Relevance of omental pericellular adipose tissue collagen in the pathophysiology of human abdominal obesity and related cardiometabolic risk.

BACKGROUND: Adipose tissue fibrosis is a relatively new notion and its relationship with visceral obesity and cardiometabolic alterations remains unclear, particularly in moderate obesity. OBJECTIVE: Our objective was to examine if total and pericellular collagen accumulation are relevant for the pathophysiology of visceral obesity and related cardiometabolic risk. SUBJECTS AND METHODS: Surgical omental (OM) and subcutaneous (SC) fat samples were obtained in 56 women (age: 47.2±5.8 years; body mass index (BMI): 27.1±4.4 kg/m2). Body composition and fat distribution were measured by dual-energy X-ray absorptiometry and computed tomography, respectively. Total and pericellular collagen were measured using picrosirius red staining. CD68+ cells (total macrophages) and CD163+ cells (M2-macrophages) were identified using immunohistochemistry. RESULTS: We found that only pericellular collagen percentage, especially in OM fat, was associated with higher BMI, body fat mass and adipose tissue areas as well as lower radiologic attenuation of visceral adipose tissue and altered cardiometabolic risk variables. Strong correlations between peri-adipocyte collagen percentage and total or M2-macrophage percentages were observed in both depots. Total collagen percentage in either compartment was not related to adiposity, fat distribution or cardiometabolic risk. CONCLUSIONS: As opposed to whole tissue-based assessments of adipose tissue fibrosis, collagen deposition around the adipocyte, especially in the OM fat compartment is related to total and regional adiposity as well as altered cardiometabolic risk profile.

The quality of life of older adults living in an urban environment: professional and lay perspectives.

This study aimed to identify factors affecting older adults' quality of life in urban environments and to compare older adults' and professionals' perspectives on the issue. Eleven focus groups were conducted (eight involving older adults, three involving professionals), each discussing a wide range of issues related to determinants of health and quality of life. The most salient themes were health and independence, financial security, social integration, health care services, housing, accessibility of community services, and decision-making power. Older adults' and professionals' comments strongly converged, with specific issues also raised by each. Older adults provided the richest and most in-depth data on intrapersonal factors, such as personal growth, personal qualities, and spirituality. Professionals discussed community environment issues in greater depth. Health promotion interventions to maximize older adults' quality of life are needed. These results contribute to building a knowledge base to guide such efforts, by identifying a variety of possible intervention sectors for future programs.

Changes in brain cholecystokinin and anxiety-like behavior following exposure of mice to predator odor.

Exposure of CD-1 mice to a familiar environment lined with clean shavings (control odor) as well as a familiar environment lined with soiled rat shavings (predator odor) induced anxiety in the light/dark box. Mice exposed to the familiar environment or predator odor displayed decreased latency to enter the dark chamber of the light/dark box and spent less time in the light portion of the apparatus relative to home-caged mice. Mice exposed to the familiar environment lined with clean shavings or predator odor displayed elevated cholecystokinin mRNA levels from the ventral tegmental area, medial and basolateral nuclei of the amygdala relative to home-caged mice. Exposure of CD-1 mice to 2, 5 or 10 min of predator odor increased acoustic startle relative to mice merely exposed to the familiar environment lined with clean shavings at protracted intervals. Mice exposed to the familiar environment lined with clean shavings did not exhibit enhanced startle relative to home-caged mice. Exaggerated startle reactivity was in evidence immediately, 24, and 48 h following a 5-min exposure of mice to predator odor. In contrast, a 10-min exposure of mice to predator odor produced an oscillating pattern of enhanced startle evident during the immediate and 48-h post-stressor intervals only. However, when the startle stimulus was withheld 1 h following odor presentation, mice exhibited enhanced startle patterns reminiscent of the 5-min exposure. The 2-min exposure of mice to predator odor produced a delayed onset of enhanced startle observed at the 168-h test interval only. Potential anxiogenic influences of mesocorticolimbic cholecystokinin availability as well as the time course and underlying neuronal substrates of long-term behavioral disturbances as a result of psychogenic stressor manipulations are discussed.

Role of endogenous opioid system in the regulation of the stress response.

Numerous studies and reviews support an important contribution of endogenous opioid peptide systems in the mediation, modulation, and regulation of stress responses including endocrine (hypothalamopituitary-adrenal, HPA axis), autonomic nervous system (ANS axis), and behavioral responses. Although several discrepancies exist, the most consistent finding among such studies using different species and stressors is that opioids not only diminish stress-induced neuroendocrine and autonomic responses, but also stimulate these effector systems in the non-stressed state. A distinctive feature of the analgesic action of opioids is the blunting of the distressing, affective component of pain without dulling the sensation itself. Therefore, opioid peptides may diminish the impact of stress by attenuating an array of physiologic responses including emotional and affective states. The widespread distribution of enkephalin (ENK) throughout the limbic system (including the extended amygdala, cingulate cortex, entorhinal cortex, septum, hippocampus, and the hypothalamus) is consistent with a direct role in the modulation the stress responses. The predictability of stressful events reduces the impact of a wide range of stressors and ENK appears to play an important role in this process. Therefore, ENK and its receptors could represent a major modulatory system in the adaptation of an organism to stress, balancing the response that the stressor places on the central stress system with the potentially detrimental effects that a sustained stress may produce. Chronic neurogenic stressors will induce changes in specific components of the stress-induced ENKergic system, including ENK, delta- and mu-opioid receptors. This review presents evidences for adaptive cellular mechanisms underlying the response of the central stress system when assaulted by repeated psychogenic stress, and the involvement of ENK in these processes.

Surface characteristics, equipment height, and the occurrence and severity of playground injuries.

OBJECTIVES: To evaluate whether surface characteristics (absorption level (g-max), material) and the height of play equipment are related to the occurrence and severity of injuries from falls. SETTING AND METHODS: During the summers of 1991 and 1995, conformity of play equipment to Canadian standards was assessed in a random sample (n = 102) of Montreal public playgrounds. Surface absorption (g-max) was tested using a Max Hic instrument and the height of equipment was measured. Concurrently, all injuries presenting at the emergency department of Montreal's two children's hospitals were recorded and parents were interviewed. Inspected equipment was implicated in 185 injuries. The g-max measurements (1995 only) were available for 110 of these playground accidents. RESULTS: One third of falls (35 %) occurred on a surface exceeding 200 g and the risk of injury was three times greater than for g level lower than 150 (95% confidence interval (CI) 1.45 to 6.35). On surfaces having absorption levels between 150 g and 200 g, injuries were 1.8 times more likely (95% CI 0.91 to 3.57). Injuries were 2.56 times more likely to occur on equipment higher than 2 m compared with equipment lower than 1.5 m. Analysis of risk factors by severity of injury failed to show any positive relationships between the g-max or height and severity, whereas surface material was a good predictor of severity. CONCLUSIONS: This study confirms the relationships between risk of injury, surface resilience, and height of equipment, as well as between type of material and severity of injury. Our data suggest that acceptable limits for surface resilience be set at less than 200 g, and perhaps even less than 150 g, and not exceed 2 m for equipment height. These findings reinforce the importance of installing recommended materials, such as sand, beneath play equipment.

Pharmacotherapy of systolic heart failure: a review of recent literature and practical applications.

Since the publication of the Agency for Health Care Policy and Research Guidelines for treatment of heart failure, a number of new agents have been investigated for this indication. beta-Blockers have now been shown to improve outcomes in mild to moderate heart failure when added to standard therapy. Angiotensin II receptor antagonists have also been investigated and show promise. In general, calcium channel blockers are second- or third-line agents in patients refractory to other therapy. Investigational agents including spironolactone may also hold promise for future therapy.

Effect of stress exposure on the activation pattern of enkephalin-containing perikarya in the rat ventral medulla.

We examined the effects of acute and chronic psychogenic stress on the activation pattern of enkephalin-containing perikarya in the rat ventrolateral medulla. Rats allocated to the chronic stress groups were subjected to 90 min of immobilization for 10 days. On the 11th day, the chronically stressed rats were exposed to homotypic (90-min immobilization) or to heterotypic but still psychogenic (90-min immobilization coupled to air jet stress) stress. The acute stress group was subjected once to an acute 90-min immobilization. For each group, the rats were anesthetized either before stress (time 0) or 90, 180, and 270 min after the onset of stress. Brain sections were then processed using immunocytochemistry (Fos protein) followed by radioactive in situ hybridization histochemistry (enkephalin mRNA). Following immobilization, the acute group displayed a marked increase in the number of activated enkephalin-containing perikarya within the paragigantocellularis and lateral reticular nuclei. This level of activation was sustained up to 180 min following the onset of the immobilization stress and had returned to baseline levels by 270 min from the initiation of the stress. However, this stress-induced activation of enkephalin-containing perikarya of the ventrolateral medulla was not seen following either homotypic or heterotypic stress in the chronically stressed group. These results provide evidence that enkephalin-containing perikarya of the ventrolateral medulla may constitute a potential circuit through which they regulate some aspect of the stress responses. Conversely, this enkephalinergic influence from the ventrolateral medulla was shown to be absent following chronic stress exposure. This would suggest a decrease in enkephalin inhibitory input originating from the ventrolateral medulla, thereby allowing a neuroendocrine and/or autonomic response to chronic stress.

Tolerability of extended duration intravenous milrinone in patients hospitalized for advanced heart failure and the usefulness of uptitration of oral angiotensin-converting enzyme inhibitors.

Milrinone is a phosphodiesterase inhibitor that has been shown to improve hemodynamic parameters in patients with class III to IV heart failure when administered intravenously for < or =48 hours. This study examines the tolerability of long-term intravenous milrinone therapy and assesses its utility in allowing upward titration of oral vasodilator agents. A retrospective review of hospital records identified 63 patients who underwent hemodynamic monitoring and received intravenous milrinone for >24 hours in a critical care setting. Hemodynamics and medications were recorded before and after 24 hours of milrinone therapy. Additional medications, as well as any adverse events, were recorded throughout milrinone therapy. The mean dose of milrinone was 0.43 +/- 0.10 microg/kg/min, with a mean duration of 12 +/- 15 days (range 1 to 70). Therapy was continued for >48 hours in 89% of patients. After 24 hours of milrinone therapy, patients exhibited significant improvements in pulmonary artery pressures, pulmonary capillary wedge pressures, and cardiac index. When compared with baseline, significantly more patients received angiotensin-converting enzyme (ACE) inhibitors after 24 hours of milrinone and at the end of milrinone therapy (67% vs 86%, p <0.01). Likewise, significantly more patients also received oral hydralazine and/or nitrates at the end of milrinone therapy (38% vs 65%, p <0.01) when compared with baseline. The mean doses of most oral medications at the 3 time periods were similar. The ACE inhibitor dose was significantly higher at the end of milrinone therapy when compared with baseline, and hydralazine dose was significantly higher at the end of therapy when compared with 24 hours. Few adverse effects were noted, with only 10% of patients experiencing symptomatic ventricular tachycardia and 2 patients with significant hypotension requiring discontinuation of the drug. The adverse events were similar in the group of patients who received milrinone for > or =7 days compared with the entire cohort. Milrinone was well tolerated over the long term in a controlled inpatient setting, and allowed uptitration of oral vasodilator therapy.

Involvement of central angiotensin receptors in stress adaptation.

The present study examined the effects of acute and chronic neurogenic stressors on the expression of two distinct angiotensin receptors in two stress-related brain nuclei: angiotensin type 1A receptor in the paraventricular nucleus of the hypothalamus and angiotensin type 2 receptor in the nucleus locus coeruleus. Male Wistar rats were divided into four experimental groups. The first two groups were subjected once to an acute 90-min immobilization or air-jet stress session, respectively. The other two groups were subjected to 10 days of daily 90-min immobilization sessions and, on the 11th day, one group was exposed to an additional 90-min immobilization and the other to a single air-jet stress (heterotypic but still neurogenic) session. In each group, rats were perfused before stress (0 min), immediately following stress (90 min) or 150, 180, 270 or 360 min (and 24 h in chronic immobilization) after the beginning of the last stress session. Basal expression of both angiotensin receptor subtype 1A and angiotensin receptor subtype 2 messenger RNA was minimal in non-stressed animals. Acute immobilization as well as air-jet stress induced similar patterns (time-course and maximal values) of angiotensin receptor subtype 1A messenger RNA expression in the paraventricular nucleus. Angiotensin receptor subtype 1A messenger RNA expression increased 90-150 min after the beginning of the stress and returned to basal levels by 360 min. Chronic stress immobilization slightly modified the pattern, but not maximal values of angiotensin receptor subtype 1A messenger RNA expression to further immobilization (homotypic) or air-jet stress (heterotypic). Acute immobilization and air-jet stress sessions induced similar locus coeruleus-specific angiotensin receptor subtype 2 messenger RNA expression. This expression increased 90 min following the onset of the stress session and remained elevated for at least 360 min. Chronic immobilization stress increased angiotensin receptor subtype 2 messenger RNA expression to levels comparable to those observed in acute stress conditions. Novel acute exposure to neurogenic stressors did not further increase these levels in either homotypic (immobilization) or in heterotypic (air-jet stress) conditions. These results suggest that central angiotensin receptors are targets of regulation in stress; therefore, stress may modulate angiotensin function in the paraventricular nucleus and locus coeruleus during chronic exposure to neurogenic stressors.

Intraspecific nucleotide variation at the pheromone binding protein locus in the turnip moth, Agrotis segetum.

Inter- and intraspecific amino acid variability in the pheromone binding proteins (PBPs) of the Lepidoptera is believed to contribute to a molecular mechanism of pheromone blend discrimination. Messenger RNA coding for PBP sequence in Agrotis segetum (Noctuidae) was cloned, and nucleotide and inferred amino acid variation across a 769-bp region of a PBP locus was studied in two populations. A single gene copy was fully sequenced, revealing an intron/exon structure conserved with distant saturniids. While several nucleotide substitutions are predicted to result in amino acid replacement, tests for the presence of natural selection suggest that the observed variation is neutral. A phylogenetic analysis provides evidence that the two populations are in the process of genetic isolation.

Patterns of gene duplication in lepidopteran pheromone binding proteins.

We have isolated and characterized cDNAs representing two distinct pheromone binding proteins (PBPs) from the gypsy moth, Lymantria dispar. We use the L. dispar protein sequences, along with other published lepidopteran PBPs, to investigate the evolutionary relationships among genes within the PBP multigene family. Our analyses suggest that the presence of two distinct PBPs in genera representing separate moth superfamilies is the result of relatively recent, independent, gene duplication events rather than a single, ancient, duplication. We discuss this result with respect to the biochemical diversification of moth PBPs.

Policies regarding the transplantation of hepatitis C-positive candidates and donor organs.

Whether hepatitis C virus (HCV)-positive candidates or donor organs should undergo transplantation remains controversial. Seventy-two thoracic transplantation centers responded to a survey soliciting specific information about policies regarding the listing of HCV-positive candidates and the use of HCV-positive donor organs. Most centers (64%) list HCV-positive candidates for heart transplantation. Twenty-six percent of centers refuse to use HCV-positive organs, whereas the remainder restrict the use of HCV-positive organs to status 1 recipients or HCV-positive candidates. More information is needed regarding the clinical outcomes of HCV-positive candidates and recipients of HCV-positive organs before clear-cut candidate selection and organ allocation policies can be established.

How is pheromone specificity encoded in proteins?

Pheromone specificity in the Lepidoptera is encoded in protein components of the antennal sensillum lymph and dendritic membrane. In this paper, we highlight recent work on the molecular determinants of pheromone binding affinity of pheromone binding proteins (PBPs) of three genera. First, we describe new cDNA sequences for Lymantria dispar (Lymantriidae) and Agrotis segetum (Noctuidae). These data enrich the conclusions derived from our functional studies. Secondly, we indicate how preparation of multimilligram quantities of the recombinant PBP 'Apol-3' (originally from Antheraea polyphemus) has provided a platform (i) to determine the ligand binding sites using photoaffinity labeling, (ii) to conduct structural analysis by CD and NMR, and (iii) to measure binding affinities using a new binding assay. Thirdly, we describe the use of expression-cassette PCR technology to prepare two related PBPs from Antheraea perneyi to test binding affinities of naturally-occurring homologous PBPs. Our results support a model in which ligand specificity for chain length, double bond position, and terminal functionality is partially encoded in the PBPs. We propose that the final decoding is accomplished when the PBP-pheromone complex activates a G-protein coupled seven-transmembrane domain receptor that contains recognition sites for both the presented pheromone and the presenting PBP.

[Relationship between exposure to stress and development of hypertension]. / De la relation entre l'exposition au stress et le développement de l'hypertension artérielle.

The relationship between stress and hypertension has long been a topic of debate. Until recently, no animal (nor physical) model existed which incorporated these two parameters together, hence accurate assessments of their interactions were postulations, at best. The borderline hypertensive rat (BHR) is an animal model in which arterial hypertension will ensue only when the rat is subjected to a chronic stressor. Therefore, this animal model offers an opportunity to study the physiological consequences of a given stressor on the entire organism during the course of the development of hypertension. The cardiovascular and humoral effects of chronic exposure to a physiological stressor on the BHR, at rest and during exposure to an acute and novel stress, have been examined and are presented in this paper. The involvement of the central nervous system in the regulation of this stress induced hypertensive state has been hypothesized to play a major role in the regulation of the stress and hypertensive relationship. Of particular importance are the endogenous opioids and their influence on the maintenance of homeostasis during periods of physiological stress. The localization of the endogenous opioid enkephalin in the paraventricular nucleus of the hypothalamus (PVN), an important brain region in the regulation of the stress response further substantiates the involvement of the opioid system during stress induced hypertension. Immunohistochemical data on the localization of ENKergic fibers in the PVN and other brain regions are similarly discussed in this paper.

The Functional Independence Measure for Children (WeeFIM). Conceptual basis and pilot use in children with developmental disabilities.

Few tools are available to pediatricians for tracking and monitoring disability status in children. We describe the conceptual basis and pilot use of the Functional Independence Measure for Children (WeeFIM). Our pilot use of this instrument in children with limb deficiency, Down's syndrome, spina bifida, cerebral palsy, and extreme prematurity demonstrates that the WeeFIM is a valid measure for tracking disability in preschool age and middle childhood. The WeeFIM measures the impact of developmental strengths and difficulties on independence at home, in school, and in the community. This allows the pediatrician to prioritize interventions for enhancing comprehensive functional outcomes and supporting families.

WeeFIM. Normative sample of an instrument for tracking functional independence in children.

A cross-sectional community sample of 417 children, ages 6 months to 8 years without developmental delays or in developmental programs, was seen. The Functional Independence Measure for Children (WeeFIM) was used to assess independence in self-care, sphincter control, transfers, locomotion, communication, and social cognition. Mean total WeeFIM was similar for males and females. There was a significant correlation between the age of the child in months and total WeeFIM scores for children ages 2 to 5 years (n = 222, r = .80, P < .01). There was a progressive increase of functional independence with increasing chronological age across all WeeFIM domains. We conclude that the WeeFIM is a useful instrument for measuring disability in children.

Isokinetic rehabilitation after arthroscopic meniscectomy.

The aim of this study was to assess the effects in humans of early (2 weeks) and delayed (6 weeks) isokinetic strength training in the recovery of muscle strength following an arthroscopic partial meniscectomy. The peak torque developed in the quadriceps and hamstrings and the torque developed at a knee angle of 1.05 rad were evaluated in 16 subjects, pre-operatively (pre-op), and 2, 6, and 10 weeks post-operatively (post-op), on an isokinetic device at four different velocities (1.05, 2.09, 3.14, and 4.19 rad.s-1). The fatigue characteristics of the muscles were evaluated by having the subject perform 15 maximal contractions at 3.14 rad.s-1. Training was done on the same device (three times a week for 1-2 months), beginning either 2 or 6 weeks post-op. A repeated measures analysis of variance demonstrated a time effect but no differences between groups and no interactions. Torques developed by the knee flexors and extensors were significantly smaller 2 weeks post-op than pre-op, at all velocities tested. Torques developed in the quadriceps recovered to their pre-op values by 6 weeks, and further gained significantly in strength from 6 to 10 weeks. Quadriceps torques remained weaker than the contralateral side at 10 weeks. Hamstrings torques were either higher or similar to pre-op values by 6 weeks, and demonstrated increases from 6 to 10 weeks post-op at 1.05 and 4.19 rad.s-1 only. Total work and average power developed by the quadriceps and hamstrings during the fatigue protocol changed with time in a similar manner to torque.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of age and regular exercise on muscle strength and endurance.

Twenty male and 20 female non-professional tennis players were classified into two different age groups (n = 10 per group): young active men (30.4 +/- 3.3 years), young active women (27.5 +/- 4.3 years), elderly active men (64.4 +/- 3.7 years), and elderly active women (65.3 +/- 4.5 years). These individuals were matched (n = 10 per group) according to sex, age, height and mass to sedentary individuals of the same socio-economical background: young sedentary men (29.2 +/- 3.4 years), young sedentary women (25.6 +/- 4.4 years), elderly sedentary men (65.2 +/- 3.2 years) and elderly sedentary women (65.6 +/- 4.4 years). An isokinetic dynamometer was used to measure the strength of the knee extensors and flexors (two separate occasions) and the endurance of the extensors. Vastus lateralis electromyogram (EMG) was measured concomitantly. Significant sex, age and exercise effects (P less than 0.001) were observed for peak torque of both muscle groups. The effect of age on extensor strength was more pronounced at high speeds where men were also able to generate larger relative torques than women. No age or sex effects were noted for muscle endurance. However, muscles of active individuals demonstrated a greater resistance to fatigue than those of sedentary individuals. In conclusion, men were found to be stronger than women, age was associated with a decrease in muscle strength, but not of muscle endurance, and tennis players were stronger and had muscles that were more resistant to fatigue than their sedentary pairs in both age groups.(ABSTRACT TRUNCATED AT 250 WORDS)