Self suppression of phosphoinositide turnover and contraction by stimulating release of endogenous endothelium derived relaxing factor in vascular action of histamine

STUDY OBJECTIVE--The aim of the study was to examine the relationship between phosphoinositide turnover and vascular contraction in response to histamine, and the role of endothelium derived relaxing factor (EDRF) in these activities. DESIGN--Thoracic aortic strips were studied under isometric tension in an organ bath. Phosphoinositide turnover was studied using [32P]Pi labelling. Cumulative concentration-response curves were obtained for histamine, and for histamine plus H1 and H2 antagonists. The effect of endothelial denudation was examined, as was that of removing Ca2+ from buffer medium, and of adding methylene blue, an inhibitor of EDRF. EXPERIMENTAL PREPARATIONS--Thoracic aortic rings were obtained from 81 male Japanese white rabbits, weight 2.0-2.4 kg. MEASUREMENTS AND MAIN RESULTS--Histamine (0.1 mumol-0.1 mmol.litre-1) caused concentration dependent contractions and increases of [32P]Pi incorporation into phosphatidylinositol (ED50 = 4.6 mumol.litre-1 and 4.0 mumol.litre-1 respectively). Diphenhydramine inhibited contractile response and phosphatidylinositol labelling by histamine. Cimetidine potentiated contractile response but had no effect on phosphatidylinositol labelling. Endothelial denudation potentiated maximum contraction by 15% and augmented phosphatidylinositol labelling at 0.1 mmol.litre-1 histamine by 30%. In intact aortic rings, methylene blue (10 mumol.litre-1), an inhibitor of EDRF, potentiated histamine induced phosphatidylinositol labelling, but had no influence on denuded rings. A-23187 (0.01 mumol.litre-1), which caused release of EDRF from intact endothelium, suppressed histamine induced phosphatidylinositol labelling in intact aortic rings. CONCLUSIONS--The results suggest that stimulation of the release of EDRF in response to histamine causes self suppression of phosphoinositide turnover and contraction.     

Behaviour of permeation and separation for aqueous organic acid solutions through poly(vinyl chloride) and poly[(vinyl chloride)-co-(vinyl acetate)] membranes

The permeation and separation characteristics of poly(vinyl chloride) (PVC) and poly[(vinyl chloride)-co-(vinyl acetate)] (poly(VC-co-VAc)) membranes were investigated for aqueous organic acid solutions by pervaporation and evapomeation. The PVC membrane preferentially incorporates organic acids and predominantly permeates water from aqueous organic acid solutions. Water permselectivities of these aqueous solutions through the PVC membrane are significantly dependent on high diffusivity of water across the membrane. It was found that the permeation rate increases and the separation factor for the water permselectivity decreases with increasing vinyl acetate (VAc) content in the poly(VC-co-VAc) membrane. Preferential solubility of acetic acid into the poly(VC-co-VAc) membrane increases with the VAc content. This result was explained by a strong affinity between acetic acid and the VAc unit in the poly(VC-co-VAc) membrane.     

Assessment of damage to cerebral white matter fiber in the subacute phase after carbon monoxide poisoning using fractional anisotropy in diffusion tensor imaging

Introduction  

Chronic neuropsychiatric symptoms after carbon monoxide (CO) poisoning are caused by demyelination of cerebral white matter fibers. We examined whether diffusion tensor imaging can sensitively represent damage to fibers of the centrum semiovale in the subacute phase after CO intoxication.     

Venous reconstructions in lower limbs associated with resection of malignancies

BACKGROUND: Patients with tumors in the limbs who undergo surgical treatment may have involvement of major vessels. Major arteries are always reconstructed for limb salvage. Major veins may be reconstructed to avoid the onset of venous hypertension signs and symptoms. The objective of this study was to analyze the results from surgical treatment of a sample of patients who underwent lower limb venous reconstructions associated with the resection of malignant tumors. METHODS: Follow-up was performed of 17 patients with malignant tumors involving major vessels in the lower limbs. The median length of follow-up was 22 months. Venous reconstruction concomitant to arterial reconstruction was performed in 15 patients, and an isolated venous reconstruction was performed in 2 patients. The venous substitutes used were the contralateral long saphenous vein (n = 12), expanded polytetrafluoroethylene prosthesis (n = 3), and Dacron prosthesis (n = 2). RESULTS: Vascular complications occurred in seven patients: three occlusions of the venous graft, edema in seven patients, and one rupture of the arterial graft. The primary 2- and 5-year patency rates of venous reconstructions were 79.3% and 79.3%, respectively. Nonvascular complications occurred in six patients: neurological deficit (n = 3), partial necrosis of the flap (n = 2), wound infection (n = 1), hematoma (n = 1), and enteric fistula (n = 1). Eight patients were still alive and disease free, although one of them underwent above-knee amputation as a result of local disease recurrence. One patient experienced regional disease recurrence and is undergoing chemotherapy. Eight patients died due to pulmonary metastases. The 2- and 5-year overall survival rates were 58.6% and 42.4%, respectively. The 2- and 5-year thrombosis-free survival rates were 51.9% and 35.2%, respectively. CONCLUSIONS: Lower limb venous reconstructions associated with tumor resection in this study gave good functional results, although the prognosis for these patients had been unfavorable. The saphenous vein is a suitable substitute.     

Blood identification and discrimination between human and nonhuman blood using portable Raman spectroscopy

Raman spectroscopy is commonly used in chemistry to identify molecular structure. This technique is a nondestructive analysis and needs no sample preparation. Recently, Raman spectroscopy has been shown to be effective as a multipurpose analytical method for forensic applications. In the present study, blood identification and discrimination between human and nonhuman blood were performed by a portable Raman spectrometer, which can be used at a crime scene. To identify the blood and to discriminate between human and nonhuman blood, Raman spectra of bloodstains from 11 species (human, rat, mouse, cow, horse, sheep, pig, rabbit, cat, dog, and chicken) were taken using a portable Raman spectrometer. Raman peaks for blood (742, 1001, 1123, 1247, 1341, 1368, 1446, 1576, and 1619 cm⁻¹) could be observed by the portable Raman spectrometer in all 11 species, and the human bloodstain could be distinguished from the nonhuman ones by using a principal component analysis. This analysis can be performed on a bloodstain sample of at least 3 months old. The portable Raman spectrometer can be used at a crime scene, and this analysis is useful for forensic examination.

     

Glomerular hypertrophy in preeclamptic patients with focal segmental glomerulosclerosis. A morphometric analysis

BACKGROUND: Focal segmental glomerulosclerotic lesion (FSGS lesion) is frequently observed in preeclamptic patients with nephrotic syndrome. PATIENTS AND METHODS: We performed a morphometric analysis of renal biopsies from 20 patients with severe preeclampsia to evaluate the pathogenetic role of glomerular hypertrophy in preeclamptic nephropathy associated with FSGS lesion. We also analyzed biopsies obtained from 6 preeclamptic patients without FSGS lesion and 10 patients with isolated hematuria. Nonsclerotic glomeruli were examined. RESULTS: The mean glomerular tuft area (GTA), the whole glomerular area (WGA), and the extracellular matrix area (EMA) were significantly and negatively correlated with the postpartum day at biopsy in preeclamptic patients with FSGS lesion who underwent renal biopsy within 40 days after delivery. The mean GTA, WGA, EMA and number of mesangial cells (MN) were significantly increased in preeclamptic patients with FSGS lesion compared with patients with isolated hematuria and compared with those without FSGS lesion when the biopsy time was matched between patients with and without FSGS lesion. The GTA and WGA were not different between preeclamptic patients without FSGS lesion and patients with isolated hematuria. CONCLUSION: These results support the assumption that glomerular hypertrophy that develops during severe toxemic pregnancy plays an important role in the pathogenesis of FSGS lesion and is reversible about 40 days after delivery.     

Quinapril treatment restores the vasodilator action of insulin in fructose-hypertensive rats

1. Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve insulin-resistance both experimentally and clinically. We therefore investigated the effects of quinapril, which has high tissue specificity for ACE, regarding the contribution of insulin to vascular contractions, as well as insulin sensitivity in a dietary rat model of insulin resistance. 2. Male Sprague-Dawley rats were divided into three groups: (i) rats fed normal chow (normal diet group); (ii) rats fed fructose-rich chow containing 40% fructose and 7% lard (fructose diet group); and (iii) rats fed fructose-rich chow plus quinapril (10 mg/kg per day; quinapril-treated group). 3. After 2 weeks, we evaluated systolic blood pressure, insulin sensitivity as assessed by steady state plasma glucose (SSPG) levels, response of aortic rings to phenylephrine (10-9 to 10-6 mol/L) in the presence or absence of insulin and the response of aortic rings to acetylcholine. 4. Feeding rats fructose-rich chow resulted in an elevation of blood pressure (P < 0.01) and SSPG levels (P < 0.01). Quinapril treatment significantly prevented increases in both blood pressure and SSPG, with a return to the levels seen in the normal diet group. 5. In the absence of insulin, the maximal contractile response to phenylephrine did not differ between the three groups. However, in the presence of insulin (100 mU/mL), the contractile response to phenylephrine (10-6 mol/L) was reduced by 22.8 +/- 1.2% in the normal diet group, although no insulin effects were observed in the fructose diet group (P < 0.01). Quinapril restored the inhibitory effect of insulin on phenylephrine-induced contractions. 6. In addition, the reduction in relaxation induced by acetylcholine in the fructose diet group was significantly reversed by quinapril treatment. 7. It is concluded that the fructose diet impairs the vasodilator effects of insulin as well as acetylcholine-induced relaxation in rat thoracic aortas. Quinapril prevented deterioration in the responses of the aortic rings, suggesting that ACE inhibitors may be useful for treating vascular insulin resistance.     

"Death and survival of neuronal cells exposed to Alzheimer's disease-relevant insults"

The mechanism for neuronal cell death by familial Alzheimer's disease (FAD) genes turned out to consist of various elemental combinations by the different types of cytotoxicity. We therefore tried a new approach toward identifying novel anti-AD suppressors of neuronal death, termed disease-based death trap screening. The identified genes were classified into three categories. In the first category, there were known anti-cell death genes; in the second, there were known genes with unknown function; and in the third, there were novel genes. The cDNA that encodes a 24-residue peptide, termed HN, is in the third category. HN protects neuronal death caused not only by all known kinds of FAD genes (mutant APP, PS1 and PS2), but also by anti-APP antibody and Abeta peptides, but not by long polyQ or SOD1 mutants. HN is a secretory peptide and exerts its protective function from the outside of the cell. The function of HN strictly depends on the structure. C8A-HN lost the activity and S14G-HN had approximately 1000 times increased potency of its action. Immunoblot analysis detected 3-kDa HN immunoreactive peptide in the testis and the colon in 3-week-old mice and only in the testis in 12-week-old mice. Notably, no HN immunoreactivity was detected in the brain. However, in an AD brain, not in an age-matched control, HN immunoreactivity was detected in neurons in the occipital lobe and in reactive glias in the hippocampal sections. The specific binding for HN exists on the neuronal cells and the rescue action of HN is specifically inhibited by genistein but not by wortmannin, suggesting that HN acts through the neuronal surface receptor linked to certain tyrosine kinases, but different from typical receptor tyrosine kinases. This study will provide a new insight into the research of AD.     

Death and survival of neuronal cells exposed to Alzheimer's insults

Neuronal cell death is the central abnormality occurring in brains suffering from Alzheimer's disease (AD). The notion that AD is a disease caused by loss of neurons points toward suppression of neuronal death as the most important therapeutic target. Nevertheless, the mechanisms for neuronal death in AD are still relatively unclear. Three known mutant genes cause familial AD (FAD): amyloid precursor protein, presenilin 1, and presenilin 2. Detailed analysis of cytotoxic mechanisms of the FAD-linked mutant genes reveals that they cause neuronal cell death at physiologically low expression levels. Unexpectedly, cytotoxic mechanisms vary depending on the type of mutations and genes, suggesting that various mechanisms for neuronal cell death are involved in AD patients. In support of this, activity-dependent neurotrophic factor, basic fibroblast growth factor, and insulin-like growth factor-I can completely protect neurons from beta-amyloid (A beta) cytotoxicity but exhibit incomplete or little effect on cytotoxicity by FAD mutant genes. By contrast, Humanin, a newly identified 24-residue peptide, suppresses neuronal cell death by various FAD mutants and A beta, whereas this factor has no effect on cytotoxicity from AD-irrelevant insults. Studies investigating death and survival of neuronal cells exposed to AD insults will open a new horizon in developing therapy aimed at neuroprotection.     

Surgical management of acute type A aortic dissection with a complaint of disturbance of consciousness; report of a case

A 50-year-old female was admitted to our hospital with a chief complaint of disturbance of consciousness (DOC). Left-sided hemiparalysis was noted on examination and cerebral infarction was diagnosed with total occlusion of the right common carotid artery revealed by cerebral angiography. Pharmacological thrombolysis (urokinase 720,000 U) was performed. Dissection of the right common carotid artery was noted after successful thrombolytic therapy. Enhanced chest computed tomography (CT) showed the acute type A aortic dissection involving the cerebral artery. Ascending aortic replacement was performed 4 days after the thrombolytic therapy to avoid brain edema and hemorrhagic infarction during cardiopulmonary bypass. The postoperative course was uneventful. In the case of acute type A aortic dissection with DOC, proper indication and optimal timing of the operation may help to improve patient survival.