Effects of Creatine Supplementation on Histopathological and Biochemical Parameters in the Kidney and Pancreas of Streptozotocin-Induced Diabetic Rats

Diabetes mellitus (DM) is a worldwide health concern, and projections state that cases will reach 578 million by 2030. Adjuvant therapies that can help the standard treatment and mitigate DM effects are necessary, especially those using nutritional supplements to improve glycemic control. Previous studies suggest creatine supplementation as a possible adjuvant therapy for DM, but they lack the evaluation of potential morphological parameters alterations and tissue injury caused by this compound. The present study aimed to elucidate clinical, histomorphometric, and histopathological consequences and the cellular oxidative alterations of creatine supplementation in streptozotocin (STZ)-induced type 1 DM rats. We could estimate whether the findings are due to DM or the supplementation from a factorial experimental design. Although creatine supplementation attenuated some biochemical parameters, the morphological analyses of pancreatic and renal tissues made clear that the supplementation did not improve the STZ-induced DM1 injuries. Moreover, creatine-supplemented non-diabetic animals were diagnosed with pancreatitis and showed renal tubular necrosis. Therefore, even in the absence of clinical symptoms and unaltered biochemical parameters, creatine supplementation as adjuvant therapy for DM should be carefully evaluated.     

Effects of Oral Creatine Supplementation on Power Output during Repeated Treadmill Sprinting

The aim of the present study was to examine the effects of creatine (Cr) supplementation on power output during repeated sprints on a non-motorized treadmill. Sixteen recreationally active males volunteered for this study (age 25.5 ± 4.8 y, height 179 ± 5 cm, body mass 74.8 ± 6.8 kg). All participants received placebo supplementation (75 mg of glucose·kg⁻¹·day⁻¹) for 5 days and then performed a baseline repeated sprints test (6 × 10 s sprints on a non-motorised treadmill). Thereafter, they were randomly assigned into a Cr (75 mg of Cr monohydrate·kg⁻¹·day⁻¹) or placebo supplementation, as above, and the repeated sprints test was repeated. After Cr supplementation, body mass was increased by 0.99 ± 0.83 kg (p = 0.007), peak power output and peak running speed remained unchanged throughout the test in both groups, while the mean power output and mean running speed during the last 5 s of the sprints increased by 4.5% (p = 0.005) and 4.2% to 7.0%, respectively, during the last three sprints (p = 0.005 to 0.001). The reduction in speed within each sprint was also blunted by 16.2% (p = 0.003) following Cr supplementation. Plasma ammonia decreased by 20.1% (p = 0.037) after Cr supplementation, despite the increase in performance. VO₂ and blood lactate during the repeated sprints test remained unchanged after supplementation, suggesting no alteration of aerobic or glycolytic contribution to adenosine triphosphate production. In conclusion, Cr supplementation improved the mean power and speed in the second half of a repeated sprint running protocol, despite the increased body mass. This improvement was due to the higher power output and running speed in the last 5 s of each 10 s sprint.     

Diagnostic and Pharmacological Potency of Creatine in Post-Viral Fatigue Syndrome

Post-viral fatigue syndrome (PVFS) is a widespread chronic neurological disease with no definite etiological factor(s), no actual diagnostic test, and no approved pharmacological treatment, therapy, or cure. Among other features, PVFS could be accompanied by various irregularities in creatine metabolism, perturbing either tissue levels of creatine in the brain, the rates of phosphocreatine resynthesis in the skeletal muscle, or the concentrations of the enzyme creatine kinase in the blood. Furthermore, supplemental creatine and related guanidino compounds appear to impact both patient- and clinician-reported outcomes in syndromes and maladies with chronic fatigue. This paper critically overviews the most common disturbances in creatine metabolism in various PVFS populations, summarizes human trials on dietary creatine and creatine analogs in the syndrome, and discusses new frontiers and open questions for using creatine in a post-COVID-19 world.     

Chronic Dialysis Patients Are Depleted of Creatine: Review and Rationale for Intradialytic Creatine Supplementation

There is great need for the identification of new, potentially modifiable risk factors for the poor health-related quality of life (HRQoL) and of the excess risk of mortality in dialysis-dependent chronic kidney disease patients. Creatine is an essential contributor to cellular energy homeostasis, yet, on a daily basis, 1.6–1.7% of the total creatine pool is non-enzymatically degraded to creatinine and subsequently lost via urinary excretion, thereby necessitating a continuous supply of new creatine in order to remain in steady-state. Because of an insufficient ability to synthesize creatine, unopposed losses to the dialysis fluid, and insufficient intake due to dietary recommendations that are increasingly steered towards more plant-based diets, hemodialysis patients are prone to creatine deficiency, and may benefit from creatine supplementation. To avoid problems with compliance and fluid balance, and, furthermore, to prevent intradialytic losses of creatine to the dialysate, we aim to investigate the potential of intradialytic creatine supplementation in improving outcomes. Given the known physiological effects of creatine, intradialytic creatine supplementation may help to maintain creatine homeostasis among dialysis-dependent chronic kidney disease patients, and consequently improve muscle status, nutritional status, neurocognitive status, HRQoL. Additionally, we describe the rationale and design for a block-randomized, double-blind, placebo-controlled pilot study. The aim of the pilot study is to explore the creatine uptake in the circulation and tissues following different creatine supplementation dosages.     

Effects of Low Doses of L-Carnitine Tartrate and Lipid Multi-Particulate Formulated Creatine Monohydrate on Muscle Protein Synthesis in Myoblasts and Bioavailability in Humans and Rodents

The primary objective of this study was to investigate the potential synergy between low doses of L-carnitine tartrate and creatine monohydrate to induce muscle protein synthesis and anabolic pathway activation in primary human myoblasts. In addition, the effects of Lipid multi-particulates (LMP) formulation on creatine stability and bioavailability were assessed in rodents and healthy human subjects. When used individually, L-carnitine tartrate at 50 µM and creatine monohydrate at 0.5 µM did not affect myoblast protein synthesis and signaling. However, when combined, they led to a significant increase in protein synthesis. Increased AKT and RPS6 phosphorylation were observed with 50 µM L-carnitine tartrate 5 µM creatine in combination in primary human myoblasts. When Wistar rats were administered creatine with LMP formulation at either 21 or 51 mg/kg, bioavailability was increased by 27% based on the increase in the area under the curve (AUC) at a 51 mg/kg dose compared to without LMP formulation. Tmax and Cmax were unchanged. Finally, in human subjects, a combination of LMP formulated L-carnitine at 500 mg (from L-carnitine tartrate) with LMP formulated creatine at 100, 200, or 500 mg revealed a significant and dose-dependent increase in plasma creatine concentrations. Serum total L-carnitine levels rose in a similar manner in the three combinations. These results suggest that a combination of low doses of L-carnitine tartrate and creatine monohydrate may lead to a significant and synergistic enhancement of muscle protein synthesis and activation of anabolic signaling. In addition, the LMP formulation of creatine improved its bioavailability. L-carnitine at 500 mg and LMP-formulated creatine at 200 or 500 mg may be useful for future clinical trials to evaluate the effects on muscle protein synthesis.     

Glycerol Monocaprylate Modulates Gut Microbiota and Increases Short-Chain Fatty Acids Production without Adverse Effects on Metabolism and Inflammation

Glycerol monocaprylate (GMC) is a glycerol derivative of medium-chain fatty acids (MCFAs) and is widely used as a preservative in food processing. However, GMC and its hydrolytic acid (octylic acid) have antibacterial properties that may affect the physiology and intestinal microecology of the human body. Therefore, in this study, the effects of two different dosages of GMC (150 and 1600 mg kg⁻¹) on glucose, lipid metabolism, inflammation, and intestinal microecology of normal diet-fed C57BL/6 mice were comprehensively investigated. The obtained results showed that the level of triglycerides (TGs) in the low-dose group down-regulated significantly, and the anti-inflammatory cytokine interleukin 10 (IL-10) significantly increased, while the pro-inflammatory cytokines monocyte chemotactic protein 1 (MCP-1) and interleukin 1beta (IL-1β) in the high-dose group were significantly decreased. Importantly, GMC promoted the α-diversity of gut microbiota in normal-diet-fed mice, regardless of dosages. Additionally, it was found that the low-dose treatment of GMC significantly increased the abundance of Lactobacillus, while the high-dose treatment of GMC significantly increased the abundance of SCFA-producers such as Clostridiales, Lachnospiraceae, and Ruminococcus. Moreover, the content of short-chain fatty acids (SCFAs) was significantly increased by GMC supplementation. Thus, our research provides a novel insight into the effects of GMC on gut microbiota and physiological characteristics.     

A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation

Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose–response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.     

Creatine Supplementation,Physical Exercise and Oxidative Stress Markers: A Review of the Mechanisms and Effectiveness

Oxidative stress is the result of an imbalance between the generation of reactive oxygen species (ROS) and their elimination by antioxidant mechanisms. ROS degrade biogenic substances such as deoxyribonucleic acid, lipids, and proteins, which in turn may lead to oxidative tissue damage. One of the physiological conditions currently associated with enhanced oxidative stress is exercise. Although a period of intense training may cause oxidative damage to muscle fibers, regular exercise helps increase the cells’ ability to reduce the ROS over-accumulation. Regular moderate-intensity exercise has been shown to increase antioxidant defense. Endogenous antioxidants cannot completely prevent oxidative damage under the physiological and pathological conditions (intense exercise and exercise at altitude). These conditions may disturb the endogenous antioxidant balance and increase oxidative stress. In this case, the use of antioxidant supplements such as creatine can have positive effects on the antioxidant system. Creatine is made up of two essential amino acids, arginine and methionine, and one non-essential amino acid, glycine. The exact action mechanism of creatine as an antioxidant is not known. However, it has been shown to increase the activity of antioxidant enzymes and the capability to eliminate ROS and reactive nitrogen species (RNS). It seems that the antioxidant effects of creatine may be due to various mechanisms such as its indirect (i.e., increased or normalized cell energy status) and direct (i.e., maintaining mitochondrial integrity) mechanisms. Creatine supplement consumption may have a synergistic effect with training, but the intensity and duration of training can play an important role in the antioxidant activity. In this study, the researchers attempted to review the literature on the effects of creatine supplementation and physical exercise on oxidative stress.     

The Dietary Supplement Creatyl-l-Leucine Does Not Bioaccumulate in Muscle,Brain or Plasma and Is Not a Significant Bioavailable Source of Creatine

Creatine is an important energy metabolite that is concentrated in tissues such as the muscles and brain. Creatine is reversibly converted to creatine phosphate through a reaction with ATP or ADP, which is catalyzed by the enzyme creatine kinase. Dietary supplementation with relatively large amounts of creatine monohydrate has been proven as an effective sports supplement that can enhances athletic performance during acute high-energy demand physical activity. Some side effects have been reported with creatine monohydrate supplementation, which have stimulated research into new potential molecules that could be used as supplements to potentially provide bioavailable creatine. Recently, a popular supplement, creatyl-l-leucine, has been proposed as a potential dietary ingredient that may potentially provide bioavailable creatine. This study tests whether creatyl-l-leucine is a bioavailable compound and determines whether it can furnish creatine as a dietary supplement. Rats were deprived of dietary creatine for a period of two weeks and then given one of three treatments: a control AIN-93G creatine-free diet, AIN-93G supplemented with creatine monohydrate or AIN-93G with an equimolar amount of creatyl-l-leucine supplement in the diet for one week. When compared to the control and the creatine monohydrate-supplemented diet, creatyl-l-leucine supplementation resulted in no bioaccumulation of either creatyl-l-leucine or creatine in tissue.     

Role of Creatine in the Heart: Health and Disease

Creatine is a key player in heart contraction and energy metabolism. Creatine supplementation (throughout the paper, only supplementation with creatine monohydrate will be reviewed, as this is by far the most used and best-known way of supplementing creatine) increases creatine content even in the normal heart, and it is generally safe. In heart failure, creatine and phosphocreatine decrease because of decreased expression of the creatine transporter, and because phosphocreatine degrades to prevent adenosine triphosphate (ATP) exhaustion. This causes decreased contractility reserve of the myocardium and correlates with left ventricular ejection fraction, and it is a predictor of mortality. Thus, there is a strong rationale to supplement with creatine the failing heart. Pending additional trials, creatine supplementation in heart failure may be useful given data showing its effectiveness (1) against specific parameters of heart failure, and (2) against the decrease in muscle strength and endurance of heart failure patients. In heart ischemia, the majority of trials used phosphocreatine, whose mechanism of action is mostly unrelated to changes in the ergogenic creatine-phosphocreatine system. Nevertheless, preliminary data with creatine supplementation are encouraging, and warrant additional studies. Prevention of cardiac toxicity of the chemotherapy compounds anthracyclines is a novel field where creatine supplementation may also be useful. Creatine effectiveness in this case may be because anthracyclines reduce expression of the creatine transporter, and because of the pleiotropic antioxidant properties of creatine. Moreover, creatine may also reduce concomitant muscle damage by anthracyclines.     

Effects of Dietary Arabinogalactan on Gastrointestinal and Blood Parameters in Healthy Human Subjects

Objectives: Arabinogalactan (AG) is a non-digestible soluble dietary fiber that resists hydrolytic enzyme action and enters the large bowel intact where it is fermented by resident microflora. To determine whether AG has similar physiological properties to other soluble dietary fibers, we examined the effect of 15 and 30 g per day of a commercially available AG from Western Larch on several gastrointestinal and blood parameters.

Methods: Gastrointestinal parameters included fecal microflora, fecal enzyme activity, fecal short-chain fatty acids, fecal pH, fecal weight, transit time and bowel frequency. Blood parameters included total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, Apo-A1, Apo-B, glucose and insulin. The study consisted of two three-week diet treatments with no washout period. Participants (n=20, 11 males, 9 females) consumed their usual diet in addition to 15 or 30 g AG in a beverage sweetened with aspartame as compared to their usual diet with the control beverage.

Results: Significant increases in total fecal anaerobes were observed with 15 g (p=0.01) and 30 g AG (p=0.001). A significant increase (p=0.02) in Lactobacillus spp. was observed when subjects consumed AG for a total of six weeks regardless of dose. There were no significant changes in other microflora, fecal enzyme activity, transit time, frequency, fecal weight, fecal pH and short-chain fatty acids. Fecal ammonia levels decreased with 15 g (p=0.001) and 30 g (p=0.002) AG. No significant changes in blood lipids or blood insulin were observed.

Conclusions: These data suggest that dietary AG is easily incorporated into the diet, well tolerated in subjects and has some positive effects on fecal chemistry.     

Metabolic Basis of Creatine in Health and Disease: A Bioinformatics-Assisted Review

Creatine (Cr) is a ubiquitous molecule that is synthesized mainly in the liver, kidneys, and pancreas. Most of the Cr pool is found in tissues with high-energy demands. Cr enters target cells through a specific symporter called Na⁺/Cl⁻-dependent Cr transporter (CRT). Once within cells, creatine kinase (CK) catalyzes the reversible transphosphorylation reaction between [Mg²⁺:ATP⁴⁻]²⁻ and Cr to produce phosphocreatine (PCr) and [Mg²⁺:ADP³⁻]⁻. We aimed to perform a comprehensive and bioinformatics-assisted review of the most recent research findings regarding Cr metabolism. Specifically, several public databases, repositories, and bioinformatics tools were utilized for this endeavor. Topics of biological complexity ranging from structural biology to cellular dynamics were addressed herein. In this sense, we sought to address certain pre-specified questions including: (i) What happens when creatine is transported into cells? (ii) How is the CK/PCr system involved in cellular bioenergetics? (iii) How is the CK/PCr system compartmentalized throughout the cell? (iv) What is the role of creatine amongst different tissues? and (v) What is the basis of creatine transport? Under the cellular allostasis paradigm, the CK/PCr system is physiologically essential for life (cell survival, growth, proliferation, differentiation, and migration/motility) by providing an evolutionary advantage for rapid, local, and temporal support of energy- and mechanical-dependent processes. Thus, we suggest the CK/PCr system acts as a dynamic biosensor based on chemo-mechanical energy transduction, which might explain why dysregulation in Cr metabolism contributes to a wide range of diseases besides the mitigating effect that Cr supplementation may have in some of these disease states.     

Effects of Creatine Supplementation on Brain Function and Health

While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.     

Sex-Specific Effects of Chronic Creatine Supplementation on Hippocampal-Mediated Spatial Cognition in the 3xTg Mouse Model of Alzheimer’s Disease

The creatine (Cr) energy system has been implicated in Alzheimer’s disease (AD), including reductions in brain phosphoCr and Cr kinase, yet no studies have examined the neurobehavioral effects of Cr supplementation in AD, including the 3xTg mouse model. This studied investigated the effects of Cr supplementation on spatial cognition, plasticity- and disease-related protein levels, and mitochondrial function in the 3xTg hippocampus. Here, 3xTg mice were fed a control or Cr-supplemented (3% Cr (w/w)) diet for 8–9 weeks and tested in the Morris water maze. Mitochondrial oxygen consumption (Seahorse) and protein levels (Western blots) were measured in the hippocampus in subsets of mice. Overall, 3xTg females exhibited impaired memory as compared to males. In females, Cr supplementation decreased escape latency and was associated with increased spatial search strategy use. In males, Cr supplementation decreased the use of spatial search strategies. Pilot data indicated mitochondrial enhancements with Cr supplementation in both sexes. In females, Cr supplementation increased CREB phosphorylation and levels of IκB (NF-κB suppressor), CaMKII, PSD-95, and high-molecular-weight amyloid β (Aβ) species, whereas Aβ trimers were reduced. These data suggest a beneficial preventative effect of Cr supplementation in females and warrant caution against Cr supplementation in males in the AD-like brain.     

Studies on the Reaction of Dietary Methylglyoxal and Creatine during Simulated Gastrointestinal Digestion and in Human Volunteers

The reactive 1,2-dicarbonyl compound methylglyoxal (MGO) is consumed with food and its concentrations decrease during digestion. In the present paper, the reaction of MGO with creatine, arginine, and lysine during simulated digestion, and its reaction with creatine during the digestion in human volunteers, was studied. Therefore, simulated digestion experiments with a gastric and an intestinal phase were performed. Additionally, an intervention study with 12 subjects consuming MGO-containing Manuka honey and creatine simultaneously or separately was conducted. Derivatization with o-phenylenediamine and HPLC–UV was used to measure MGO, while creatine and glycated amino compounds were analyzed via HPLC–MS/MS. We show that MGO quickly reacts with creatine and arginine, but not lysine, during simulated digestion. Creatine reacts with 56% of MGO to form the hydroimidazolone MG-HCr, and arginine reacted with 4% of MGO to form the hydroimidazolone MG-H1. In the intervention study, urinary MG-HCr excretion is higher in subjects who consumed MGO and creatine simultaneously compared to subjects who ingested the substances separately. This demonstrates that the 1,2-dicarbonyl compound MGO reacts with amino compounds during human digestion, and glycated adducts are formed. These contribute to dietary glycation products consumed, and should be considered in studies investigating their physiological consequences.     

Creatine Supplementation Upregulates mTORC1 Signaling and Markers of Synaptic Plasticity in the Dentate Gyrus While Ameliorating LPS-Induced Cognitive Impairment in Female Rats

Mild cognitive impairment (MCI) designates the boundary area between cognitive function in natural aging and dementia, and this is viewed as a therapeutic window to prevent the occurrence of dementia. The current study investigated the neurocognitive effects of oral creatine (Cr) supplementation in young female Wistar rats that received intracerebroventricular injections of lipopolysaccharide (LPS) to mimic MCI. Neuromolecular changes within the dentate gyrus were analyzed following behavioral testing. We also investigated both neurocognitive and neuromolecular changes following Cr supplementation in the absence of LPS in young female Wistar rats to further investigate mechanisms. Interestingly, based on trial 2 of Barnes maze test, Cr supplementation ameliorated spatial learning and memory deficit induced by LPS, shown by decreased latency time and errors to reach the escape box (p < 0.0001, n = 12). Cr supplementation also attenuated recognition memory deficit induced by LPS, shown by increased amount of time taken to explore the new object (p = 0.002, n = 12) during novel object recognition testing. Within the dentate gyrus, Cr supplementation in LPS injected rats upregulated mTORC1 signaling (p = 0.026 for mTOR phosphorylation, p = 0.002 for p70S6K phosphorylation, n = 8) as well as the synapsin (p = 0.008) and PSD-95 synaptic proteins (p = 0.015), in comparisons to LPS injected rats. However, Cr supplementation failed to further enhance spatial memory and recognition memory in the absence of LPS. In conclusion, Cr ameliorates LPS-induced cognitive impairment in a rodent MCI model. Mechanistically, these phenotypic effects may, in part, be mitigated via an upregulation of mTORC1 signaling, and an enhancement in synaptogenesis in the dentate gyrus. While preliminary, these findings may inform future research investigating neurocognitive effects of Cr for MCI patients.     

中医配合磷酸肌酸钠治疗一氧化碳中毒的疗效分析

目的分析与评价中医配合磷酸肌酸钠在治疗一氧化碳中毒过程中的疗效,为一氧化碳中毒的治疗提供指导。方法选择2012年6月至2014年12月该院收治的120例一氧化碳中毒患者为研究对象,按照治疗方式不同分为观察组和对照组,每组各60例。对照组患者采用高压氧等常规治疗,观察组患者加用中医药方配合磷酸肌酸钠治疗。比较2组患者治疗前后HDS评分、P300潜伏期、神经功能损伤评分和心肌损伤标志物变化,评价2组患者疗效差异。结果治疗后观察组患者与对照组相比HDS评分明显升高,P300潜伏期明显缩短(P0.05),NIHSS评分和血清c TNI、CKMB、IMA水平明显降低(P0.05),观察组患者的治疗效果显著优于对照组(P0.05)。结论中医配合磷酸肌酸钠治疗一氧化碳中毒能够有效改善心脏和脑组织缺氧状态,减轻神经功能损伤,疗效显著优于单一高压氧常规治疗。     

The Effects of Copper on Blood and Biochemical Parameters of Rainbow Trout (Oncorhynchus mykiss)

Metals are released into aquatic systems from many sources, often at sublethal concentrations. The effects of sublethal concentrations of metals on fish are not entirely understood. The objective of this study was to determine the hematological and biochemical effects of a range of copper concentrations (6.4, 16.0, 26.9 μg Cu/L) on rainbow trout (Oncorhynchus mykiss) over a prolonged period of time. Trout were exposed to copper, and, at intervals of 3, 7, 14, and 21 days, selected parameters were evaluated. Hemoglobin, hematocrit, plasma glucose, and plasma cortisol levels were elevated in trout exposed to 26.9 μg Cu/L at day 3 and then returned to levels comparable to control fish. Plasma protein and lactate levels were not significantly altered in trout from any copper treatment. Hepatic copper concentration and hepatic metallothionein mRNA expression were consistently elevated in trout exposed to 26.9 μg Cu/L. Both of these parameters stabilized by day 3, with only hepatic copper concentration showing a further increase at day 21. Hepatic copper concentration and hepatic metallothionein mRNA expression appear to be robust indicators of copper exposure. Most blood-based parameters evaluated appear to be associated with a transitory, nonspecific stress response. The return of elevated hematological and biochemical parameters to control levels after 3 days and the stabilization of hepatic metallothionein mRNA expression and copper concentration over a similar time period suggested acclimation to dissolved copper at 26.9 μg/L. Further analysis of the data on blood-based parameters indicated that certain parameters (hemoglobin, hematocrit, plasma glucose, plasma cortisol) may be useful in field monitoring. Received: 12 July 1998/Accepted: 13 December 1998     

注射用磷酸肌酸钠治疗难治性心力衰竭的临床观察

目的探讨注射用磷酸肌酸钠治疗难治性心力衰竭的临床疗效。方法将26例难治性心力衰竭患者随机分为对照组（13例）和治疗组（13例）。对照组给予吸氧、休息、强心、利尿、扩血管、抗感染、纠正心律失常和电解质紊乱,控制液体入量。治疗组在对照组治疗的基础上加生理盐水100—250m1加注射用磷酸肌酸钠1—2g,静脉滴注,1次／d。两组均两周为一疗程。结果治疗组临床疗效优于对照组（总有效率92．3％对76．9％,P〈0．05）;治疗组治疗后LVEF明显改善（P〈0．01）,且优于对照组（P〈0．05）;治疗组治疗后V1导联P波终末电势较对照组明显改善（P〈0．01）。结论注射用磷酸肌酸钠能提高临床疗效,改善左心室射血分数（LVEF）和V1导联P波终末电势,是治疗难治性心力衰竭的有效药物。