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There is a lack of evidence on the additional benefits of combining caffeine (CAF) and creatine (CRE) supplementation on anaerobic power and capacity. Thus, the aim of the present study was to test the effects of combined and isolated supplementation of CAF and CRE on anaerobic power and capacity. Twenty-four healthy men performed a baseline Wingate anaerobic test and were then allocated into a CRE (n = 12) or placebo (PLA; n = 12) group. The CRE group ingested 20 g/day of CRE for 8 days, while the PLA group ingested 20 g/day of maltodextrin for the same period. On the sixth and eighth days of the loading period, both groups performed a Wingate anaerobic test 1 hr after either CAF (5 mg/kg of body mass; CRE + CAF and PLA + CAF conditions) or PLA (5 mg/kg of body mass of cellulose; CRE + PLA and PLA + PLA conditions) ingestion. After the loading period, changes in body mass were greater (p <.05) in the CRE (+0.87 ± 0.23 kg) than in the PLA group (+0.13 ± 0.27 kg). In both groups, peak power was higher (p =.01) in the CAF (1,033.4 ± 209.3 W) than in the PLA trial (1,003.3 ± 204.4 W), but mean power was not different between PLA and CAF trials (p >.05). In conclusion, CAF, but not CRE ingestion, increases anaerobic power. Conversely, neither CRE nor CAF has an effect on anaerobic capacity. [ABSTRACT FROM AUTHOR]

Initial definitions of sarcopenia included the age-associated loss of skeletal muscle mass that was presumed to be associated with late-life reduced functional capacity, disability and loss of independence. Because no method for determination of muscle mass was available for large cohort studies of aging men and women, lean body mass determined by dual X-ray absorptiometry or bioelectrical impedance was used as a surrogate measure of muscle mass. The data from these studies showed either no or a poor relationship between LBM and functional capacity and health related outcomes, leading to the conclusion of many that the amount of muscle may not be associated with these age-associated outcomes. It was assumed that some undefined index of muscle quality is the critical contributor. These studies also consistently showed that muscle strength is lost more quickly than lean mass. Total body muscle mass can now be measured directly, accurately and non-invasively using the D3creatine (D3Cr) dilution method. D3Cr muscle mass, but not DXA derived LBM, is strongly associated with functional capacity, falls and insulin resistance in older men and women. In addition, D3Cr muscle mass is associated with risk of disability, hip fracture and mortality. New and emerging data demonstrate that low muscle mass may serve as a diagnostic criterion for sarcopenia.

Background: Severe trauma is the leading cause of disability and mortality in the patients under 35 years of age. Surgical site infections (SSI) represent a significant complication in this patient population. However, they are often inadequately investigated, potentially impacting the quality of patient outcomes. The aim of this study was to investigate the epidemiology of SSI and risk factors in severe trauma patients. Methods: We conducted a multicenter retrospective cohort study screening the severe trauma patients (STP) admitted to two intensive care units of an academic institution in Marseille between years2018 and 2019. Those who underwent orthopedic or spinal surgery within 5 days after admission were included and classified into two groups according to the occurrence of SSI (defined by the Centers for Disease Control (CDC) international diagnostic criteria) or not. Our secondary goal was to evaluate STP survival at 48 months, risk factors for SSI and microbiological features of SSI. Results: Forty-seven (23%) out of 207 STP developed an SSI. Mortality at 48-months did not differ between SSI and non-SSI patients (12.7% vs. 10.0%; p = 0.59). The fractures of 22 (47%) severe trauma patients with SSI were classified as Cauchoix 3 grade and 18 (38%) SSI were associated with the need for external fixators. Thirty (64%) severe trauma patients with SSI had polymicrobial infection, including 34 (72%) due to Gram-positive cocci. Empirical antibiotic therapy was effective in 31 (66%) cases. Multivariate analysis revealed that risk factors such as low hemoglobin, arterial oxygenation levels, hyperlactatemia, high serum creatinine and glycemia, and Cauchoix 3 grade on the day of surgery were associated with SSI in severe trauma patients. The generated predictive model showed a good prognosis performance with an AUC of 0.80 [0.73–0.88] and a high NPV of 95.9 [88.6–98.5] %. Conclusions: Our study found a high rate of SSI in severe trauma patients, although SSI was not associated with 48-month mortality. Several modifiable risk factors for SSI may be effectively managed through enhanced perioperative monitoring and the implementation of a patient blood management strategy. [ABSTRACT FROM AUTHOR]

Simple Summary: Guanidinoacetic acid (GAA) is a natural derivative of amino acids. They are acted upon by enzymes in the liver and transformed into essential components of the energy metabolism of muscle and nervous tissue. Although the animal synthesizes creatine, the amount is less than necessary for high growth rates, according to researchers. GAA consumed by cattle reduces fat between muscle fibers and serum cholesterol. It has a mild but positive effect on the fatty acid profile of meat—i.e., it increases myristoleic, linoleic, and arachidonic acids. We also concluded that GAA consumption increases the amount of volatile fatty acids in the rumen, especially acetic, propionic, and butyric acid. We draw attention to the acetic acid related to lipid synthesis. With the increase in population, it is increasingly necessary to produce food more efficiently. This has expanded the market for additives, which are products that directly (nutritional effect) or indirectly (effect on animal health) favor productivity. Guanidinoacetic acid (GAA) is a natural precursor of creatine. It acts as an energy reserve in skeletal muscle. In addition to being a compound with more significant bioavailability, it is more thermally stable and less expensive than creatine. Therefore, this study aimed to determine whether adding GAA to the cattle diet would alter the meat's composition and fatty acid profile. We used 24 Holstein cattle males (409 ± 5.6 kg), approximately 15 months old, and separated them into four homogeneous groups, one being the control group and three groups with various dosages of GAA in the diets (3.3; 6.6, and 9.9 g/animal/day), for an experimental period of 60 days. Blood, rumen fluid, and animal weighing were performed at three points (days 1, 30, and 60), and daily feed consumption was measured. Steers fed with GAA (9.9 g/d) showed a 16.9% increase in average daily gain (ADG) compared to the control group. These same animals (T-9.9 group) fed with GAA showed a 20% increase in fed efficiency compared to the control group. Lower leukocyte, lymphocyte, and granulocyte counts and lower cholesterol levels were observed in animals that consumed 6.6 g and 9.9 g/d GAA compared to the control group. Animals from the T-6.6 and T-9.9 groups showed 30% and 27.6% reduced bacterial activity in the rumen compared to the control group, respectively. Steers from the T-6.6 and T-9.9 groups fed with GAA showed a 20% and 37% increase in short-chain fatty acids (SCFAs) compared to the control group, respectively. A higher concentration of acetic, propionic, and butyric acids in the ruminal fluid of cattle T-9.9 group was observed at day 60. The two highest doses of GAA showed lower fat levels in the meat, just as the cattle that received 9.9 g/d showed higher levels of total polyunsaturated fatty acids. Complementary data results draw attention to the dose of 9.9 g/d GAA in cattle diets, as anti-inflammatory action can be seen and combined with a higher concentration of SCFAs, consequently increases weight gain. We concluded that consuming this GAA increases the concentration of some unsaturated fatty acids (omegas) in the meat, which adds quality to the product for the consumer. [ABSTRACT FROM AUTHOR]

Summary: Retinopathy and albuminuria are associated with hip fracture risk. We investigated whether these disorders and endothelial dysfunction (which underlies microvascular diseases) were associated with low trabecular bone density. No significant associations were found, suggesting that microvascular diseases are not related to fracture risk through low trabecular bone density. Purpose: Microvascular diseases of the eye, kidney, and brain are associated with endothelial dysfunction and increased hip fracture risk. To explore the basis for higher hip fracture risk, we comprehensively examined whether markers of microvascular disease and/or endothelial dysfunction are related to trabecular bone mineral density (BMD), a proximate risk factor for osteoporotic fractures. Methods: Among 6814 participants in the Multi-Ethnic Study of Atherosclerosis study (MESA), we derived thoracic vertebral trabecular BMD from computed tomography of the chest and measured urine albumin to creatinine ratios (UACR), retinal arteriolar and venular widths, flow mediated dilation (FMD) of the brachial artery after 5 min of ischemia; and levels of five soluble endothelial adhesion markers (ICAM-1, VCAM-1, L-selectin, P-selectin, and E-selectin). Linear regression models were used to examine the association of trabecular BMD with markers of microvascular disease and with markers of endothelial dysfunction. Results: We observed no significant associations of UACR, retinal arteriolar or venular widths, or FMD with BMD. We also observed no statistically significant association of spine trabecular BMD with levels of endothelial adhesion markers. Men and women had largely similar results. Conclusion: We conclude that there is little evidence to connect thoracic spine trabecular BMD to microvascular disorders or to endothelial dysfunction among multi-ethnic middle-aged and older adults. Other factors beyond trabecular BMD (e.g., bone quality or predisposition to falling) may be responsible for the associations of microvascular disease with osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Relaxation correction is an integral step in quantifying brain metabolite concentrations measured by in vivo magnetic resonance spectroscopy (MRS). While most quantification routines assume constant T1 relaxation across age, it is possible that aging alters T1 relaxation rates, as is seen for T2 relaxation. Here, we investigate the age dependence of metabolite T1 relaxation times at 3 T in both gray‐ and white‐matter‐rich voxels using publicly available metabolite and metabolite‐nulled (single inversion recovery TI = 600 ms) spectra acquired at 3 T using Point RESolved Spectroscopy (PRESS) localization. Data were acquired from voxels in the posterior cingulate cortex (PCC) and centrum semiovale (CSO) in 102 healthy volunteers across 5 decades of life (aged 20–69 years). All spectra were analyzed in Osprey v.2.4.0. To estimate T1 relaxation times for total N‐acetyl aspartate at 2.0 ppm (tNAA2.0) and total creatine at 3.0 ppm (tCr3.0), the ratio of modeled metabolite residual amplitudes in the metabolite‐nulled spectrum to the full metabolite signal was calculated using the single‐inversion‐recovery signal equation. Correlations between T1 and subject age were evaluated. Spearman correlations revealed that estimated T1 relaxation times of tNAA2.0 (rs = −0.27; p < 0.006) and tCr3.0 (rs = −0.40; p < 0.001) decreased significantly with age in white‐matter‐rich CSO, and less steeply for tNAA2.0 (rs = −0.228; p = 0.005) and (not significantly for) tCr3.0 (rs = −0.13; p = 0.196) in graymatter‐rich PCC. The analysis harnessed a large publicly available cross‐sectional dataset to test an important hypothesis, that metabolite T1 relaxation times change with age. This preliminary study stresses the importance of further work to measure age‐normed metabolite T1 relaxation times for accurate quantification of metabolite levels in studies of aging. [ABSTRACT FROM AUTHOR]

Purpose: Demonstrate the feasibility and evaluate the performance of single‐shot diffusion trace‐weighted radial echo planar spectroscopic imaging (Trace DW‐REPSI) for quantifying the trace ADC in phantom and in vivo using a 3T clinical scanner. Theory and Methods: Trace DW‐REPSI datasets were acquired in 10 phantom and 10 healthy volunteers, with a maximum b‐value of 1601 s/mm2 and diffusion time of 10.75 ms. The self‐navigation properties of radial acquisitions were used for corrections of shot‐to‐shot phase and frequency shift fluctuations of the raw data. In vivo trace ADCs of total NAA (tNAA), total creatine (tCr), and total choline (tCho) extrapolated to pure gray and white matter fractions were compared, as well as trace ADCs estimated in voxels within white or gray matter‐dominant regions. Results: Trace ADCs in phantom show excellent agreement with reported values, and in vivo ADCs agree well with the expected differences between gray and white matter. For tNAA, tCr, and tCho, the trace ADCs extrapolated to pure gray and white matter ranged from 0.18–0.27 and 0.26–0.38 μm2/ms, respectively. In sets of gray and white matter‐dominant voxels, the values ranged from 0.21 to 0.27 and 0.24 to 0.31 μm2/ms, respectively. The overestimated trace ADCs from this sequence can be attributed to the short diffusion time. Conclusion: This study presents the first demonstration of the single‐shot diffusion trace‐weighted spectroscopic imaging sequence using radial echo planar trajectories. The Trace DW‐REPSI sequence could provide an estimate of the trace ADC in a much shorter scan time compared to conventional approaches that require three separate measurements. [ABSTRACT FROM AUTHOR]

Introduction: Some papers describe the presence of creatine in plants, based on a singlet signal at 3.02-3.05 ppm in the 1H NMR spectra. Although is there creatine in plants? Therefore, to answer this question, a comprehensive NMR investigation has been performed aiming the unambiguous assignment of the compound responsible for that signal. Objective: Determine whether the compound behind the signal at 3.05 ppm is truly creatine or if it was just a misassignment, instead. Methods: Samples of leaves and cherries from Eugenia uniflora in their natural swollen state were submitted to HR-MAS NMR analysis. Results: It was found that the signal at 3.05 ppm was misassigned to creatine. The exhaustive NMR investigation revealed that the signal is related to the amino acid 4-hydroxy-N-methyl proline, instead. Conclusion: The comprehensive NMR investigation revealed that there is no creatine in plants, it was just a misassignment. [ABSTRACT FROM AUTHOR]

AbstractDoxorubicin (Dox) is an effective and commonly used anticancer drug; however, it leads to several side effects including cardiotoxicity which contributes to poor quality of life for cancer patients. Creatine (Cr) is a promising intervention to alleviate Dox-induced cardiotoxicity. This study aimed to examine the effects of Cr beforeDox on cardiac mitochondrial creatine kinase (MtCK). Male rats were randomly assigned to one of two 4-week Cr feeding interventions (standard Cr diet or Cr loading diet) or a control diet (Con, n = 20). Rats in the standard Cr diet (Cr1, n = 20) were fed 2% Cr for 4-weeks. Rats in the Cr loading diet (Cr2, n = 20) were fed 4% Cr for 1-week followed by 2% Cr for 3-weeks. After 4-weeks, rats received either a bolus injection of 15 mg/kg Dox or a placebo saline injection (Sal). Five days post-injections left ventricle (LV) was excised and analyzed for MtCK expression using Western blot and ELISA. A significant drug effect was observed for LV mass (p < 0.05), post hoc testing revealed LV mass of Con + Dox and Cr2 + Dox was significantly lower than Con + Sal (p < 0.05). A significant drug effect was observed for MtCK (p = 0.03) through Western blot. A significant drug effect (p = 0.03) and interaction (p = 0.02) was observed for MtCK using ELISA. Post hoc testing revealed that Cr2 + Dox had significantly higher MtCK than Cr1 + Sal and Cr2 + Sal. Data suggest that a reduction in LV mass and MtCK may contribute to Dox-induced cardiotoxicity, and Cr supplementation may play a potential role in mitigating cardiotoxicity by preserving mitochondrial CK. [ABSTRACT FROM AUTHOR]

Epilepsy can be caused by a variety of causes, such as inborn errors of metabolism, organic acid disorders are the most significant type of metabolic disorders that cause seizures. The clinical manifestations of these diseases are generally nonspecific, and the types of seizures are different. Screening for multisystem clinical symptoms and identifying the underlying etiology are crucial for early treatment of epileptic seizures. This article provides a comprehensive summary of the pathogenesis, clinical features, diagnosis and treatment of epilepsy associated with organic acid metabolism disorders. Furthermore, relevant literature has also been reviewed to assist clinicians in the diagnosis of cases characterized by the coexistence of multisystemic symptoms and epileptic manifestations. [ABSTRACT FROM AUTHOR]

Introduction Creatine, a supplement popular especially among athletes, is gaining increasive attention from scientists worldwide due to its potential health benefits, among other things, in the context of its anti-cancer application. Materials and methods The following review of studies is based on scientific articles from recent years available in the PubMed and Google Scholar databases. Key search terms included: "creatine", "creatine supplementation", "creatine in sports", "supplementation in sports", "creatine in cancer”. Results The literature review unequivocally demonstrates the beneficial impact of creatine supplementation on numerous health and athletic aspects. Creatine has been observed to have a positive effect on selected aspects of cancer treatment, such as reducing tumor mass, complementing the action of commonly used anticancer drugs, and slowing down the wasting associated with cancer diseases. Conclusion The promising results of the cited studies indicate that further research into creatine supplementation and its mechanisms of action is necessary. There is a need for further research on the positive impact of creatine supplementation in the treatment of cancer diseases. The significant potential of creatine supplementation may enable its inclusion in clinical practice in the future and the development of an effective therapeutic strategy based on it in the treatment of cancer diseases. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia is a prevalent psychiatric disorder that affects 1% of the global population. Schizophrenia frequently begins in late adolescence or early adulthood, causing significant educational, social, and economic costs for people and society. Functional neuroimaging research on schizophrenia physiopathology has been beneficial. Arterial spin labelling (ASL) is one of functional magnetic resonance imaging (fMRI) technologies that assess brain function without radiation. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Arterial spin labelling (ASL) is one of the functional magnetic resonance imaging (fMRI) technologies that assess the brain function without radiation hazards. ASL uses magnetic resonance (MR) imaging to quantify tissue-level brain perfusion non-invasively. Many publications were performed on role of different advanced MRI techniques in schizophrenia, but our study insisted on the added value of combined ASL and MRS over the conventional MRI in schizophrenic Egyptian population sample. Aim of the work: The purpose of this work was to evaluate the added value of combined ASL-perfusion MRI and MRS in schizophrenic patients. Methods: This prospective case–control study was carried out on two groups: First group was 30 patients who were diagnosed clinically as schizophrenic patients, and second group was 20 healthy volunteers as a control group for comparison in the period from August 2021 till July 2022. Results: The majority of newly diagnosed cases had significant higher positive symptoms than chronic cases. According to arterial spin labelling (ASL) data, rCBF was noticed to be reduced in anterior cingulate, frontal lobe, and parietal lobe of both patients' subgroups but more significant in chronically ill patients. Convergent results of decreased rCBF were also found in the parietal lobe and occipital lobe. Magnetic resonance spectroscopic analysis showed that NAA was decreased in the anterior cingulate cortex, thalami and basal ganglia of the newly diagnosed cases more than chronic cases. The ASL-MRI perfusion accurately detected the hypo-perfusion of different brain regions with sensitivity 100%, specificity 66.67%, positive predictive value 96.43%, negative predictive value 100%, and accuracy 96.67%, while MR spectroscopy showed sensitivity 100%, specificity 33.33%, positive predictive value 93.10%, negative predictive value 100%, and accuracy 93.33% in evaluation of changes of brain metabolites. Conclusion: ASL is a promising functional MRI technique that can produce together with MRS quantitative information about the metabolites of different brain regions. The ASL-MRI appears as a reliable non-invasive technique to measure cerebral blood flow and identify decreased rCBF without any contrast administration, and it could be repeatable which helps in early diagnosis as well as follow-up of the progression of the disease. [ABSTRACT FROM AUTHOR]

OBJECTIVES Pharmacological postconditioning can protect against myocardial ischaemia-reperfusion injury during cardiac surgery with extracorporeal circulation. The aim of this study was to observe the protective effects of fructose-1,6-bisphosphate (FDP) postconditioning on myocardial ischaemia-reperfusion injury in patients undergoing cardiac valve replacement with extracorporeal circulation. METHODS Patients undergoing elective mitral valve replacement and/or aortic valve replacement were divided into normal saline postconditioning group (NS group) and FDP postconditioning group (FDP group). The primary outcome was the plasma concentration of creatine kinase-MB (CK-MB). The secondary outcomes were the plasma concentrations of lactate dehydrogenase, CK, high-sensitivity C-reactive protein, alpha-hydroxybutyrate dehydrogenase and cardiac troponin I, the spontaneous cardiac rhythm recovery profile, the extracorporeal circulation time and duration of surgery, intensive care unit and postoperative hospitalization. RESULTS Forty patients were randomly assigned to receive intervention and included in the analysis. The serum concentrations of CK-MB, lactate dehydrogenase, CK, cardiac troponin I, alpha-hydroxybutyrate dehydrogenase and high-sensitivity C-reactive protein at T1∼4 were lower in the FDP group than in the NS group (P  <   0.001). Compared with the NS group, the dosage of dopamine administered 1–90 min after cardiac resuscitation, the spontaneous cardiac rhythm recovery time and the incidence of ventricular fibrillation were lower in the FDP group (P  <   0.001, P  <   0.001 and P  =   0.040, respectively). The values of ST- changes were increased more significantly in the NS group than in the FDP group (median [standard deviation] 1.3 [0.3] mm vs 0.7 [0.2] mm; P  <   0.001). Compared with the NS group, the time of recovery of ST-segment deviations was shorter in the FDP group (50.3 [12.3] min vs 34.6 [6.9] min; P  <   0.001). CONCLUSIONS The FDP postconditioning could improve both myocardial ischaemia-reperfusion injury and the spontaneous cardiac rhythm recovery during cardiac valve surgery with extracorporeal circulation. [ABSTRACT FROM AUTHOR]

Total amount of creatine (Cr) and phosphocreatine, or total creatine (tCr), may have a significant impact on the performance of skeletal muscles. In sports such as bodybuilding, it is popular to take Cr supplements to maintain tCr level. However, no study has explored the quantitative relationship between exercise intensity and the induced change in muscle's tCr. In this well‐controlled study, straight‐leg plantar flexion with specific load and duration was performed by 10 healthy subjects inside an MRI scanner, immediately followed by 1H MR spectroscopy (MRS) for measuring tCr concentration in gastrocnemius. For repeatability assessment, the experiment was repeated for each subject on two different days. Across all the subjects, baseline tCr was 46.6 ± 2.4 mM, ranging from 40.6 to 50.1 mM; with exercise, tCr significantly decreased by 10.9% ± 1.0% with 6‐lb load and 21.0% ± 1.3% with 12‐lb load (p < 0.0001). Between two different days, baseline tCr, percentage decrease induced by exercise with a 6‐lb and 12‐lb load differed by 2.2% ± 2.3%, 11.7% ± 6.0% and 4.9% ± 3.2%, respectively. In conclusion, the proposed protocol of controlled exercise stimulation and MRS acquisition can reproducibly monitor tCr level and its exercise‐induced change in skeletal muscles. The measured tCr level is sensitive to exercise intensity, so can be used to quantitatively assess muscle performance or fatigue. [ABSTRACT FROM AUTHOR]

Background: Older patients with cardiovascular disease (CVD) are highly susceptible to adverse drug reactions due to age-related physiological changes and the presence of multiple comorbidities, polypharmacy, and potentially inappropriate medications (PIMs). Objective: This study aimed to develop a predictive model to identify the use of PIMs in older patients with CVD. Methods: Data from 2012 to 2021 from the Changhua Christian Hospital Clinical Research Database (CCHRD) and the Kaohsiung Medical University Hospital Research Database (KMUHRD) were analyzed. Participants over the age of 65 years with CVD diagnoses were included. The CCHRD data were randomly divided into a training set (80% of the database) and an internal validation set (20% of the database), while the KMUHRD data served as an external validation set. The training set was used to construct the prediction models, and both validation sets were used to validate the proposed models. Results: A total of 48,569 patients were included. Comprehensive data analysis revealed significant associations between the use of PIMs and clinical factors such as total cholesterol, glycated hemoglobin (HbA1c), creatinine, and uric acid levels, as well as the presence of diabetes, hypertension, and cerebrovascular accidents. The predictive models demonstrated moderate power, indicating the importance of these factors in assessing the risk of PIMs. Conclusions: This study developed predictive models that improve understanding of the use of PIMs in older patients with CVD. These models may assist clinicians in making informed decisions regarding medication safety. [ABSTRACT FROM AUTHOR]

Cyclophosphamide (CYP) is widely used to treat various types of cancer. In addition to the therapeutic properties of this drug, unfortunately, its side effects are still not fully understood. This study investigated the protective effect of curcumin (CURC) and berberine (BER) on CYP‐induced cardiac damage. Thirty‐six male rats were equally divided into the control, dimethyl sulfoxide (DMSO), CYP, CYP + CURC, CYP + BER and CYP + BER + CURC groups. Troponin‐I, Creatine kinase‐myocardial band (CK‐MB), total cholesterol, triglyceride levels in serum samples, and reactive oxygen species (ROS), poly(ADP‐ribose) polymerase‐1 (PARP‐1), and transient receptor potential melastatin 2 (TRPM2) channel levels in heart tissue were measured using an enzyme‐linked immunoassay (ELISA) kit. In addition, histopathological examination and immunohistochemical investigation of the TRPM2 channel, fibroblast specific protein‐1 (FSP1), transforming growth factor‐beta‐ 1 (TGF‐β1) and α‐smooth muscle actin (α‐SMA) expressions were determined in heart tissue. The CYP group's troponin‐I, total cholesterol, triglyceride, CK‐MB, ROS, PARP‐1 and TRPM2 channel levels were higher than in the other groups in the ELISA measurements (p < 0.05). In contrast, these parameters in the group treated with CURC and BER together with CYP were lower than in the CYP group (p < 0.05). Additionally, CUR and BER reduced CYP‐induced pathological damage, TRPM2, FSP1, TGF‐β1 and α‐SMA expressions. The data showed that CYP administration can cause cardiac damage by increasing the TRPM2 channel, TGF‐β1, FSP1 and α‐SMA expression levels. Therefore, we concluded that CURC and BER administration following CYP application may be used as therapeutic agents to prevent CYP‐induced cardiac damage. [ABSTRACT FROM AUTHOR]

Background/Objectives: The aim of this study was to evaluate brain metabolism using MR spectroscopy (MRS) after recovery from Coronavirus disease (COVID-19) and to test the impact of disease severity on brain metabolites. Methods: We performed MRS on 81 individuals (45 males, 36 females, aged 40–60), who had normal MRI findings and had recovered from COVID-19, classifying them into mild (17), moderate (36), and severe (28) groups based on disease severity during the acute phase. The study employed two-dimensional spectroscopic imaging above the corpus callosum, focusing on choline (Cho), creatine (Cr), and N-acetylaspartate (NAA). We analyzed Cho/Cr and NAA/Cr ratios as well as absolute concentrations using water as an internal reference. Results: Results indicated that the Cho/Cr ratio was higher with increasing disease severity, while absolute Cho and NAA/Cr ratios showed no significant differences across the groups. Notably, absolute Cr and NAA levels were significantly lower in patients with severe disease. Conclusions: These findings suggest that the severity of COVID-19 during the acute phase is associated with significant changes in brain metabolism, marked by an increase in Cho/Cr ratios and a reduction in Cr and NAA levels, reflecting substantial metabolic alterations post-recovery. [ABSTRACT FROM AUTHOR]

In this work, the solubility of creatine, creatinine, guanidinoacetic acid and their hydrochlorides in water at atmospheric pressure and in the temperature range T 293.15-313.15 K was determined by the gravimetric method. The thermodynamic parameters of dissolution in water for the mentioned compounds were calculated. The solubility increases significantly by converting the zwitterionic structures of creatine and guanidinoacetic acid into a cationic form, i.e., hydrochloride salt. The effect of increasing solubility is more pronounced for guanidinoacetic acid and decreases with temperature for both compounds. A simple process of transforming the electrically neutral zwitterionic structures into cations represents a good way to increase the solubility in water and bioavailability of biologically active compounds. [ABSTRACT FROM AUTHOR]

Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research. [ABSTRACT FROM AUTHOR]

Objective: To identify the lifetime prevalence and correlates of appearance- and performance-enhancing drugs and substances (APEDS) use among a national sample of US college and university students. Participants: Student participants from the 2020–2021 Healthy Minds Study (N = 7,401; ages 18–30 years). Methods: Lifetime prevalence of five forms of APEDS was estimated. Modified Poisson regression analyses were conducted to determine the sociodemographic correlates of protein and creatine supplement use. Results: Lifetime protein (23.8%) and creatine (7.7%) supplement use were most common among the sample. Older age within young adulthood, male sex, perceiving oneself to be normal weight or somewhat overweight, any athletics participation, and 2–3 or ≥ 5 h/week of exercise were associated with greater likelihood of lifetime protein and creatine supplement use. Conclusions: Awareness and prevention efforts on the potential harms of APEDS use are needed on campuses, particularly among males and those who participate in athletics and high-frequency exercise. [ABSTRACT FROM AUTHOR]

The use of nutritional supplements can lead to doping risk and no data exist on high school athletes' use of certified third-party tested supplements. A cross-sectional cohort design was developed using an anonymous survey. Descriptive data for supplement use, use of third-party tested supplements, and knowledge in high school athletes were reported. A total of 225 high school athletes, ranging from 14-19 years of age, from a private high school in the western US, were included in the analysis of the results. A total of 94% (n=211) of athletes reported nutritional supplement use within the past year with an average of six (interquartile range: 3-9) individual supplements, ranging from 0-20 supplements per person. Most frequently reported were sports drinks (72%), vitamins (65%), sports bars (60%), protein powder (58%), caffeine (37%, as part of normal beverages, or 13% as a supplement), followed by creatine (23%). A total of 24% claimed to know for sure that all their supplements were third-party tested. In addition, the recognition of third-party testing organization icons was low (46% in supplement users vs. 14% in nonusers). Athletes also scored low in reporting how to find (22%) and how to order (25%) third-party tested supplements. In conclusion, almost all athletes in this study reported the use of multiple nutritional supplements annually. Only one-fourth of the athletes reported consistently using third-party tested supplements. Knowledge of where and how tested supplements could be purchased was limited in this high school athlete population. [ABSTRACT FROM AUTHOR]

The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset containing females aged 12 years and above who provided details about their reproductive health and dietary habits. Daily creatine intake was quantified as a relative amount (mg per kg body mass) and did not include creatine from dietary supplements and pharmacological agents. A daily requirement for dietary creatine for healthy women was employed to classify respondents into two separate subpopulations: (1) suboptimal intake of creatine (<13 mg per kg body mass per day) or (2) recommended intake (dietary creatine ≥ 13 mg per kg body mass per day). A total of 4522 female participants from the NHANES study (age 44.5 ± 20.5 years) provided data on their reproductive health and dietary intake. The average daily creatine intake for the group was 10.5 ± 10.8 mg per kg body mass. The odds ratio for having irregular periods in women consuming ≥13 mg of creatine per kg body mass daily (recommended intake) compared to those with suboptimal intake was 0.75 (95% CI, from 0.66 to 0.86), indicating a significant association between higher intake of dietary creatine and lower risk of oligomenorrhea (p <.001). Moreover, women consuming less than 13 mg of creatine per kg body mass faced an increased risk of fetal macrosomia (OR 1.26; p =.04), pelvic infection (OR 1.68; p =.01), hysterectomy (OR 1.42; p <.001), oophorectomy (OR 1.54; p <.001), and receiving hormone replacement therapy (OR 1.26; p =.02). Consuming a creatine‐rich diet has been linked to lower risks of reproductive issues in US women aged 12 and above. Those consuming ≥13 mg of creatine per kg body mass daily showed notably lower risks of irregular menstrual periods, obstetric conditions, and pelvic pathology. Further studies are needed to confirm these potential benefits. [ABSTRACT FROM AUTHOR]

The 1,2‐dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC‐UV for MGO and HPLC–MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM‐1 to form the hydroimidazolone MG‐HCr in similar amounts as in a human intervention study. 28%–69% of MGO from the meal were passively absorbed in TIM‐1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct Nε‐carboxyethyllysine (CEL) and the methylglyoxal‐derived hydroimidazolone of arginine (MG‐H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed. [ABSTRACT FROM AUTHOR]

Background: The intestine of young ruminants is in the developmental stage and has weaker resistance to the changes of external environment. Improving intestinal health is vital to promoting growth of young ruminants. This study investigated effects of guanidino acetic acid (GAA) and rumen‐protected betaine (RPB) supplementation on growth, dietary nutrient digestion and GAA metabolism in the small intestine of sheep. Methods: Eighteen healthy Kazakh rams (27.46 ± 0.10 kg of body weight and 3‐month old) were categorized into control, test group I and test group II, which were fed a basal diet, 1500 mg/kg GAA and 1500 mg/kg GAA + 600 mg/kg RPB, respectively. Results: Compared with control group, test group II had increased (p < 0.05) average daily gain, plasma creatine level, ether extract (EE) and phosphorus digestibility on day 30. On day 60, the EE apparent digestibility, jugular venous plasma GAA, GAA content in the duodenal mucosa and GAA content in the jejunal and ileal mucosa of test group II were higher (p < 0.05) than other groups. Transcriptome analysis revealed that the differentially expressed genes (DEGs) involved in the duodenal pathways of oxidative phosphorylation and non‐alcoholic fatty liver disease were significantly altered in test group II versus test group I (p < 0.05). Moreover, in the jejunum, the MAPK signalling pathway, complement and coagulation cascade and B‐cell receptor signalling pathway were significantly enriched, with ATPase, solute carrier transporter protein, DHFR, SI, GCK, ACACA and FASN being the significantly DEGs (p < 0.05). Conclusion: Dietary supplementation of RPB on top of GAA in sheep diets may promote sheep growth and development by improving the body's energy, amino acid, glucose and lipid metabolism capacity. [ABSTRACT FROM AUTHOR]

Creatine is a naturally occurring compound found in muscles that plays a vital role in energy metabolism. It has been shown to have beneficial effects on skeletal muscle function and exercise performance, but recent studies have investigated its potential role in various fields of medicine. The study aimed to analyze accessible literature and illustrate the current state of knowledge on the use of creatine in these settings, as well as make predictions for further research. A link between low creatine concentrations and poorer mental well-being has been proven in the central nervous system. After many studies and insightful conclusions about the molecular mechanisms of action of creatine in the brain and the finding that it acts as a neurotransmitter, creatine began to be successfully studied as an antidepressant - both in monotherapy and as an adjunct to treatment with SSRI drugs. Years of research have shown creatine to act in various, not fully understood mechanisms on the course and recovery of stroke. The use of creatine as an additional treatment in stroke prevention for at-risk groups and rehabilitation of stroke patients seems possible shortly. One of the most important aspects of chronic heart failure is metabolic dysfunction that occurs in cardiomyocytes, including impairment of CR/PCR/ATP shuttle. Multiple studies undertaking the role of creatine supplementation in patients with cardiovascular diseases present various findings. Therefore, creatine appears as a promising substance with supportive effects in the above-mentioned conditions; however, further research is needed to confirm that the benefit outweighs the risks. [ABSTRACT FROM AUTHOR]

Chorioamnionitis is a common antecedent of preterm birth and induces inflammation and oxidative stress in the fetal lungs. Reducing inflammation and oxidative stress in the fetal lungs may improve respiratory outcomes in preterm infants. Creatine is an organic acid with known anti-inflammatory and antioxidant properties. The objective of the study was to evaluate the efficacy of direct fetal creatine supplementation to reduce inflammation and oxidative stress in fetal lungs arising from an in utero proinflammatory stimulus. Fetal lambs (n = 51) were instrumented at 90 days gestation to receive a continuous infusion of creatine monohydrate (6 mg·kg-1 ·h-1) or saline for 17 days. Maternal chorioamnionitis was induced with intra-amniotic lipopolysaccharide (LPS; 1 mg, O55:H6) or saline 7 days before delivery at 110 days gestation. Tissue creatine content was assessed with capillary electrophoresis, and inflammatory markers were analyzed with Luminex Magpix and immunohistochemistry. Oxidative stress was measured as the level of protein thiol oxidation. The effects of LPS and creatine were analyzed using a two-way ANOVA. Fetal creatine supplementation increased lung creatine content by 149% (PCr < 0.0001) and had no adverse effects on lung morphology. LPS-exposed groups showed increased levels of interleukin-8 in the bronchoalveolar lavage (PLPS < 0.0001) and increased levels of CD45 þ leukocytes (PLPS < 0.0001) and MPO þ (PLPS < 0.0001) cells in the lung parenchyma. Creatine supplementation significantly reduced the levels of CD45 þ (PCr = 0.045) and MPO þ cells (PCr = 0.012) in the lungs and reduced thiol oxidation in plasma (PCr < 0.01) and lung tissue (PCr = 0.02). In conclusion, fetal creatine supplementation reduced markers of inflammation and oxidative stress in the fetal lungs arising from chorioamnionitis.NEW & NOTEWORTHY We evaluated the effect of antenatal creatine supplementation to reduce pulmonary inflammation and oxidative stress in the fetal lamb lungs arising from lipopolysaccharide (LPS)-induced chorioamnionitis. Fetal creatine supplementation increased lung creatine content and had no adverse effects on systemic fetal physiology and overall lung architecture. Importantly, fetuses that received creatine had significantly lower levels of inflammation and oxidative stress in the lungs, suggesting an anti-inflammatory and antioxidant benefit of creatine. [ABSTRACT FROM AUTHOR]

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Cigarette smoking has a major impact on global health and morbidity, and positron emission tomographic research has provided evidence for reduced inflammation in the human brain associated with cigarette smoking. Given the consequences of inflammatory dysfunction for health, the question of whether cigarette smoking affects neuroinflammation warrants further investigation. The goal of this project therefore was to validate and extend evidence of hypoinflammation related to smoking, and to examine the potential contribution of inflammation to clinical features of smoking. Using magnetic resonance spectroscopy, we measured levels of neurometabolites that are putative neuroinflammatory markers. N-acetyl compounds (N-acetylaspartate + N-acetylaspartylglutamate), glutamate, creatine, choline-compounds (phosphocholine + glycerophosphocholine), and myo-inositol, have all been linked to neuroinflammation, but they have not been examined as such with respect to smoking. We tested whether people who smoke cigarettes have brain levels of these metabolites consistent with decreased neuroinflammation, and whether clinical features of smoking are associated with levels of these metabolites. The dorsal anterior cingulate cortex was chosen as the region-of-interest because of previous evidence linking it to smoking and related states. Fifty-four adults who smoked daily maintained overnight smoking abstinence before testing and were compared with 37 nonsmoking participants. Among the smoking participants, we tested for associations of metabolite levels with tobacco dependence, smoking history, craving, and withdrawal. Levels of N-acetyl compounds and glutamate were higher, whereas levels of creatine and choline compounds were lower in the smoking group as compared with the nonsmoking group. In the smoking group, glutamate and creatine levels correlated negatively with tobacco dependence, and creatine correlated negatively with lifetime smoking, but none of the metabolite levels correlated with craving or withdrawal. The findings indicate a link between smoking and a hypoinflammatory state in the brain, specifically in the dorsal anterior cingulate cortex. Smoking may thereby increase vulnerability to infection and brain injury.

Abstract The 1,2‐dicarbonyl compound methylglyoxal (MGO) can react with and thereby impair the function of proteins and DNA, leading to pathophysiological pathways in vivo. However, studies on the bioavailability of dietary MGO and its reactions during digestion have diverging results. Therefore, simulated digestion experiments of MGO, protein, and creatine were performed in the dynamic, in vitro model of the upper gastrointestinal tract (TIM‐1). This multicompartment model continuously adjusts pH values and has realistic gastrointestinal transit times while also removing water and metabolites by dialysis. Samples were analyzed with HPLC‐UV for MGO and HPLC–MS/MS for creatine and glycated amino compounds. MGO reacted with creatine during simulated digestion in TIM‐1 to form the hydroimidazolone MG‐HCr in similar amounts as in a human intervention study. 28%–69% of MGO from the meal were passively absorbed in TIM‐1, depending on the addition of creatine and protein. Simultaneous digestion of MGO with ovalbumin led to the formation of the lysine adduct Nε‐carboxyethyllysine (CEL) and the methylglyoxal‐derived hydroimidazolone of arginine (MG‐H1). The formation of both compounds decreased with added creatine. Hence, glycation compounds are formed during digestion and significantly contribute to other ingested dietary glycation compounds, whose physiological consequences are critically discussed.

Abstract The hormonal changes in women influence creatine dynamics, emphasizing its potential importance during menstruation, pregnancy, postpartum, menopause, and postmenopause. Yet, limited research explores creatine's impact on female reproductive health at the population level. Our study investigated the relationship between dietary creatine intake and reproductive health indices in US women using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). We extracted a dataset containing females aged 12 years and above who provided details about their reproductive health and dietary habits. Daily creatine intake was quantified as a relative amount (mg per kg body mass) and did not include creatine from dietary supplements and pharmacological agents. A daily requirement for dietary creatine for healthy women was employed to classify respondents into two separate subpopulations: (1) suboptimal intake of creatine (

Abstract Maintaining skeletal muscle mass is important for improving muscle strength and function. Hence, maximizing lean body mass (LBM) is the primary goal for both elite athletes and fitness enthusiasts. The use of amino acids as dietary supplements is widespread among athletes and physically active individuals. Extensive literature analysis reveals that branched-chain amino acids (BCAA), creatine, glutamine and β-alanine may be beneficial in regulating skeletal muscle metabolism, enhancing LBM and mitigating exercise-induced muscle damage. This review details the mechanisms of these amino acids, offering insights into their efficacy as supplements. Recommended dosage and potential side effects are then outlined to aid athletes in making informed choices and safeguard their health. Lastly, limitations within the current literature are addressed, highlighting opportunities for future research.

BackgroundGiven limited experience in applying the creatine-(methyl-D3) (D3Cr) dilution method to measure skeletal muscle mass (SMM) in young children, the feasibility of deployment in a fielding setting and performance of the method was assessed in a cohort of 4-year-old children in Dhaka, Bangladesh.MethodsFollowing D3Cr oral dose (10 mg) administration, single fasting urine samples were collected at 2-4 days (n = 100). Twenty-four-hour post-dose collections and serial spot urine samples on days 2, 3 and 4 were obtained in a subset of participants (n = 10). Urinary creatine, creatinine, D3Cr and D3-creatinine enrichment were analyzed by liquid chromatography-tandem mass spectrometry. Appendicular lean mass (ALM) was measured by dual-energy x-ray absorptiometry and grip strength was measured by a hand-held dynamometer.ResultsSMM was measured successfully in 91% of participants, and there were no adverse events. Mean ± SD SMM was greater than ALM (4.5 ± 0.4 and 3.2 ± 0.6 kg, respectively). Precision of SMM was low (intraclass correlation = 0.20; 95% CI: 0.02, 0.75; n = 10). Grip strength was not associated with SMM in multivariable analysis (0.004 kg per 100 g of SMM; 95% CI: -0.031, 0.038; n = 91).ConclusionsThe D3Cr dilution method was feasible in a community setting. However, high within-child variability in SMM estimates suggests the need for further optimization of this approach.ImpactThe D3-creatine (D3Cr) stable isotope dilution method was considered a feasible method for the estimation of skeletal muscle mass (SMM) in young children in a community setting and was well accepted among participants. SMM was weakly associated with both dual-energy x-ray absorptiometry-derived values of appendicular lean mass and grip strength. High within-child variability in estimated values of SMM suggests that further optimization of the D3Cr stable isotope dilution method is required prior to implementation in community research settings.

Developing accurate methods to quantify age-related muscle loss (sarcopenia) could greatly accelerate development of therapies to treat muscle loss in the elderly, as current methods are inaccurate or expensive. The current gold standard method for quantifying sarcopenia is dual-energy X-ray absorptiometry (DXA) but does not measure muscle directly-it is a composite measure quantifying lean mass (muscle) excluding fat and bone. In humans, DXA overestimates muscle mass, which has led to erroneous conclusions about the importance of skeletal muscle in human health and disease. In animal models, DXA is a popular method for measuring lean mass. However, instrumentation is expensive and is potentially limited by anesthesia concerns. Recently, the D3 -creatine (D3 Cr) dilution method for quantifying muscle mass was developed in humans and rats. This method is faster, cheaper, and more accurate than DXA. Here, we demonstrate that the D3 Cr method is a specific assay for muscle mass in mice, and we test associations with DXA and body weight. We evaluated the D3 Cr method compared to DXA-determined lean body mass (LBM) in aged mice and reported that DXA consistently overestimates muscle mass with age. Overall, we provide evidence that the D3 Cr dilution method directly measures muscle mass in mice. Combined with its ease of use, accessibility, and non-invasive nature, the method may prove to more quickly advance development of preclinical therapies targeting sarcopenia.

BackgroundAlthough proton magnetic resonance spectroscopy (MRS) has been used to study metabolite alterations in stimulant (methamphetamine and cocaine) substance use disorders (SUDs) for over 25 years, data-driven consensus regarding the nature and magnitude of these alterations is lacking.MethodIn this meta-analysis, we examined associations between SUD and regional metabolites (N-acetyl aspartate (NAA), choline, myo-inositol, creatine, glutamate, and glutamate+glutamine (glx)) in the medial prefrontal cortex (mPFC), frontal white matter (FWM), occipital cortex, and basal ganglia as measured by 1 H-MRS. We also examined moderating effects of MRS acquisition parameters (echo time (TE), field strength), data quality (coefficient of variation (COV)), and demographic/clinical variables.ResultsA MEDLINE search revealed 28 articles that met meta-analytic criteria. Significant effects included lower mPFC NAA, higher mPFC myo-inositol, and lower mPFC creatine in SUD relative to people without SUD. mPFC NAA effects were moderated by TE, with larger effects at longer TEs. For choline, although no group effects were observed, effect sizes in the mPFC were related to MRS technical indicators (field strength, COV). No effects of age, sex, primary drug of use (methamphetamine vs. cocaine), duration of use, or duration of abstinence were observed. Evidence for moderating effects of TE and COV may have implications for future MRS studies in SUDs.ConclusionsThe observed metabolite profile in methamphetamine and cocaine SUD (lower NAA and creatine with higher myo-inositol) parallels that observed in Alzheimer's disease and mild cognitive impairment, suggesting these drugs are associated with neurometabolic differences similar to those characterizing these neurodegenerative conditions.

Background: Creatine, a naturally occurring compound plays a crucial role in cellular energy metabolism, particularly in tissues with high energy demands like muscles and the brain. Beyond its well-established role in physical performance enhancement, recent research has revealed its potential benefits for cognitive functions and mood regulation. This review paper aims to comprehensively analyze the existing literature on creatine supplementation's effects on cognitive functions and mood. State of Knowledge: Findings suggest that creatine supplementation enhances memory, attention, and executive functions, especially under conditions of stress or sleep deprivation. Moreover, it exhibits mood-stabilizing effects, potentially offering relief for symptoms of depression and fatigue. Creatine's ability to augment brain energy metabolism, alongside its neuroprotective properties, underlies its cognitive and mood-enhancing effects. While generally safe, caution is advised, particularly in populations with kidney diseases or those using medications affecting kidney function. Summary: Creatine emerges as a promising adjunct therapy for enhancing cognitive functions and promoting emotional well-being beyond its traditional role in physical performance. The review underscores the need for further research to elucidate the precise mechanisms of creatine's effects and explore its synergistic potential with other cognitive-enhancing supplements. [ABSTRACT FROM AUTHOR]

Although physical exercise is extremely important for health and a good lifestyle, it can trigger oxidative stress, inflammation, and muscle fatigue. The aim of this study was to determine changes in dental tissues and the mandible created by creatines monohydrate (CrM) supplementation together with low and high‐intensity exercise (HIE). The study material comprised Balb/c male mices, which were separated into two groups for the application of low and HIE on a running band. CrM supplement was administered together with the exercise. At the end of the experiment period, dental tissue samples were surgically removed and examined histopathologically and immunohistochemically (TNF‐α and lL‐1β).As a result of the histopathological examinations, in the pulp, oedema, vascular congestion, and capillary dilatation were seen to be statistically significantly increased in the Group 3 mices that performed HIE compared to the control group (p = 0.001, p = 0.003, p = 0.001, respectively). A statistically significant increase was observed in periodontal ligament (PDL) degeneration, and disruption of the continuity and separation of collagen fibers in Group 3 compared to the control group (p = 0.001). In the immunohistochemical examination, TNF‐α and IL‐1β positivity was observed in Group 3, and this was significantly increased compared to the control group (p = 0.001, p = 0.000).Exposure of the mices to low and HIE caused histological and immunohistochemical changes in dental pulp and PDL, and it was determined that the use of CrM could have a protective effect against these changes. Research Highlights: The results of this study showed negative effects of HIE in the dental pulp and PDL, which play an important role in dental health.CrM was seen to be effective in preventing these negative effects. [ABSTRACT FROM AUTHOR]

Abstract Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest l-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy.

Abstract Background We recently reported that supplementing glycine to soybean meal-based diets is necessary for the optimum growth of 5- to 40-g (Phase-I) and 110- to 240-g (Phase-II) hybrid striped bass (HSB), as well as their intestinal health. Although glycine serves as an essential substrate for syntheses of creatine and glutathione (GSH) in mammals (e.g., pigs), little is known about these metabolic pathways or their nutritional regulation in fish. This study tested the hypothesis that glycine supplementation enhances the activities of creatine- and GSH-forming enzymes as well as creatine and GSH availabilities in tissues of hybrid striped bass (HSB; Morone saxatilis♀ × Morone chrysops♂). Methods Phase-I and Phase-II HSB were fed a soybean meal-based diet supplemented with 0%, 1%, or 2% glycine for 8 weeks. At the end of the 56-d feeding, tissues (liver, intestine, skeletal muscle, kidneys, and pancreas) were collected for biochemical analyses. Results In contrast to terrestrial mammals and birds, creatine synthesis occurred primarily in skeletal muscle from all HSB. The liver was most active in GSH synthesis among the HSB tissues studied. In Phase-I HSB, supplementation with 1% or 2% glycine increased (P 0.05) in these variables between the 1% and 2% glycine groups. In Phase-II HSB, supplementation with 1% and 2% glycine increased (P

Posttraumatic stress disorder (PTSD) is a psychiatric condition characterized by a prolonged stress response to potentially life-threatening events long after the event has passed. Understanding factors related to recovery from traumatic life events may inform novel targets for intervention. There is emerging preclinical evidence that creatine (Cr), a molecule critical to brain bioenergetics, may be a neurobiological marker of stress reactivity and recovery. 25 US Veterans (8 female) completed the Life Events Checklist for DSM-5, which assessed different types of traumatic events. Veterans were also asked to rate the subjective stress of each traumatic event on a 1–10 scale currently (Current Stress) and at the time the event occurred (Past Stress). Stress recovery was quantified as the difference between Current and Past Stress. Current PTSD symptoms were also assessed using the PTSD Checklist for DSM-5. Cr concentrations in the anterior cingulate cortex (ACC) were measured in the anterior cingulate cortex using proton magnetic resonance spectroscopy (1H-MRS). Higher levels of Cr were associated with self-reported stress recovery from participants' most traumatic life event. Cr was not related to number of different types of traumatic life events or current PTSD symptoms. The sample size was relatively small. Stress recovery was measured via retrospective self-report. Future experimental work in humans should clarify the protective role of Cr in recovery from trauma. ACC concentrations of Cr may be an important neurochemical factor related to stress recovery. Future work should investigate Cr as a possible protective factor against the effects of traumatic stress. • Creatine is necessary for healthy brain metabolism and changes with stress. • Creatine levels were measured in trauma-exposed veterans. • Higher creatine levels were associated with greater recovery from trauma. • The role of creatine in posttraumatic stress disorder should be further studied. [ABSTRACT FROM AUTHOR]

Creatine transporter (CrT1) mediates cellular uptake of creatine (Cr), a nutrient pivotal in maintaining energy homeostasis in various tissues including intestinal epithelial cells (IECs). The impact of CrT1 deficiency on the pathogenesis of various psychiatric and neurological disorders has been extensively investigated. However, there are no studies on its regulation in IECs in health and disease. Current studies have determined differential expression of CrT1 along the length of the mammalian intestine and its dysregulation in inflammatory bowel disease (IBD)-associated inflammation and Adherent Invasive E. coli (AIEC) infection. CrT1 mRNA and protein levels in normal intestines and their alterations in inflammation and following AIEC infection were determined in vitro in model IECs (Caco-2/IEC-6) and in vivo in SAMP1/YitFc mice, a model of spontaneous ileitis resembling human IBD. CrT1 is differentially expressed in different regions of mammalian intestines with its highest expression in jejunum. In vitro, CrT1 function (Na+-dependent 14C-Cr uptake), expression and promoter activity significantly decreased following TNFα/IL1β treatments and AIEC infection. SAMP1 mice and ileal organoids generated from SAMP1 mice also showed decreased CrT1 mRNA and protein compared to AKR controls. Our studies suggest that Cr deficiency in IECs secondary to CrT1 dysregulation could be a key factor contributing to IBD pathogenesis. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is an age-related condition characterized by progressive loss of muscle mass, strength, and function. The occurrence of sarcopenia has a huge impact on physical, psychological, and social health. Therefore, the prevention and treatment of sarcopenia is becoming an important public health issue. Method: 35 six-week-old male C57BL/6 mice were randomly divided into five groups, one of which served as a control group, while the rest of the groups were constructed as a model of sarcopenia by intraperitoneal injection of D-galactose. The intervention with lactoferrin, creatine, and their mixtures, respectively, was carried out through gavage for 8 weeks. Muscle function was assessed based on their endurance, hanging time, and grip strength. The muscle tissues were weighed to assess the changes in mass, and the muscle RNA was extracted for myogenic factor expression and transcriptome sequencing to speculate on the potential mechanism of action by GO and KEGG enrichment analysis. Result: The muscle mass (lean mass, GAS index), and muscle function (endurance, hanging time, and grip strength) decreased, and the size and structure of myofiber was smaller in the model group compared to the control group. The intervention with lactoferrin and creatine, either alone or combination, improved muscle mass and function, restored muscle tissue, and increased the expression of myogenic regulators. The combined group demonstrated the most significant improvement in these indexes. The RNA-seq results revealed enrichment in the longevity-regulated pathway, MAPK pathway, focal adhesion, and ECM–receptor interaction pathway in the intervention group. The intervention group may influence muscle function by affecting the proliferation, differentiation, senescence of skeletal muscle cell, and contraction of muscle fiber. The combined group also enriched the mTOR-S6K/4E-BPs signaling pathway, PI3K-Akt signaling pathway, and energy metabolism-related pathways, including Apelin signaling, insulin resistance pathway, and adipocytokine signaling pathway, which affect energy metabolism in muscle. Conclusions: Lactoferrin and creatine, either alone or in combination, were found to inhibit the progression of sarcopenia by influencing the number and cross-sectional area of muscle fibers and muscle protein synthesis. The combined intervention appears to exert a more significant effect on energy metabolism. [ABSTRACT FROM AUTHOR]

Creatine is a natural nitrogenous organic acid that is integral to energy metabolism and crucial for proper cell functioning. The kidneys are involved in the first step of creatine production. With kidney transplantation being the gold-standard treatment for end-stage kidney disease, kidney transplant recipients (KTR) may be at risk of impaired creatine synthesis. We aimed to compare creatine homeostasis between KTR and controls. Plasma and urine concentrations of arginine, glycine, guanidinoacetate, creatine and creatinine were measured in 553 KTR and 168 healthy controls. Creatine intake was assessed using food frequency questionnaires. Iothalamate-measured GFR data were available in subsets of 157 KTR and 167 controls. KTR and controls had comparable body weight, height and creatine intake (all P > 0.05). However, the total creatine pool was 14% lower in KTR as compared to controls (651 ± 178 vs. 753 ± 239 mmol, P < 0.001). The endogenous creatine synthesis rate was 22% lower in KTR as compared to controls (7.8 ± 3.0 vs. 10.0 ± 4.1 mmol per day, P < 0.001). Despite lower GFR, the plasma guanidinoacetate and creatine concentrations were 21% and 41% lower in KTR as compared to controls (both P < 0.001). Urinary excretion of guanidinoacetate and creatine were 66% and 59% lower in KTR as compared to controls (both P < 0.001). In KTR, but not in controls, a higher measured GFR was associated with a higher endogenous creatine synthesis rate (std. beta: 0.21, 95% CI: 0.08; 0.33; P = 0.002), as well as a higher total creatine pool (std. beta: 0.22, 95% CI: 0.11; 0.33; P < 0.001). These associations were fully mediated (93% and 95%; P < 0.001) by urinary guanidinoacetate excretion which is consistent with production of the creatine precursor guanidinoacetate as rate-limiting factor. Our findings highlight that KTR have a disturbed creatine homeostasis as compared to controls. Given the direct relationship of measured GFR with endogenous creatine synthesis rate and the total creatine pool, creatine supplementation might be beneficial in KTR with low kidney function. Trial registration ID: NCT02811835. Trial registration URL: https://clinicaltrials.gov/ct2/show/NCT02811835. [ABSTRACT FROM AUTHOR]

Lamin A/C gene (LMNA) mutations contribute to severe striated muscle laminopathies, affecting cardiac and skeletal muscles, with limited treatment options. In this study, we delve into the investigations of five distinct LMNA mutations, including three novel variants and two pathogenic variants identified in patients with muscular laminopathy. Our approach employs zebrafish models to comprehensively study these variants. Transgenic zebrafish expressing wild-type LMNA and each mutation undergo extensive morphological profiling, swimming behavior assessments, muscle endurance evaluations, heartbeat measurement, and histopathological analysis of skeletal muscles. Additionally, these models serve as platform for focused drug screening. We explore the transcriptomic landscape through qPCR and RNAseq to unveil altered gene expression profiles in muscle tissues. Larvae of LMNA(L35P), LMNA(E358K), and LMNA(R453W) transgenic fish exhibit reduced swim speed compared to LMNA(WT) measured by DanioVision. All LMNA transgenic adult fish exhibit reduced swim speed compared to LMNA(WT) in T-maze. Moreover, all LMNA transgenic adult fish, except LMNA(E358K), display weaker muscle endurance than LMNA(WT) measured by swimming tunnel. Histochemical staining reveals decreased fiber size in all LMNA mutations transgenic fish, excluding LMNA(WT) fish. Interestingly, LMNA(A539V) and LMNA(E358K) exhibited elevated heartbeats. We recognize potential limitations with transgene overexpression and conducted association calculations to explore its effects on zebrafish phenotypes. Our results suggest lamin A/C overexpression may not directly impact mutant phenotypes, such as impaired swim speed, increased heart rates, or decreased muscle fiber diameter. Utilizing LMNA zebrafish models for drug screening, we identify l-carnitine treatment rescuing muscle endurance in LMNA(L35P) and creatine treatment reversing muscle endurance in LMNA(R453W) zebrafish models. Creatine activates AMPK and mTOR pathways, improving muscle endurance and swim speed in LMNA(R453W) fish. Transcriptomic profiling reveals upstream regulators and affected genes contributing to motor dysfunction, cardiac anomalies, and ion flux dysregulation in LMNA mutant transgenic fish. These findings faithfully mimic clinical manifestations of muscular laminopathies, including dysmorphism, early mortality, decreased fiber size, and muscle dysfunction in zebrafish. Furthermore, our drug screening results suggest l-carnitine and creatine treatments as potential rescuers of muscle endurance in LMNA(L35P) and LMNA(R453W) zebrafish models. Our study offers valuable insights into the future development of potential treatments for LMNA-related muscular laminopathy. [ABSTRACT FROM AUTHOR]

Creatine (Cr) and l-arginine are naturally occurring guanidino compounds, commonly used as ergogenic dietary supplements. Creatine and l-arginine exhibit also a number of non-energy-related features, such as antioxidant, anti-apoptotic, and anti-inflammatory properties, which contribute to their protective action against oxidative stress (OS). In this regard, there are a number of studies emphasizing the protective effect of Cr against OS, which develops in the process of aging, increased physical loads as part of athletes' workouts, as well as a number of neurological diseases and toxic effects associated with xenobiotics and UV irradiation. Against this backdrop, and since ionizing radiation causes OS in cells, leading to radiotoxicity, there is an increasing interest to understand whether Cr has the full potential to serve as an effective radioprotective agent. The extensive literature search did not provide any data on this issue. In this narrative review, we have summarized some of our own experimental data published over the last years addressing the respective radioprotective effects of Cr. Next, we have additionally reviewed the existing data on the radiomodifying effects of l-arginine presented earlier by other research groups. Creatine possesses significant radioprotective potential including: (1) radioprotective effect on the survival rate of rats subjected to acute whole-body X-ray irradiation in a LD70/30 dose of 6.5 Gy, (2) radioprotective effect on the population composition of peripheral blood cells, (3) radioprotective effect on the DNA damage of peripheral blood mononuclear cells, (4) radioprotective effect on the hepatocyte nucleus-nucleolar apparatus, and (5) radioprotective effect on the brain and liver Cr–Cr kinase systems of the respective animals. Taking into account these cytoprotective, gene-protective, hepatoprotective and energy-stimulating features of Cr, as well as its significant radioprotective effect on the survival rate of rats, it can be considered as a potentially promising radioprotector for further preclinical and clinical studies. The review of the currently available data on radiomodifying effects of l-arginine has indicated its significant potential as a radioprotector, radiomitigator, and radiosensitizer. However, to prove the effectiveness of arginine (Arg) as a radioprotective agent, it appears necessary to expand and deepen the relevant preclinical studies, and, most importantly, increase the number of proof-of-concept clinical trials, which are evidently lacking as of now. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Sport for All & Recreation / Herkes Için Spor ve Rekreasyon is the property of Journal of Sport for All & Recreation / Herkes icin Spor ve Rekreasyon Dergisi and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: Postoperative Acute renal failure related to cardiac surgery is a common complication due to cardiac surgery and is estimated to influence up to 30% of patients. Serum lactate is a famous biomarker of tissue ischemia and is regularly checked during surgery. Methods: In this retrospective observational research, the records of 395 patients undergoing CABG were examined. Patients were classified into 4 groups based on the difference between the maximum lactate level measured during surgery and its baseline level. Also creatinine and urea levels, blood sugar, hemoglobin, and hematocrit pre, postoperative were recorded. The intraoperative and postoperative use of inotropes and the durations of surgery, cardiopulmonary bypass pump, and aortic cross-clamping were also recorded. Results: According to the results, pre, post and 24-hour postoperative blood urea nitrogen were not significantly related to intraoperative lactate changes. Also, pre and 24-hour postoperative creatinine had no significant relationship with intraoperative lactate changes, while postoperative creatinine was significantly associated with intraoperative lactate changes (P value = 0.05). The duration of cardiopulmonary bypass (P value = 0.02), intraoperative inotrope infusion (P value = 0.03), inotrope infusion during the first six hours in ICU (P value = 0.049), and receiving packed cell (P value = 0.006) and receiving platelets during surgery (P value = 0.04) were significantly related to intraoperative lactate changes. Furthermore, no significant relationship was observed between the duration of hospitalization in the ICU and the hospital and intraoperative lactate changes. Conclusion: According to the results, blood lactate level is an unreliable marker for predicting renal dysfunction postoperative. [ABSTRACT FROM AUTHOR]

Copyright of Food & Fermentation Industries is the property of Food & Fermentation Industries and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: We recently reported that supplementing glycine to soybean meal-based diets is necessary for the optimum growth of 5- to 40-g (Phase-I) and 110- to 240-g (Phase-II) hybrid striped bass (HSB), as well as their intestinal health. Although glycine serves as an essential substrate for syntheses of creatine and glutathione (GSH) in mammals (e.g., pigs), little is known about these metabolic pathways or their nutritional regulation in fish. This study tested the hypothesis that glycine supplementation enhances the activities of creatine- and GSH-forming enzymes as well as creatine and GSH availabilities in tissues of hybrid striped bass (HSB; Morone saxatilis♀ × Morone chrysops♂). Methods: Phase-I and Phase-II HSB were fed a soybean meal-based diet supplemented with 0%, 1%, or 2% glycine for 8 weeks. At the end of the 56-d feeding, tissues (liver, intestine, skeletal muscle, kidneys, and pancreas) were collected for biochemical analyses. Results: In contrast to terrestrial mammals and birds, creatine synthesis occurred primarily in skeletal muscle from all HSB. The liver was most active in GSH synthesis among the HSB tissues studied. In Phase-I HSB, supplementation with 1% or 2% glycine increased (P < 0.05) concentrations of intramuscular creatine (15%–19%) and hepatic GSH (8%–11%), while reducing (P < 0.05) hepatic GSH sulfide (GSSG)/GSH ratios by 14%–15%, compared with the 0-glycine group; there were no differences (P > 0.05) in these variables between the 1% and 2% glycine groups. In Phase-II HSB, supplementation with 1% and 2% glycine increased (P < 0.05) concentrations of creatine and GSH in the muscle (15%–27%) and liver (11%–20%) in a dose-dependent manner, with reduced ratios of hepatic GSSG/GSH in the 1% or 2% glycine group. In all HSB, supplementation with 1% and 2% glycine dose-dependently increased (P < 0.05) activities of intramuscular arginine:glycine amidinotransferase (22%–41%) and hepatic γ-glutamylcysteine synthetase (17%–37%), with elevated activities of intramuscular guanidinoacetate methyltransferase and hepatic GSH synthetase and GSH reductase in the 1% or 2% glycine group. Glycine supplementation also increased (P < 0.05) concentrations of creatine and activities of its synthetic enzymes in tail kidneys and pancreas, and concentrations of GSH and activities of its synthetic enzymes in the proximal intestine. Conclusions: Skeletal muscle and liver are the major organs for creatine and GSH syntheses in HSB, respectively. Dietary glycine intake regulates creatine and GSH syntheses by both Phase-I and Phase-II HSB in a tissue-specific manner. Based on the metabolic data, glycine is a conditionally essential amino acid for the growing fish. [ABSTRACT FROM AUTHOR]