The effects of cortisol supplementation on the metabolic and hormonal response to surgery

Summary. The role of Cortisol in determining the metabolic and hormonal changes associated with a standardized surgical operation was investigated. Twelve patients undergoing pelvic surgery were studied. Six received steroid supplementation with an infusion of hydrocortisone sodium succinate at a rate of 8 mg/h for 24 h, together with 1·5 g hydrocortisone acetate intraperitoneally at the completion of surgery, while the remainder acted as a control group. Steroid supplementation resulted in plasma Cortisol values in the range 1913–2265 nmol/1 from 4 to 24 h after the start of surgery. However, this marked hyper-cortisolaemia had no significant effects on circulating metabolites other than glucose, and did not alter plasma ACTH, GH and insulin values. The usual glycaemic response to surgery was significantly augmented by 1·0–1·5 mmol/1 in the cortisol group. We conclude that changes in substrate mobilization observed after cortisol administration in normal volunteers may not accurately predict the effects found after surgery, when catabolic hormones and other modulators such as interleukin-1 may influence metabolism.     

NMR-based metabolomic analysis of the effects of alanyl-glutamine supplementation on C2C12 myoblasts injured by energy deprivation

The dipeptide alanyl-glutamine (Ala-Gln) is a well-known parenteral nutritional supplement. The Ala-Gln supplementation is a potential treatment for muscle-related diseases and injuries. However, molecular mechanisms underlying the polyphenic effects of Ala-Gln supplementation remain elusive. Here, we performed NMR-based metabolomic profiling to analyze the effects of Ala-Gln, and the free alanine (Ala) and glutamine (Gln) supplementations on the mouse myoblast cell line C2C12 injured by glucose and glutamine deprivation. All the three supplementations can promote the differentiation ability of the injured C2C12 cells, while only Ala-Gln supplementation can facilitate the proliferation of the injured cells. Ala-Gln supplementation can partially restore the metabolic profile of C2C12 myoblasts disturbed by glucose and glutamine deprivation, and exhibits more significant effects than Ala and Gln supplementations. Our results suggest that Ala-Gln supplementation can promote MyoD1 protein synthesis, upregulate the muscle ATP-storage phosphocreatine (PCr), maintain TCA cycle anaplerosis, enhance the antioxidant capacity through promoting GSH biosynthesis, and stabilize lipid membranes by suppressing glycerophospholipids metabolism. This work provides new insight into mechanistic understanding of the polyphenic effects of Ala-Gln supplementation on muscle cells injured by energy deprivation.

The alanyl-glutamine (Ala-Gln) supplementation can promote the differentiation and proliferation abilities of the injured C2C12 cells, and is a potential treatment for muscle-related diseases and injuries.     

Effect of alcohol on the lactate/pyruvate ratio of recently injured adults

OBJECTIVE: To compare the ability of plasma (lactate) and the plasma lactate/pyruvate (L/P) ratio to predict shock-related outcome after injury and also to examine the influence of plasma ethanol on any relationships found. DESIGN: Prospective observational study. SETTING: Emergency departments in the UK and the Republic of South Africa. PATIENTS: Blood samples were taken at presentation from 232 adult patients 1-23 hrs (median, 3.5 hrs) after sustaining an injury or injuries deemed sufficiently severe to require inpatient care. MEASUREMENTS: Plasma concentrations of lactate, pyruvate, and ethanol, anatomical severity of injury, development of multiple organ failure, and 30-day survival were determined. RESULTS: At 90% specificity for predicting subsequent mortality and/or multiple organ failure, plasma lactate >or=3.85 mmol/L was 23% (5% to 41%) more sensitive than an L/P ratio of >or=42.76. At 90% sensitivity for ruling out morbidity, plasma lactate <1.6 mmol/L is 6% (-1% to 13%) more specific than an L/P ratio of <14.08. High L/P ratios were noted to be associated with a detectable plasma alcohol level. A post hoc regression analysis showed that alcohol-positive/-negative status was a much stronger predictor of the L/P ratio than was anatomical severity of injury, shock, or time after injury. CONCLUSIONS: Plasma lactate alone is a better predictor than the L/P ratio of shock-related outcome after injury. The interpretation of L/P ratios after injury is confounded in the presence of elevated plasma ethanol.     

Non-invasive detection of fluorescence from exogenous chromophores in the adult human brain

This is the first report on results proving that fluorescence of exogenous dyes inside the human brain can be excited and detected non-invasively at the surface of the adult head. Boli of indocyanine green (ICG) were intravenously applied to healthy volunteers, and the passage of the contrast agent in the brain was monitored by detecting the corresponding fluorescence signal following pulsed laser excitation at 780 nm. Our hypothesis that the observed fluorescence signal contains a considerable cortical fraction was corroborated by performing measurements with picosecond temporal resolution and analyzing distributions of times of arrival of photons, hence taking advantage of the well-known depth selectivity of that method. Our experimental findings are explained by Monte Carlo simulations modeling the head as a layered medium and taking into account realistic bolus kinetics within the extra- and intracerebral compartment. Although a particular non-specific dye (ICG) was used, the results clearly demonstrate that fluorescence-mediated imaging of the adult human brain is generally feasible. In particular, we will discuss how these results serve as proof of concept for non-invasive fluorescence brain imaging and may thus open the door towards optical molecular imaging of the human brain.     

The effects of arterial CO2 on the injured brain: Two faces of the same coin

Serum levels of carbon dioxide (CO₂) closely regulate cerebral blood flow (CBF) and actively participate in different aspects of brain physiology such as hemodynamics, oxygenation, and metabolism. Fluctuations in the partial pressure of arterial CO₂ (PaCO₂) modify the aforementioned variables, and at the same time influence physiologic parameters in organs such as the lungs, heart, kidneys, and the gastrointestinal tract. In general, during acute brain injury (ABI), maintaining normal PaCO₂ is the target to be achieved. Both hypercapnia and hypocapnia may comprise secondary insults and should be avoided during ABI. The risks of hypocapnia mostly outweigh the potential benefits. Therefore, its therapeutic applicability is limited to transient and second-stage control of intracranial hypertension. On the other hand, inducing hypercapnia could be beneficial when certain specific situations require increasing CBF. The evidence supporting this claim is very weak. This review attempts providing an update on the physiology of CO₂, its risks, benefits, and potential utility in the neurocritical care setting.     

Neuroimaging acupuncture effects in the human brain

Acupuncture is an ancient East Asian healing modality that has been in use for more than 2000 years. Unfortunately, its mechanisms of action are not well understood, and controversy regarding its clinical efficacy remains. Importantly, acupuncture needling often evokes complex somatosensory sensations and may modulate the cognitive/affective perception of pain, suggesting that many effects are supported by the brain and extending central nervous system (CNS) networks. Modern neuroimaging techniques such as functional magnetic resonance imaging, positron emission tomography, electroencephalography, and magnetoencephalography provide a means to safely monitor brain activity in humans and may be used to help map the neurophysiological correlates of acupuncture. In this review, we will summarize data from acupuncture neuroimaging research and discuss how these findings contribute to current hypotheses of acupuncture action.     

Effects of exogenous zinc supplementation on intestinal epithelial repair in vitro

BACKGROUND: Substitution of zinc modulates antioxidant capabilities within the intestinal mucosa and improves intestinal wound healing in zinc-deficient patients with inflammatory bowel diseases. The aim of this study was to characterize the modulating effects of zinc on intestinal epithelial cell function in vitro. MATERIALS AND METHODS: The effects of zinc on intestinal epithelial cell morphology were assessed by phase contrast and transmission electron microscopy using the non-transformed small intestinal epithelial cell line IEC-6. Zinc-induced apoptosis was assessed by DNA fragmentation analysis, lactate dehydrogluase (LDH) release and flow cytometry with propidium iodine staining. Furthermore, the effects of zinc on IEC-6 cell proliferation were assessed using a colorimetric thiazolyl blue (MTT) assay and on IEC-6 cell restitution using an in vitro wounding model. RESULTS: Physiological concentrations of zinc (25 microM) did not significantly alter the morphological appearance of IEC-6 cells. However, a 10-fold higher dose of zinc (250 microM) induced epithelial cell rounding, loss of adherence and apoptotic characteristics. While physiological zinc concentrations (< 100 microM) did not induce apoptosis, supraphysiological zinc concentrations (> 100 microM) caused apoptosis. Physiological concentrations of zinc (6.25-50 microM) had no significant effect on intestinal epithelial cell proliferation. In contrast, physiological concentrations of zinc (12.5-50 microM) significantly enhanced epithelial cell restitution through a transforming growth factor-beta (TGFbeta)-independent mechanism. Simultaneous addition of TGFbeta and zinc resulted in an additive stimulation of IEC-6 cell restitution. CONCLUSION: Zinc may promote intestinal epithelial wound healing by enhancement of epithelial cell restitution, the initial step of epithelial wound healing. Zinc supplementation may improve epithelial repair; however, excessive amounts of zinc may cause tissue injury and impair epithelial wound healing.     

Sleep-anticipating effects of melatonin in the human brain

Melatonin, the hormone produced nocturnally by the pineal gland, is an endogenous regulator of the sleep-wake cycle. The effects of melatonin on brain activities and their relation to induction of sleepiness were studied in a randomized, double-blind, placebo controlled functional magnetic resonance imaging (fMRI) study. Melatonin, but not placebo, reduced task-related activity in the rostro-medial aspect of the occipital cortex during a visual-search task and in the auditory cortex during a music task. These effects correlated with subjective measurements of fatigue. In addition, melatonin enhanced the activation in the left parahippocampus in an autobiographic memory task. Results demonstrate that melatonin modulates brain activity in a manner resembling actual sleep although subjects are fully awake. Furthermore, the fatigue inducing effect of melatonin on brain activity is essentially different from that of sleep deprivation thus revealing differences between fatigues related to the circadian sleep regulation as opposed to increased homeostatic sleep need. Our findings highlight the role of melatonin in priming sleep-associated brain activation patterns in anticipation of sleep.     

Home follow-up for the brain injured patient

The brain injured person deserves all the help possible to achieve maximum rehabilitation. Many disciplines are involved, with the rehabilitation nurse having a key role. This paper describes the ways a field rehabilitation nurse specialist helps provide for continuity and progress after discharge.     

外源性维生素对电离辐射损伤小鼠网织红细胞参数的影响

目的:观察系统使用抗氧化剂后辐射对小鼠网织红细胞损伤作用的变化,探讨抗氧化剂保护红系造血系统免受电离辐射损伤的作用。方法:实验于2004-03/06在军事医学科学院完成。连续给予小鼠维生素E·C复合剂后接受全身γ射线照射,随后取血观察网织红细胞参数。结果:网织红细胞参数检查结果表明,γ射线导致小鼠网织红细胞明显损伤,数量减少,功能下降,而预先给予维生素E·C复合剂能够明显减少射线对网织红细胞的损伤作用。结论:外源性维生素等抗氧化剂能够减缓电离辐射对造血系统的损伤,具有明显的辐射防护作用,并提示外源性补充维生素可能在辐射损伤后的康复过程中发挥重要作用。     

Cardio-cerebral and metabolic effects of methylene blue in hypertonic sodium lactate during experimental cardiopulmonary resuscitation

BACKGROUND: Methylene blue (MB) administered with a hypertonic-hyperoncotic solution reduces the myocardial and cerebral damage due to ischaemia and reperfusion injury after experimental cardiac arrest and also increases short-term survival. As MB precipitates in hypertonic sodium chloride, an alternative mixture of methylene blue in hypertonic sodium lactate (MBL) was developed and investigated during and after cardiopulmonary resuscitation (CPR). METHODS: Using an experimental pig model of cardiac arrest (12 min cardiac arrest and 8 min CPR) the cardio-cerebral and metabolic effects of MBL (n=10), MB in normal saline (MBS; n=10) or in hypertonic saline dextran (MBHSD; n=10) were compared. Haemodynamic variables and cerebral cortical blood flow (CCBF) were recorded. Biochemical markers of cerebral oxidative injury (8-iso-PGF2alpha), inflammation (15-keto-dihydro-PGF2alpha), and neuronal damage (protein S-100beta) were measured in blood from the sagittal sinus, whereas markers of myocardial injury, electrolytes, and lactate were measured in arterial plasma. RESULTS: There were no differences between groups in survival, or in biochemical markers of cerebral injury. In contrast, the MBS group exhibited not only increased CKMB (P<0.001) and troponin I in comparison with MBHSD (P=0.019) and MBL (P=0.037), but also greater pulmonary capillary wedge pressure 120 min after return of spontaneous circulation (ROSC). Lactate administration had an alkalinizing effect started 120 min after ROSC. CONCLUSIONS: Methylene blue in hypertonic sodium lactate may be used against reperfusion injury during experimental cardiac arrest, having similar effects as MB with hypertonic saline-dextran, but in addition better myocardial protection than MB with normal saline. The neuroprotective effects did not differ.     

Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains

We used voxel-based morphometry (VBM) to examine human brain asymmetry and the effects of sex and handedness on brain structure in 465 normal adults. We observed significant asymmetry of cerebral grey and white matter in the occipital, frontal, and temporal lobes (petalia), including Heschl's gyrus, planum temporale (PT) and the hippocampal formation. Males demonstrated increased leftward asymmetry within Heschl's gyrus and PT compared to females. There was no significant interaction between asymmetry and handedness and no main effect of handedness. There was a significant main effect of sex on brain morphology, even after accounting for the larger global volumes of grey and white matter in males. Females had increased grey matter volume adjacent to the depths of both central sulci and the left superior temporal sulcus, in right Heschl's gyrus and PT, in right inferior frontal and frontomarginal gyri and in the cingulate gyrus. Females had significantly increased grey matter concentration extensively and relatively symmetrically in the cortical mantle, parahippocampal gyri, and in the banks of the cingulate and calcarine sulci. Males had increased grey matter volume bilaterally in the mesial temporal lobes, entorhinal and perirhinal cortex, and in the anterior lobes of the cerebellum, but no regions of increased grey matter concentration.     

Dose-response effects of lactate infusions on gluconeogenesis from lactate in normal man

Abstract. Lactate is the predominant gluconeogenic precursor in man. To determine the dose-response relationships between plasma lactate concentration and rates of lactate incorporation in plasma glucose (lactate gluconeogenesis, LGN), we infused 17 normal volunteers with sodium lactate for 180 min at rates ranging from 6 to 40 γmol kg^-1 min^-1 and measured [U-¹⁴C]lactate incorporation into plasma glucose, as well as rates of lactate and glucose appearance in plasma. With the highest lactate infusions, plasma lactate increased up to 7 mM (compared to 1.1±0.13 mM during control sodium bicarbonate infusions, n=10) and LGN averaged 4.73 ± 0.23 μmol kg^-1 min^-1 (compared to 1.57 ± 0.26 μmol kg^-1 min^-l in bicarbonate control experiments, P< 0.001). The data relating plasma lactate concentration to LGN best fit a sigmoidal curve which plateaued at plasma lactate concentrations of approximately 6 mM and yielded an ED₅₀ of 2.04 ± 0.20 (SD) mM and a Vmax (6.25±1.2) (SD) (mUmol kg^-1 min^-1). The sum of the basal rate of lactate appearance and the rate of lactate infusion was not significantly different from the overall rates of lactate appearance during the lactate infusions (35.8±2.2 vs. 34.8±2.9 μmol kg^-1 min^-1, P = 0.23). Thus, our results support the view that infusion of exogenous lactate does not suppress endogenous lactate appearance in plasma.     

Metabonomic strategy for the detection of metabolic effects of probiotics combined with prebiotic supplementation in weaned rats

The purpose of this study is to investigate the effects of probiotics combined with prebiotics (PP) supplementation on weaned rat metabolism. A metabonomic strategy employing ¹H-NMR spectroscopy and multivariate data analysis was used to examine weaned rat biological responses to PP supplementation. Male Sprague-Dawley rats (post-natal day 21, PD 21) received probiotics (Lactobacillus acidophilus NCFM (L-NCFM) and Bifidobacterium lactis Bi-07 (B-LBi07), 1 : 1, 1.0 × 10¹¹ cfu kg⁻¹) and prebiotics (Lycium barbarum polysaccharides (LBP), Poria cocos polysaccharides (PCPs) and Lentinan, 1 : 1 : 1, 24 g kg⁻¹) via intragastric administration for 28 consecutive days. Urine and feces were collected for analysis. Significant topographical metabolic variations were present in urine and feces. Urinary metabolites upregulated by PP treatment included alanine, N-acetylglycine, glutamine, dimethylamine, phosphorylcholine, ethylene glycol, mannitol, phenylacetylglycine and glycoate, which were related to alanine, aspartate and glutamate metabolism, and choline metabolism. Feces-derived metabolites, including caproate, valerate, butyrate, propionate, lactate, acetate, succinate, methanol, threonine and methionine, were significantly increased, which were related to short-chain fatty acid (SCFA) metabolism and TCA cycle metabolism. These results indicate that dietary PP supplementation can regulate common systemic metabolic processes, including energy metabolism, amino acid metabolism, lipid metabolism, nucleic acid metabolism, and gut microbiota-related metabolism. This study also illuminates the vital role of PP supplementation in regulating the metabolism of weaned rats.

Dietary probiotic supplementation is beneficial to the growth of weaned rats by regulating the metabolism.     

Half-molar sodium lactate infusion to prevent intracranial hypertensive episodes in severe traumatic brain injured patients: a randomized controlled trial

Purpose

Preventive treatments of traumatic intracranial hypertension are not yet established. We aimed to compare the efficiency of half-molar sodium lactate (SL) versus saline serum solutions in preventing episodes of raised intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI).

Methods

This was a double-blind, randomized controlled trial including 60 patients with severe TBI requiring ICP monitoring. Patients were randomly allocated to receive a 48-h continuous infusion at 0.5 ml/kg/h of either SL (SL group) or isotonic saline solution (control group) within the first 12 h post-trauma. Serial measurements of ICP, as well as fluid, sodium, and chloride balance were performed over the 48-h study period. The primary outcome was the number of raised ICP (≥20 mmHg) requiring a specific treatment.

Results

Raised ICP episodes were reduced in the SL group as compared to the control group within the 48-h study period: 23 versus 53 episodes, respectively (p < 0.05). The proportion of patients presenting raised ICP episodes was smaller in the SL group than in the saline group: 11 (36 %) versus 20 patients (66 %) (p < 0.05). Cumulative 48-h fluid and chloride balances were reduced in the SL group compared to the control group (both p < 0.01).

Conclusion

A 48-h infusion of SL decreased the occurrence of raised ICP episodes in patients with severe TBI, while reducing fluid and chloride balances. These findings suggest that SL solution could be considered as an alternative treatment to prevent raised ICP following severe TBI.