Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.

The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.     

CO2 reactivity and autoregulation in fetal brain

Intraventricular hemorrhage (IVH) in preterm infants is well known to be associated with the high morbidity and mortality of this group. Previous studies have suggested altered cerebral blood flow (CBF) as an important pathologic factor. We measured the CBF in nearterm rabbit fetuses using the hydrogen clearance technique. The local CBF of the rabbit fetuses was significantly low compared with that of the maternal rabbits. The response of CBF to changes in PaCO₂ was observed in rabbit fetuses. The CO₂ reactivity index of the fetal rabbit was lower than that of the maternal rabbit. This low CO₂ reactivity might reflect the immaturity of the fetal brain and its low CBF. We were unable to monitor the fetal blood pressure, but the fetal CBF remained stable when the maternal blood pressure was altered. It is well known that IVH in preterm infants originates from the subependymal germinal matrix and that this has many fragile vessels. Our observation suggests that even a small increase of CBF during hypercapnia might have a large effect towards producing hemorrhage.     

Novel antifungal antibiotics maniwamycins A and B. I. Taxonomy of the producing organism, fermentation, isolation, physico-chemical properties and biological properties

Two antifungal antibiotics maniwamycins A and B were isolated from the culture broth of a strain of actinomycetes, which were classified as Streptomyces prasinopilosus. These antibiotics were isolated by resin absorption and extraction with EtOAc and purified by column chromatography. Both antibiotics were found to be new azoxy substances from their physico-chemical properties. They showed broad antifungal spectra.     

Purification and characterization of aplysianin E, an antitumor factor from sea hare eggs

An antitumor factor, aplysianin E, inducing tumor lysis was purified to apparent homogeneity from the supernatant of a homogenate of eggs of the sea hare Aplysia kurodai. Purified aplysianin E was a 250-kDa glycoprotein containing three different subunits. This factor was half-maximally active at 2-114 ng protein/ml and lysed all the tumor cells tested but did not lyse normal white or red blood cells. Aplysianin E was labile on treatments with heat, low pH, urea, guanidine, sodium lauryl sulfate, and periodate, but not with proteases or organic solvents, Aplysianin E completely inhibited the syntheses of DNA, RNA, and protein by tumor cells within 2 h and caused their complete cytolysis within 15 h. Tumor lysis by aplysianin E was inhibited by N-acetylneuraminic acid, suggesting that recognition of the sugar moiety is a key step in cytolysis induced by aplysianin E. Aplysianin E also prolonged the survival of mice bearing syngeneic MM46 ascites or solid tumors. These results suggest that aplysianin E, found in an invertebrate, the sea hare, is a new antitumor factor.     

Effects of gender on prognosis of patients with known or suspected coronary artery disease undergoing contrast-enhanced dobutamine stress echocardiography.

BACKGROUND: Gender differences in the predictors of outcome among patients with known or suspected coronary artery disease (CAD) undergoing contrast-enhanced dobutamine stress echocardiography (CE-DSE) have not been completely determined. METHODS AND RESULTS: Follow-up (30+/-17 months) data for 581 men and 309 women with known or suspected CAD who underwent CE-DSE (mean age: 66 years) were obtained. Hard cardiac events included cardiac death and nonfatal myocardial infarction. Total cardiac events included hard cardiac events, unstable angina, congestive heart failure, and late revascularization (>3 months). Cardiac events occurred in 123 male and 50 female patients. Positive results for CE-DSE were associated with worse prognosis in both men and women (2-year total event free rate: 73.5% vs 88.2% in men, p<0.0001, 80.3% vs 91.3% in women, p<0.01). Addition of CE-DSE results, including abnormal left ventricular end-systolic volume response and left ventricular ejection fraction at peak stress <50%, to the clinical and rest echocardiography model provided incremental information for predicting total cardiac events (increase in chi-square value for the model from 60 to 72, p<0.001) in men and (increase in chi-square value for the model from 17 to 32, p<0.001) in women. CONCLUSIONS: CE-DSE provides incremental information for predicting future cardiac events in both men and women.     

Resetting of the arterial baroreflex increases orthostatic sympathetic activation and prevents postural hypotension in rabbits

Since humans are under ceaseless orthostatic stress, the mechanism to maintain arterial pressure (AP) under orthostatic stress against gravitational fluid shift is of great importance. We hypothesized that (1) orthostatic stress resets the arterial baroreflex control of sympathetic nerve activity (SNA) to a higher SNA, and (2) resetting of the arterial baroreflex contributes to preventing postural hypotension. Renal SNA and AP were recorded in eight anaesthetized, vagotomized and aortic-denervated rabbits. Isolated intracarotid sinus pressure (CSP) was increased stepwise from 40 to 160 mmHg with increments of 20 mmHg (60 s for each CSP level) while the animal was placed supine and at 60 deg upright tilt. Upright tilt shifted the CSP–SNA relationship (the baroreflex neural arc) to a higher SNA, shifted the SNA–AP relationship (the baroreflex peripheral arc) to a lower AP, and consequently moved the operating point to marked high SNA while maintaining AP. A simulation study suggests that resetting in the neural arc would double the orthostatic activation of SNA and increase the operating AP in upright tilt by 10 mmHg, compared with the absence of resetting. In addition, upright tilt did not change the CSP–AP relationship (the baroreflex total arc). A simulation study suggests that although a downward shift of the peripheral arc could shift the total arc downward, resetting in the neural arc would compensate this fall and prevent the total arc from shifting downward to a lower AP. In conclusion, upright tilt increases SNA by resetting the baroreflex neural arc. This resetting may compensate for the reduced pressor responses to SNA in the peripheral cardiovascular system and contribute to preventing postural hypotension.     

Clinical significance of selective middle hepatic venography

Selective middle hepatic venography was performed in 86 patients who had been scheduled to undergo liver resection because of hepatobiliary diseases. Special catheters were used of which tips were bended counterclockwise at an angle of 45 degrees. Successful middle hepatic venograms were obtained in 65 cases (76%). Abnormal findings were observed in 27 cases (42%), and it was difficult to diagnose them by ultrasonography or computed tomography. Selective middle hepatic venogram is very useful to understand surgical anatomy of the liver in each case preoperatively. In 5 cases of giant tumor, middle hepatic venography is necessary to identify the exact site of the tumor. Selective middle hepatic venography is considered to be one of the indispensable, examinations for liver resection.