Longitudinal relationship of severe periodontitis with cognitive decline in older Japanese.

BACKGROUND AND OBJECTIVE: Epidemiologic data examining the longitudinal relationship between periodontitis and cognitive status are very limited, especially in Asian populations. The present study examined the longitudinal relationship of periodontitis with cognitive decline in 85 Japanese community-dwelling individuals (average age: 79.3 years) for whom data were available from comprehensive health examinations conducted in 2010 and 2013. MATERIAL AND METHODS: Based on a baseline full-mouth periodontal examination, severe periodontitis was defined using a Centers for Disease Control and Prevention/American Academy of Periodontology definition. Cognitive decline during the 3-year study period was defined using the results of the Mini-Mental State Examination (MMSE). Information on age, gender, education, depression, body mass index, smoking status, alcohol use, exercise, hypertension, diabetes, history of cardiovascular disease and stroke, and baseline MMSE scores were obtained and tested as potential confounders in the statistical models. RESULTS: Among 85 study participants, 21 (24.7%) were defined as having severe periodontitis. Multivariable Poisson regression analyses revealed that severe periodontitis was significantly associated with an increased risk of cognitive decline [adjusted relative risk = 2.2; 95% confidence interval (95% CI): 1.1-4.5]. Furthermore, multivariable linear regression analyses revealed that participants with severe periodontitis had a 1.8-point greater decrease (95% CI: -3.3 to -0.2) in MMSE score than those without severe periodontitis. CONCLUSION: Within the limitations related to its small sample size, the findings of the present study suggest that severe periodontitis is significantly associated with future decline in cognitive function among community-dwelling older Japanese subjects.

Maximum bite force at age 70 years predicts all-cause mortality during the following 13 years in Japanese men.

There is limited information on the impact of oral function on mortality among older adults. The aim of this prospective cohort study was to examine whether an objective measure of oral function, maximum bite force (MBF), is associated with mortality in older adults during a 13-year follow-up period. Five hundred and fifty-nine community-dwelling Japanese (282 men and 277 women) aged 70 years at baseline were included in the study. Medical and dental examinations and a questionnaire survey were conducted at baseline. Maximum bite force was measured using an electronic recording device (Occlusal Force-Meter GM10). Follow-up investigation to ascertain vital status was conducted 13 years after baseline examinations. Survival rates among MBF tertiles were compared using Cox proportional hazards regression models stratified by sex. There were a total of 111 deaths (82 events for men and 29 for women). Univariable analysis revealed that male participants in the lower MBF tertile had increased risk of all-cause mortality [hazard ratio (HR) = 1·94, 95% confidence interval (CI) = 1·13-3·34] compared with those in the upper MBF tertile. This association remained significant after adjustment for confounders (adjusted HR = 1·84, 95% CI = 1·07-3·19). Conversely, no association between MBF and all-cause mortality was observed in female participants. Maximum bite force was independently associated with all-cause mortality in older Japanese male adults. These data provide additional evidence for the association between oral function and geriatric health.

Adhesions and incisional hernias following laparoscopic versus open surgery for colorectal cancer in the CLASICC trial.

BACKGROUND: This study investigated adhesive intestinal obstruction (AIO) and incisional hernia (IH) in patients undergoing laparoscopically assisted and open surgery for colorectal cancer. METHODS: In a case-note review of patients randomized to the Medical Research Council's Conventional versus Laparoscopic-Assisted Surgery In Colorectal Cancer (CLASICC) trial, primary and key secondary endpoints were AIO and IH admission rates respectively. RESULTS: Of 411 patients, 11 were admitted for AIO: four (3.1 per cent) of 131 patients in the open arm of the trial versus seven (2.5 per cent) of 280 in the laparoscopic arm (difference 0.6 (95 per cent confidence interval (c.i.) - 2.9 to 4.0) per cent). Thirty-six patients developed IH: 12 (9.2 per cent) after open versus 24 (8.6 per cent) after laparoscopic surgery (difference 0.6 (95 per cent c.i. - 5.3 to 6.5) per cent). Results by actual procedure showed higher AIO and IH rates in the 24.5 per cent of patients who converted from laparoscopic to open surgery (AIO: 2.3, 2.0 and 6 per cent; IH: 8.6, 7.4 and 11 per cent-for open, laparoscopic and converted operations respectively). CONCLUSION: Although this study has not confirmed that laparoscopic surgery reduces rates of AIO and IH after colorectal cancer surgery, trends suggest that a reduction in conversion to open surgery and elimination of port-site hernias may produce such an effect. Registration number for CLASICC trial: ISRCTN74883561 (http://www.controlled-trials.com).

Periodontal disease: associations with diabetes, glycemic control and complications.

OBJECTIVE: This report reviews the evidence for adverse effects of diabetes on periodontal health and periodontal disease on glycemic control and complications of diabetes. DESIGN: MEDLINE search of the English language literature identified primary research reports published on (a) relationships between diabetes and periodontal diseases since 2000 and (b) effects of periodontal infection on glycemic control and diabetes complications since 1960. RESULTS: Observational studies provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal disease in 13/17 reports reviewed. Treatment and longitudinal observational studies provided evidence to support periodontal infection having an adverse effect on glycemic control, although not all investigations reported an improvement in glycemic control after periodontal treatment. Additionally, evidence from three observational studies supported periodontal disease increasing the risk for diabetes complications and no published reports refuted the findings. CONCLUSION: The evidence reviewed supports diabetes having an adverse effect on periodontal health and periodontal infection having an adverse effect on glycemic control and incidence of diabetes complications. Further rigorous study is necessary to establish unequivocally that treating periodontal infections can contribute to glycemic control management and to the reduction of the burden of diabetes complications.

Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions.

House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens.

Generation of hydroxyeicosatetraenoic acids by human inflammatory cells: analysis by thermospray liquid chromatography-mass spectrometry.

Arachidonic acid was converted to a series of hydroxyeicosatetraenoic acids (HETEs) by mixed human inflammatory cells following stimulation with the calcium ionophore A23187. HETEs were purified by a simple one-step extraction procedure followed by HPLC. The HPLC was coupled to a Finnigan quadrupole mass spectrometer using the now commercially available thermospray liquid chromatography-mass spectrometry interface. The HPLC eluant was monitored 'on line' by the mass spectrometer. Soft ionisation occurs, generating intense molecular ion species in the negative ion mode (M - H-:m/z 319) for each of the isomeric HETEs. The (M + H+ - H2O) ion at m/z 303 is the major species in the positive ion spectra of HETEs. Mass spectra were obtained on-line post-HPLC for HETEs formed by the human cells, and the HPLC-MS profile compared with that obtained from standards; species corresponding to the 11-, 9- and 5-HETEs were observed.

Eicosanoid biosynthesis in an advanced deuterostomate invertebrate, the sea squirt (Ciona intestinalis).

The eicosanoid generating potential of tunic, branchial basket, intestine, ovary and tadpole larvae from the sea squirt, Ciona intestinalis, was examined using a combination of reverse phase high performance liquid chromatography, gas chromatography-mass spectrometry and enzyme immunoassay. All organs examined synthesized the lipoxygenase products 12-hydroxyeicosapentaenoic acid (12-HEPE) and 8-HEPE implying that both 8- and 12-lipoxygenase activity are widely distributed in this species. In addition, tunic and branchial basket generated significant amounts of 8,15-diHEPE and smaller amounts of 8,15-dihydroxyeicosatetraenoic acid (8,15-diHETE), while tunic alone generated small amounts of conjugated tetraene-containing material with a UV chromophore and mass ion characteristic of a lipoxin-like compound. The broad range lipoxygenase inhibitors, esculetin and nordihydroguaiaretic acid, both caused a significant dose dependent inhibition of 12-HEPE and 8,15-diHEPE biosynthesis in tunic, while the specific 5-lipoxygenase inhibitor, REV-5901, and the specific 5-lipoxygenase activating protein inhibitor, MK-866, had no observable effect on the lipoxygenase profile of this tissue. Tunic, branchial basket, intestine and ovary all generated significant amounts of prostaglandin (PG) E and PGF immunoreactive material and smaller amounts of thromboxane B immunoreactive material as measured by enzyme immunoassay. The non-specific cyclooxygenase (COX) inhibitor, indomethacin, the selective COX-1 inhibitors, resveratrol and valerylsalicylate, and the specific COX-2 inhibitors, NS-398, etolodac and DFU (5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone) all caused a significant dose dependent inhibition of the biosynthesis of PGE immunoreactive material. However, the specific COX-2 inhibitors were most effective, perhaps implying that a COX-2-like enzyme may be present in this species.

Formation and metabolism of 14,15-epoxyeicosatrienoic acid by human reproductive tissues.

Human granulosa-luteal cells cultured in the presence of arachidonic acid produced low levels of the epoxygenase metabolite 14,15-epoxy-5,8,11-(Z,Z,Z)-eicosatrienoic acid (14,15-EpETrE) as determined by HPLC analysis and gas chromatography mass spectrometry. When authentic 14,15-[3H]EpETrE was incubated with these cells in the absence of serum it was metabolised initially to the dihydroxy derivative (14,15-dihydroxy-5,8,11-eicosatrienoic acid, 14,15-DiHETrE) and subsequently to a number of more polar metabolites as determined by HPLC. Fetal calf serum protected 14,15-EpETrE from metabolism for at least 2 h. A similar pattern of metabolism was obtained when 14,15-[3H]EpETrE was incubated with a human choriocarcinoma cell line (BeWo). Microsomes from this cell line converted arachidonic acid to a large number of radioactive metabolites including 14,15-DiHETrE and 11,12-DiHETrE although there was no evidence for the parent epoxides. These results extend earlier findings that human reproductive tissues produce epoxygenase metabolites, and demonstrate the rapid metabolism of these compounds by intact cells in the absence of serum.

Characterisation of Pseudomonas rhamnolipids.

The Gram negative organism, Pseudomonas aeruginosa, is often found in the lungs of patients with cystic fibrosis and other forms of severe bronchiectasis, where it secretes a number of extracellular toxins including the mono- and dirhamnolipids. The principal monorhamnolipid from P. aeruginosa has previously been identified as rhamnosyl-3-hydroxydecanoyl-3-hydroxydecanoate (Rh-C10.C10). A number of related mono- and dirhamnolipids have been purified from cultures of a clinical isolate of P. aeruginosa and identified by fast atom bombardment and electron impact mass spectrometry: these contain the 3-hydroxyoctanoyl-3-hydroxydecanoate (C8.C10) and 3-hydroxydecanoyl-3-hydroxydodecanoate (C10.C12) homologues. Structural isomers were also present where the order of the lipid linkage was transposed (Rh-C10.C8 and Rh-C12.C10). Unsaturated mono- and dirhamnolipids containing the 3-hydroxydecanoyl-3-hydroxydodec-5-enoate (C10.C12:1) lipid were also present.

Metabolism of prostaglandins E2 and F2 alpha by human fetal membranes.

Prostaglandin E2 (PGE2) is important in the early stages of human labour, leading particularly to cervical ripening and dilatation. The source of PGE2 is thought to be either the amnion or the decidua, but the chorion interposes between the amnion and the target tissues, namely the myometrium and cervix. In order to investigate the role of the chorion in modulating prostanoid production, [3H]PGE2 was added to the amnion side of fetal membranes, and the production of metabolites on both sides of the fetal membrane followed by HPLC. The major metabolite was 13,14-dihydro-15-oxo-PGE2 with smaller amounts of 13,14-dihydro-15-oxo-PGA2 and PGB2. The production of all metabolites of PGE2 was time dependent. [3H]PGF2 alpha, which is normally produced by the decidua, was also added to fetal membranes and found to be metabolised to 13,14-dihydro-15-oxo-PGF2 alpha and PGE2. These results suggest that the metabolic enzymes in the chorion may determine intra-uterine levels of prostaglandins, and may also determine the identity of the eicosanoids released by intact fetal membranes.

Cholesterol synthesis is increased in mixed hyperlipidaemia.

We showed previously that hypertriglyceridaemia, but not hypercholesterolaemia, is correlated with increases in cholesterol synthesis and apolipoprotein B secretion in patients with secondary hypertriglyceridaemia. The aim of the present study was to compare the rate of cholesterol synthesis, using fasting plasma mevalonic acid (MVA) as an index, in patients with primary mixed hyperlipidaemia (type IIb phenotype, n=45) and primary hypercholesterolaemia (type IIa phenotype, n=92). LDL cholesterol was significantly higher in types IIa (6.38+/-0.18 mmol/l) and IIb (5.89+/-0.25 mmol/l) compared to 40 normolipidaemic controls (2. 99+/-0.1 mmol/l, P<0.0001), whereas serum triglyceride was higher in type IIb (2.62 (range 2.2-3.0) mmol/l) than type IIa (1.22 (range 0. 85-1.60) mmol/l, P<0.001) and controls (0.90 (range 0.68-1.24) mmol/l, P<0.001). Similarly, MVA was higher in type IIb (7.0+/-0.46 ng/ml) than IIa (5.6+/-0.23 ng/ml, P<0.0) and controls (5.6+/-0.36 ng/ml, P<0.05). Plasma MVA correlated positively with serum triglyceride (r=0.22, P=0.004) and negatively with LDL cholesterol (r=-0.21, P=0.014). These results are in accordance with previous observations that VLDL-apolipoprotein B secretion and cholesterol synthesis are linked and demonstrate that the latter is increased in mixed hyperlipidaemia.

Pathological effects of extensive radiofrequency energy applications in the pulmonary veins in dogs.

INTRODUCTION: The long-term complications of catheter ablation within the pulmonary veins are unknown. The development of pulmonary vein stenosis has recently been described after catheter ablation to treat either chronic or paroxysmal atrial fibrillation. The purpose of this study was to examine the pathological and hemodynamic effects of radiofrequency (RF) energy application within the pulmonary veins. METHODS AND RESULTS: Right heart and transseptal catheterization were performed in 9 anesthetized mongrel dogs. The pulmonary vein ostia were cannulated and pulmonary venous pressure was measured before RF energy application in up to 4 separate pulmonary veins. Animals were euthanized at intervals of 2 to 4 weeks (n=3), 6 to 8 weeks (n=3), or 10 to 14 weeks (n=3) after ablation. Repeat catheterization before euthanasia demonstrated statistically significant differences in pulmonary capillary wedge pressure, cardiac output, pulmonary vascular resistance, and systemic vascular resistance (P<0.05) compared with the baseline. Luminal narrowing was observed in 22 of 33 pulmonary veins to which RF energy was applied. Of these, 7 were totally occluded, 7 had severe stenosis, and 8 were only minimally narrowed. Histological examination revealed intimal proliferation with organizing thrombus, necrotic myocardium in various stages of collagen replacement, endovascular contraction, and a proliferation of elastic lamina. CONCLUSIONS: Applications of RF current within the pulmonary veins may result in pulmonary vein narrowing or complete occlusion. These observations should be considered in treatment of arrhythmias originating within the pulmonary veins.

Inhibition of prostaglandin E2 synthesis in abdominal aortic aneurysms: implications for smooth muscle cell viability, inflammatory processes, and the expansion of abdominal aortic aneurysms.

BACKGROUND: There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS: Aneurysm biopsies were used for explant cultures, the preparation of smooth muscle cell cultures, and isolation of macrophages. Tissue macrophages stained strongly for cyclooxygenase 2. Prostaglandin E2 (PGE2) concentrations in aneurysm tissue homogenates, conditioned medium from explants, and isolated macrophages were 49+/-22 ng/g, 319+/-38 ng/mL, and 22+/-21 ng/mL, respectively. PGE2 inhibited DNA synthesis and proliferation in normal aortic smooth muscle cells (IC50, 23.2+/-3.8 and 23.6+/-4.5 ng/mL, respectively). In smooth muscle cells derived from aneurysmal aorta, PGE2 also caused cell death, with generation of oligonucleosomes. Conditioned medium from the mixed smooth muscle and monocyte cultures derived from explants also had potent growth-inhibitory effects, and fractionation of this medium showed that the growth-inhibitory molecule(s) coeluted with PGE2. In explants, indomethacin 10 micromol/L or mefenamic acid 10 micromol/L abolished PGE2 secretion and significantly reduced IL-1beta and IL-6 secretion. In a separate case-control study, the expansion of abdominal aortic aneurysms was compared in 15 patients taking nonsteroidal anti-inflammatory drugs and 63 control subjects; median growth rates were 1.5 and 3.2 mm/y, respectively, P=0.001. CONCLUSIONS: The adverse effects of PGE2 on aortic smooth muscle cell viability and cytokine secretion in vitro and the apparent effect of anti-inflammatory drugs to lower aneurysm growth rates suggest that selective inhibition of PGE2 synthesis could be an effective treatment to curtail aneurysm expansion.

Smokeless tobacco and severe active periodontal disease, NHANES III.

Whereas smoking is a major risk factor for periodontal disease, the role of smokeless tobacco is unclear. The purpose of this US population-based study of 12,932 adults participating in the Third National Health and Nutrition Examination Survey was to evaluate the association between smokeless tobacco use and severe active periodontal disease. Univariable and multivariable logistic regression modeling quantified the associations between tobacco use and severe active periodontal disease. All adults and never-smokers who currently used smokeless tobacco were twice as likely to have severe active periodontal disease at any site [respective odds ratios (OR(Adj)) and 95% confidence intervals: OR(Adj) = 2.1; 1.2-3.7 and OR(Adj) = 2.1; 1.0-4.4] or restricted to any interproximal site [respective OR(Adj) = 2.1; 1.0-4.2 and OR(Adj) = 2.3; 0.9-6.3], simultaneously adjusted for smoking, age, race, gender, diabetes, and having a dental visit in the past year. These results indicate that smokeless tobacco may also be an important risk factor for severe active periodontal disease.

Prevalence and trends in periodontitis in the USA: the [corrected] NHANES, 1988 to 2000.

Trends in periodontal diseases in the USA have been documented for years. However, the results have been mixed, mostly due to different periodontal assessment protocols. This study examined change in the prevalence of periodontitis between the NHANES III and the NHANES 1999-2000, and differences in the prevalence of periodontitis among racial/ethnic groups in the USA. Analysis was limited to non-Hispanic black, non-Hispanic white, and Mexican-American adults aged 18+ yrs in the NHANES III (n=12,088) or the NHANES 1999-2000 (n=3214). The prevalences of periodontitis for the NHANES III and the NHANES 1999-2000 were 7.3% and 4.2%, respectively. In multivariable analyses, blacks were 1.88 times (95%CI: 1.42, 2.50) more likely to have periodontitis than whites surveyed in the NHANES III. However, the odds of periodontitis for blacks and Mexican-Americans did not differ from those for whites surveyed in the NHANES 1999-2000. Our findings indicate that the prevalence of periodontitis has decreased between the NHANES III and the NHANES 1999-2000 for all racial/ethnic groups in the USA.

Determinants of variable response to statin treatment in patients with refractory familial hypercholesterolemia.

Interindividual variability in low density lipoprotein (LDL) cholesterol (LDL-C) response during treatment with statins is well documented but poorly understood. To investigate potential metabolic and genetic determinants of statin responsiveness, 19 patients with refractory heterozygous familial hypercholesterolemia were sequentially treated with placebo, atorvastatin (10 mg/d), bile acid sequestrant, and the 2 combined, each for 4 weeks. Levels of LDL-C, mevalonic acid (MVA), 7-alpha-OH-4-cholesten-3-one, and leukocyte LDL receptor and hydroxymethylglutaryl coenzyme A reductase mRNA were determined after each treatment period. Atorvastatin (10 mg/d) reduced LDL-C by an overall mean of 32.5%. Above-average responders (LDL-C -39.5%) had higher basal MVA levels (34.4+/-6.1 micromol/L) than did below-average responders (LDL-C -23.6%, P<0.02; basal MVA 26.3+/-6.1 micromol/L, P<0.01). Fewer good responders compared with the poor responders had an apolipoprotein E4 allele (3 of 11 versus 6 of 8, respectively; P<0.05). There were no baseline differences between them in 7-alpha-OH-4-cholesten-3-one, hydroxymethylglutaryl coenzyme A reductase mRNA, or LDL receptor mRNA, but the latter increased in the good responders on combination therapy (P<0.05). Severe mutations were not more common in poor than in good responders. We conclude that poor responders to statins have a low basal rate of cholesterol synthesis that may be secondary to a genetically determined increase in cholesterol absorption, possibly mediated by apolipoprotein E4. If so, statin responsiveness could be enhanced by reducing dietary cholesterol intake or inhibiting absorption.

Plasma mevalonic acid, an index of cholesterol synthesis in vivo, and responsiveness to HMG-CoA reductase inhibitors in familial hypercholesterolaemia.

Fasting plasma mevalonic acid (MVA), an indicator of in vivo cholesterol synthesis, was measured in 35 patients with familial hypercholesterolaemia (FH) of whom 7 were treated with pravastatin 10-40 mg/day, 7 with simvastatin 10-40 mg/day and 21 with atorvastatin 80 mg/day. Reductions in low density lipoprotein (LDL) cholesterol and MVA on maximal dose therapy differed significantly between the three drugs: 34.7%, 42.9% and 54.0% (P = 0.0001), and 31.6%, 48.9% and 58.8% (P = 0.004), respectively. Patients on atorvastatin were subdivided according to whether their reduction in LDL cholesterol on treatment was above or below the mean percentage change for the whole group. Basal values of LDL cholesterol did not differ significantly, but above average responders had a significantly higher mean pre-treatment level of MVA (6.2 +/- 0.60 vs. 4.3 +/- 0.61 ng/ml, P < 0.05) than below average responders. When all three drug groups were pooled above average responders showed a significantly greater absolute decrease in MVA on treatment than below average responders (3.85 +/- 0.48 vs. 2.33 +/- 0.40 ng/ml, P < 0.05). However, there was no significant correlation between the magnitude of the decreases in LDL cholesterol and MVA. These findings suggest that FH patients who responded well to statins had a higher basal level of plasma MVA, i.e. a higher rate of cholesterol synthesis, which was more susceptible to pharmacological inhibition. The more marked cholesterol lowering effect of atorvastatin 80 mg/day presumably reflects, at least in part, its ability to inhibit HMG-CoA reductase to a greater extent than maximal recommended doses of pravastatin and simvastatin of 40 mg/day.

Upregulation of cholesterol synthesis after acute reduction of low density lipoprotein by apheresis in normocholesterolaemic subjects: evidence for a threshold effect.

The influence of low density lipoproteins (LDL) in the plasma on the regulation of cholesterol biosynthesis is not clear. We studied the changes in plasma mevalonic acid (MVA) concentration and the lathosterol/cholesterol (L/C) ratio, which are well established indices of whole body cholesterol synthesis, in four normocholesterolaemic subjects after each had undergone LDL apheresis on two occasions. LDL apheresis of 75% of the calculated plasma volume reduced LDL-cholesterol by 44% to 1.5 +/- 0.2 mmol/l without changing plasma MVA levels or L/C ratios. Apheresis of 125% of the calculated plasma volume decreased plasma LDL-cholesterol by 69% to 0.9 +/- 0.2 mmol/l, with significant increases in plasma MVA and L/C ratio on the day after the procedure. These results imply that LDL-cholesterol is an integral part of the sterol regulatory pool and suggest that plasma levels cannot be lowered below 1-1.4 mmol/l in normal subjects without upregulating cholesterol biosynthesis.

Plasma lipid and apolipoprotein profiles of women with two types of peripheral arterial disease.

The purpose of this study was to establish whether women with peripheral arterial disease can be distinguished from controls on the basis of plasma lipid and apolipoprotein profiles. One group of patients with peripheral arterial disease (n = 20) was characterized by a localized aortic stenosis referred to as the 'small aorta syndrome' (SAS). The other group of patients with peripheral arterial disease (n = 23) had a diffuse segmental pattern of stenoses referred to as the 'stenosing peripheral arterial disease' (SPAD). After correcting for the effects of age and body mass index, the SAS group had elevated plasma total cholesterol (TC) levels when compared to normal controls (P less than or equal to 0.008), while the SPAD group had triacylglycerol (TG) levels different from controls (P = 0.02). Both groups of patients were characterized by reduced levels of apolipoprotein A-I (P less than or equal to 0.04) and increased levels of apolipoprotein C-III (P less than or equal to 0.002). Apolipoproteins B and E were also elevated in both groups of patients but not significantly. Mutivariate analyses indicated that the A-I/C-III ratio correctly discriminated 97.8% of the SAS and the A-I/C-III ratio plus A-I discriminated 89.8% of the SPAD patient from the controls. In addition, multivariate analyses showed that the variables age, TC/Apo B, Apo B/C-III and TG/C-III discriminated SPAD from SAS patients with a correct classification of 93.2%. Results of this study showed that the measurement of apolipoproteins A-I, B and C-III in conjunction with TC and TG is of potential use for differentiating patients with peripheral arterial disease from normal controls as well as for distinguishing patients with SAS from those with SPAD. It seems that particular patterns of peripheral arterial disease in women may be associated with slightly different alterations in the plasma lipoprotein system.

Preparation, purification, and structure elucidation of slow-reacting substance of anaphylaxis from guinea pig lung.

The work that we have described had originally three main aims: (a) to design a new purification system for SRS-A from which we would obtain pure material for the structural analysis: (b) to define the functional groups in the pure material by spectrophotometric, chemical, and enzymic inactivation methods; and (c) to deduce the complete covalent structure by an accepted spectroscopic method capable of defining structure in atomic detail. These aims have been achieved. The structure of SRS-A, the physiologically more relevant example of the SRSs that were studied, because it was derived immunologically from an animal model of an acute hypersensitivity reaction, has been rigorously defined. Of paramount importance in the determination of this structure was the mass spectrometric analysis of the intact molecule. Degradative and comparative studies are not capable of unequivocally defining structure. For example, the mass spectrum clearly showed the absence of an amide or similar C-terminal blocking groups or, as has been suggested, a sulfone in the molecule; such conclusions could not be drawn from comparative chromatographic data even on multiple systems. Mass spectrometric analysis of the intact molecule could overcome these problems by allowing the complete covalent structure to be collated from the information obtained from each fragmentation. The use of stable isotopes and accurate mass measurement removed possible ambiguities in the interpretation, and the sensitivity and specificity of mass spectrometry made it the method of choice for the structural analysis.