We examined changes in the blood flow velocity of brain stem artery (BSA) and middle cerebral artery (MCA) in response to hypercapnic, normocapnic and hypocapnic hyperventilation in seven awake subjects with a transcranial Doppler to determine if there are differences in blood flow control in regional brain perfused by these respective arteries, and to separate the effects of CO2 and ventilation itself on blood flow velocity during CO2 loading. During hypercapnic hyperventilation, BSA flow velocity increased linearly with an increase in end-tidal partial pressure of CO2 (PETCO2). During hypocapnic hyperventilation, BSA flow velocity decreased linearly with decrease in PETCO2, but did not change during normocapnic hyperventilation. The mean CO2 reactivity of BSA was 2.8%/mmHg. The responses of MCA to these hyperventilations and CO2 reactivity were similar to those of BSA. These findings suggest that CO2 rather than ventilation per se is the important stimulus to changes in brain blood flow velocity and that the CO2 responses of brain arteries are not affected by differences in vascular beds.

Adult↗

PubMedDate not supplied

Pharmacological analysis of wine-stimulated gastric acid secretion in dogs.

Wine apparently stimulates gastric acid secretion both in man and animals, yet the underlying mechanism remains unclear. The present study was attempted to clarify the pharmacological properties involved in gastric acid secretion stimulated by wine in beagle dogs. Commercially available red or white wine, 14% ethanol, or 10% peptone meal was intragastrically administered to dogs with vagally denervated Heidenhain pouches. Gastric acid secretion was stimulated by both red and white wines (25-50 ml) for 45-60 min. While S-0509 only tended to inhibit wine-stimulated gastric acid secretion, both atropine and famotidine significantly inhibited wine-stimulated gastric acid secretion. Plasma gastrin level was not significantly increased by administration of red and white wines. Administration of 14% ethanol also stimulated gastric acid secretion, but the effect was about half of that of wine. Combined administration of wine and peptone resulted in a biphasic stimulation of gastric acid secretion. S-0509, atropine and famotidine significantly inhibited wine+peptone meal stimulation, yet the order of inhibition of cumulative acid secretion was in the order, famotidine>atropine>S-0509. It was concluded that wine stimulated gastric acid secretion in denervated dogs via acethylcholine- and histamine-dependent mechanisms, but nearly independent from the intervention of gastrin.

Animals↗

PubMedDate not supplied

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication.

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.

Animals↗

PubMedDate not supplied

Effects of dexamethasone and FK506 on Helicobacter pylori-induced gastritis and bacterial viability in Mongolian gerbils.

FK506 and dexamethasone were used to investigate whether or not immunosuppression affects H. pylori colonization and gastric mucosal damage induced by Helicobacter pylori in Mongolian gerbils. Two weeks after H. pylori infection, FK506 and dexamethasone or vehicle alone were subcutaneously administered once daily for the following 2 weeks. FK506 or vehicle alone was administered subcutaneously once daily for 5 weeks (1 week before and 4 weeks after infection). In H. pylori-infected animals for 4 weeks, hemorrhagic erosions and inflammatory responses (neutrophil infiltration and lymphoid follicle formation) were induced in gastric mucosa at an incidence of 100%. Both FK506 and dexamethasone administered for 2 weeks markedly reduced such mucosal changes. In these animals, H. pylori viability in the stomach was significantly elevated. FK506 administered for 5 weeks also significantly inhibited the hemorrhagic erosions, edema and neutrophil infiltration in the stomach. H. pylori viability was slightly elevated as compared with the control. It was concluded that the host immune responses might play dual roles both by deteriorating gastritis induced by H. pylori and by protecting against H. pylori infection in its early stage.

Animals↗

PubMedDate not supplied

Membranous glomerulonephritis with nephrotic syndrome associated with chronic lymphocytic leukemia.

A 66-year-old woman was admitted to our hospital for evaluation of edema of the extremities. Laboratory findings suggested that she had nephrotic syndrome and chronic lymphocytic leukemia (CLL). Renal biopsy (with PAM staining) showed a spike formation in the capillary wall. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG) and the third component of complement in the glomerular basement membrane. Electron microscopy showed fibrillary deposits in the subepithelium. These findings indicated membranous glomerulonephritis (MGN). In addition, focal segmental sclerosis and interstitial lymphocytic infiltration were observed in the renal biopsy specimen. In CLL patients nephrotic syndrome occurs rarely. Even if the complication occurs, MGN is not frequent. Both diseases are suspected to occur in association with each other, and immunologic abnormality contributes to their coexistence. Although administration of prednisolone and endoxan improved leukocytosis, proteinuria was not sufficiently improved with combination therapy.

Aged↗

PubMedDate not supplied

The role of interleukin-6 in inhibition of lung metastasis in subcutaneous tumor-bearing mice.

Metastasis is the most important factor for prognosis in cancer patients, and its occurrence is largely associated with host immune response. We found that the presence of a growing tumor of colon 26, a mouse colon cancer cell line, completely inhibited lung colony formation in a mouse injected with colon 26 intravenously, whereas depletion of effector cells, such as natural killer and T cell subsets, did not affect antimetastasis of colon 26. Since colon 26 releases large amounts of interleukin-6 (IL-6) spontaneously, we studied the association of IL-6 with lung metastasis. Serum IL-6 level increased gradually and reached 12.6 pg/ml five days after inoculation of colon 26 in the back of mice, while at the same time, lung colony formation was inhibited. Moreover, expression of IL-6 mRNA in lung was observed to be associated with elevated serum IL-6 level. We show the first evidence that inhibition of lung metastases in tumor-bearing mice by colon 26 is closely associated with an increase in serum IL-6, but not in cellular immunity.

Animals↗

PubMedDate not supplied

Effect of YM-14673, an analogue of thyrotropin-releasing hormone, on duodenal bicarbonate secretion in the rat.

The effects of YM-14673, an analogue of thyrotropin-releasing hormone, on duodenal HCO3- secretion were characterized in comparison with those of prostaglandin E2 and carbachol in anesthetized rats. The proximal duodenum was perfused with saline (pH 4.5), the pH of the perfusate and of the transmucosal potential difference were continuously monitored, and HCO3- output was determined by back-titration of the perfusate and by pH change. YM-14673 (0.1, 0.3 and 1 mg/kg) increased these parameters in a dose-related manner; the total HCO3- output at 1 mg/kg (5.8 +/- 0.7 mumol) was about 50% of that induced by prostaglandin E2 (1 mg/kg, i.v.) and 2 times greater than that induced by carbachol (4 micrograms/kg, i.v.). These responses, induced by YM-14673, were almost completely blocked by bilateral vagotomy and significantly inhibited by atropine (0.3 mg/kg, i.v.) or cyclooxygenase inhibitors, such as indomethacin (5 mg/kg, s.c.) and acetylsalicylic acid (40 mg/kg, s.c.), but not affected by pirenzepine (1 mg/kg, i.v.), a selective M1 antagonist. None of the latter agents had any effect on the HCO3(-)-stimulating action of prostaglandin E2, while the carbachol-induced HCO3- output was significantly reduced by atropine. These results suggest that YM-14673 induces the vagal-dependent HCO3- secretion in the rat duodenum and that this mechanism is mediated by muscarinic cholinoceptors, excluding the M1-subtype, and may involve endogenous prostaglandins.

Animals↗