327 research outputs found
The association between lipoprotein-associated phospholipase A2 and cardiovascular disease and total mortality in vascular medicine patients
IntroductionIn some community-based studies, lipoprotein-associated phospholipase A2 (Lp-PLA2) has been shown to be independently predictive of future fatal and nonfatal cardiovascular disease (CVD) events. We tested the hypothesis that Lp-PLA2 is independently predictive of mortality in high-risk patients from a vascular laboratory.MethodsBetween 1990 and 1994, patients seen in the previous 10 years for noninvasive lower extremity arterial testing were invited to return for a vascular examination of the lower extremities. By medical record review, we identified 2265 eligible patients; of these, 508 returned for interviews, blood collection, and arterial examination and represent those who had survived, could be located, and were willing to participate. The 508 subjects were followed up for an average of 6.7 years until the end of the study period on December 31, 2001. Vital status was ascertained by multiple searches of the Social Security Death Index. The primary outcomes for this study were time to any, CVD, and coronary heart disease (CHD) mortality.ResultsThe mean age was 68.2 years, 88% were men, 87% were non-Hispanic white, 39.1% were diagnosed with peripheral arterial disease only, 9.2% with other CVD only, and 28.5% with both peripheral arterial disease and other CVD. During the entire follow-up period, 299 (59.7%) patients died, 167 from CVD, of which 88 deaths were due to coronary heart disease. With adjustment for CVD risk factors and baseline peripheral arterial disease and other CVD, an increment of one standard deviation in Lp-PLA2 activity was associated with a 40% higher risk for CHD mortality at 5 years of follow-up (P = .04). Additional adjustment for triglycerides, high-density lipoprotein, and low-density lipoprotein cholesterol reduced this association to nonsignificance (hazard risk, 1.12).ConclusionIn a vascular laboratory patient population, higher levels of LpPLA2 mass and activity were not significantly associated with total, CVD, or CHD mortality at 5 years of follow-up and after adjustment for traditional CVD risk factors and the presence of PAD and other CVD at baseline. An apparent elevated risk of CHD death associated with elevated Lp-PLA2 was largely explained by associated elevations in lipids and lipoproteins
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Femoral Artery Atherosclerosis Is Associated With Physical Function Across the Spectrum of the Ankle-Brachial Index: The San Diego Population Study.
BackgroundThe ankle-brachial index (ABI) is inadequate to detect early-stage atherosclerotic disease, when interventions to prevent functional decline may be the most effective. We determined associations of femoral artery atherosclerosis with physical functioning, across the spectrum of the ABI, and within the normal ABI range.Methods and resultsIn 2007-2011, 1103 multiethnic men and women participated in the San Diego Population Study, and completed all components of the summary performance score. Using Doppler ultrasound, superficial and common femoral intima media thickness and plaques were ascertained. Logistic regression was used to assess associations of femoral atherosclerosis with the summary performance score and its individual components. Models were adjusted for demographics, lifestyle factors, comorbidities, lipids, and kidney function. In adjusted models, among participants with a normal-range ABI (1.00-1.30), the highest tertile of superficial intima media thickness was associated with lower odds of a perfect summary performance score of 12 (odds ratio=0.56 [0.36, 0.87], P=0.009), and lower odds of a 4-m walk score of 4 (0.34 [0.16, 0.73], P=0.006) and chair rise score of 4 (0.56 [0.34, 0.94], P=0.03). Plaque presence (0.53 [0.29, 0.99], P=0.04) and greater total plaque burden (0.61 [0.43, 0.87], P=0.006) were associated with worse 4-m walk performance in the normal-range ABI group. Higher superficial intima media thickness was associated with lower summary performance score in all individuals (P=0.02).ConclusionsFindings suggest that use of femoral artery atherosclerosis measures may be effective in individuals with a normal-range ABI, especially, for example, those with diabetes mellitus or a family history of peripheral artery disease, when detection can lead to earlier intervention to prevent functional declines and improve quality of life
Quantification of structural changes in the corpus callosumin children with profound hypoxic-ischaemic brain injury
Background Birth-related acute profound hypoxic–ischaemic
brain injury has specific patterns of damage including the
paracentral lobules.
Objective To test the hypothesis that there is anatomically coherent
regional volume loss of the corpus callosum as a result of
this hemispheric abnormality.
Materials and methods Study subjects included 13 children
with proven acute profound hypoxic–ischaemic brain injury
and 13 children with developmental delay but no brain abnormalities.
A computerised system divided the corpus callosum
into 100 segments, measuring each width. Principal component
analysis grouped the widths into contiguous anatomical regions.
We conducted analysis of variance of corpus callosum widths as
well as support vector machine stratification into patient groups.
Results There was statistically significant narrowing of the
mid–posterior body and genu of the corpus callosum in children
with hypoxic–ischaemic brain injury. Support vector machine
analysis yielded over 95% accuracy in patient group stratification
using the corpus callosum centile widths.
Conclusion Focal volume loss is seen in the corpus callosum
of children with hypoxic–ischaemic brain injury secondary to
loss of commissural fibres arising in the paracentral lobules.
Support vector machine stratification into the hypoxic–ischaemic
brain injury group or the control group on the basis of
corpus callosum width is highly accurate and points towards
rapid clinical translation of this technique as a potential biomarker
of hypoxic–ischaemic brain injur
Functional and neurometabolic asymmetry in SHR and WKY rats following vasoactive treatments
A lateralized distribution of neuropeptidase activities in the frontal cortex of normotensive and
hypertensive rats has been described depending on the use of some vasoactive drugs and linked to
certain mood disorders. Asymmetrical neuroperipheral connections involving neuropeptidases from the
left or right hemisphere and aminopeptidases from the heart or plasma have been suggested to play
a role in this asymmetry. We hypothesize that such asymmetries could be extended to the connection
between the brain and physiologic parameters and metabolic factors from plasma and urine. To
assess this hypothesis, we analyzed the possible correlation between neuropeptidases from the left
and right frontal cortex with peripheral parameters in normotensive (Wistar Kyoto [WKY]) rats and
hypertensive rats (spontaneously hypertensive rats [SHR]) untreated or treated with vasoactive drugs
such as captopril, propranolol and L-nitro-arginine methyl ester. Neuropeptidase activities from the
frontal cortex were analyzed fluorometrically using arylamide derivatives as substrates. Physiological
parameters and metabolic factors from plasma and urine were determined using routine laboratory
techniques. Vasoactive drug treatments differentially modified the asymmetrical neuroperipheral
pattern by changing the predominance of the correlations between peripheral parameters and central
neuropeptidase activities of the left and right frontal cortex. The response pattern also differed between
SHR and WKY rats. These results support an asymmetric integrative function of the organism and
suggest the possibility of a different neurometabolic response coupled to particular mood disorders,
depending on the selected vasoactive drug.This work was supported by the Ministry of Science and Innovation through project no. SAF 2008 04685 C02 01
Cerebellar Asymmetry and Cortical Connectivity in Monozygotic Twins with Discordant Handedness
Handedness differentiates patterns of neural asymmetry and interhemispheric connectivity in cortical systems that underpin manual and language functions. Contemporary models of cerebellar function incorporate complex motor behaviour and higher-order cognition, expanding upon earlier, traditional associations between the cerebellum and motor control. Structural MRI defined cerebellar volume asymmetries and correlations with corpus callosum (CC) size were compared in 19 pairs of adult female monozygotic twins strongly discordant for handedness (MZHd). Volume and asymmetry of cerebellar lobules were obtained using automated parcellation.CC area and regional widths were obtained from midsagittal planimetric measurements. Within the cerebellum and CC, neurofunctional distinctions were drawn between motor and higher-order cognitive systems. Relationships amongst regional cerebellar asymmetry and cortical connectivity (as indicated by CC widths) were investigated. Interactions between hemisphere and handedness in the anterior cerebellum were due to a larger right-greater-than-left hemispheric asymmetry in right-handed (RH) compared to left-handed (LH) twins. In LH twins only, anterior cerebellar lobule volumes (IV, V) for motor control were associated with CC size, particularly in callosal regions associated with motor cortex connectivity. Superior posterior cerebellar lobule volumes (VI, Crus I, Crus II, VIIb) showed no correlation with CC size in either handedness group. These novel results reflected distinct patterns of cerebellar-cortical relationships delineated by specific CC regions and an anterior-posterior cerebellar topographical mapping. Hence, anterior cerebellar asymmetry may contribute to the greater degree of bilateral cortical organisation of frontal motor function in LH individuals
Distinct Neurobehavioural Effects of Cannabidiol in Transmembrane Domain Neuregulin 1 Mutant Mice
The cannabis constituent cannabidiol (CBD) possesses anxiolytic and antipsychotic properties. We have previously shown that transmembrane domain neuregulin 1 mutant (Nrg1 TM HET) mice display altered neurobehavioural responses to the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol. Here we investigated whether Nrg1 TM HET mice respond differently to CBD and whether CBD reverses schizophrenia-related phenotypes expressed by these mice. Adult male Nrg1 TM HET and wild type-like littermates (WT) received vehicle or CBD (1, 50 or 100 mg/kg i.p.) for 21 days. During treatment and 48 h after withdrawal we measured behaviour, whole blood CBD concentrations and autoradiographic receptor binding. Nrg1 HET mice displayed locomotor hyperactivity, PPI deficits and reduced 5-HT2A receptor binding density in the substantia nigra, but these phenotypes were not reversed by CBD. However, long-term CBD (50 and 100 mg/kg) selectively enhanced social interaction in Nrg1 TM HET mice. Furthermore, acute CBD (100 mg/kg) selectively increased PPI in Nrg1 TM HET mice, although tolerance to this effect was manifest upon repeated CBD administration. Long-term CBD (50 mg/kg) also selectively increased GABAA receptor binding in the granular retrosplenial cortex in Nrg1 TM HET mice and reduced 5-HT2A binding in the substantia nigra in WT mice. Nrg1 appears necessary for CBD-induced anxiolysis since only WT mice developed decreased anxiety-related behaviour with repeated CBD treatment. Altered pharmacokinetics in mutant mice could not explain our findings since no genotype differences existed in CBD blood concentrations. Here we demonstrate that Nrg1 modulates acute and long-term neurobehavioural effects of CBD, which does not reverse the schizophrenia-relevant phenotypes
Social Competitiveness and Plasticity of Neuroendocrine Function in Old Age: Influence of Neonatal Novelty Exposure and Maternal Care Reliability
Early experience is known to have a profound impact on brain and behavioral function later in life. Relatively few studies, however, have examined whether the effects of early experience remain detectable in the aging animal. Here, we examined the effects of neonatal novelty exposure, an early stimulation procedure, on late senescent rats' ability to win in social competition. During the first 3 weeks of life, half of each litter received daily 3-min exposures to a novel environment while the other half stayed in the home cage. At 24 months of age, pairs of rats competed against each other for exclusive access to chocolate rewards. We found that novelty-exposed rats won more rewards than home-staying rats, indicating that early experience exerts a life-long effect on this aspect of social dominance. Furthermore, novelty-exposed but not home-staying rats exhibited habituation of corticosterone release across repeated days of social competition testing, suggesting that early experience permanently enhances plasticity of the stress response system. Finally, we report a surprising finding that across individual rat families, greater effects of neonatal novelty exposure on stress response plasticity were found among families whose dams provided more reliable, instead of a greater total quantity of, maternal care
Short-Term Enrichment Makes Male Rats More Attractive, More Defensive and Alters Hypothalamic Neurons
Innate behaviors are shaped by contingencies built during evolutionary history. On the other hand, environmental stimuli play a significant role in shaping behavior. In particular, a short period of environmental enrichment can enhance cognitive behavior, modify effects of stress on learned behaviors and induce brain plasticity. It is unclear if modulation by environment can extend to innate behaviors which are preserved by intense selection pressure. In the present report we investigate this issue by studying effects of relatively short (14-days) environmental enrichment on two prominent innate behaviors in rats, avoidance of predator odors and ability of males to attract mates. We show that enrichment has strong effects on both the innate behaviors: a) enriched males were more avoidant of a predator odor than non-enriched controls, and had a greater rise in corticosterone levels in response to the odor; and b) had higher testosterone levels and were more attractive to females. Additionally, we demonstrate decrease in dendritic length of neurons of ventrolateral nucleus of hypothalamus, important for reproductive mate-choice and increase in the same in dorsomedial nucleus, important for defensive behavior. Thus, behavioral and hormonal observations provide evidence that a short period of environmental manipulation can alter innate behaviors, providing a good example of gene-environment interaction
Neonatal Handling Affects Durably Bonding and Social Development
The neonatal period in humans and in most mammals is characterized by intense mother-young interactions favoring pair bonding and the adaptation of neonates to their new environment. However, in many post-delivery procedures, human babies commonly experience combined maternal separation and intense handling for about one hour post-birth. Currently, the effects of such disturbances on later attachment and on the development of newborns are still debated: clearly, further investigations are required. As animals present good models for controlled experimentation, we chose domestic horses to investigate this issue. Horses, like humans, are characterized by single births, long lactating periods and selective mother-infant bonds. Routine postnatal procedures for foals, as for human babies, also involve intense handling and maternal separation. In the present study, we monitored the behavior of foals from early stages of development to “adolescence”, in a normal ecological context (social groups with adults and peers). Experimental foals, separated from their mothers and handled for only 1 hour post-birth, were compared to control foals, left undisturbed after birth. Our results revealed short- and long-term effects of this unique neonatal experience on attachment and subsequent social competences. Thus, experimental foals presented patterns of insecure attachment to their mothers (strong dependence on their mothers, little play) and impaired social competences (social withdrawal, aggressiveness) at all ages. We discuss these results in terms of mother-young interactions, timing of interactions and relationships between bonding and subsequent social competences. Our results indicate that this ungulate species could become an interesting animal model. To our knowledge, this is the first clear demonstration that intervention just after birth affects bonding and subsequent social competences (at least until “adolescence”). It opens new research directions for studies on both humans and other animals
Acesso a cuidados relativos à saúde sexual entre mulheres que fazem sexo com mulheres em São Paulo, Brasil
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