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Plasma proteomics reveals markers of metabolic stress in HIV infected children with severe acute malnutrition.
Gonzales, GB, Njunge, JM, Gichuki, BM, Wen, B, Potani, I, Voskuijl, W, Bandsma, RHJ, Berkley, JA
Scientific reports. 2020;(1):11235
Abstract
HIV infection affects up to 30% of children presenting with severe acute malnutrition (SAM) in Africa and is associated with increased mortality. Children with SAM are treated similarly regardless of HIV status, although mechanisms of nutritional recovery in HIV and/or SAM are not well understood. We performed a secondary analysis of a clinical trial and plasma proteomics data among children with complicated SAM in Kenya and Malawi. Compared to children with SAM without HIV (n = 113), HIV-infected children (n = 54) had evidence (false discovery rate (FDR) corrected p < 0.05) of metabolic stress, including enriched pathways related to inflammation and lipid metabolism. Moreover, we observed reduced plasma levels of zinc-α-2-glycoprotein, butyrylcholinesterase, and increased levels of complement C2 resembling findings in metabolic syndrome, diabetes and other non-communicable diseases. HIV was also associated (FDR corrected p < 0.05) with higher plasma levels of inflammatory chemokines. Considering evidence of biomarkers of metabolic stress, it is of potential concern that our current treatment strategy for SAM regardless of HIV status involves a high-fat therapeutic diet. The results of this study suggest a need for clinical trials of therapeutic foods that meet the specific metabolic needs of children with HIV and SAM.
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Smokeless tobacco consumption impedes metabolic, cellular, apoptotic and systemic stress pattern: A study on Government employees in Kolkata, India.
Biswas, S, Manna, K, Das, U, Khan, A, Pradhan, A, Sengupta, A, Bose, S, Ghosh, S, Dey, S
Scientific reports. 2015;:18284
Abstract
Smokeless tobacco (SLT) remains a threat amongst a large population across the globe and particularly in India. The oral use of tobacco has been implicated to cause physiological stress leading to extreme toxicological challenge. The study included 47 SLT-users and 44 non-users providing a spectrum of pathophysiological, clinico-biochemical, antioxidant parameters, cell cycle progression study of PBMC and morphological changes of red blood cells (RBC). The expressions of p53, p21, Bax, Bcl-2, IL-6, TNF- α, Cox-2, iNOS were analyzed from thirteen representative SLT-users and twelve non-users. Difference in CRP, random glucose, serum cholesterol, TG, HLDL-C, LDL-C, VLDL-C, neutrophil count, monocyte count, ESR, SOD (PBMC) and TBARS (RBC membrane) were found to be statistically significant (p < 0.05) between the studied groups. The current study confers crucial insight into SLT mediated effects on systemic toxicity and stress. This has challenged the metabolic condition leading to a rise in the inflammatory status, increased apoptosis and RBC membrane damage. The above findings were substantiated with metabolic, clinical and biochemical parameters. This is possibly the first ever in-depth report and remains an invaluable document on the fatal effects of SLT.
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Craving and physiological reactivity to trauma and alcohol cues in posttraumatic stress disorder and alcohol dependence.
Coffey, SF, Schumacher, JA, Stasiewicz, PR, Henslee, AM, Baillie, LE, Landy, N
Experimental and clinical psychopharmacology. 2010;(4):340-9
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Abstract
The high comorbidity of posttraumatic stress disorder (PTSD) and alcohol dependence (AD) has been firmly established. Although laboratory studies have examined self-reported craving in response to trauma and alcohol cues, no studies have reported on alcohol-related physiological responding in response to trauma cues in PTSD-AD individuals. Using a cue reactivity paradigm, this study examined the impact of personalized trauma-image cues and in vivo alcohol cues on alcohol-related responding (e.g., salivation, craving) in individuals with PTSD and AD (n = 40). Participants displayed reactivity to both trauma and alcohol cues when compared to neutral cues, including increased self-reported craving and distress, as well as greater salivation. These findings suggest that through repeated pairings of trauma memories and alcohol consumption, salivation may become classically conditioned to trauma cues. Moreover, the fact that the trauma-alcohol cue combination elicited greater alcohol craving, salivary responding, distress, and arousal than either the trauma-neutral or neutral-alcohol cue combinations suggests that effects of the trauma and alcohol cues were additive in nature. Evidence that AD individuals with PTSD report increased alcohol craving and display greater salivation in response to trauma memories, supplements prior research indicating that PTSD-related negative emotion and trauma-related alcohol craving may play an important role in the maintenance of AD.
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Oral L-arginine improves hemodynamic responses to stress and reduces plasma homocysteine in hypercholesterolemic men.
West, SG, Likos-Krick, A, Brown, P, Mariotti, F
The Journal of nutrition. 2005;(2):212-7
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Abstract
When administered intravenously, L-arginine substantially reduces blood pressure (BP) and peripheral vascular resistance in healthy adults and in patients with vascular disease. Oral L-arginine has been shown to improve endothelial function; however, it is not clear whether oral administration has significant effects on systemic hemodynamics. In a randomized, placebo-controlled, crossover study we tested whether oral L-arginine (12 g/d for 3 wk) affected hemodynamics, glucose, insulin, or C-reactive protein in 16 middle-age men with hypercholesterolemia. After each treatment, hemodynamic variables were measured at rest and during 2 standardized stressor tasks (a simulated public-speaking task and the cold pressor). Regardless of treatment, the stressor tasks increased BP and heart rate (P < or = 0.02). Relative to placebo, L-arginine changed cardiac output (-0.4 L/m), diastolic BP (-1.9 mm Hg), pre-ejection period (+3.4 ms), and plasma homocysteine (-2.0 micromol/L) (P < or = 0.03). The change in plasma L-arginine was inversely correlated with the change in plasma homocysteine (r = -0.57, P = 0.03). Contrary to the results of previous studies of L-arginine administered intravenously, oral administration did not affect total peripheral resistance or plasma insulin. Oral L-arginine also did not affect plasma glucose, C-reactive protein, or lipids. This pattern of findings is consistent with the hypothesis that oral L-arginine reduces BP. This study is the first to describe a hemodynamic mechanism for the hypotensive effect of oral L-arginine and the first to show substantial reductions in homocysteine with oral administration.
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High spinal anesthesia for cardiac surgery: effects on beta-adrenergic receptor function, stress response, and hemodynamics.
Lee, TW, Grocott, HP, Schwinn, D, Jacobsohn, E, ,
Anesthesiology. 2003;(2):499-510
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Abstract
BACKGROUND This double-blind, randomized, controlled trial examined the effect of high-dose intrathecal bupivacaine in combination with general anesthesia on atrial beta-adrenergic receptor function, the stress response, and hemodynamics during coronary artery bypass graft surgery. METHODS Thirty-eight patients were randomized to either control (n = 19) or intrathecal bupivacaine (ITB) groups (n = 19). Patients in the ITB group received 37.5 mg intrathecal hyperbaric bupivacaine before induction of general anesthesia. Control patients received an injection of local anesthetic into the skin and subcutaneous tissues (sham spinal). Comparisons were made between groups with respect to atrial receptor desensitization and down-regulation, in addition to circulating catecholamines and hemodynamics. RESULTS In patients with cardiopulmonary bypass (CPB) times in excess of 1 h, the ITB group had significantly less atrial beta-receptor dysfunction, as measured by maximal isproteronol, 50% maximal isoproterenol, sodium fluoride-stimulated activity, and zinterol stimulation assays of adenylyl cyclase activity (P < or = 0.02) and beta-adrenergic receptor density (P = 0.02). Serum epinephrine, norepinephrine, and cortisol concentrations were significantly lower in the ITB group, independent of CPB times (P < 0.0001, P < 0.001, and P < 0.05, respectively). ITB patients had a higher cardiac index and a lower pulmonary vascular resistance index in the post-CPB time period (P < 0.01 and P < 0.05, respectively). In the pre-CPB period, mean arterial pressure and systemic vascular resistance index were significantly lower in the ITB group. CONCLUSIONS High-dose intrathecal bupivacaine, when combined with general anesthesia, resulted in less beta-receptor dysfunction and a lower stress response during coronary artery bypass graft surgery.
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Prostaglandin modulation of venoconstriction to physiological stress in normals and heart failure patients.
Dzeka, TN, Arnold, JM
American journal of physiology. Heart and circulatory physiology. 2003;(3):H790-7
Abstract
Prostaglandins released from blood vessels modulate vascular tone, and inhibition of their production during exogenous infusions of catecholamines causes increased venoconstriction. To determine the influence of prostaglandin production on venoconstriction during physiological stimuli known to cause sympathetic activation, and to assess its importance in chronic heart failure (CHF), we studied 11 normal subjects (62 +/- 4 yr) and 14 patients with CHF (64 +/- 2 yr, left ventricular ejection fraction 23 +/- 1%, New York Heart Association classes II and III) (means +/- SE). Dorsal hand vein distension was measured during mental arithmetic (MA), cold pressor test (CPT), and lower body negative pressure (LBNP; -10 and -40 mmHg), with saline infusion in one hand and local indomethacin (cyclooxygenase inhibitor) infusion (3 microg/min) in the other. Acetylcholine (0.01-1 nmol/min) dilated veins preconstricted with PGF(2alpha) in normals but, consistent with endothelial dysfunction, barely did so in CHF patients (P = 0.001). Nonendothelial venodilation to sodium nitroprusside (0.3-10 nmol/min) was not different between normals and CHF patients. Resting venous norepinephrine levels were higher in CHF patients (2,812 +/- 420 pmol/l) than normals (1,418 +/- 145 pmol/l, P = 0.007). In normals, indomethacin caused increased venoconstriction to MA (from 4.9 +/- 1.5 to 19.2 +/- 4.5%, P = 0.022) and CPT (from 2.9 +/- 3.8 to 17.6 +/- 4.2%, P = 0.007). In CHF, indomethacin caused increased venoconstriction to MA (from 6.6 +/- 3.9% to 19.0 +/- 4.5%, P = 0.014), CPT (from 9.6 +/- 2.1% to 20.1 +/- 3.7%, P = 0.001), and -40 mmHg LBNP (from 10.7 +/- 3.0% to 23.2 +/- 3.8%, P = 0.041). Control responses for all tests were not different between normals and CHF patients. The effects of indomethacin on venoconstriction to MA and CPT were not different between normals and CHF patients, but venoconstriction to -40 mmHg LBNP was accentuated in CHF patients (P = 0.036). Inhibition of prostaglandins by indomethacin significantly enhances hand vein constriction to physiological stimuli in both normals and CHF patients, although a differential effect exists for LBNP.
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No effect of mild heat stress on the regulation of carbohydrate metabolism at the onset of exercise.
Saunders, PU, Watt, MJ, Garnham, AP, Spriet, LL, Hargreaves, M, Febbraio, MA
Journal of applied physiology (Bethesda, Md. : 1985). 2001;(5):2282-8
Abstract
To investigate the influence of heat stress on the regulation of skeletal muscle carbohydrate metabolism, six active, but not specifically trained, men performed 5 min of cycling at a power output eliciting 70% maximal O2 uptake in either 20 degrees C (Con) or 40 degrees C (Heat) after 20 min of passive exposure to either environmental condition. Although muscle temperature (T(mu)) was similar at rest when comparing trials, 20 min of passive exposure and 5 min of exercise increased (P < 0.05) T(mu) in Heat compared with Con (37.5 +/- 0.1 vs. 36.9 +/- 0.1 degrees C at 5 min for Heat and Con, respectively). Rectal temperature and plasma epinephrine were not different at rest, preexercise, or 5 min of exercise between trials. Although intramuscular glycogen phosphorylase and pyruvate dehydrogenase activity increased (P < 0.05) at the onset of exercise, there were no differences in the activities of these regulatory enzymes when comparing Heat with Con. Accordingly, glycogen use in the first 5 min of exercise was not different when comparing Heat with Con. Similarly, no differences in intramuscular concentrations of glucose 6-phosphate, lactate, pyruvate, acetyl-CoA, creatine, phosphocreatine, or ATP were observed at any time point when comparing Heat with Con. These results demonstrate that, whereas mild heat stress results in a small difference in contracting T(mu), it does not alter the activities of the key regulatory enzymes for carbohydrate metabolism or glycogen use at the onset of exercise, when plasma epinephrine levels are unaltered.