Augmentation of intrarenal angiotensin II levels in uninephrectomized aldosterone/salt-treated hypertensive rats; renoprotective effects of an ultrahigh dose of olmesartan.

Recent studies have suggested that aldosterone plays a role in the pathogenesis of renal injury. In this study, we investigated whether local angiotensin II (Ang II) activity contributes to the progression of renal injury in aldosterone/salt-induced hypertensive rats. Uninephrectomized rats were treated with 1% NaCl in a drinking solution and one of the following combinations for 6 weeks: vehicle (2% ethanol, s.c.; n=9), aldosterone (0.75 mug/h, s.c.; n=8), aldosterone+Ang II type 1 receptor blocker olmesartan (10 mg/kg/day, p.o.; n=8), or aldosterone+olmesartan (100 mg/kg/day, p.o.; n=9). Aldosterone/salt-treated hypertensive rats exhibited severe proteinuria and renal injury characterized by glomerular sclerosis and tubulointerstitial fibrosis. Aldosterone/salt-induced renal injury was associated with augmented expression of angiotensin converting enzyme and Ang II levels in the renal cortex and medullary tissues. Renal cortical and medullary mRNA expression of transforming growth factor-beta (TGF-beta) and connective tissue growth factor (CTGF) as well as the collagen contents were increased in aldosterone/salt-treated hypertensive rats. Treatment with olmesartan (10 or 100 mg/kg/day) had no effect on blood pressure but attenuated proteinuria in a dose-dependent manner. Olmesartan at 10 mg/kg/day tended to decrease renal cortical and medullary Ang II levels, TGF-beta and CTGF expression, and collagen contents; however, these changes were not significant. On the other hand, an ultrahigh dose of olmesartan (100 mg/kg/day) significantly decreased these values and ameliorated renal injury. These data suggest that augmented local Ang II activity contributes, at least partially, to the progression of aldosterone/salt-dependent renal injury.     

ENDOSCOPIC MANAGEMENT OF A DIEULAFOY‐LIKE LESION IN A DUODENAL DIVERTICULUM

We present a 70‐year‐old man who had two episodes of melena during the preceding 8‐year period. He had a Dieulafoy‐like lesion in a diverticulum in the third portion of the duodenum. While emergency endoscopy revealed neither apparent blood nor clots around the diverticular orifice, there was a non‐bleeding vessel in the fundus of the diverticulum. The vessel ceased bleeding after argon plasma coagulation and, since then, the patient has not experienced bleeding. In cases of gastrointestinal bleeding of obscure origin, duodenal diverticulum should be considered as a possible source of bleeding, even when endoscopy discloses no apparent bleeding.     

Blood pressure response to erythropoietin injection in hemodialysis and predialysis patients.

Recombinant human erythropoietin (rHuEPO) has been reported to induce hypertension. We investigated the effect of a single injection of rHuEPO on blood pressure in patients receiving hemodialysis (HD) and in patients with predialysis chronic renal failure (CRF). Forty-one patients receiving HD and 36 patients with predialysis CRF received an intravenous injection of rHuEPO, and blood pressure and plasma endothelin-1 were measured before and 30 min after the injection. Mean blood pressure was increased significantly in HD patients, but not in CRF patients (HD: 103+/-5 to 105+/-6 mmHg, p<0.05; CRF: 103+/-4 to 103+/-6, NS). The percentage of patients with increased mean blood pressure of more than 10 mmHg after rHuEPO injection was significantly larger in the HD than in the CRF group (27.0% vs. 5.5%, p<0.01). A positive correlation was found between changes in endothelin-1 level and mean blood pressure in the HD (r=0.43, p<0.01) but not in predialysis chronic renal failure. In conclusion, a single injection of rHuEPO increased blood pressure with a positive correlation with endothelin-1 release in hemodialysis patients, but not in predialysis chronic renal failure patients.     

Clinical evaluation of a potassium nitrate dentifrice for the treatment of dentinal hypersensitivity

Abstract The effectiveness of a 5% potassium nitrate dentifrice as a daily home treatment for dentinal hypersensitivity was evaluated in a double-blind study in 36 Japanese subjects who complained of cold and/or tactile hypersensitivity. The subjects were divided into 2 groups, with 18 being given a 5% potassium nitrate dentifrice (treated group) and the other 18 a vehicle paste (control group). Both groups were instructed to brush their teeth 2 × a day. The hypersensitivity levels of the affected teeth were assessed by 2 stimuli, one tactile and the other cold air, and by the perception of pain. The results of all 3 assessment methods indicated that the potassium nitrate dentifrice significantly decreased the level of hypersensitivity at weeks 4, 8, and 12. In the treated group, a rapid decrease of positive scores for both the cold air stimulus and the subjective symptoms appeared from week 2. Although a significant decrease of the assessment score was also observed in the control group, the reduction rate of the score was much greater in the treated group by ail 3 assessment methods at weeks 4, 8, and 12. Complete relief of subjective symptoms throughout the 12 weeks’examination was noted in 67% of the subjects in the treated group, but in only 6% in the control group. These results suggest the usefulness of a 5% potassium nitrate dentifrice in Japanese patients with dentinal hypersensitivity.     

Primary linitis plastica of the descending colon: A case report

A rare case of primary linitis plastica carcinoma of the colon seen in a 44 year old Japanese man is described herein. The patient had a complete obstruction of the descending colon and was treated with a loop colostomy followed shortly afterward by a left hemicolectomy. At the time of the second operation, the entire thickness of the colonic wall was found to be infiltrated by cancer cells, however, the other intraabdominal organs were free of cancerous involvement. The histopathological diagnosis made at this time was primary linitis plastica carcinoma of the descending colon. Nine months later, the patient developed an intestinal obstruction and relaparotomy revealed diffuse peritoneal dissemination. Two years after the first operation, upper GI films and a gastrofiberscopic examination revealed gastric involvement. The patient died 28 months after his initial operation, and autopsy revealed widespread metastases in the peritoneal surface, paraaortic lymph nodes, small intestine, remaining colon and stomach.     

Effects of Zinc on Production of Active Oxygen Species by Rat Neutrophils

Abstract: The effects of zinc on the production of active oxygen species were investigated in rat neutrophils by chemilumi-nescence and spectrophotometric assays. The luminol-dependent chemiluminescence in unstimulated neutrophils showed a single peak. Zinc at concentrations lower than 0.1 mM augmented the intensity of chemiluminescence and showed a bimodal pattern, the first peak of which was inhibited by superoxide dismutase and catalase, while the second peak disappeared in the presence of catalase, but was unaffected by superoxide dismutase. At the same concentrations of zinc, O₂^? and H₂O₂ production increased, but secretion and activity of myeloperoxidase were not affected. Zinc at 0.1 mM enhanced the second peak of luminol-dependent chemiluminescence, and concomitantly O₂^? and H₂O₂ production of neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine. Homogenized neutrophils showed a bimodal pattern on induction by zinc, the second peak of which was inhibited slightly by catalase and completely by sodium azide, but was not inhibited by superoxide dismutase. Zinc-induced O₂^? production was inhibited by pertussis toxin, but was not significantly inhibited by a protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), or a calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7). These results suggest that zinc can augment luminol-dependent chemiluminescence by increasing O₂^? production through the classical signal transduction pathway, and by increasing H₂O₂ not via O₂^?.     

Hepatic infarction with portal thrombosis

A case of hepatic infarction with portal thrombosis is reported. A 63-year-old woman with liver cirrhosis and esophageal varices was admitted for treatment of the esophagel varices. Endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS) were performed. Two months later, she experienced right hypochondralgia and right flank pain. Serum transaminase levels were suddenly elevated, and computed tomography scans of the liver showed multiple small nodular lesions. Her condition worsened, and she died of hepatic failure. Autopsy revealed splenic and portal vein thrombosis, multiple hepatic infarction, and evidence of chronic pancreatitis. We believe that liver cirrhosis and chronic pancreatitis were the main risk factors for the portal thrombosis, and the treatment for esophageal varices appeared to have triggered the thrombosis. The hepatic infarction was caused by the portal thrombosis.     

Isolated tricuspid valve stenosis caused by infective endocarditis in an adult: Report of a case

We report herein the case of a 42-year-old man in whom dyspnea on exertion was found to be caused by isolated tricuspid stenosis. Two-dimensional echocardiogram showed thickening of the tricuspid valve with a markedly enlarged right atrium. A color-flow Doppler examination-revealed severe tricuspid stenosis without regurgitation and a Doppler-derived tricuspid diastolic pressure gradient of 23 mmHg. At the time of surgery, the patient was noted to have a stenotic tricuspid valve with thickened leaflets, fused commissures, and almost normal chorda tendineae. The valve leaflets were teased apart to the scattered specimen, and tricuspid valve replacement was successfully performed. Microscopic examination of the specimen demonstrated infective endocarditis. Isolated acquired tricuspid stenosis is extremely rare and, to our knowledge, this is the first case of infective endocarditis being involved as the primary cause.     

Evaluation of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (sandwich therapy) for hepatocellular carcinoma

The significance of preoperative chemoembolization using ethiodized oil, cisplatin and gelatin sponge (Sandwich therapy) for resectable hepatocellular carcinoma (HCC) was evaluated. One hundred and thirteen patients with solitary and less than 10 cm sized HCC who underwent radical hepatic resection were chosen for this study. Fifty-three patients received Sandwich therapy before surgery (Group A), and the remaining 60 patients under-went surgery without any preoperative treatments (Group B). Any background factors between two groups were not significantly different. The anticancer effects of this therapy were evaluated by histologic examination in 31 patients who had preoperative Sandwich therapy. In 22 of 31 patients (71%), the main nodules were completely necrotic. The ratios of patients with complete necrosis in daughter nodules were 7/12 (58%), in portal vein tumor emboli, 7/10 (70%), in intracapsular invasions, 11/21 (52%), in extracapsular invasions, 4/11 (36%). The 4-year disease-free survival rates in Group A and Group B were 56% and 27% respectively, and the rate of the former was significantly higher than that of the latter (p less than 0.05). The 4-year survival rates in Group A and Group B were 83% and 53% respectively. The rate of Group A was also significantly higher than that of Group B (p less than 0.01). We concluded that preoperative Sandwich therapy was very significant to obtain successful long-term disease-free survival and survival in regard to relatively early stage HCC.     

Disposition Characteristics of Macromolecules in Tumor-Bearing Mice

As part of the strategy for the design of macromolecular carriers for drug targeting, the disposition characteristics of macromolecules were studied in mice bearing tumors that served as target tissues. Eight kinds of macromolecules including four polysaccharides and four proteins with different molecular weights and electric charges were used; tissue distribution and tumor localization after intravenous injection were studied. Pharmacokinetic analysis revealed that the tissue radioactivity uptake rate index calculated in terms of clearance was different among the tested compounds; especially, the urinary radioactivity excretion clearances and the total hepatic radioactivity uptake clearances varied widely. Compounds with low molecular weights (approximately 10 kD) or positive charges showed lower tumor radioactivity accumulation; radioactivity was rapidly eliminated from the plasma via rapid urinary excretion or extensive hepatic uptake, respectively. On the other hand, large and negatively charged compounds, carboxymethyl dextran, bovine serum albumin, and mouse immunoglobulin G, showed higher radioactivity accumulation in the tumor (calculated total amounts were 15.6, 10.8, and 20.8% of the dose, respectively) and prolonged retention in the circulation. These results demonstrated that the total systemic exposure rather than the uptake rate index was correlated with total tumor uptake. Molecular weight and electric charge of the macromolecules significantly affected their disposition characteristics and, consequently, determined radioactivity accumulation in the tumor. It was concluded that a drug–carrier complex designed for systemic tumor targeting should be polyanionic in nature and larger than 70,000 in molecular weight.