Influence of venous emptying on the reactive hyperemic blood flow response

BACKGROUND: Previous research indicates that venous emptying serves as a stimulus for vasodilation in the human forearm. This suggests the importance of recognizing the potential influence of venous volume on reactive hyperemic blood flow (RHBF) following occlusion. The purpose of this study was to examine the influence of venous emptying on forearm vascular function. METHODS: Forearm RHBF, venous capacitance and venous outflow were examined in 35 individuals (age = 22 ± 2 years), using mercury in-Silastic strain gauge plethysmography, at rest and following five minutes of upper arm occlusion using standard procedures (Control). In addition, the same measures were obtained following five minutes of upper arm occlusion preceded by two minutes of passive arm elevation (Pre-elevation). RESULTS: Average resting arterial inflow was 2.42 ± 1.11 ml·100 ml(-1)·min(-1). RHBF and venous capacitance were significantly greater during Pre-elevation compared to Control (RHBF; Pre-elevation: 23.76 ± 5.95 ml·100 ml(-1 )·min(-1 )vs. Control: 19.33 ± 4.50; p = 0.001), (venous capacitance; Pre-elevation: 2.74 ± 0.89 % vs. Control: 2.19 ± 0.97, p = 0.001). Venous outflow did not differ between the two conditions. CONCLUSION: Venous emptying prior to upper arm occlusion results in a significant greater RHBF response and venous capacitance. Recognition of the influence of venous volume on RHBF is particularly important in studies focusing on arterial inflow, and also provides further evidence for the interplay between the venous and arterial system

Resistance exercise training restores bone mineral density in heart transplant recipients

AbstractObjectives. This was a prospective, randomized, controlled study designed to determine the effect of resistance exercise traning on bone metabolism in heart transplant recipients.Background. Osteoporosis frequently complicates heart transplantation. No preventative strategy is generally accepted for glucocorticoid-induced bone loss.Methods. Sixteen male heart transplant recipients were randomly assigned to a resistance exercise group that trained for 6 months (mean [±SD] age 56 ± 6 years) or a control group (mean age 52 ± 10 years) that did not perform resistance exercise. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L2 to L3) was measured by dual-energy X-ray absorptiometry before and 2 months after transplantation and after 3 and 6 months of resistance exercise or a control period. The exercise regimen consisted of lumbar extension exercise (MedX) performed 1 day/week and variable resistance exercises (Nautilus) performed 2 days/week. Each exercise consisted of one set of 10 to 15 repetitions performed to volitional fatigue.Results. Pretransplantation baseline values for regional BMD did not differ in the control and training groups. Bone mineral density of the total body, femur neck and lumbar vertebra (L2 to L3) were significantly decreased below baseline at 2 months after transplantation in both the control (−3.3 ± 1.3%, − 4.5 ± 2.8%, −12.7 ± 6.2%, respectly) and training groups (−2.9 ± 1.1%, 5.9 ± 3.2%, −14.8 ± 3.1%, respectively). Six months of resistance exercise restored BMD of the whole body, femur neck and lumbar vertebra to within 1%, 1.9% and 3.6% of pretransplantation levels, respectively. Bone mineral density of the control group remained unchanged from the 2-month posttransplantation levels.Conclusions. Within 2 months after heart transplantation, ≈ 3% of whole-body BMD is lost, mostly due to decreases in trabecular bone (−12% to −15% of lumbar vertebra). Six months of resistance exercise, consisting of low back exercise that isolates the lumbar spine and a regimen of variable resistance exercises, restores BMD toward pretransplantation levels. Our results suggest that resistance exercise is osteogenic and should be initiated early after heart transplantation

Ocular Biomarkers of Disease: Employing Routine Eye Exams to Promote Better Health Surveillance

America’s burden of vision impairment, Alzheimer’s disease and related dementias (ADRD), and cardiovascular disease will continue to rise over the next 40 years. The burden of these diseases will be greater for women, Hispanics, African-Americans, and those from lower socio-economic regions. A key challenge is to develop strategies to deny the organization of the pathologies that eventually lead to the manifestation of the disease. An important feature within this battle is the development of appropriate tools and biomarkers for early reconnaissance of the enemy. Recent advances in Optical Coherence Tomography Angiography (OCTA) present a unique opportunity to examine physiological features of the eyes that overlap with structures within the brain and heart. Specifically, tracking of the vessel density and thickness of the nerve fiber layers of the eye may provide valuable information regarding an individual’s path towards visual impairment, ADRD, and cardiovascular disease. Thus, OCTA can extend eye care beyond capturing those who are at risk for vision loss, and include examination of biomarkers which provide information concerning trajectories of cognitive and cardiovascular health. Given loss of vision is perceived as ‘the worst ailment that could happen to person’ across all ethnic and racial groups, Ophthalmologists and Optometrists can not only provide a path toward improved eye health, but also serve as an innovative access point for early detection of individuals at risk for ADRD and Cardiovascular disease

Biphasic responses of the brachial artery diameter following forearm occlusion: a blunted response in the elderly

BACKGROUND: The purpose was to examine the temporal response of the brachial artery diameter following 5 minutes of forearm occlusion in young men. A secondary objective was to compare the main features of the temporal pattern between young and old. METHODS: Sixteen young (28 ± 8 yrs) and fifteen older (85 ± 8 yrs) men underwent high-resolution ultrasonography of the brachial artery before and after five minutes of forearm occlusion. RESULTS: Following release of the pressure cuff the brachial artery diameter exhibits a temporal biphasic response. Initially, there is a significant reduction in brachial diameter (NIL) compared to baseline (BASE), followed by a rapid increase to a PEAK at 41 sec post release. When comparing the magnitude of the decrease in diameter and the Brachial Artery Flow Mediated Dilation (BAFMD) between Young and Old, older subjects demonstrated a blunted response (Magnitude of Decrease: Young: 2.0%; Old: 0.4%, p = 0.015, and BAFMD: Young: 7.7%; Old: 2.3%, p = 0.001). Finally, a significant relationship was noted between the magnitude of decrease and BAFMD (r = -0.44, p = 0.04). CONCLUSION: Examination of the temporal response of the brachial artery diameter following 5 minutes of forearm occlusion reveals a biphasic pattern in all participants. Specific features of this pattern are blunted in older adults compared with younger subjects. Finally, the magnitude of the drop in diameter following forearm occlusion correlates with the magnitude of the BAFMD

Vascular Function and Handgrip Strength in Rheumatoid Arthritis Patients

Objective. To examine the relationship of handgrip strength with forearm blood flow (BF) and vascular resistance (VR) in rheumatoid arthritis (RA) patients. Methods. Forearm BF at rest (RBF) and after upper arm occlusion (RHBF), and handgrip strength were examined in 78 individuals (RA = 42 and controls (CT) = 36). Subsequently, VR at rest (RVR) and after occlusion (RHVR) were calculated. Results. The patients' RBF (P = 0.02) and RHBF (P = 0.0001) were less, whereas RVR (P = 0.002) and RHVR (P = 0.0001) were greater as compared to the CTs. Similarly, handgrip strength was lower in the RAs (P = 0.0001). Finally, handgrip strength was directly associated with RBF (r = 0.43; P = 0.0001), and RHBF (r = 0.5; P = 0.0001), and inversely related to RVR (r = −0.3; P = 0.009) and RHVR (r = −0.3; P = 0.007). Conclusion. The present study uniquely identifies an association between regional measures of forearm blood flow and handgrip strength in patients and healthy control. In addition, this study confirms the presence of vascular and muscle dysfunction in patients with rheumatoid arthritis, as evidenced by lower forearm blood flow indices, at rest and following occlusion, and lower handgrip strength as compared to healthy individuals

HRAS1 and LASS1 with APOE are associated with human longevity and healthy aging

The search for longevity-determining genes in human has largely neglected the operation of genetic interactions. We have identified a novel combination of common variants of three genes that has a marked association with human lifespan and healthy aging. Subjects were recruited and stratified according to their genetically inferred ethnic affiliation to account for population structure. Haplotype analysis was performed in three candidate genes, and the haplotype combinations were tested for association with exceptional longevity. An HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude. These results were replicated in a second population. A profile of healthy aging was developed using a deficit accumulation index, which showed that this combination of gene variants is associated with healthy aging. The variation in LASS1 is functional, causing enhanced expression of the gene, and it contributes to healthy aging and greater survival in the tenth decade of life. Thus, rare gene variants need not be invoked to explain complex traits such as aging; instead rare congruence of common gene variants readily fulfills this role. The interaction between the three genes described here suggests new models for cellular and molecular mechanisms underlying exceptional survival and healthy aging that involve lipotoxicity. © 2010 The Authors Aging Cell © 2010 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland

HIV Traffics through a Specialized, Surface-Accessible Intracellular Compartment during trans-Infection of T Cells by Mature Dendritic Cells

In vitro, dendritic cells (DCs) bind and transfer intact, infectious HIV to CD4 T cells without first becoming infected, a process known as trans-infection. trans-infection is accomplished by recruitment of HIV and its receptors to the site of DC–T cell contact and transfer of virions at a structure known as the infectious synapse. In this study, we used fluorescent microscopy to track individual HIV particles trafficking in DCs during virus uptake and trans-infection. Mature DCs rapidly concentrated HIV into an apparently intracellular compartment that lacked markers characteristic of early endosomes, lysosomes, or antigen-processing vesicles. Live cell microscopy demonstrated that the HIV-containing compartment was rapidly polarized toward the infectious synapse after contact with a T cell; however, the bulk of the concentrated virus remained in the DCs after T cell engagement. Individual virions were observed emerging from the compartment and fusing with the T cell membrane at the infectious synapse. The compartmentalized HIV, although engulfed by the cytoplasm, was fully accessible to HIV envelope-specific inhibitors and other membrane-impermeable probes that were delivered to the cell surface. These results demonstrate that HIV resides in an invaginated domain within DCs that is both contiguous with the plasma membrane and distinct from endocytic vesicles. We conclude that HIV virions are routed through this specialized compartment, which allows individual particles to be delivered to T cells during trans-infection

Regional changes in reactive hyperemic blood flow during exercise training: time-course adaptations

BACKGROUND: Few studies have examined the time-course of localized exercise training on regional blood flow in humans. The study examined the influence of handgrip exercise training on forearm reactive hyperemic blood flow and vascular resistance in apparently healthy men. METHODS: Forearm blood flow and vascular resistance were evaluated, in 17 individuals [Age: 22.6 ± 3.5], in both arms, at rest and following 5 minutes of arterial occlusion, using strain gauge plethysmography, prior to training (V1) and every week thereafter (V2-5) for 4 weeks. Handgrip exercise was performed in the non-dominant arm 5 d/wk for 20 minutes at 60% of maximum voluntary contraction, while the dominant arm served as control. RESULTS: Resting HR, BP, and forearm blood flow and vascular resistance were not altered with training. The trained arm handgrip strength and circumference increased by 14.5% (p = 0.014) and 1.56% (p = 0.03), respectively. ANOVA tests revealed an arms by visit interaction for the trained arm for reactive hyperemic blood flow (p = 0.02) and vascular resistance (p = 0.009). Post-hoc comparison demonstrated increased reactive hyperemic blood flow (p = 0.0013), and decreased post-occlusion vascular resistance (p = 0.05), following the 1(st )week of training, with no significant changes in subsequent visits. CONCLUSION: The results indicate unilateral improvements in forearm reactive hyperemic blood flow and vascular resistance following 1 week of handgrip exercise training and leveled off for the rest of the study

A Vaccine against Nicotine for Smoking Cessation: A Randomized Controlled Trial

BACKGROUND: Tobacco dependence is the leading cause of preventable death and disabilities worldwide and nicotine is the main substance responsible for the addiction to tobacco. A vaccine against nicotine was tested in a 6-month randomized, double blind phase II smoking cessation study in 341 smokers with a subsequent 6-month follow-up period. METHODOLOGY/PRINCIPAL FINDINGS: 229 subjects were randomized to receive five intramuscular injections of the nicotine vaccine and 112 to receive placebo at monthly intervals. All subjects received individual behavioral smoking cessation counseling. The vaccine was safe, generally well tolerated and highly immunogenic, inducing a 100% antibody responder rate after the first injection. Point prevalence of abstinence at month 2 showed a statistically significant difference between subjects treated with Nicotine-Qbeta (47.2%) and placebo (35.1%) (P = 0.036), but continuous abstinence between months 2 and 6 was not significantly different. However, in subgroup analysis of the per-protocol population, the third of subjects with highest antibody levels showed higher continuous abstinence from month 2 until month 6 (56.6%) than placebo treated participants (31.3%) (OR 2.9; P = 0.004) while medium and low antibody levels did not increase abstinence rates. After 12 month, the difference in continuous abstinence rate between subjects on placebo and those with high antibody response was maintained (difference 20.2%, P = 0.012). CONCLUSIONS: Whereas Nicotine-Qbeta did not significantly increase continuous abstinence rates in the intention-to-treat population, subgroup analyses of the per-protocol population suggest that such a vaccination against nicotine can significantly increase continuous abstinence rates in smokers when sufficiently high antibody levels are achieved. Immunotherapy might open a new avenue to the treatment of nicotine addiction. TRIAL REGISTRATION: Swiss Medical Registry 2003DR2327; ClinicalTrials.gov NCT00369616