Blunted Arterial Blood Pressure Responses to Whole-Body Cold Stress in Individuals with Multiple Sclerosis

Multiple sclerosis (MS) is a neurological disease in which demyelination disrupts signal transmission and/or integration within the central nervous system. Reduced resting MSNA has been previously reported in MS patients (Keller et al., 2014). The aim of this study was to test the hypothesis that individuals with MS will have blunted sympathetic-mediated responses to a whole-body cold stress stimulus compared to healthy controls (CON). Ten subjects with relapsing-remitting MS (age, 35±7 years old; height: 163±9 cm; weight: 64±12 kg; BSA: 1.7±0.2 m2) and 4 healthy controls (31±5 years old; height: 168±6 cm; weight: 66±14 kg; BSA: 1.7±0.2 m2) participated in the study. Subjects were instrumented with a tube-lined water perfusion suit in which they were exposed to a thermoneutral (34 °C circulating water) condition for a baseline period of 10 minutes, followed by a 3-minute whole-body cold stress (5 °C circulating water) condition. Skin blood flow (laser-Doppler flowmetry), beat-to-beat arterial pressure (photoplethysmography), heart rate (ECG), and mean skin temperature were continuously measured. Cutaneous vascular conductance was calculated from the ratio of laser-Doppler flux to mean arterial pressure (CVC) and normalized to maximal responses obtained by local heating at 42 °C following cooling (%CVCmax). Mean arterial pressures (MAP) were derived during the final minute of baseline and cooling. There were no differences in ΔLDF flux (CON: -2.83±3.76; MS: -3.73±4.29, p=0.72), ΔCVC (CON:-0.05± 0.06; MS: -0.05±0.06, p=0.89), and Δ%CVCmax (CON: -2.43±3.75; MS: -0.24, p=0.12) from baseline to cooling. However, there was a significant difference in ΔMAP between groups (CON: 12.17±9.70; MS: -0.99±7.00, p=0.01). While cutaneous vasoconstrictor responsiveness was similar between groups, these data suggest individuals with MS exhibit reduced sympathetic-mediated changes in blood pressure in response to a whole body cold stress

The effect of multiple sclerosis on carotid baroreflex control of heart rate and blood pressure

Multiple sclerosis (MS) is marked by conduction abnormalities within the central nervous system that can lead to impaired blood pressure regulation. However, the impact of this disease on dynamic neural control—responsiveness and timing (i.e., latency)—of blood pressure has not been examined. Utilizing a variable neck chamber system, we tested the hypothesis that patients with MS (MS: n=4) exhibit an altered response following baroreflex perturbation compared to sex and age matched healthy controls (CON: n=4). At rest, 5-sec pulses of neck suction (NS; -60 Torr) and neck pressure (NP; +40 Torr) were applied to simulate carotid hypertension and hypotension, respectively. Mean arterial pressure (MAP; Finometer) and heart rate (HR) were continuously measured in response to the perturbations. Carotid baroreflex (CBR) latencies (i.e., time-to-peak responses) were examined using carotid-cardiac (peak HR responses), carotid-vasomotor (peak MAP responses), and change in MAP at the peak HR response of the corresponding stimuli (MAP@HRpeak), all of which were not significant for both NP and NS. Following NS, responses in MAP (MS: -12±5, CON: -10±3 mmHg; p=0.43) and HR (MS: -9±3, CON: -8±4 BPM; p=0.58) were similar between groups. Following administration of NP, HR responses (MS: 4±2, CON: 5±4 BPM; p=0.47) were no different. However, the differences found in MAP were significant (MS: 5±2, CON: 8±2 mmHg; p=0.05), providing some evidence that baroreceptor responsiveness may be compromised when faced with a hypotensive challenge

The Effect of Type II Diabetes Mellitus on Oxygen Uptake Kinetics during Heavy Exercise

The kinetics of oxygen uptake (Vo2) during the rest to exercise transition are thought to be modulated by intracellular metabolic processes. Diabetes has been shown to slow Vo2 kinetics, likely due to the impact of diabetes upon microvascular oxygen exchange (Padilla et al, 2007). However, to date, recovery from exercise has yet to be studied in these patients. Thus, the purpose of this study was to test the hypothesis that the existence of diabetes would hamper Vo2 kinetics during transitions to and from heavy leg cycling (H: Supra-LT). Nine subjects (4 control, 5 diabetic) completed three separate H exercise bouts. Vo2 was measured continuously at the mouth during exercise and recovery for each bout. During the on-transient, the total amplitude was decreased (Atot: Control 2.16±0.29 vs Diabetic 1.33±0.42 L/min, p=0.01). In an attempt to correct for differences in Atot, the rate of change in Vo2 (A1/T1 ) was calculated. This variable was significant reduced in diabetics during both the on-(A1/T1: Control 0.059±0.03 vs Diabetic 0.016±0.01, p=0.02), and off-transients (Control -0.10±0.10 vs Diabetic 0.035±0.012, p=0.09). In addition, the time constant during the on-transition was greatly slowed in diabetes (Tau: Control 24.07±8.39 vs Diabetic 76.76±37.94 sec, p=0.03). These findings suggest strongly that diabetes and it’s sequelae lead to impairments in oxidative metabolism during both exercise and recovery, which would serve to cause a faster rate of fatigue and a longer temporal course of recovery

Impaired Sweating Responses to a Passive Whole-body Heat Stress in Individuals with Multiple Sclerosis

Multiple sclerosis (MS) is an autoimmune disease that affects the central nervous system (CNS), disrupting autonomic function. PURPOSE: The aim of this study was to test the hypothesis that individuals with MS have blunted control of thermoregulatory reflex increases in sweat rate (SR) and cutaneous vasodilation compared to controls during a passive whole-body heat stress (WBH). METHODS: Eighteen individuals with relapsing-remitting MS and 18 healthy controls (CON) participated in the study. Core temperature (Tcore), skin temperature, heart rate, arterial blood pressure (10 min intervals), skin blood flow (laser-Doppler flowmetry: LDF), and SR were continuously measured during normothermic baseline (34 °C water perfusing a tube-lined suit) and WBH (increased Tcore 0.8 °C via 48 °C water perfusing the suit). Following WBH, local heaters were warmed to 42 °C, inducing maximal cutaneous vasodilation at the site of LDF collection. Cutaneous vascular conductance (CVC) was calculated as the ratio of LDF to mean arterial pressure and expressed as a percentage of maximum. RESULTS: Individuals with MS had attenuated SR responses to WBH (∆SR from baseline: CON: 0.65±0.27; MS: 0.42±0.17 mg/cm2/min, p=0.003), while ∆%CVCmax from baseline was similar between groups (CON: 42±16%; MS: 38±12 %, p=0.39). SR responses were blunted as a function of Tcore in MS (interaction: group*Tcore,p=0.03), of which differences were evident at ∆Tcore 0.7 °C and 0.8 °C (p\u3c0.05). No interaction was observed in ∆%CVCmax. CONCLUSION: Taken together, MS blunts sweating responses, while control of the cutaneous vasculature is preserved in response to WBH

Carotid Baroreflex Responses to Simulated Hypotension are Blunted During Passive Whole-body Heat Stress in Young Women

Previous studies have proposed that carotid baroreflex (CBR) function is potentially compromised during heat stress, thus possibly disrupting the ability to maintain arterial blood pressure in the heat (e.g., decreased orthostatic tolerance during hyperthermia). Recently, we demonstrated that CBR function is preserved, if not enhanced, during a passive whole-body heat stress (WBH) in young healthy men. What remains unknown is how CBR function is impacted by hyperthermia in women. PURPOSE: Therefore, the purpose of this study was to test the hypothesis that CBR-mediated responses are preserved during a passive WBH in young women. METHODS: Changes in mean arterial pressure (MAP) and HR were assessed in 7 healthy women (age: 21±1 yrs, height: 171±5 cm, weight: 66±5 kg, BMI: 23±2 kg/m2) using 5-s trials of neck pressure (NP, carotid hypotension) and neck suction (NS, carotid hypertension) ranging from +40 to -80 Torr during normothermia (NT) and WBH (increased core temp ~1.0 °C) conditions. To assess the CBR control of MAP and HR, a separate two-way repeated measures ANOVA was utilized for 1) hypertensive stimuli (i.e., NS: -20, -40, -60 & -80 Torr) and 2) hypotensive-stimuli (i.e., NP: +20 & +40 Torr). Additionally, the time-to-peak responses for HR and MAP, separately, in response +40 Torr & -80 Torr trials were examined between thermal conditions using paired t-tests. RESULTS: During WBH, the CBR-mediated increases in MAP and HR in response to NP were blunted (main effect of thermal condition p=0.02 and p=0.02, respectively). While the CBR-mediated decreases in MAP in response to NS were not different between thermal conditions (main effect of thermal condition p=0.34), decreases in HR were markedly greater during WBH (main effect of thermal condition p\u3c0.001). Additionally, the time-to-peak responses for MAP and HR were not altered between thermal conditions for either NP or NS trials (p \u3e 0.05 for all comparisons). CONCLUSION: Taken together, these data suggest the CBR control of MAP and HR during simulated hypotension is blunted in females during passive WBH, while the control of MAP and HR seems to be preserved, if not enhanced, during simulated hypertension. Contrary to our findings in young men, these results suggest there are sex differences in CBR function during WBH. This diminished ability to increase MAP and HR in response to a hypotensive stimulus during hyperthermia may be a key component in reduced orthostatic tolerance in females during WBH

Biological invasions, ecological resilience and adaptive governance

In a world of increasing interconnections in global trade as well as rapid change in climate and land cover, the accelerating introduction and spread of invasive species is a critical concern due to associated negative social and ecological impacts, both real and perceived. Much of the societal response to invasive species to date has been associated with negative economic consequences of invasions. This response has shaped a war-like approach to addressing invasions, one with an agenda of eradications and intense ecological restoration efforts towards prior or more desirable ecological regimes. This trajectory often ignores the concept of ecological resilience and associated approaches of resilience-based governance. We argue that the relationship between ecological resilience and invasive species has been understudied to the detriment of attempts to govern invasions, and that most management actions fail, primarily because they do not incorporate adaptive, learning-based approaches. Invasive species can decrease resilience by reducing the biodiversity that underpins ecological functions and processes, making ecosystems more prone to regime shifts. However, invasions do not always result in a shift to an alternative regime; invasions can also increase resilience by introducing novelty, replacing lost ecological functions or adding redundancy that strengthens already existing structures and processes in an ecosystem. This paper examines the potential impacts of species invasions on the resilience of ecosystems and suggests that resilience-based approaches can inform policy by linking the governance of biological invasions to the negotiation of tradeoffs between ecosystem services

The ICAM-3/LFA-1 interaction is critical for epidermal Langerhans cell alloantigen presentation to CD4 + T cells

Intercellular adhesion molecule (ICAM)-3 is a recently described member of the immunoglobulin superfamily and, as such, is closely related to ICAM-1 and ICAM-2. All three ICAMS are cognate for the counter-receptor lymphocyte function associated antigen-1 (LFA-L CD11a/CD18). Unlike ICAM-1 and ICAM-2. ICAM-3 is constitutively expressed at high levels on resting leucocytes. We investigated the expression and function of ICAM-3 in normal skin ( n = 5), as well as its expression in psoriasis ( n = 4). atopic eczema ( n = 4), allergic (rhus) contact dermatitis ( n =3). and cutaneous T-cell lymphoma (CTCL. n =2). Five-micrometre cryostat sections of skin were stained using monoclonal antibodies to ICAM-3 and A well characterized immunoperoxidase technique. In normal skin. ICAM-3 was expressed by all cutaneous leucocytes hut most striking was the strong expression of ICAM-3 by Langerhans cells within both epidermis and dermis. This observation was confirmed by double-labelling with CD1a and negative staining with an IgG1 isotype control. In psoriasis, atopic eczema, allergic contact dermatitis, and CTCL. ICAM-3 was co-expressed on all CD1a + cells, although, in psoriasis, the intensity of ICAM-3 expression was reduced. Functional blocking experiments were performed to determine whether the observed ICAM-3 expression on Langerhans cells was functionally important in antigen presentation. CD4 + T cells were prepared from peripheral blood and 10 5 CD4 + T cells combined with 10 5 epidermal cells harvested from keratome biopsies of normal skin of an individual allogeneic to the T-cell donor. Addition of 50 Μg anti-ICAM-3 to the co-culture resulted in a consistent (50%) reduction in degree of alloantigen presentation by Langerhans cells to T cells. Inhibition was 77% of that produced by the addition of anti-LFA-1. These data indicate that ICAM-3 is constitutively expressed by Langerhans cells and is a major ligand for LFA-1 on CD4 + T cells during their response to Langerhans cells. Because fresh Langerhans ceils constitutively express little ICAM-1. whereas ICAM-3 is constitutively expressed at high levels, it would appear that 1CAM-3 is the dominant functional ICAM on in situ Langerhans cells in the normal epidermis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73969/1/j.1365-2133.1995.tb06911.x.pd

Techno–ecological synergies of solar energy for global sustainability

The strategic engineering of solar energy technologies—from individual rooftop modules to large solar energy power plants—can confer significant synergistic outcomes across industrial and ecological boundaries. Here, we propose techno–ecological synergy (TES), a framework for engineering mutually beneficial relationships between technological and ecological systems, as an approach to augment the sustainability of solar energy across a diverse suite of recipient environments, including land, food, water, and built-up systems. We provide a conceptual model and framework to describe 16 TESs of solar energy and characterize 20 potential techno–ecological synergistic outcomes of their use. For each solar energy TES, we also introduce metrics and illustrative assessments to demonstrate techno–ecological potential across multiple dimensions. The numerous applications of TES to solar energy technologies are unique among energy systems and represent a powerful frontier in sustainable engineering to minimize unintended consequences on nature associated with a rapid energy transition

Tetraazamacrocyclic derivatives and their metal complexes as antileishmanial leads

© 2019 A total of 44 bis-aryl-monocyclic polyamines, monoaryl-monocyclic polyamines and their transition metal complexes were prepared, chemically characterized, and screened in vitro against the Leishmania donovani promastigotes, axenic amastigotes and intracellular amastigotes in THP1 cells. The IC 50 and/or IC 90 values showed that 10 compounds were similarly active at about 2-fold less potent than known drug pentamidine against promastigotes. The most potent compound had an IC 50 of 2.82 µM (compared to 2.93 µM for pentamidine). Nine compounds were 1.1–13.6-fold more potent than pentamidine against axenic amastigotes, the most potent one being about 2-fold less potent than amphotericin B. Fourteen compounds were about 2–10 fold more potent than pentamidine, the most potent one is about 2-fold less potent than amphotericin B against intracellular amastigotes in THP1 cells. The 2 most promising compounds (FeL7Cl 2 and MnL7Cl 2 ), with strong activity against both promastigotes and amastigotes and no observable toxicity against the THP1 cells are the Fe 2+ - and Mn 2+ -complexes of a dibenzyl cyclen derivative. Only 2 of the 44 compounds showed observable cytotoxicity against THP1 cells. Tetraazamacrocyclic monocyclic polyamines represent a new class of antileishmanial lead structures that warrant follow up studies