PP Levels Research Articles

Interactions of Several Lipid-Related Gene Polymorphisms and Cigarette Smoking on Blood Pressure Levels

The interactions of single nucleotide polymorphisms (SNPs) and cigarette smoking on blood pressure levels are limited. The present study was undertaken to detect nine lipid-related SNPs and their interactions with cigarette smoking on blood pressure levels. Genotyping of ATP-binding cassette transporter A1 (ABCA-1) V825I, acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) rs1044925, low density lipoprotein receptor (LDL-R) AvaⅡ, hepatic lipase gene (LIPC) -250G>A, endothelial lipase gene (LIPG) 584C>T, methylenetetrahydrofolate reductase (MTHFR) 677C>T, proprotein convertase subtilisin-like kexin type 9 (PCSK9) E670G, peroxisome proliferator-activated receptor delta (PPARD) +294T>C, and Scavenger receptor class B type 1 (SCARB1) rs5888 was performed in 935 nonsmokers and 845 smokers. The interactions were detected by factorial regression analysis. The frequencies of genotypes (ACAT-1 and LIPG), alleles (ABCA-1), and both genotypes and alleles (LDL-R, LIPC, PPARD and SCARB1) were different between nonsmokers and smokers (P < 0.05-0.001). The levels of pulse pressure (PP, ABCA-1), and systolic, diastolic blood pressure (SBP, DBP) and PP (LIPC) in nonsmokers were different among the genotypes (P < 0.01-0.001). The levels of SBP (ABCA-1, ACAT-1, LIPG and PCSK9), DBP (ACAT-1, LDL-R, LIPC, PCSK9 and PPARD), and PP (LIPC, LIPG, MTHFR and PCSK9) in smokers were different among the genotypes (P < 0.01-0.001). The SNPs of ABCA-1, ACAT-1 and PCSK9; ACAT-1, LDL-R, MTHFR and PCSK9; and ABCA-1, LIPC, PCSK9 and PPARD were shown interactions with cigarette smoking to influence SBP, DBP and PP levels (P < 0.05-0.001); respectively. The differences in blood pressure levels between the nonsmokers and smokers might partly result from different interactions of several SNPs and cigarette smoking.

Soft Speaking

- 347 milton babbitt a composers’ memorial texts - 348 Soft Speaking Jeffrey Kresky It was Milton Babbitt’s 90th birthday, and William Paterson University was awarding him an honorary doctorate. For an associated concert of his music its director Peter Jarvis asked him if he had anything squirreled away that might now come forth, and in response he produced a 1999 manuscript, Composition for One Instrument and Ben, a 15-second celesta solo, which I undertook to perform. (The “Ben” is Ben Weber, to whose work as copyist for the score of Composition for Four Instruments the title refers; both pieces start with the same solo trichordal succession, B-Eb-C. There had apparently been one prior performance.) As a keyboardist of only modest attainment, I had never performed any of Babbitt’s music, and was naturally concerned for its difficulty. But in the event, though I was able to execute the notes in their rhythm (if not quite up to tempo), it was, surprisingly, the specified dynamics that quite defeated me. In this tiny piece all attacks occur at either pp, p or mp levels. But it was not the expected difficulties of distinguishing such relatively close-together values and asserting them reliably across the whole registral spread of the keyboard (perhaps the performer’s version of the perceptual problem of judging different dynamic levels in different registers), or even of doing this on so notoriously unreliable an instrument, that got the better of me. (Never knowing if a note will “speak” leads one to over-attack, especially when two events are close together in time but far apart in space. Imagine leaping the length of the keyboard in the time of a 32nd -note at quarter = 80, but having to pull one’s punch in order to scale down from a p to a pp.) Rather, it was what I came to suspect to be a cognitive issue: I could never learn to “feel” – even in so brief a piece – just when a dynamic shift ought to occur. That is, it never became natural – a real problem when one has to respond to the notation so quickly; I had in a sense to force myself to strike a note at one or another level of loudness, rather than to come in time to “absorb” the dynamic life of the piece as a conveyer of some (real or imagined) expressive content that I could accept and then assert. This experience gave me a new appreciation of just how radical Babbitt’s use of dynamics may be. Though his music is always cited for its achievements in pitch and in rhythm, with the trademark “scatter” of his dynamics (like that of his registers) widely recognized as a stylistic hallmark even apart from any technical apprehension of their possible structural workings, my difficulties at the keyboard brought home how challengingly his use of dynamics departs from our deeply-rooted sense of their traditional, “proper” role, with its expressive and dramatic capacities so compellingly grounded in our everyday experience - 349 Soft Speaking of the material world, even to so basic a level as, for example, loud sounds being literally assaultive as they move through the air and strike the listening body. After all, we wouldn’t sing a lullaby at triple forte if we want the baby to fall asleep. Was I, then – quite unawares – disabled for the lack of a suitable (if irrelevant) “rhetorical” track in the succession of dynamics? Very near the end of the piece there is a moment when a single pitch followed by a dyad form a group at p that is immediately repeated, in the identical rhythm, at pp, and this particular dynamic adjustment I never failed to execute – it seemed “natural,” probably because it invoked the familiar trope of “echo.” I have often noticed that in performances of Phonemona the soprano seems to project, by intention or not, an invented rhetorical stratum of groupings of phonemes: her facial expressions, hand gestures and other bits of body language seem to suggest exclamation points, question marks and other, subtler, inflections, as if the absence of any such rhetorical “sense” was intolerable when making utterances of a sort that...

Modulation of Phosphate/Pyrophosphate Metabolism to Regenerate the Periodontium: A Novel In Vivo Approach

The developing periodontium is sensitive to local levels of inorganic phosphate (P(i)) and inorganic pyrophosphate (PP(i)) as demonstrated by cementum phenotypes resulting from the loss of function of protein regulators of P(i)/PP(i) homeostasis. The progressive ankylosis protein (ANK) regulates the transport of PP(i), and progressive ankylosis gene (Ank) and knock-out (KO) mice feature a rapidly forming and thick cementum. We hypothesized that, besides affecting cementum formation, decreased extracellular PP(i) levels in Ank KO mice would also impact cementum regeneration. Periodontal fenestration defects (approximately 2 mm in length, 1 mm in width, and 0.5 mm in depth) were created on buccal aspects of mandibular molars in Ank KO and wild-type (WT) mice. Mandibles were harvested at 15 and 30 days post-surgery for histology, histomorphometry, evaluation of in vivo fluorochrome labeling, and immunohistochemistry (IHC) for proteins including bone sialoprotein (BSP), osteopontin (OPN), dentin matrix protein 1 (DMP1), and ectonucleotide pyrophosphatase/phosphodiesterase 1 (NPP1). A greater amount of new cementum was observed in Ank KO mice at 15 and 30 days post-surgery (P <0.05), which was confirmed by fluorochrome labeling showing a higher new cementum appositional activity in defect areas in Ank KO mice versus controls. At days 15 and 30 during healing, regenerating cementum and associated cells in Ank KO samples recapitulated expression patterns mapped during development, including limited BSP and positive OPN and DMP1 in the cementum matrix as well as elevated NPP1 in cementoblasts. Within the limits of the study, these findings suggest that reduced local levels of PP(i) could promote increased cementum regeneration. Therefore, the local modulation of P(i)/PP(i) may be a potential therapeutic approach for achieving improved cementum regeneration.

Arterial stiffness is associated with minimally elevated high-sensitivity cardiac, troponin T levels in a community-dwelling population

ObjectivesArterial stiffness predicts an increased risk of future cardiovascular events, possibly via myocardial damage. Minimally elevated levels of plasma cardiac troponin T (TnT), a marker of cardiomyocyte injury, can be detected by the high-sensitivity TnT (hsTnT) assay. The current study investigated the relationship between plasma hsTnT levels and alterations in arterial stiffness in a community-based population. MethodsWe related levels of plasma hsTnT to measures of arterial stiffness (carotid–femoral pulse wave velocity [PWV], office pulse pressure [PP] and carotid–radial PWV) in 1479 participants (mean age, 62.3 years; 619 men, 860 women) from a community-based population in Beijing, China. ResultsIn multiple logistic regression models, carotid–femoral PWV (OR: 1.84; 95% CI: 1.06–3.17; P=0.028) and office PP (OR: 2.02; 95% CI: 1.31–3.11; P=0.002) were associated with a higher likelihood of detectable hsTnT. In addition, carotid–femoral PWV (OR: 2.34; 95% CI: 1.03–5.30; P=0.042) and office PP (OR: 2.30; 95% CI: 1.13–4.66; P=0.022) were significantly related to elevated hsTnT levels. A subsequent subgroup analysis found that, in subjects aged 60 years and older, the associations between carotid–femoral PWV and office PP and hsTnT levels were strengthened. The associations between hsTnT with any of the arterial stiffness measures were not present in the younger subgroup (<60 years old). ConclusionsCarotid–femoral PWV and office PP are associated with minimally elevated hsTnT levels in the elderly, indicating a relationship between central artery stiffness and subclinical myocardial damage.

Loss of skeletal mineralization by the simultaneous ablation of PHOSPHO1 and alkaline phosphatase function: A unified model of the mechanisms of initiation of skeletal calcification

Endochondral ossification is a carefully orchestrated process mediated by promoters and inhibitors of mineralization. Phosphatases are implicated, but their identities and functions remain unclear. Alkaline phosphatase (TNAP) plays a crucial role promoting mineralization of the extracellular matrix by restricting the concentration of the calcification inhibitor inorganic pyrophosphate (PPi). Mutations in the TNAP gene cause hypophosphatasia, a heritable form of rickets and osteomalacia. Here we show that PHOSPHO1, a phosphatase with specificity for phosphoethanolamine and phosphocholine, plays a functional role in the initiation of calcification and that ablation of PHOSPHO1 and TNAP function prevents skeletal mineralization. Phospho1−/− mice display growth plate abnormalities, spontaneous fractures, bowed long bones, osteomalacia, and scoliosis in early life. Primary cultures of Phospho1−/− tibial growth plate chondrocytes and chondrocyte-derived matrix vesicles (MVs) show reduced mineralizing ability, and plasma samples from Phospho1−/− mice show reduced levels of TNAP and elevated plasma PPi concentrations. However, transgenic overexpression of TNAP does not correct the bone phenotype in Phospho1−/− mice despite normalization of their plasma PPi levels. In contrast, double ablation of PHOSPHO1 and TNAP function leads to the complete absence of skeletal mineralization and perinatal lethality. We conclude that PHOSPHO1 has a nonredundant functional role during endochondral ossification, and based on these data and a review of the current literature, we propose an inclusive model of skeletal calcification that involves intravesicular PHOSPHO1 function and Pi influx into MVs in the initiation of mineralization and the functions of TNAP, nucleotide pyrophosphatase phosphodiesterase-1, and collagen in the extravesicular progression of mineralization. © 2011 American Society for Bone and Mineral Research.

RELATION BETWEEN PHYSICAL ACTIVITY AND BLOOD PRESSURE LEVELS IN YOUNG GREEK ADOLESCENTS (THE LEONTIO LYCEUM STUDY): PP.23.424

Objective: Elevated blood pressure during childhood and adolescence is not so rare and increases the risk of hypertension in adulthood, contributing also in adverse cardiovascular outcomes. Physical activity is a key component of the therapeutic lifestyle changes recommended for the prevention and treatment of hypertension in children and adolescents. Thus the purpose of the present study was to assess the level of physical activity in Greek adolescents and its relation to blood pressure levels. Design and Method: The study included 496 students aged 12 to 17 years who were enrolled on a volunteer basis. Subjects were subjected to BP measurement on two different occasions during a routine school day, and measurement of their anthropometric features. Demographic, socio-economic and lifestyle characteristics were assessed by means of a standard questionnaire. Information on the frequency and duration of physical activities and on the amount of time spent on sedentary activities was obtained by the short-form self-administered questionnaire International Physical Activity Questionnaire-IPAQ. Results: The study population was divided in three groups according to the score achieved in IPAQ questionnaire: low PA (n = 39), moderate PA (n = 230) and high PA (n = 231). A significant higher level of SBP and PP was observed in subjects of high PA, while heart rate was significantly lower as the level of PA rose (p = 0.002). Furthermore, a positive correlation of METs vigorous to SBP (r = 0.139, p = 0.003) and to PP (r = 0.22, p = 0.0001) was observed. Conclusions: There is an association between intense physical activity and higher SBP, PP levels and lower heart rate, within normal range, in healthy young adolescents.

Physiologic and pathologic functions of the NPP nucleotide pyrophosphatase/phosphodiesterase family focusing on NPP1 in calcification

The catabolism of ATP and other nucleotides participates partly in the important function of nucleotide salvage by activated cells and also in removal or de novo generation of compounds including ATP, ADP, and adenosine that stimulate purinergic signaling. Seven nucleotide pyrophosphatase/phosphodiesterase NPP family members have been identified to date. These isoenzymes, related by up conservation of catalytic domains and certain other modular domains, exert generally non-redundant functions via distinctions in substrates and/or cellular localization. But they share the capacity to hydrolyze phosphodiester or pyrophosphate bonds, though generally acting on distinct substrates that include nucleoside triphosphates, lysophospholipids and choline phosphate esters. PPi generation from nucleoside triphosphates, catalyzed by NPP1 in tissues including cartilage, bone, and artery media smooth muscle cells, supports normal tissue extracellular PPi levels. Balance in PPi generation relative to PPi degradation by pyrophosphatases holds extracellular PPi levels in check. Moreover, physiologic levels of extracellular PPi suppress hydroxyapatite crystal growth, but concurrently providing a reservoir for generation of pro-mineralizing Pi. Extracellular PPi levels must be supported by cells in mineralization-competent tissues to prevent pathologic calcification. This support mechanism becomes dysregulated in aging cartilage, where extracellular PPi excess, mediated in part by upregulated NPP1 expression stimulates calcification. PPi generated by NPP1modulates not only hydroxyapatite crystal growth but also chondrogenesis and expression of the mineralization regulator osteopontin. This review pays particular attention to the role of NPP1-catalyzed PPi generation in the pathogenesis of certain disorders associated with pathologic calcification.

Altered redox status in patients with Diabetes Mellitus type I

Diabetes mellitus is a complex metabolic disorder characterized by a disturbance in glucose metabolism. Recent evidences suggest that increased oxidative damage as well as deficits in antioxidants defence systems could be related to the complications in Diabetes patients’ type I. The aim of this study was to investigate an extensive array of redox status indices: glutathione (GSH), malondialdehyde (MDA), peroxidation potential, superoxide dismutase (SOD), catalase (CAT), total hydroperoxide (TH) and advanced oxidation protein products (AOPP) in relation to blood glucose and glucose indicators control such as glycosylated haemoglobin (HbA 1c) and fructosamine by spectophotometric techniques. Forty Diabetes Mellitus patients’ type I and 40 healthy subjects were recruited. Both a reduction of GSH levels and an increase in MDA and TH levels were observed in the serum of patients. These patients also showed an increase of AOPP and PP levels as well as an increase of both CAT and SOD activity. Relatively to the control group, patients had significant differences in global indices of oxidant/antioxidant status and indicators of glycaemia control. These results contribute both to the evidences that substantial oxidative stress occurs during Diabetes Mellitus type I without early complications and to an integral overview of the oxidant/antioxidant balance in these patients.

Role of the progressive ankylosis gene (ank) in cartilage mineralization.

Mineralization of growth plate cartilage is a critical event during endochondral bone formation, which allows replacement of cartilage by bone. Ankylosis protein (Ank), which transports intracellular inorganic pyrophosphate (PP(i)) to the extracellular milieu, is expressed by hypertrophic and, especially highly, by terminally differentiated mineralizing growth plate chondrocytes. Blocking Ank transport activity or ank expression in terminally differentiated mineralizing growth plate chondrocytes led to increases of intra- and extracellular PP(i) concentrations, decreases of alkaline phosphatase (APase) expression and activity, and inhibition of mineralization, whereas treatment of these cells with the APase inhibitor levamisole led to an increase of extracellular PP(i) concentration and inhibition of mineralization. Ank-overexpressing hypertrophic nonmineralizing growth plate chondrocytes showed decreased intra- and extracellular PP(i) levels; increased mineralization-related gene expression of APase, type I collagen, and osteocalcin; increased APase activity; and mineralization. Treatment of Ank-expressing growth plate chondrocytes with a phosphate transport blocker (phosphonoformic acid [PFA]) inhibited uptake of inorganic phosphate (P(i)) and gene expression of the type III Na(+)/P(i) cotransporters Pit-1 and Pit-2. Furthermore, PFA or levamisole treatment of Ank-overexpressing hypertrophic chondrocytes inhibited APase expression and activity and subsequent mineralization. In conclusion, increased Ank activity results in elevated intracellular PP(i) transport to the extracellular milieu, initial hydrolysis of PP(i) to P(i), P(i)-mediated upregulation of APase gene expression and activity, further hydrolysis and removal of the mineralization inhibitor PP(i), and subsequent mineralization.

Pulse Pressure in Acute Stroke Is an Independent Predictor of Long-Term Mortality

The management of blood pressure (BP) during the acute phase of stroke remains a matter of debate. The aim of the present study was to evaluate a possible association between long-term mortality and BP values in acute stroke by means of BP monitoring. We studied a consecutive series of 198 first-ever acute stroke patients. BP monitoring was initiated in all subjects within 24 h of ictus. One year after stroke onset, 34 (17.7%) patients had died. Multivariate Cox regression analysis revealed only age, level of consciousness on admission, lacunar stroke and 24-hour pulse pressure (24-hour PP) as significant outcome predictors. The hazards ratio for 1-year mortality associated with every 10 mm Hg increase in 24 h PP was 1.39 (95% CI: 1.04–1.86, p = 0.028). The present results demonstrate that increasing 24-hour PP levels in patients with acute stroke are independently associated with higher long-term mortality. This may have implications in acute stroke BP management and warrants further investigation.

Concerted Regulation of Inorganic Pyrophosphate and Osteopontin by Akp2, Enpp1, and Ank: An Integrated Model of the Pathogenesis of Mineralization Disorders

Tissue-nonspecific alkaline phosphatase (TNAP) hydrolyzes the mineralization inhibitor inorganic pyrophosphate (PP(i)). Deletion of the TNAP gene (Akp2) in mice results in hypophosphatasia characterized by elevated levels of PP(i) and poorly mineralized bones, which are rescued by deletion of nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) that generates PP(i). Mice deficient in NPP1 (Enpp1(-/-)), or defective in the PP(i) channeling function of ANK (ank/ank), have decreased levels of extracellular PP(i) and are hypermineralized. Given the similarity in function between ANK and NPP1 we crossbred Akp2(-/-) mice to ank/ank mice and found a partial normalization of the mineralization phenotypes and PP(i) levels. Examination of Enpp1(-/-) and ank/ank mice revealed that Enpp1(-/-) mice have a more severe hypermineralized phenotype than ank/ank mice and that NPP1 but not ANK localizes to matrix vesicles, suggesting that failure of ANK deficiency to correct hypomineralization in Akp2(-/-) mice reflects the lack of ANK activity in the matrix vesicle compartment. We also found that the mineralization inhibitor osteopontin (OPN) was increased in Akp2(-/-), and decreased in ank/ank mice. PP(i) and OPN levels were normalized in [Akp2(-/-); Enpp1(-/-)] and [Akp2(-/-); ank/ank] mice, at both the mRNA level and in serum. Wild-type osteoblasts treated with PP(i) showed an increase in OPN, and a decrease in Enpp1 and Ank expression. Thus TNAP, NPP1, and ANK coordinately regulate PP(i) and OPN levels. The hypomineralization observed in Akp2(-/-) mice arises from the combined inhibitory effects of PP(i) and OPN. In contrast, NPP1 or ANK deficiencies cause a decrease in the PP(i) and OPN pools that leads to hypermineralization.

Anterior lumbar fusion with paired BAK standard andpaired BAK Proximity cages: subsidence incidence, subsidence factors,and clinical outcome

BACKGROUND CONTEXT: Anterior lumbar interbody fusion (ALIF) procedures have a known incidence of subsidence. The individual risk of subsidence for specific lumbar levels in ALIF procedures has not been determined. PURPOSE: To evaluate the incidence of subsidence with two ALIF constructs. A paired Bagby and Kuslich (BAK) standard cage construct is compared with a paired BAK Proximity construct (Sulzer Spine-Tech, Minneapolis, MN). Study purpose is to evaluate lumbar intervertebral disc subsidence including the subsidence incidence for each disc level and with single- and two-level constructs. Also evaluated is the site of maximal subsidence within each end plate, risk with increased reaming depth, fusion incidence and clinical outcome. STUDY DESIGN: A consecutive series of 70 fused levels fused with paired standard BAK cages is compared with a subsequent series of 70 fused levels using paired Proximity BAK cages. PATIENT SAMPLE: The study population is derived from a consecutive series of ALIF procedures completed by a single surgeon. In 1998 the construct was changed from dual-standard to dual-Proximity cages. In the year 2000 there were 52 patients with a 2-year follow-up. These were matched to the previous 52 patients with dual-standard construct. OUTCOME MEASURES: Clinical outcome was determined using pre- and postoperative Oswestry questionnaires. Postoperative questionnaires were completed at the yearly follow-up. Radiographic outcome was determined by fusion status and evaluation of subsidence. Also evaluated was reaming depth and cage size for each fused level. METHODS: A total of 52 patients with ALIF procedures using paired BAK standard cages (the SS group) were studied with a group of 52 patients using paired BAK Proximity cages (the PP group). The study population was derived from an ongoing prospective study of consecutive ALIF fusion procedures completed by a single surgeon. Disc height measurements were used to determine subsidence. Reaming depth, fusion status and the site of maximal subsidence were all recorded. Clinical outcome was determined with a pre- and postoperative Oswestry functional questionnaire. RESULTS: Subsidence greater than 2 mm was noted in 5 of the 70 SS fused levels and in 9 of the 70 fused PP levels. Subsidence was always at the L4–L5 level in the SS subsided levels. Subsidence was in two-level fusions in all but one of the SS constructs. Subsidence was at the L4–L5 level in eight of the nine subsided PP levels. Subsidence was associated with increased reaming depth and the use of larger cage sizes. Subsidence was usually in the posterior and superior end plate. The clinical outcome was not affected by subsidence. Subsidence incidence was not associated with the age, sex or weight of the patient. CONCLUSIONS: There is a statistically significant increased incidence of subsidence at the L4–L5 level as opposed to other fused lumbar levels in ALIF fusions with BAK cage constructs. There is an increased incidence of subsidence with the PP constructs. Subsidence also is associated with increased reaming depth and with larger cage sizes. The lowest risk for subsidence was with single-level dual-standard cage constructs.

Heterotrophic bacterioplankton in the Arabian Sea:

Heterotrophic bacterial abundance and productivity were measured during ve and four cruises, respectively, in the northwest Arabian Sea as part of the US JGOFS Process Study, which provided a new view of seasonal bacterial dynamics in that part of the basin in#uenced by monsoonal forcing. In this paper, surface layer data are used to address two questions concerning the in#uence of the monsoon cycle on bacterial dynamics: (1) Is there a bacterial bloom in the SW Monsoon? and (2) Is bacterial production low during the oligotrophic Spring Intermonsoon? An extensive comparison of epi#uorescence microscopy and #ow cytometry, unprecedented at this scale, detected essentially the same heterotrophic bacterial populations and distributions, with some between-cruise di!erences. Use of the two methods allowed us to extend our observations in space and time. Bacterial productivity, both in the surface layer and integrated over the euphotic zone, was elevated less than 2-fold during the Southwest Monsoon. Levels of bacterial abundance and production were low during the Northeast Monsoon, then increased in March during the Spring Intermonsoon. There was some stimulation of abundance or production inshore in response to coastal upwelling. In general, the basin was enriched in bacterial biomass '510 cells l throughout the year, relative to other tropical regimes, presumably in response to overall high PP and DOC levels. Seasonally uniformDOC levels may be regulated in part by intense bacterial utilization rates, but also re #ect seasonal consistency in PP. 2001 Elsevier Science Ltd. All rights reserved.

Lipoprotein lipase (C/G)447 polymorphism and blood pressure in the Stanislas Cohort.

Association between blood pressure and triglyceride levels, and between lipoprotein lipase (LPL) (C/G)447 polymorphism and triglyceride levels has been described. We investigated whether the LPL (C/G)447 polymorphism was associated with blood pressure (BP) levels and longitudinal changes. For cross-sectional analysis, 767 men and 816 women (29-55 years) were selected from the Stanislas Cohort, a cohort of volunteers for a free health check-up. Only subjects without anti-hypertensive or lipid-lowering medication were included in the study. A subset of this sample population, 359 men and 337 women, had been followed during the 11 years prior to recruitment in the Stanislas Cohort and was used for longitudinal analysis. The cross-sectional study showed that serum triglyceride levels differed significantly according to LPL genotypes in both genders, the G447 allele being associated with the lowest triglyceride levels (P < or = 0.01). Univariate and multivariate analysis found that LPL polymorphism was not related to BP levels in men. In contrast, women with the LPL-G447 allele had lower systolic (SBP) and pulse (PP) pressure levels than those with the LPL-CC genotype (P < or = 0.01 and P < or = 0.05, respectively); this association being independent of triglyceride level. The longitudinal study showed LPL genotype was an independent predictor of PP and SBP follow-up levels in women; changes over 11 years being lower for LPL-G447 allele carriers (P < or = 0.05). These associations were independent of triglyceride level. The LPL-G447 allele was found associated with lower PP and SBP independently of triglyceride level in women. This result suggests that the LPL gene may influence blood pressure.

Pavlovian conditioning of taste aversion using a motion sickness paradigm.

Pavlovian conditioning of taste aversion has rarely been investigated in healthy humans using motion sickness as the unconditioned stimulus (US). Ninety subjects were pretested for susceptibility to illusory motion (vection) in a rotating drum. Thirty-two subjects susceptible to pseudomotion were assigned randomly to two groups and received either water 1 hour before rotation and a novel taste (elderberry juice, conditioned stimulus, [CS]) immediately before rotation in a rotating chair (conditioning group), or the sequence of water and juice was reversed (control group). During the test session 1 week later, all subjects were exposed to water 1 hour before and juice immediately before rotation. The amount of liquids ingested, nausea ratings, rotation tolerance, and blood levels of hormones (ACTH, ADH, PP) were evaluated. Subjects in the conditioning group developed taste aversion toward the novel taste, but not subjects in the control group. Postrotation nausea rating was affected marginally by conditioning, but rotation tolerance was not changed by conditioning. ACTH and ADH but not PP levels increased with rotation, but were unaffected by conditioning. Pavlovian conditioning of behavioral, but not of endocrine, indicators was effective in susceptible subjects using a rotating chair as US and a single CS-US pairing.

Lack of age-associated elevations in 24-h systolic and pulse pressures in women who exercise regularly.

We tested the hypothesis that the elevations in 24-h arterial systolic (SBP) and pulse (PP) pressures with age in sedentary adult females are absent or smaller in women who exercise regularly. Four groups of healthy normotensive women were studied: premenopausal (n = 12; 29 +/- 1 yr, mean +/- SE) and postmenopausal (n = 20; 62 +/- 1) sedentary, and premenopausal (n = 14; 30 +/- 1) and postmenopausal (n = 12; 58 +/- 1) endurance-exercise trained (distance runners). In the sedentary group, 24-h SBP and PP (Spacelabs ambulatory monitor 90207) were approximately 10 mmHg higher (P < 0.05) in the postmenopausal women than in the premenopausal controls; this was because of higher daytime and nighttime SBP and PP levels in the postmenopausal women. In contrast, 24-h, daytime and nighttime SBP and PP were not different with age in the endurance-trained women. SBP variability and SBP load (% of all recordings > 140 mmHg) generally were greater with age in the sedentary women (e.g., SBP load = 14 +/- 4 vs. 3 +/- 1%, P < 0.05) but not in the endurance-trained women. In the pooled population, 24-h SBP and PP were related to waist-to-hip ratio (measure of abdominal adiposity) (r = 0.48 and 0.49, respectively, P < 0.001) and carotid augmentation index (measure of arterial stiffness) (r = 0.43 and 0.53, P < 0.005). In the sedentary women, accounting for the influence of either of these factors eliminated the significant age-associated differences in 24-h SBP and PP (P > 0.3). Our results suggest that the elevations in 24-h SBP and PP with age in sedentary adult females may not occur in women who regularly perform endurance exercise. This appears to be related to the absence of age-associated increases in abdominal adiposity and arterial stiffness in the exercising women.

Desvios porta-jugular e cava-jugular passivos em cães: Investigação de pressões sangüíneas

Os principais objetivos dos desvios veno-venosos durante o transplante ortotópico de fígado são: atenuação da estase venosa subdiafragmática, manutenção do retorno satisfatório de sangue ao coração e perfusão tissular eficiente. Investigações sobre PP, PVCIIH, PVC, PAM e PPR, bem como &lt;FONT FACE="Symbol"&gt;D&lt;/font&gt; PP e &lt;FONT FACE="Symbol"&gt;D&lt;/font&gt; PVCIIH foram conduzidas em seis cães, sob anestesia geral, com fígados perfundidos pela Artéria Hepática, submetidos a desvios porta-jugular e cava-jugular passivos durante 2 horas. Estes desvios não foram capazes de evitar estagnação de sangue na VP e VCIIH, acarretando estase e menor retorno sangüíneo ao coração, sugeridos por aumentos significativos de PP e PVCIIH e quedas significantes nos níveis de PVC. Os valores de PAM não apresentaram diferenças significativas em relação ao tempo T0, na maior parte dos tempos avaliados, enquanto que os valores de PPR foram significativamente menores que os verificados no tempo T0, na maioria dos tempos estudados. Tais pressões mantiveram-se, respectivamente, acima de 100 e 50 mm de Hg, atribuindo-se tais resultados, em parte, à vasoconstricção arteriolar generalizada. Incrementos de pressão na VP (&lt;FONT FACE="Symbol"&gt;D&lt;/font&gt; PP) foram significativamente menos elevados que aqueles verificados na VCIIH (&lt;FONT FACE="Symbol"&gt;D&lt;/font&gt; PVCIIH), atribuindo-se tal diferença à complacência esplâncnica. Decréscimos ulteriores dos níveis de PP e PVCIIH sugerem queda do fluxo arterial para os territórios esplâncnico e sistêmico, decorrente de diminuição do retorno sangüíneo ao coração. Determinações de PP, PVCIIH, PVC, PAM e PPR podem constituir meio prático de avaliação hemodinâmica do desvio veno-venoso.

Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin stimulated exocrine pancreatic secretion in humans

Pancreatico-biliary secretion is reduced during acute hyperglycemia. We investigated whether alterations in pancreatico-biliary flow or volume output are responsible for the observed reduction in duodenal output of pancreatic enzymes and bilirubin during hyperglycemia. Eight healthy subjects were studied on two occasions during normoglycemia and hyperglycemia (15 mmol/l). Pancreatico-biliary output was measured by aspiration using a recovery marker under basal conditions (60 min), during secretin infusion (0.1 CU/kg.h) for 60 min and during secretin + CCK (0.5 IDU/kg.h) infusion for 60 min. Secretin was infused to stimulate pancreatico-biliary flow and volume output. Secretin significantly (P < 0.005–P < 0.05) increased volume and bicarbonate output and CCK significantly (P < 0.01) increased the output of bilirubin, pancreatic enzymes, bicarbonate and volume, both during normoglycemia and hyperglycemia. During hyperglycemia basal, secretin stimulated and secretin + CCK stimulated total pancreatico-biliary output were significantly (P < 0.005–P < 0.05) reduced compared to normoglycemia. The incremental outputs, however, were not significantly different between hyper- and normoglycemia. Pancreatic volume output was significantly (P < 0.05) reduced during hyperglycemia compared to normoglycemia under basal conditions (31 ± 16 ml/h versus 132 ± 33 ml/h) during secretin infusion (130 ± 17 ml/h versus 200 ± 34 ml/h) and during secretin + CCK infusion (370 ± 39 ml/h versus 573 ± 82 ml/h). Plasma PP levels were significantly (P < 0.05) reduced during hyperglycemia. It is concluded that 1) hyperglycemia significantly reduces basal pancreatico-biliary output 2) the incremental pancreaticobiliary output in response to secretin or secretin + CCK infusion is not significantly affected during hyperglycemia, 3) a reduction in volume output contributes to the inhibitory effect of hyperglycemia on pancreatico-biliary secretion, 4) hyperglycemia reduces PP secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion and volume during hyperglycemia.

Effect of acute hyperglycemia on basal and cholecystokinin stimulated exocrine pancreatic secretion in humans

This study was undertaken to investigate the effect of acute hyperglycemia on pancreatico-biliary secretion in healthy subjects. Duodenal outputs of bilirubin, amylase, trypsin and bicarbonate were measured by aspiration using a recovery marker under basal condition for 75 min and during continuous infusion of CCK (0.5 IDU kg.h for 60 min). Seven healthy subjects participated in two experiments performed in random order during normoglycemia and during acute hyperglycemie clamping at 15 mmol I . At regular intervals plasma PP levels were determined as an indirect measure of vagal-cholinergic tone. Basal pancreatico-biliary secretion was significantly (p <0.05) reduced during acute hyperglycemia. CCK significantly (p < 0.05) increased bilirubin, amylase and trypsin output both during normo- and hyperglycemia. During the initial 30 min of CCK infusion the bilirubin, amylase and trypsin outputs were significantly (p < 0.05) inhibited in the hyperglycemic experiment compared to normoglycemia. In the following 30 min of CCK infusion the bilirubin, amylase and trypsin output were not different between hyper- and normoglycemia. Basal and CCK-stimulated plasma PP concentrations were significantly (p <0.05) reduced during hyperglycemia. In summary: 1) basal pancreatico-biliary secretion is significantly reduced during acute hyperglycemia 2) during hyperglycemia CCK-stimulated pancreatico-biliary secretion is also significantly reduced with the pattern of a delayed response 3) hyperglycemia inhibits basal and CCK-stimulated PP secretion suggesting impaired vagal-cholinergic activity during hyperglycemia.

On-line fluorescence of human tissues after oral administration of 5-aminolevulinic acid

It is important to have a frame of reference for the timing of photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) so that PDT can occur when the tissue levels of protoporphyrin IX (PP) are at a maximum. This study describes a non-invasive fluorescence technique for detecting tissue PP levels after systemic ALA administration in patients with gastrointestinal cancer. The data suggest that the intensity of tumor surface fluorescence correlates with the tumor PP concentration. Spectrophotofluorometric measurements of skin and buccal mucosa also offer an easily acquired and rapid means for determining changes in plasma concentrations of PP. A number of potential variables, including blood flow, affect the intensity of fluorescence. We report that fluorescence measurements in situ are best adapted to the measurement of changes in the porphyrin levels in tissues rather than the absolute concentrations.