Dominant effect of supplemented-sucrose on the low protein diet-induced increase in blood pressure of Sprague-Dawley rats.

A low-protein diet (LPD) is known to affect the regulation of hemodynamics, and could contribute to the genesis of hypertension. We investigated the mechanism for the LPD-induced elevation of blood pressure in 52 Sprague-Dawley rats. Rats fed the LPD for 8 weeks showed a significantly higher blood pressure than those fed on a normal-protein diet (NPD) when the LPD included sucrose as a predominant component of carbohydrate (LPD with a high sucrose content, 135 +/- 2 mmHg; NPD, 124 +/- 2 mmHg; p<0.05). However, LPD with a low sucrose content, in which corn starch was the main component of carbohydrate, did not have a hypertensive effect (125 +/- 2 mmHg). Urinary epinephrine and norepinephrine excretion was significantly higher in the LPD high-sucrose group than in the NPD and LPD low-sucrose groups, and there was a significant positive correlation between urinary norepinephrine excretion and systolic blood pressure. Urinary nitric oxide excretion was no different between these groups, and 2 % L-arginine administration exerted no antihypertensive effect on the LPD-induced elevation of blood pressure. Sodium restriction also did not attenuate the LPD-induced elevation of blood pressure. These results suggest that the effect of LPD on blood pressure could be interpreted as the effect of the high sucrose content supplemented to the LPD rather than the direct effect of protein restriction, and that the stimulation of sympathetic nervous activity was associated with this elevation of blood pressure.

Efficacy of pertussis vaccines consisted of antigens detoxified with tea-leaf catechins.

The ability of tea-leaf catechins to detoxify agents was examined. Filamentous hemagglutinin (FHA) and pertussis toxin (PT) were detoxified by the catechins at an extraordinarily lower concentration compared with that of formalin. The sera from the mice immunized by the catechin-treated antigens recognized, not only catechin-treated, but also untreated antigens. Furthermore, catechin-treated PT induced the antibody to neutralize PT activity in the sera of the immunized mice. Pertussis vaccines were prepared including antigens detoxified by the treatment of catechins and intraperitoneally injected into mice. Protection against Bordetella pertussis infection was shown in mice immunized with the vaccines prepared by treatment with catechins. These data suggest that catechins are effective toxoiding agents for preparing a pertussis vaccine.

Differential alteration of cardiotonic effects of EMD 57033 and beta-adrenoceptor agonists in volume-overload rabbit ventricular myocytes.

BACKGROUND: We investigated the effects of EMD 57033, a prototype Ca2+ sensitizer, and beta-adrenoceptor agonists in ventricular myocytes isolated from the volume-overload (V-O) heart failure model of the rabbit. METHODS AND RESULTS: V-O cardiac hypertrophy was induced in rabbits by the formation of an arterio-venous shunt between the carotid artery and jugular vein 12 to 15 weeks after the operation. Ventricular myocytes were enzymically isolated from normal and V-O rabbit hearts. The myocyte was loaded with a fluorescence Ca2+ dye, indo-1, and Ca2+ transients, and cell lengths were measured simultaneously. V-O myocytes were significantly larger than control myocytes. Duration of Ca2+ transients and cell shortening was significantly longer in the V-O myocytes than in control myocytes. Effects of cardiotonic interventions, including EMD 57033, isoproterenol, and dobutamine, on Ca2+ transients and cell shortening in V-O myocytes were compared with those in control rabbit myocytes. Isoproterenol and dobutamine increased the systolic cell shortening and peak Ca2+ transients and abbreviated the duration of cell shortening and Ca2+ transients. These responses were markedly attenuated in V-O myocytes. By contrast, the response of cell shortening to EMD 57033 was unaltered, and the Ca2+ sensitizing effect of EMD 57033 was rather enhanced in V-O myocytes. CONCLUSION: Our results indicate that the effectiveness of Ca2+ sensitizers is maintained in the V-O rabbit hypertrophy and heart failure model in contrast to the blunted response to beta-adrenoceptor agonists, which provides an insight on therapeutic strategy with Ca2+ sensitizers for the treatment of contractile dysfunction in congestive heart failure.

Studies on differentiation inducers. IV. Pregnane derivatives from condurango cortex.

In connection with the study of differentiation inducers from plants, the methanol extract of Condurango Cortex (bark of Marsdenia condurango REICH, Asclepiadaceae) was investigated to examine its differentiation-inducing activity towards mouse myeloid leukemia (M1) cell line. Six pregnane glycosides, including three new compounds, were isolated as differentiation inducers. Each of the six active glycosides has three or four deoxylated sugars which are well-known to occur in Asclepiadaceae plants. M1 cells were differentiated into phagocytic cells by these glycosides, and they were found to be more effective than their aglycones. Condurangoglycosides A (7) and C (8), having a cinnamoyl group in their aglycones, were the most potent differentiation inducers and M1 cells became phagocytic cells after 24 h treatment with these compounds.

[Significance of a mass survey for colorectal cancer at the workplace].

Two thousand four hundred and forty workers from 2 plants were enrolled in a mass survey for colorectal cancer using a single immunological fecal occult blood test as screening. The occult blood test was positive in 71 (4.0%) out of 1,759 subjects in whom the test was conducted. A further investigation, including total colonoscopy or barium enema, was performed on 52 (73.2%) of the 71. Colon cancer was detected in 5 cases: 1 with advanced cancer and 4 with early cancer (cancer in the adenoma). The advanced cancer was successfully resected by surgery and the early cancers were removed by endoscopic polypectomy. Adenomas were found in 21 cases, 11 of which were polypectomized. From these results, it can be seen that a survey for colorectal cancer at the workplace is important, and by expanding the number of subjects for the survey in the workplace we can expect more and earlier detections of colorectal cancer.

[Multimodality treatment of esophageal carcinoma: evaluation of preoperative (neoadjuvant) chemotherapy].

Recently, esophageal carcinoma has shown a wide variation in spread, from carcinoma in situ to the far-advanced type. Therefore, the treatment must be performed on the basis of accurate clinical stagings, and not only the prognosis but also the quality of life of patients should be considered. Surgical resection has been regarded as standard treatment for patients with advanced carcinoma, but in some cases, preoperative treatments should be added to perform curative resections. Our objectives in preoperative (neoadjuvant) chemotherapy with cisplatin and other chemotherapeutic agents are three-fold: 1) To reduce the extent of direct invasion of neighboring structures (e.g., aorta, trachea or bronchus). 2) To reduce the degree of lymph node metastasis. 3) To preserve the larynx in cases of cervical esophageal carcinoma. For the past 4 years, we treated 13 cases of advanced esophageal carcinoma with this chemotherapy method preoperatively. Two of 13 patients showed a partial clinical response, including one with no viable carcinoma cells pathologically, and 4 had a minor clinical response. However, the impact on overall survival must be further investigated. We conclude that this multimodality treatment is effective for local tumor control, but should be applied for selected patients with careful management of its side effects.

Pharmacokinetic studies on pharmacologic response of captopril in rats.

After administration of captopril, a decrease in mean arterial blood pressure was observed in low sodium rats which were used as animal models of hyper-renin-active pathema. In normal rats, however, this marked decrease in blood pressure was not observed, even with high dose levels. In spite of the fact that captopril does not lower the blood pressure in normal rats, it was demonstrated that converting-enzyme activity was inhibited by captopril. No differences were observed between low sodium rats and normal rats in characteristics of angiotensin-converting enzyme. It was concluded that disposition of captopril might be different in the respective rats.