increment. Results showed that the pulse strongly captured the flashes in its temporal vicinity, resulting in flash fusion. Moreover, when one of the successive pulses was given a higher frequency than others, the luminance increment was perceptually paired with the pulse with the higher frequency. The pairing of audiovisual features disappeared when the temporal pattern of the pulse frequency was difficult for the observer to anticipate. These data indicate that flash fusion is caused by temporal capture of flashes by the pulse, and that feature matching between auditory and visual signals also contributes to the modulation of perceived temporal structure of flashes during flash fusion.     

SURVEILLANCE OF SMALL INTESTINAL ABNORMALITIES IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: A PROSPECTIVE CAPSULE ENDOSCOPY STUDY

Background: Patients with hepatocellular carcinoma (HCC) sometimes suffer from obscure gastrointestinal bleeding. Portal hypertension (PH), common in cirrhosis, induces esophagogastric varices. Because of the location, PH also may influence mucosal abnormalities in the small intestine. The objective of this study is to estimate the prevalence of small intestinal mucosal abnormalities in HCC patients using capsule endoscopy (CE). Patients and Methods: We prospectively conducted CE in HCC patients, and analyzed the findings in relation to hepatic function, the number and size of HCC tumor and findings obtained by conventional endoscopy. Results: Thirty‐six patients (aged 66.7 ± 7.5 years, 29 men) underwent CE. Abnormal findings in the small bowel were found in 16 patients (44%), angioectasias in eight patients (22%), erosions in five (14%), varices in four (11%), polyps in four (11%), and submucosal tumor in one (3%). The patients with angioectasia had a larger spleen index than the no abnormal lesions group (85.4 ± 15.8 vs 59.0 ± 24.4, P = 0.02). The former group had been more frequently treated for esophageal varices endoscopically (62% vs 15%, P = 0.02). Large HCC nodules seemed more common in the patients with angioectasia than subjects without abnormal lesions (38% vs 5%, P = 0.06). Small intestinal varices also seemed to have a positive association with large HCC. During the follow up after CE, one patient with small intestinal polyps suffered from obscure gastrointestinal bleeding. Conclusions: CE revealed that HCC patients frequently have small intestinal mucosal lesions. In particular, small intestinal angioectasia, which may cause obscure gastrointestinal bleeding, seems to be associated with portal hypertension.     

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine

The potential of purple sweet potato color (PSPC) and red cabbage color (RCC), natural anthocyanin food colors, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH) and receiving 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PSPC and RCC were given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PSPC or RCC-treatment-related changes in clinical signs and body weight were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by RCC, or tended to be inhibited by PSPC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci (ACF) by PhIP was significantly decreased by RCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PSPC or 5.0% RCC in a diet under the present experimental conditions.     

Habitual intake of lactic acid bacteria and risk reduction of bladder cancer

INTRODUCTION: A kind of lactic acid bacteria, Lactobacillus casei strain Shirota, shows antitumor activity in experimental animals. One clinical trial using L. casei showed a significant decrease in the recurrence of superficial bladder cancer. So, to assess the preventive effect of the intake of L. casei, widely taken as fermented milk products in Japan, against bladder cancer, we conducted a case-control study. METHODS: A total of 180 cases (mean age: 67 years, SD 10) were selected from 7 hospitals, and 445 population-based controls matched by gender and age were also selected. Interviewers asked them 81 items. The conditional logistic regression was used to estimate adjusted odds ratios (OR). RESULTS: The OR of smoking was 1.61 (95% confidence interval: 1.10-2.36). Those of previous (10-15 years ago) intake of fermented milk products were 0.46 (0.27-0.79) for 1-2 times/week and 0.61 (0.38-0.99) for 3-4 or more times/week, respectively. CONCLUSION: It was strongly suggested that the habitual intake of lactic acid bacteria reduces the risk of bladder cancer.     

Effect of phenylephrine injected into the nucleus tractus solitarius of Sprague-Dawley rats and spontaneously hypertensive rats

In alpha-chloralose-anesthetized Sprague-Dawley (SD) rats with unilateral nucleus tractus solitarius (NTS) lesions, injection of the alpha(1)-adrenergic receptor agonist phenylephrine into the contralateral NTS dose-dependently increased arterial pressure (AP). Bunazosin (0.1 nmol) or prazosin (0.36 nmol), an alpha(1)-adrenergic receptor antagonist, also increased AP. When injected into the NTS, pre-treatment with phenylephrine (10 nmol) or both antagonists abolished the cardiovascular effects of glutamate and acetylcholine. In contrast, pre-treatment with prazosin or methylatropine did not alter the effect of phenylephrine. Phenylephrine (30 nmol) injected into the NTS abolished aortic depressor nerve (ADN) evoked-responses. The pressor effect of phenylephrine in the NTS was exaggerated in spontaneously hypertensive rats (SHR). These results suggest that when injected into the NTS, the effect of phenylephrine may be due to a baroreflex blockade resulting from direct modulatory actions or non-specific neuronal alterations rather than stimulating the alpha(1)-adrenergic receptor. Additionally, this effect is enhanced in SHR.     

Western blotting analysis of the beta-hexosaminidase alpha- and beta-subunits in cultured fibroblasts from cases of various forms of GM2 gangliosidosis

OBJECTIVES: The GM2 gangliosidoses are a group of genetic disorders caused by the accumulation of ganglioside GM2 in neuronal cells. We examined the alpha- and beta-subunits of beta-hexosaminidases by a non-radioisotopes detecting system to evaluate whether it was a useful method for understanding of the pathophysiologies of GM2 gangliosidoses. MATERIALS AND METHODS: We investigated the alpha- and beta-subunits of beta-hexosaminidases in cultured fibroblasts from cases of various forms of GM2 gangliosidosis by means of Western blotting and a chemiluminescence detection system. RESULTS: In a patient with infantile Tay-Sachs disease [HEXA genotype, Int5-SA(g-1-->t)/Int5-SA(g-1-->t)], the mature alpha-subunit was undetectable. In a patient with infantile Sandhoff disease (HEXB genotype, C534Y/C534Y), the mature beta-subunit was deficient. However, a small amount of the mature beta-subunit was detected in a patient with adult Sandhoff disease (HEXB genotype, R505Q(+I207V)/R505Q(+I207V)), which may have resulted in the residual enzyme activity and mild clinical course. Normal amounts of alpha- and beta-subunits were detected in a patient with GM2 activator deficiency. CONCLUSION: This method is easy and sensitive for detecting target proteins, and is useful for clarification of the pathophysiologies of GM2 gangliosidoses.     

The usefulness of 18F-FDG PET images obtained 2 hours after intravenous injection in liver tumor

Liver tumors, especially hepatocellular carcinomas (HCCs), often exhibit no contrast with surrounding non-tumorous liver tissue in F-18-fluoro-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) images obtained at the usual interval of one hour after intravenous FDG injection. We evaluated the usefulness of FDG PET studies of liver tumors performed 2 hours after intravenous injection. METHODS AND MATERIALS: Fifteen pretherapeutic patients with 33 liver tumors were studied, including 11 patients with 18 HCCs, and 4 patients with 15 metastatic liver tumors (METAs) from 3 colorectal carcinomas and 1 esophageal carcinoma. After transmission scans, emission scans were obtained 45-55 minutes and 115-125 minutes after intravenous injection of 185-370 MBq FDG as early images and delayed FDG PET images, respectively. Visual analysis of early and delayed images was performed, and the FDG uptake in the tumor to that in nontumorous liver ratio (T/N ratio), the FDG uptake in tumor to that in soft-tissue ratio (T/S ratio) and the FDG uptake in non-tumorous liver to that in soft-tissue ratio (N/S ratio) were calculated for each image. RESULTS: In visual analysis, visual improvement seen in images was observed in 6 of 18 HCC lesions and all 15 META lesions. In quantitative analysis, the mean T/S ratio and T/N ratio of HCCs in early images were 4.97 and 1.90, respectively, and those in delayed images were 6.24 and 2.20, respectively. The mean T/S ratio and T/N ratio of METAs in early images were 5.97 and 2.21, respectively, and those in delayed images were 6.99 and 3.80, respectively. The T/S ratio of HCCs and T/S ratio and T/N ratio of METAs were significantly higher in delayed images than in early images. The mean N/S ratios of HCC cases were 2.58 in the early images and 2.57 in the delayed images, but the ratio showed no constant tendency in the images. All N/S ratios of META cases were decreased in delayed images, although the significance of the difference between early and delayed images in N/S ratios was not analyzed because of the small number of cases. CONCLUSION: FDG PET studies performed 2 hours after intravenous injection were useful for clear visualization of liver tumors, especially metastatic liver tumors.     

A case of gastric duplication evaluated by gastric emptying scintigraphy

Gastric duplications are relatively rare, and communication with the gastric lumen is extremely rare. A 67-year-old man was referred to our hospital because of recurrence of epigastric pain and fullness. An upper gastrointestinal contrast study revealed a double compartment stomach, with gastric duplication starting at the esophagogastric junction outside the greater curvature. Computed tomography of the stomach with gastrografin as contrast demonstrated complete communication of the gastric duplication and primary stomach. The patient was diagnosed with complete gastric duplication. Gastric emptying scintigraphy with Tc-99m diethyltriamine pentaacetic acid was performed. Test meal entered the primary stomach and duplication cyst simultaneously, and radioactivity in the primary stomach decreased linearly and gastric emptying was not delayed. In the duplication cyst, about 70% of the food that entered the cyst once was immediately evacuated from it, but the remaining 30% remained in the cyst for a long time. Gastric emptying of the primary stomach was not affected by formation of the duplication cyst.