Balanced branched-chain amino acids modulate meat quality by adjusting muscle fiber type conversion and intramuscular fat deposition in finishing pigs.

BACKGROUND: Pork is an important food for humans and improving the quality of pork is closely related to human health. This study was designed to investigate the effects of balanced branched-chain amino acid (BCAA)-supplemented protein-restricted diets on meat quality, muscle fiber types, and intramuscular fat (IMF) in finishing pigs. RESULTS: The results showed that, compared with the normal protein diet (160 g kg-1 crude protein), the reduced-protein diet (120 g kg-1 crude protein) supplemented with BCAAs to the ratio of 2:1:2 not only had higher average daily gain (P < 0.05) and carcass weight (P < 0.05) but also improved meat tenderness and juiciness by decreasing shear force (P < 0.05) and increasing water-holding capacity (P < 0.05). In particular, this treatment showed higher (P < 0.05) levels of phospho-acetyl-CoA carboxylase (P-ACC) and peroxisome proliferation-activated receptor-γ (PPARγ), and lower (P < 0.05) levels of P-adenosine 5'-monophosphate (AMP)-activated protein kinase (P-AMPK), increasing the composition of IMF and MyHC I (P < 0.05) in the longissimus dorsi muscle (LDM). In terms of health, this group increased eicosapentaenoic acid (EPA) (P < 0.01) and desirable hypocholesterolemic fatty acids (DHFA) (P < 0.05), and decreased atherogenicity (AI) (P < 0.01) and hypercholesterolemic saturated fatty acids (HSFA) (P < 0.05). CONCLUSION: Our findings suggest a novel role for a balanced BCAA-supplemented restricted protein (RP) diet in the epigenetic regulation of more tender and healthier pork by increasing IMF deposition and fiber type conversion, providing a cross-regulatory molecular basis for revealing the nutritional regulation network of meat quality. © 2021 Society of Chemical Industry.

Effects of Dietary Eucommia ulmoides Leaf Extract Supplementation on Growth Performance, Meat Quality, Antioxidant Capacity, and Lipid Metabolism of Finishing Pigs.

This study aimed to investigate the effects of dietary Eucommia ulmoides leaf extract (ELE) on meat quality, antioxidant capacity, and lipid metabolism in finishing pigs. A total of 240 "Duroc × Landrace × Yorkshire" crossbred pigs with an initial weight of 74.70 ± 0.77 kg were randomly assigned to two groups: control group and 0.2% ELE group, with each group containing 10 replicates of 12 pigs per pen (half barrows and half gilts). The data showed dietary 0.2% ELE supplementation did not affect growth performance but tended to reduce the backfat thickness of the finishing pigs (p = 0.07). ELE diets increased pH value (p < 0.05) and meat color score (p = 0.01) and decreased 45 min L* value (p < 0.05), 24 h L* value (p = 0.01), pressurization loss (p = 0.01), and 24 h drip loss (p < 0.05) in longissimus dorsi (LD) muscle, accompanied by an increased (p < 0.05) proportion of monounsaturated fatty acids (MUFA) and decreased polyunsaturated fatty acids (PUFA) (p = 0.06) and n-6/n-3 PUFA ratio (p = 0.05) compared to controls. In addition, ELE supplementation increased inosine monophosphate (IMP) (p = 0.01), sweet amino acids (AAs) (p < 0.05), and total free AA content (p = 0.05) in LD. Meanwhile, increased activity of glutathione peroxidase (p < 0.05) and superoxide dismutase (p < 0.01) in both serum and LD muscle and decreased malondialdehyde content (p < 0.01) in LD muscle were detected with ELE treatment. Moreover, pigs fed ELE had a higher total protein (p < 0.01), albumin (p < 0.05), and high-density lipoprotein cholesterol (p < 0.05) and a lower total cholesterol (p < 0.01) and triacylglycerols (p = 0.06) in serum. Consistently, significant effects of dietary ELE were observed on the relative mRNA expression of lipid metabolism in the backfat and the LD muscle, respectively. ELE attenuated lipogenic processes in backfat, decreasing the relative expression of acetyl-CoA carboxylase and upregulating the relative expression of adipose triacyl glyceride lipase, carnitine palmitoyl transferase 1B, and fatty acid-binding protein 4 (p < 0.05). ELE also decreased the relative expression of CCAAT/enhancer-binding protein α (p < 0.05), fatty acid translocase (p < 0.05), carnitine palmitoyl transferase 1B (p < 0.01), and adipose triacyl glyceride lipase (p < 0.05) in LD muscle (p < 0.05). More specifically, lipogenesis appeared to be inhibited in both LD muscle and backfat, with the difference being that lipolysis was enhanced in backfat and inhibited in LD muscle. In conclusion, dietary ELE supplementation can potentially enhance carcass traits, sensory quality, and nutritional value of pork without negatively affecting intramuscular fat content. The underlying mechanism for these positive effects may be linked to the alterations in lipid metabolism and increased antioxidant capacity induced by ELE.

Leucine regulates lipid metabolism in adipose tissue through adipokine-mTOR-SIRT1 signaling pathway and bile acid-microbe axis in a finishing pig model.

This study was conducted to explore the regulatory mechanism of leucine (Leu) on lipid metabolism of finishing pigs. Twenty-four Duroc × Landrace × Large cross pigs with an average body weight of 68.33 ± 0.97 kg were randomly allocated into 3 treatment groups with 8 replicates per group (1 pig per replicate). The dietary treatments were as follows: control group (CON), 0.25% Leu group and 0.50% Leu group. The experimental period was 42 d. The results showed as follows. (1) Compared with the CON, 0.25% and 0.50% Leu increased (P < 0.01) the average daily gain (ADG), while the average backfat thickness (ABT) and the ratio of feed intake to body weight gain (F:G ratio) were decreased (P < 0.05). (2) In the 0.25% Leu group, the relative mRNA expression levels of sterol regulatory element binding protein-1c (SREBP1c), recombinant fatty acid transport protein 1 (FATP1), chemerin and peroxisome proliferator-activated receptor γ (PPARγ) were decreased but the level of fatty acid binding protein 4 (FABP4) and fatty acid translocase (FAT/CD36) were increased in backfat tissue. In the 0.25% Leu group, the protein levels of p-Rictor, p-Raptor, p-eIF4E-binding protein 1 (p-4EBP1), p-silent mating type information regulator 2 homolog 1 (p-SIRT1) and acetylation ribosome s6 protein kinase 1 (Ac-S6K1) were increased (P < 0.05). (3) Compared to the CON, the diversity of gut microbiota in the 0.25% Leu group was increased. Principal component analysis showed that the relative abundance of Bacteroidetes, Lactobacillus and Desulfovibrio was higher in the 0.25% Leu group than the CON, but the relative abundance of Firmicutes, Treponema and Shigella was lower than in the CON (P < 0.05). (4) Four different metabolites were screened out from the serum of finishing pigs including allolithocholic acid (alloLCA), isolithocholic acid (isoLCA), ursodeoxycholic acid (UDCA) and hyodeoxycholic acid (HDCA), which correlate to various degrees with the above microorganisms. In conclusion, Leu could promote adipose tissue lipolysis of finishing pigs through the mTOR-SIRT1 signaling pathway, and S6K1 is acetylated at the same time, and the interaction between gut microbiota and bile acid metabolism is also involved.

Dietary leucine and fish oil cooperatively regulate skeletal myofiber type transformation via the CaMKII signaling pathway of pigs.

The study investigated the effects of dietary leucine (Leu) and fish oil (FO) on skeletal myofiber type transformations in pigs and their potential interactions. The results showed that Leu increased the content of Leu, upregulated myocyte enhancer factor-2C (MEF2C) and activated the CaMKII-AMPK/SIRT1-PGC-1α pathway in the longissimus dorsi (LD) muscle. FO increased adiponectin and fatty acid beta-oxidation of LD muscle. Activation of the adiponectin signaling pathway by FO further enhanced the CaMKII pathway and upregulated the expression of MEF2C. Moreover, we found that Leu increased cyclic AMP and caffeine, and FO increased linoleic acid and glutamine in muscle metabolites, which may be the cause of myofiber conversion. In conclusion, this study demonstrated that dietary Leu and FO co-regulated the transformation from glycolytic to oxidative skeletal myofiber type. It is hypothesized that there is an interaction between amino acids and polyunsaturated fatty acids, possibly via the CaMKII signaling pathway to upregulate MEF2 and mitochondrial biogenesis.

Taurine Attenuates Oxidized Fish Oil-Induced Oxidative Stress and Lipid Metabolism Disorder in Mice.

The objective of this study was to determine the effect of dietary taurine on lipid metabolism and liver injury in mice fed a diet high in oxidized fish oil. The ICR mice (six weeks old) were randomly assigned to six groups and fed different diets for 10 weeks: control (CON), normal plus 15% fresh fish oil diet (FFO), normal plus 15% oxidized fish oil diet (OFO), or OFO plus 0.6% (TAU1), 0.9% (TAU2) or 1.2% (TAU3) taurine. Compared to the CON group, OFO mice showed increased liver index, aspartate aminotransferase (AST) and malondialdehyde (MDA) levels in serum (p < 0.05). In addition, OFO mice had increased cholesterol (CHOL)/high-density lipoprotein cholesterol (HDL-C) and decreased HDL-C/low-density lipoprotein cholesterol (LDL-C) and n-6/n-3 polyunsaturated fatty acid (PUFA) ratio in serum (p < 0.05) compared with CON mice. Notably, dietary taurine ameliorated the liver index and AST and MDA levels in serum and liver in a more dose-dependent manner than OFO mice. In addition, compared to OFO mice, decreased levels of CHOL and ratio of CHOL/HDL-C and n-6 PUFA/n-3 PUFA in serum were found in TAU3-fed mice. Supplementation with TAU2 and TAU3 increased the relative mRNA expression levels of peroxisome proliferator-activated receptor α, adipose triglyceride lipase, lipoprotein lipase, hormone-sensitive lipase and carnitine palmitoyl transferase 1 in liver compared with the OFO group (p < 0.05). Moreover, impaired autophagy flux was detected in mice fed with the OFO diet, and this was prevented by taurine. These findings suggested that dietary taurine might provide a potential therapeutic choice against oxidative stress and lipid metabolism disorder.

Potential nutritional healthy-aging strategy: enhanced protein metabolism by balancing branched-chain amino acids in a finishing pig model.

Branched-chain amino acids (BCAAs) have key physiological roles in the regulation of protein synthesis, metabolism, food intake and aging. This study aimed to investigate the protective effect of balanced BCAAs on healthy aging by increasing skeletal muscle mass and muscle fiber composition in a finishing pig model. A balanced BCAA ratio (Leu : Ile : Val = 2 : 2 : 1) significantly activated the mTOR pathway and upregulated the expression of amino acid transporters, such as ASCT2, SNAT2, LAT1, PAT1, and SLC38A9, simultaneously modulating mitochondrial function and muscle fiber composition, thereby inhibiting inflammatory cytokines, such as IL-6 and TNF-α, regulating amino acid metabolism, and ultimately increasing skeletal muscle mass. Overall, our results suggest that a BCAA ratio around 2 : 2 : 1 may be a promising candidate for healthy aging in humans and animals.

Role of brain-gut-muscle axis in human health and energy homeostasis.

The interrelationship between brain, gut and skeletal muscle plays a key role in energy homeostasis of the body, and is becoming a hot topic of research. Intestinal microbial metabolites, such as short-chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites, communicate with the central nervous system (CNS) by binding to their receptors. In fact, there is a cross-talk between the CNS and the gut. The CNS, under the stimulation of pressure, will also affect the stability of the intestinal system, including the local intestinal transport, secretion and permeability of the intestinal system. After the gastrointestinal tract collects information about food absorption, it sends signals to the central system through vagus nerve and other channels to stimulate the secretion of brain-gut peptide and produce feeding behavior, which is also an important part of maintaining energy homeostasis. Skeletal muscle has receptors for SCFAs and BAs. Therefore, intestinal microbiota can participate in skeletal muscle energy metabolism and muscle fiber conversion through their metabolites. Skeletal muscles can also communicate with the gut system during exercise. Under the stimulation of exercise, myokines secreted by skeletal muscle causes the secretion of intestinal hormones, and these hormones can act on the central system and affect food intake. The idea of the brain-gut-muscle axis is gradually being confirmed, and at present it is important for regulating energy homeostasis, which also seems to be relevant to human health. This article focuses on the interaction of intestinal microbiota, central nervous, skeletal muscle energy metabolism, and feeding behavior regulation, which will provide new insight into the diagnostic and treatment strategies for obesity, diabetes, and other metabolic diseases.

The Effect of Dietary Leucine Supplementation on Antioxidant Capacity and Meat Quality of Finishing Pigs under Heat Stress.

This study examined the effects of dietary leucine supplements on antioxidant capacity and meat quality in growing-finishing pigs. A total of 24 crossbred (Duroc × Landrace × Yorkshire) pigs with an average initial weight of 68.33 ± 0.97 kg were randomly allotted to three treatment groups. All pigs were exposed to constant heat stress. Each group of pigs was fed a basal diet, or a diet supplemented with increasing levels of leucine (0.25% or 0.50%). The results showed that leucine intake could improve average daily gain and reduce feed/gain of finishing pigs under heat stress (p < 0.05). The supplementation of leucine could improve the carcass slant length (p = 0.09), and dramatically increased loin-eye area of the finishing pigs (p < 0.05) but had no significant effect on other carcass traits. Compared with the control group, 0.50% leucine markedly reduced drip loss and shear force of longissimus dorsi muscle, and increased pH value at 24 h after slaughter (p < 0.05). Dietary supplementation of 0.25% leucine increased the contents of inosine monophosphate and intramuscular fat in biceps femoris muscle (p < 0.05). Supplementation of 0.25% or 0.50% leucine significantly stimulated the activities of antioxidant enzymes while reduced the level of MDA in serum, liver and longissimus dorsi muscle (p < 0.05). Compared with the control group, 0.50% leucine supplementation markedly modulated the relative mRNA expression levels of genes related to muscle fiber type and mitochondrial function in longissimus dorsi muscle and the gene relative antioxidant in the liver (p < 0.05). In conclusion, dietary leucine supplementation could improve the growth performance and meat quality of the finishing pigs under heat stress, and the pathway of Keap1-NRF2 and PGC-1α-TFAM might be involved.

Effects of Dietary Chlorogenic Acid Supplementation Derived from Lonicera macranthoides Hand-Mazz on Growth Performance, Free Amino Acid Profile, and Muscle Protein Synthesis in a Finishing Pig Model.

Chlorogenic acid (CGA), as one of the richest polyphenol compounds in nature, has broad applications in many fields due to its various biological properties. However, initial data on the effects of dietary CGA on protein synthesis and related basal metabolic activity has rarely been reported. The current study is aimed at (1) determining whether dietary CGA supplementation improves the growth performance and carcass traits, (2) assessing whether dietary CGA alters the free amino acid profile, and (3) verifying whether dietary CGA promotes muscle protein synthesis in finishing pigs. Thirty-two (Large × White × Landrace) finishing barrows with an average initial body weight of 71.89 ± 0.92 kg were randomly allotted to 4 groups and fed diets supplemented with 0, 0.02%, 0.04%, and 0.08% CGA, respectively. The results indicated that, compared with the control group, dietary supplementation with 0.04% CGA slightly stimulated the growth performance of pigs, whereas no significant correlation was noted between the dietary CGA levels and animal growth (P > 0.05). Furthermore, the carcass traits of pigs were improved by 0.04% dietary CGA (P < 0.01). In addition, dietary CGA significantly improved the serum free amino acid profiles of pigs (P < 0.01), while 0.04% dietary CGA promoted more amino acids to translocate to skeletal muscles (P < 0.05). The relative mRNA expression levels of SNAT2 in both longissimus dorsi (LD) and biceps femoris (BF) muscles were augmented in the 0.02% and 0.04% groups (P < 0.05), and the LAT1 mRNA expression in the BF muscle was elevated in the 0.02% group (P < 0.05). We also found that dietary CGA supplementation at the levels of 0.04% or 0.08% promoted the expression of p-Akt and activated the mTOR-S6K1-4EBP1 axis in the LD muscle (P < 0.05). Besides, the MAFbx mRNA abundance in the 0.02% and 0.04% groups was significantly lower (P < 0.05). Our results revealed that dietary supplementation with CGA of 0.04% improved the free amino acid profile and enhanced muscle protein biosynthesis in the LD muscle in finishing pigs.

Regulative Mechanism of Guanidinoacetic Acid on Skeletal Muscle Development and Its Application Prospects in Animal Husbandry: A Review.

Guanidinoacetic acid is the direct precursor of creatine and its phosphorylated derivative phosphocreatine in the body. It is a safe nutritional supplement that can be used to promote muscle growth and development. Improving the growth performance of livestock and poultry and meat quality is the eternal goal of the animal husbandry, and it is also the common demand of today's society and consumers. A large number of experimental studies have shown that guanidinoacetic acid could improve the growth performance of animals, promote muscle development and improve the health of animals. However, the mechanism of how it affects muscle development needs to be further elucidated. This article discusses the physical and chemical properties of guanidinoacetic acid and its synthesis pathway, explores its mechanism of how it promotes muscle development and growth, and also classifies and summarizes the impact of its application in animal husbandry, providing a scientific basis for this application. In addition, this article also proposes future directions for the development of this substance.

Different Proportions of Branched-Chain Amino Acids Modulate Lipid Metabolism in a Finishing Pig Model.

This study aimed to investigate the effect of the supplementation of branched-chain amino acids (BCAAs) at different ratios in protein restriction diets on lipid metabolism in a finishing pig model. The BCAA supplementation (leucine/isoleucine/valine = 2:1:1 and 2:1:2) ameliorated the poor growth performance and carcass characteristics, particularly high fat mass caused by a protein-restricted diet. Serum adiponectin increased while leptin decreased in BCAA diets in comparison to the 12% CP group. BCAA supplementation also increased the low-protein expression of AMPK and SIRT1 caused by protein restriction. The mRNA and protein levels of peroxisome proliferation-activated receptor-γ (PPARγ) and acetyl-CoA carboxylase (ACC) were highest in the protein-restricted group and lowered in the 2:1:1 or 2:1:2 group. In conclusion, BCAAs supplemented in an adequate ratio range of 2:1:1 to 2:1:2 (2:1:2 is recommended) in reduced protein diets could modulate lipid metabolism by accelerating the secretion of adipokines and fatty acid oxidation.

Effects of Dietary Tea Powder on the Growth Performance, Carcass Traits, and Meat Quality of Tibetan Pig × Bama Miniature Pigs.

This study was conducted to evaluate the effects of tea powder in diets on the growth performance, meat quality, muscular amino acid, fatty acid profile, and serum biochemical indices of pigs. A total of 120 local Chinese pigs (Tibetan × Bama miniature pigs) were randomly assigned to five treatment groups, each with six pens and four pigs per pen. During a 60-day experiment, these groups of pigs were fed the normal diet and the diet supplemented with 1%, 2%, 4%, and 6% tea powder, respectively. The results showed that the supplementation of tea powder did not affect the growth performance of pigs. However, the dietary tea powder inclusion decreased (p < 0.05) the average fat thickness, total fat, and abdominal fat, and increased (p < 0.05) the total muscle as well. In addition, the dietary 2% tea powder decreased (p < 0.05) the muscle lightness (L*) and yellowness (b*). Compared with the control group, the dietary supplementation with 1%, 2%, and 4% tea powder raised (p < 0.05) the total amino acids (TAA) and essential amino acids (EAA), and dietary 4% and 6% tea powder increased (p < 0.05) the C20:5n3 in the muscle tissue. Furthermore, the serum lipid metabolism-related biochemical indices and mRNA expression levels were improved with the addition of tea powder. These results indicated that dietary tea powder might improve the carcass traits and meat quality of the Chinese native finishing pigs, but it does not affect their growth performance. Tea powder could be fully developed and reasonably applied as a dietary supplement.

Effects of Different Supplemental Levels of Eucommia ulmoides Leaf Extract in the Diet on Carcass Traits and Lipid Metabolism in Growing-Finishing Pigs.

This study examined the effects of dietary Eucommia ulmoides leaf extract (ELE) supplements on carcass traits and lipid metabolism in growing-finishing pigs. A total of 144 crossbred (Duroc × Landrace × Yorkshire) piglets with an average initial weight of 10.11 ± 0.03 kg were randomly allotted to four treatment groups, each with six replicates and six piglets per replicate. Each group of pigs was fed a basal diet or a diet supplemented with increasing levels of ELE (0.1, 0.2, or 0.3%). The results showed that adding ELE had no negative effect on the growth performance of pigs. Dietary supplements of 0.1% ELE significantly increased carcass weight (p < 0.01), dressing percentage (p < 0.01), carcass length (p < 0.05), and eye muscle area (p < 0.05). Compared with the control group, a 0.2% ELE supplement significantly increased (p < 0.01) the levels of adiponectin, insulin-like growth factor 1, and hormone-sensitive lipase and lipoprotein lipase activity in the serum. Histological examination showed that ELE inhibited fat deposition in the backfat tissue. Lipid metabolism-related biochemical indices and mRNA expression levels were improved after supplementing diets with ELE. Moreover, all three levels of ELE dramatically upregulated (p < 0.05) the protein levels of p-AMPK-α and p-ACC. In summary, adding ELE to pig diets could improve the carcass traits of growing-finishing pigs and exert a lipid-lowering effect by activating the AMPK-ACC pathway and regulating mRNA expression levels related to lipid metabolism. Supplementing the diet with 0.1-0.2% ELE is the optimal range to reduce fat deposition in pig backfat tissue.

Increased risks of tic disorders in children with epilepsy: A nation-wide population-based case-control study in Taiwan.

Both epilepsy and tic disorders may share common mechanisms with the involvement of abnormal cortical-basal ganglion circuit connection and dopaminergic dysfunction. However, the association between epilepsy and tic disorders has never been studied. This study investigated the risks of developing tic disorders among children with epilepsy using databases of a universal health insurance system in Taiwan. The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. The study cohort included children with epilepsy between 2001 and 2007 (n=2629) and a three-fold age- and gender-matched controls (n=7887). All subjects were followed up for 3 years from the date of cohort entry to identify their admissions due to tic disorders (ICD-9-CM codes 307.2, 307.20-307.23). Cox hazard regression analysis was performed to estimate the effect of epilepsy on the occurrence of tics. The epilepsy cohort had a higher prevalence of tics (1.7% vs. 0.2%), and a 8.70-fold increased risk of developing a tic disorder compared with the controls (adjusted hazard ratio (AHR) 8.70, 95% confidence interval (CI) 4.26-16.37, p<0.001). Male patients were observed to have a higher risk of developing a tic disorder (AHR 1.90, 95% CI=1.04-3.46, p<0.001) compared to female individuals. Patients with multiple antiepileptic drugs treatment also exhibited higher crude OR for developing tic disorders. This nationwide population-based cohort study, for the first time, demonstrated that there is a significantly increased risk for tic disorders among children with epilepsy. We also found males, attention deficit disorder and the use of multiple AEDs to be independent risk factors of tic disorders. Closely evaluating possible tic disorders would be crucial for improving the outcome and life quality in children with epilepsy.

Increased risk of epilepsy in children with Tourette syndrome: A population-based case-control study.

The association between epilepsy and Tourette syndrome has rarely been investigated. In this retrospective cohort study, we analyzed a dataset of 1,000,000 randomly sampled individuals from the Taiwan National Health Insurance Research Database to determine the risk of epilepsy in children with Tourette syndrome. The study cohort consisted of 1062 patients with Tourette syndrome aged ≤ 18 years, and the control group consisted of three times the number of age- and sex-matched patients without Tourette syndrome, who were insurants, from the same database during the same period. The Tourette syndrome group had an 18.38-fold increased risk of epilepsy than the control group [hazard ratio=18.38, 95% confidence interval (CI)=8.26-40.92; P<0.001]. Even after adjusting for the comorbidities, the risk of epilepsy in the Tourette syndrome group with comorbidities remained high (hazard ratio=16.27, 95% CI=6.26-18.46; P<0.001), indicating that the increased risk was not associated with comorbidities. This population-based retrospective cohort study provides the first and strong evidence that Tourette syndrome is associated with a higher risk of epilepsy. A close follow-up of children with Tourette syndrome for the development of epilepsy is warranted.

Angiotensin Receptor Blockers Decrease the Risk of Major Adverse Cardiovascular Events in Patients with End-Stage Renal Disease on Maintenance Dialysis: A Nationwide Matched-Cohort Study.

BACKGROUND: Major adverse cardiovascular events (MACE) cause the leading cause of morbidity and mortality in patients with end-stage renal disease (ESRD) on maintenance Hemodialysis (HD) or peritoneal dialysis (PD). Many randomized-controlled trials (RCTs) have proved that angiotensin receptor blockers (ARBs) can reduce the risk of MACE in the people with normal or impaired kidney function without dialysis. This study seeks to clarify whether ARBs therapy could also attenuate this risk in patients with ESRD on maintenance dialysis. MATERIALS AND METHODS: The National Health Research Institute provided a database of one million random subjects for the study. A random sample was taken of 1800 patients ≥18 years y/o with ESRD on dialysis without a history of MACE and use of ARBs within 6-months prior to enrollment. Cox proportional hazard regression analysis was used to identify the risk factors and compute the hazard ratios accompanying 95% confidence intervals. RESULTS: In these 1800 patients, 1061 had never used ARBs, while 224 had used them for 1-90 days, and 515 had used them for more than 90 days. We found that ARBs significantly decrease the incidences of acute myocardial infarctions (AMI), coronary artery diseases (CAD) requiring coronary stent or percutaneous transluminal coronary angioplasty (PTCA), peripheral artery disease (PAD) requiring percutaneous transluminal angioplasty (PTA), and acute stroke. Cumulative prescription days of ARBs beyond 365-760 days or more were found to be negatively correlated with incidence of MACEs. For patients with dual comorbidity (i.e., mellitus and hyperlipidemia), 91-365 cumulative prescription days might also attenuate the risk. CONCLUSIONS: For patients on maintenance dialysis, the use of ARBs could significantly attenuate the risk of major cardiovascular events: AMI, acute stroke, and PAD requiring PTA.

Is schizophrenia associated with an increased risk of chronic kidney disease? A nationwide matched-cohort study.

OBJECTIVE: The impact of schizophrenia on vital diseases, such as chronic kidney disease (CKD), has not as yet been verified. This study aims to establish whether there is an association between schizophrenia and CKD. DESIGN: A nationwide matched cohort study. SETTING: Taiwan's National Health Insurance Research Database. PARTICIPANTS: A total of 2338 patients with schizophrenia, and 7014 controls without schizophrenia (1:3), matched cohort for sex, age group, geography, urbanisation and monthly income, between 1 January 2003 and 31 December 2007, based on the International Classifications of Disease Ninth Edition (ICD-9), Clinical Modification codes. PRIMARY AND SECONDARY OUTCOME MEASURES: After making adjustments for confounding risk factors, a Cox proportional hazards model was used to compare the risk of developing CKD during a 3-year follow-up period from the index date. RESULTS: Of the 2338-subject case cohort, 163 (6.97%) developed a CKD, as did 365 (5.20%) of the 7014 control participants. Cox proportional hazards regression analysis revealed that patients with schizophrenia were more likely to develop CKD (HR=1.36, 95% CI 1.13 to 1.63; p<0.001). After adjusting for gender, age group, hypertension, diabetes mellitus, hyperlipidaemia, heart disease and non-steroid anti-inflammatory drugs (NSAIDs) usage, the HR for patients with schizophrenia was 1.25 (95% CI 1.04 to 1.50; p<0.05). Neither typical nor atypical antipsychotics was associated an increased risk of CKD in patients with schizophrenia. CONCLUSIONS: The findings from this population-based retrospective cohort study suggest that schizophrenia is associated with a 25% increase in the risk of developing CKD within only a 3-year follow-up period.

Is Zolpidem Associated with Increased Risk of Fractures in the Elderly with Sleep Disorders? A Nationwide Case Cross-Over Study in Taiwan.

BACKGROUND: We conducted a study using a case-crossover design to clarify the risk of acute effects of zolpidem and benzodiazepine on all-sites of fractures in the elderly. DESIGN OF STUDY: Case-crossover design. METHODS AND MATERIALS: Elderly enrollees (n = 6010) in Taiwan's National Health Insurance Research Database with zolpidem or benzodiazepine use were analyzed for the risk of developing fractures. RESULTS: After adjusting for medications such as antipsychotics, antidepressants, and diuretics, or comorbidities such as hypertension, osteoarthritis, osteoporosis, rheumatoid arthritis and depression, neither zolpidem nor benzodiazepine was found to be associated with increased risk in all-sites fractures. Subjects without depression were found to have an increased risk of fractures. Diazepam is the only benzodiazepine with increased risk of fractures after adjusting for medications and comorbidities. Hip and spine were particular sites for increased fracture risk, but following adjustment for comorbidities, the associations were found to be insignificant. CONCLUSION: Neither zolpidem nor benzodiazepine was associated with increased risk of all-site fractures in this case cross-over study after adjusting for medications or comorbidities in elderly individuals with insomnia. Clinicians should balance the benefits and risks for prescribing zolpidem or benzodiazepine in the elderly accordingly.