Roles of kallikrein-kinin system in acute inflammation: studies on high- and low-molecular weight kininogens-deficient rats (B/N-Katholiek strain)

Carrageenin-induced paw edema in HMW- and LMW-kininogens-deficient rats was significantly less than that in normal rats. There are three kininogens, HMW-, LMW- and T-kininogens, in normal rat plasma, but B/N-Katholiek rat plasma contains only T-kininogen. The pretreatment with captopril, a kiniase II inhibitor, enhanced paw swelling of normal rats, but not that of the deficient rats, indicating that bradykinin released from HMW-kininogen may have a role for the swelling but T-kinin may not be released in this inflammation.     

Silicone-Coated Polypropylene Hollow-Fiber Oxygenator: Experimental Evaluation and Preliminary Clinical Use

Background. A membrane oxygenator consisting of a microporous polypropylene hollow fiber with a 0.2-μm ultrathin silicone layer (cyclosiloxane) was developed. Animal experimental and preliminary clinical studies evaluated its reliability in bypass procedures.

Methods. Five 24-hour venoarterial bypass periods were conducted on dogs using the oxygenator (group A). In 5 controls, bypass periods were conducted using the same oxygenator without silicone coating (group B). As a preliminary clinical study, 14 patients underwent cardiopulmonary bypass with the silicone-coated oxygenator.

Results. Eight to 16 hours (mean, 12.2 hours) after initiation of bypass, plasma leakage occurred in all group B animals, but none in group A. The O₂ and CO₂ transfer rates after 24 hours in group A were significantly higher than at termination of bypass in group B (p < 0.005 and p < 0.03, respectively). Scanning electron microscopy of silicone-coated fibers after 24 hours of bypass revealed no damage to the silicone coating of the polypropylene hollow fibers. In the clinical study, the oxygenator showed good gas transfer, acceptable pressure loss, low hemolysis, and good durability.

Conclusions. This oxygenator is more durable and offers greater gas transfer capabilities than the previous generation of oxygenators.     

Ammonia: a possible promotor in Helicobacter pylori-related gastric carcinogenesis.

Helicobacter pylori (HP) has been shown to possibly be a pathogen of gastric carcinoma. HP has urease activity and produces ammonia in the stomach. In this study, the role of ammonia on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) were investigated in rats. After 24 weeks pretreatment with MNNG (83 mg/l), 0.01% ammonia or tap water as a drinking water was administered for 24 weeks. The ammonia-treated rats showed a significantly higher incidence of gastric cancer (percent of animals with tumors and number of tumors per rat). Ammonia would thus appear to have an important role in HP-related human gastric carcinogenesis.     

Limited vertical skin incision for median sternotomy.

The cosmetic deformity of the vertical skin incision for median sternotomy was decreased by using a mechanical traction system to increase exposure at the superior margin of a shorter wound. The limited vertical skin incision did not impede technical surgical maneuvers and produced a scar that was more acceptable than submammary incision or right anterior thoracotomy. The limited skin incision is especially useful in young women with congenital heart disease.     

Inhibitory effects of nisoldipine and saralasin on angiotensin II-induced antidiuresis in anesthetized dogs

Inhibitory effects of the calcium channel blocker nisoldipine on angiotensin II-induced antidiuresis were investigated in anesthetized dogs, and the findings were compared with those of saralasin. Intrarenal arterial infusion of 10 ng/kg/min angiotensin II resulted in marked decreases in renal blood flow (RBF) and urine formation, with a relatively moderate decrease in glomerular filtration rate. There were marked reductions in the fractional excretion of lithium, which is used as an index of the fractional proximal excretion of sodium, and the fractional distal excretion of sodium. Nisoldipine (50 ng/kg/min) administered intrarenally produced a partial inhibition on the decreased response of RBF to angiotensin II. The peptide-induced decreases in urine flow, urinary excretion of electrolytes and fractional excretion of electrolytes were abolished by nisoldipine. In contrast, when saralasin was administered intrarenally at 10 ng/kg/min, a dose which could partially inhibit the angiotensin II-induced decrease in RBF to the same extent as seen with nisoldipine, the antagonist attenuated, but did not abolish, the antidiuretic action of angiotensin II. Significant decreases in urine formation by angiotensin II were observed, even in the presence of saralasin. These results suggest that nisoldipine, unlike saralasin, preferentially interferes with the stimulatory effect of angiotensin II, as related to the renal tubular reabsorption of sodium and water.     

Sevoflurane Inhibits Guanosine 5′-[γ-thio]triphosphate-stimulated, Rho/Rho-kinase-mediated Contraction of Isolated Rat Aortic Smooth Muscle

Background: The Rho/Rho-kinase signaling pathway plays an important role in mediating Ca2+ sensitization of vascular smooth muscle. The effect of anesthetics on Rho/Rho-kinase-mediated vasoconstriction has not been determined to date. This study is designed to examine the possible inhibitory effects of sevoflurane on the Rho/Rho-kinase pathway by measuring guanosine 5'-[[gamma]-thio]triphosphate (GTP[gamma]S)-stimulated contraction and translocation of RhoA (one of the three Rho subtypes) and Rock-2 (one of the two Rho-kinase subtypes) from the cytosol to the membrane in rat aortic smooth muscle.

Methods: GTP[gamma]S-induced contraction of rat aortic endothelium-denuded rings was measured using an isometric force transducer, and GTP[gamma]S-stimulated membrane translocation of RhoA and Rock-2 in smooth muscle cells was detected with Western blotting in the presence and absence of sevoflurane.

Results: GTP[gamma]S (10-4 m) induced a sustained contraction, which was significantly inhibited by the Rho-kinase inhibitor, Y27632 (3 x 10-6 m). Before treatment with GTP[gamma]S, RhoA and Rock-2 were detected primarily in the cytosolic fraction. GTP[gamma]S (10-4 m) stimulated the translocation of RhoA and Rock-2 from the cytosol to the membrane, which was sustained for more than 60 min. Sevoflurane (1.7, 3.4, and 5.1%) concentration dependently inhibited the GTP[gamma]S-induced constriction of rat aortic smooth muscle with a reduction of constriction of 52-75% (P < 0.01, n = 8), and attenuated the translocation of RhoA and Rock-2 by 31-66% and 34-78%, respectively (P < 0.05-0.01, respectively; n = 4).     

Dysferlin mutation analysis in a group of Italian patients with limb-girdle muscular dystrophy and Miyoshi myopathy

Mutations in the dysferlin gene (DYSF) on chromosome 2p13 cause distinct phenotypes of muscular dystrophy: limb-girdle muscular dystrophy type 2B (LGMD2B), Miyoshi myopathy (MM), and distal anterior compartment myopathy, which are known by the term 'dysferlinopathy'. We performed mutation analyses of DYSF in 14 Italian patients from 10 unrelated families with a deficiency of dysferlin protein below 20% of the value in normal controls by immunoblotting analysis. We identified 11 different mutations, including eight missense and three deletion mutations. Nine of them were novel mutations. We also identified a unique 6-bp insertion polymorphism within the coding region of DYSF in 15% of Italian population, which was not observed in East Asian populations. The correlation between clinical phenotype and the gene mutations was unclear, which suggested the role of additional genetic and epigenetic factors in modifying clinical symptoms.     

The effect of dietary protein source on plasma cholesterol level and fecal steroid excretion in obese mice

Both goldthioglucose (GTG)-treated and the genetically obese (C57BL/6J ob/ob) mice were fed semisynthetic diets containing either soy protein isolate (SPI) or casein as a protein source, or laboratory chow. In GTG-induced obese mice, the plasma cholesterol level correlated positively with their body weight. The level was highest in mice fed high-fat diet, and lowest in ones fed laboratory chow. No difference was observed between SPI and casein groups whether the diet was low-fat or high-fat. Thus, in the GTG-treated mice, SPI did not have a hypocholesterolemic effect while dietary fat had a hypercholesterolemic effect, and laboratory chow contained some component(s) which can lower the plasma cholesterol level. Both neutral and acidic steroid contents in feces of the SPI group were not different from those of the casein group, and both groups of mice excreted a smaller amount of steroids than mice fed laboratory chow. Results of essentially the same tendency were obtained with normal mice regarding the effects of SPI and casein, although the degree of hypercholesterolemia was lower in high-fat-fed normal mice than in similarly fed GTG-treated mice. These results strengthened the inverse correlation between the amount of fecal steroids and the plasma cholesterol level upon feeding various proteins, indicating that the former is one of the important factors that determine the latter. The ob/ob mice showed a marked hypercholesterolemia irrespective of the kind of diet. The amount of fecal steroids was highest in the laboratory chow group and lowest in the casein group. This indicates that some factor(s) other than fecal steroid excretion is dominantly responsible for their hypercholesterolemia.