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.     

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.     

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.     

Effects of hypothermal and circulatory arrest on the auditory brainstem response during operation in children

Twenty-two children were monitored by the auditory brainstem response (ABR) during the open chest and/or open heart surgery for cardiac anomalies under the extracorporeal circulation (ECC) with moderate to deep hypothermia. These patients were divided into two groups, namely, the ECC only group (group A: 9 cases) and the total circulatory arrest (TCA) group (group B: 13 cases). The mean age of group A was 36 months and group B was 6.1 months. In group A, moderate hypothermia was conducted with the rectal temperature ranging from 25 degrees C to 30 degrees C, and in group B profound hypothermia was conducted lowering the temperature to 18 degrees C. The ABR recorded at the following points, namely; before inducing anesthesia, before lowering the body temperatures, during the cooling process, at the time of TCA, and during the rewarming process. Accompanying the decrease in body temperature the peak latency of waves I, III and V were markedly prolonged. When the rectal temperature fell to 23 degrees C, the peak latency of each wave was prolonged to about 150% of their precooling values at 36 degrees C. When it fell to 22 degrees C, the ABR disappeared entirely in 16 of 22 cases, and in remaining 6 cases, only I wave was detected. During rewarming, in both the A and B groups, at 24 degrees C, the wave of ABR started to reappear beginning with I waves, and on reaching 26 degrees C, I, III and V waves from became detectable. The peak latency of all waves at rectal temperature of 33 degrees C recovered to almost the same values as these at 36 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Detection of platelet-activating factor in exudates of rats with phorbol myristate acetate-induced pleurisy

PAF-likely activity, detected as aggregation of washed platelets, was found in the exudate of rats with pleurisy induced by phorbol myristate acetate (PMA, 1 nmol). At 30 min after the injection of PMA, 400-500 pg of PAF was detected in the pleural exudate. An extract of the exudate was made and analysed by HPLC and by rabbit platelet aggregation. The activity was characterized as that of PAF as a result of the inhibition seen with the PAF-antagonist CV-3988 and the loss of activity by treatment with phospholipase A2. Indirect evidence was previously reported in that CV-3988 suppressed the pleural fluid accumulation in the pleurisy induced by PMA. Taken together these facts it indicates that PAF could be an important mediator of acute inflammation, especially of the plasma exudation resulting from an increase in vascular permeability. Evidence that pleural cells produce PAF was also examined in an in vitro experiment. PAF was found in the supernatant and cellular fractions of the incubation mixture of the pleural cells from normal rats when stimulated by PMA (1 microM) or A23187 (5 microM), and the results indicate that the pleural cells produce PAF and release a portion of it.