Effects of U74006F on multifocal cerebral blood flow and metabolism after cardiac arrest in dogs

Lipid peroxidation reactions during reperfusion after cardiac arrest may contribute to postischemic cerebral hypoperfusion, which in turn can contribute to permanent neurological dysfunction. We designed this study to determine whether the aminosteroid U74006F, a putative inhibitor of lipid peroxidation, mitigates cerebral multifocal hypoperfusion after cardiac arrest. We used our established dog model of ventricular fibrillation cardiac arrest (no blood flow) of 12.5 minutes, reperfusion by cardiopulmonary bypass of less than or equal to 5 minutes, and control of extracerebral variables during 4 hours postarrest. Cerebral blood flow was monitored by the stable xenon computed tomography method. Changes in cerebral oxygen consumption were obtained from mean blood flow values of coronal slices and the cerebral arteriovenous (sagittal sinus) oxygen content difference. A treatment group (n = 5) received U74006F starting with reperfusion (1.5 mg/kg i.a. plus 1.5 mg/kg i.v.) and three additional (graded) doses over 4 hours (total dose 4.5, 7.5, or 14.5 mg/kg). The U74006F-treated group showed the same postarrest transient hyperemia and protracted hypoperfusion in terms of global (computed tomography slice), regional, and local (multifocal) cerebral blood flow values and the same global cerebral oxygen consumption pattern as a concurrent control group (n = 5). At 1-4 hours postarrest, in both groups there was mismatching of global cerebral oxygen consumption, which reached baseline values, in relation to global cerebral blood flow and oxygen delivery, which remained at 50% of baseline. We conclude that treatment with U74006F after prolonged cardiac arrest causes no deleterious side effects and does not seem to alter multifocal postarrest cerebral blood flow and oxygen consumption.     

Hypocholesterolemic activity of alpha-amylase hydrolysate of bagasse alkaline extract in rats fed atherogenic diet

Cholesterol-lowering activity of enzymatic hydrolysate of bagasse alkaline extract was studied in rats fed a cholesterol-enriched diet. The bagasse alkaline extract was found to be vulnerable to the enzymic attack of alpha-amylase. Thus the alkaline extract was degraded into two fractions: long-chain fraction (polysaccharides) and short-chain fraction (oligosaccharides). The long-chain fraction was active in lowering the serum cholesterol level while feeding the short-chain fraction resulted in a slightly elevated serum cholesterol level. The feeding by gavege of the long-chain fraction 12 h after the meal also was effective in lowering serum cholesterol concentration. These findings were compatible with the concept that the bagasse alkaline extract affect the cholesterol dynamics apart from input-output balance of cholesterol. Possible mechanisms responsible for the cholesterol-lowering activity of the extract were discussed.     

Screening method for PAF antagonist substances: on the phenolic compounds from Impatients balsamina L.

A blood pressure monitoring system was developed for studying antagonist effects against platelet activating factor (PAF), a chemical mediator of anaphylactic hypotension. Using this system, we were able to determine the inhibitory effects of a 35% ethanol extract (IB) from the petals of Impatiens balsamina L. against PAF-induced hypotension and the active principal compounds from IB. One mechanism of the antianaphylactic effects of IB was characterized as PAF-antagonist effects.     

Carotid lesions detected by B-mode ultrasonography in Takayasu's arteritis: "macaroni sign" as an indicator of the disease.

Twenty-three patients were studied to evaluate the clinical usefulness of high resolution B-mode ultrasonography in the detection of carotid lesions in patients with Takayasu's arteritis. In each patient the carotid arteries were examined using both B-mode ultrasonography (midfrequency of 7.5 MHz) and contrast angiography. In 19 of 23 patients, B-mode ultrasonography clearly demonstrated the characteristic circumferential arterial wall thickening of either one or both sides of the common carotid arteries as a macaroni-like, diffusely thickened intima-media complex. Conversely, contrast angiography demonstrated carotid lesions in only 13 of 23 patients. These results clearly show that B-mode ultrasonography is quite sensitive and superior in the detection of the characteristic thick intima-media complex of the common carotid artery in patients with Takayasu's arteritis, when compared with contrast angiography that is usually used for the definitive diagnosis of this disease.     

Size-dependent induction of accelerated blood clearance phenomenon by repeated injections of polymeric micelles

An accelerated blood clearance (ABC) phenomenon is induced by repeated injections of poly(ethylene glycol)-modified (PEGylated) liposomes. We previously indicated that the phenomenon was induced by polymeric micelles possessing PEG chains like as liposomes, although, the induction mechanism of the ABC phenomenon is not fully elucidated. In the present study, we investigate whether repeat-injection of the polymeric micelles having PEG chains trigger the phenomenon or not. Two polymeric micelles, PM-30 (polymeric micelles with 33.6nm in diameter) and PM-75 (76.2nm), were prepared with PEG-poly[Asp(pentyl)] and PEG-poly[Asp(nonyl)], respectively. We firstly examined the ABC-triggering effect of these micelles, and observed that both polymeric micelles, especially PM-75, induced the production of anti-PEG IgM antibody in treated mice. Then, PM-30 or PM-75 was preadministered into mice as a preconditioning. Seven days later, AlexaFluor594-labeled PM-30 or PM-75 was administered to determine the susceptibility of the phenomenon. As a result, rapid clearance of AlexaFluor594-labeled PM-75 from the bloodstream and accumulation in the liver were observed in PM-75 pretreated mice. Although, the ABC phenomenon of AlexaFluor594-labeled PM-30 was less obvious in PM-30 pretreated mice. Our present results indicated that the repeated injections of polymeric micelles caused the ABC phenomenon in a size-dependent manner.     

A case of slowly progressive type 1 diabetes mellitus developing myeloperoxidase-specific anti-neutrophil cytoplasmic antibody-associated vasculitis with hypertrophic pachymeningitis manifesting as multiple cranial nerve palsy

We report a 63-year-old man with a 35-year history of slowly progressive type 1 diabetes mellitus (SPIDDM), complicated with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis presenting alveolar hemorrhage and pachymeningitis. The patient was first diagnosed as having DM at age of 28 years old and deteriorated secretion of insulin and the typical clinical course led us to the diagnosis of SPIDDM. When he was 58 years old, he suffered from fever, headache, and alveolar hemorrhage. He was diagnosed as having MPO-ANCA associated vasculitis based on a high titer of MPO-ANCA and histological findings of lung biopsy. Treatment with steroid pulse therapy, followed by oral prednisolone and oral cyclophosohamide, resulted in clinical improvement. Five years later, he complained of double vision. A gadolinium-enhanced magnetic resonance imaging (MRI) study of the brain showed normal. Two months later, he developed right cranial nerve V~XII palsy. A second MRI study revealed thickening of the right temporal region and cerebellar dura mater, leading us to the diagnosis of hypertrophic pachymeningitis. He responded well to oral prednisolone (50 mg/day) and intravenous cyclophosohamide (500 mg). This is the first case report of SPIDDM complicated with MPO-ANCA-associated vasculitis, manifesting as alveolar hemorrhage and hypertrophic pachymeningitis.     

Lag-phase autophagy in the methylotrophic yeast Pichia pastoris

When microbes sense environmental changes, they often temporarily attenuate cell growth to adapt to the new situations, showing a lag phase. In this study, we report that the methylotrophic yeast, Pichia pastoris , induced autophagy during the lag phase after the cells were shifted from glucose to methanol medium. Through the autophagic process at least two proteins, aminopeptidase I precursor and cytosolic aldehyde dehydrogenase, were found to be transported into the vacuole, which was dependent on PpAtg11 and PpAtg17, respectively. Notably, PpAtg1 and PpAtg17 were required for early exit from the lag phase during the methanol adaptation. In accordance, phosphorylation states of elongation initiation factor 2α indicated reductions of intracellular amino-acid pools in the atg mutant strains. Together, these data demonstrate the importance of amino acid recycling by autophagy during a cell-remodeling process.     

Long-term comorbidity of diabetes mellitus is a risk factor for perineal wound complications after an abdominoperineal resection

Background  This report is an attempt to clarify the effect of diabetes mellitus on perineal wound complications including infectious entities and delayed wound healing after abdominoperineal resection and also tried to show the risk factors for perineal wound complications. Material and methods  The data of 80 patients who underwent an abdominoperineal resection were reviewed from April 1996 to March 2006. Results  The rate of perineal wound complications is higher in diabetics (67%) than in nondiabetics (18%, p = 0.005). In a multivariate analysis, diabetes mellitus and operation time (≥420 min) were the risk factors for perineal wound complications (p = 0.040, p = 0.027, respectively). Infectious perineal wound complication was associated with diabetes mellitus (p < 0.001) but not with the operation time (p = 0.097). Furthermore, a longer comorbid duration of diabetes (≥10 years) was a significant predictor for perineal wound complications (p = 0.008). Conclusion  This study demonstrated diabetes mellitus to be independently associated with perineal wound complications, and when the patients have diabetes mellitus, especially with a longer comorbid duration and longer operation time, the clinical path should be changed to reduce perineal wound complications.