Dietary Glycine Research Articles

Meta-analysis of the influence of dietary glycine and serine, with consideration of methionine and cysteine, on growth and feed conversion of broilers

The existing literature is inconsistent with respect to optimal dietary concentrations of glycine (Gly) and serine (Ser) in broiler feed. Therefore, we conducted a meta-analysis to investigate the response of broilers to dietary levels of Gly using a full quadratic model based on mixed model methodology. Response was measured as ADG (g/d), ADFI (g/d), and G:F (g/g). In addition, the influence of other dietary constituents was evaluated. This meta-analysis was based on a data set comprising a total of 9,626 broilers in 10 peer-reviewed papers that investigated the response of broilers to different dietary concentrations of Gly, achieved by addition of free Gly. The fitted quadratic model, with either Gly+Ser or the calculated glycine equivalent (Glyequi) of both amino acids as the independent variable, revealed that all model terms were significant (P ≤ 0.05), and hence proved a curvilinear relationship between these independent variables and response traits. The R2 value and root MS error confirmed a strong relationship between observed and predicted traits. A comparison of the influence of Gly+Ser and Glyequi on response traits revealed that both approaches produced similar results. Because Glyequi should meet the physiological values of a diet better than Gly+Ser, models with 2 independent variables were conducted using Glyequi. The second independent variables were methionine (Met):TSAA ratio and the concentrations of cysteine (Cys) and CP. In models with one or 2 independent variables, the impact of dietary Gly on ADFI was low. By contrast, G:F was markedly influenced by dietary Gly; this effect intensified at lower Met:TSAA ratios and higher Cys and CP levels. ADG was also a function of Glyequi and the second independent variables. For ADG, an optimal Met:TSAA ratio of 0.655 and Cys concentration of 0.302% was calculated. Following the nonlinear nature of relationship, generally applicable replacement values could not be calculated. However, it was concluded that consideration of dietary Cys can diminish the requirement for Glyequi, and therefore, enable a reduction in the CP of broiler diets without limiting growth performance.

Su1803 Dietary Glycine Improves Impaired Glucose Tolerance by Modulating Polarization of Kupffer Cells in Diabetic KK-aY Mice

Su1803 Dietary Glycine Improves Impaired Glucose Tolerance by Modulating Polarization of Kupffer Cells in Diabetic KK-aY Mice

Green tea and glycine aid in the recovery of tendinitis of the Achilles tendon of rats

Purpose: Green tea (GT) is widely used due to its anti-inflammatory properties. Previous studies have shown beneficial effects of a glycine diet on the remodeling process in inflamed tendons. Tendinitis is commonly observed in athletes and is of concern to surgeons due to the slowness of the recovery process. Our hypothesis is that GT + a glycine diet may improve tendinitis. Aim of the study: To analyze the effect of GT and/or glycine in the diet on tendinitis. Materials and methods: Wistar rats were divided into seven groups (G): control group (C); G1 and G4, tendinitis; G2 and G5, tendinitis supplied with GT; and G3 and G6, tendinitis supplied with GT and a glycine diet for 7 or 21 days, respectively. We performed zymography for metalloproteinase, biochemical, morphological and biomechanics tests. Results: G2, G3 and G5 showed high levels of hydroxyproline in relation to G1, while G4 showed high levels of glycosaminoglycans. High activity of metalloproteinase-2 was detected in G3. The organization of collagen bundles was better in G2 and G3. G5 showed similar birefringence measurements compared with C. G5 withstood a larger load compared with G4. Conclusions: The presence of metalloproteinase-2 indicates that a tissue is undergoing a remodeling process. High birefringence suggests a better organization of collagen bundles. After 21 days, G5 sustained a high load before rupture, unlike G4. The results suggest that GT + a glycine diet has beneficial effects that aid in the recovery process of the tendon after tendinitis.

Whole grains beyond fibre: what can metabolomics tell us about mechanisms?

Dietary fibre alone does not fully explain the frequent association between greater intake of whole grains and reduced risk of disease in observational studies, and other phytochemicals or food structure may also play an important role. For all the observational evidence for the benefits of a whole-grain-rich diet, we have only limited knowledge of the mechanisms behind this reduction in disease risk, aside from the action of specific cereal fibres on reduction of blood cholesterol and the post-prandial glucose peak. Nutritional metabolomics, the global measurement and interpretation of metabolic profiles, assesses the interaction of food with the endogenous gene-protein cascade and the gut microbiome. This approach allows the generation of new hypotheses which account for systemic effects, rather than just focusing on one or two mechanisms or metabolic pathways. To date, animal and human trials using metabolomics to investigate mechanistic changes to metabolism on eating whole grains and cereal fractions have led to new hypotheses around mechanistic effects of whole grains. These include the role of cereals as a major source of dietary glycine betaine, a possible effect on phospholipid synthesis or metabolism, the role of branched-chain amino acids and improvements in insulin sensitivity, and the possibility that whole grains may have an effect on protein metabolism. These hypotheses help explain some of the observed effects of whole grains, although mechanistic studies using stable isotopes and fully quantitative measures are required to confirm these potential mechanisms.

Glycine Stimulates Protein Synthesis and Inhibits Oxidative Stress in Pig Small Intestinal Epithelial Cells

Glycine has recently been classified as a nutritionally essential amino acid for maximal growth in young pigs. Currently, little is known about the metabolism or function of glycine in the neonatal intestine. This work was conducted to test the hypothesis that glycine has a protective effect against oxidative stress in intestinal epithelial cells. Jejunal enterocytes isolated from newborn pigs were cultured in the presence of 0.0–2 mmol/L glycine for measurements of glycine metabolism, cell proliferation, protein turnover, apoptosis, and antioxidative response. Compared with 0.0–0.5 mmol/L glycine, 1.0 mmol/L glycine enhanced (P < 0.05) cell growth (by 8–24% on day 2 and by 34–224% on day 4, respectively) and protein synthesis (by 36–419%) while reducing (P < 0.05) protein degradation (by 7–28%). This effect of glycine was associated with activation of the mammalian target of rapamycin signaling pathway in enterocytes. By using a model of oxidative stress induced by 30 μmol/L 4-hydroxynonenal (4-HNE), which was assessed by flow cytometry analysis, 1.0 mmol/L glycine inhibited (P < 0.05) activation of caspase 3 by 25% and attenuated (P < 0.05) 4-HNE–induced apoptosis by 38% in intestinal porcine epithelial cell line 1 cells through promotion of reduced glutathione synthesis and expression of glycine transporter 1 while reducing the activation of extracellular signal–regulated kinases, c-Jun amino-terminal kinases, and p38 protein in the mitogen-activated protein kinase signaling pathway. These novel findings provide a biochemical mechanism for the use of dietary glycine to improve intestinal health in neonates under conditions of oxidative stress and glycine deficiency.

Glycine improves biochemical and biomechanical properties following inflammation of the achilles tendon.

Tendinopathy of the Achilles tendon is a clinical problem that motivates the scientific community to search for treatments that assist in restoring its functional properties. Glycine has broad biological effects, acting as a modulator of the inflammatory cascade, and is the predominant amino acid in collagen. A 5% glycine diet provided beneficial effects against toxicity and inflammation since glycine may restructure the collagen molecules faster due to its broad anti-inflammatory effects. The purpose was analyze the effects of a 5% glycine diet in rats as a treatment for the inflammatory process. The experimental groups were as follows: C (control group), G1 and G3 (inflammatory group), and G2 and G4 (glycine+inflammatory group). G1 and G2 were euthanized 8 days following injury, and G3 and G4 were euthanized 22 days following injury. The concentrations of hydroxyproline, non-collagenous proteins, and glycosaminoglycans, as well as the activity of MMP-2 and -9 were analyzed. Biomechanical and morphological tests were employed. Higher concentrations of hydroxyproline and glycosaminoglycans were found in G4 and an increased activity of MMP-2 was found in G2. Higher birefringence was noted in group G2. The biomechanical results indicated that the tendon was more resistant to loading to rupture upon treatment with a glycine diet in group G4. Glycine induced the synthesis of important components of the tendon. A rapid remodeling was noted when compared with the inflamed-only groups. These data suggest that glycine may be a beneficial supplement for individuals with inflammation of the Achilles tendon.

Glycine is a nutritionally essential amino acid for maximal growth of milk-fed young pigs.

Analysis of amino acids in milk protein reveals a relatively low content of glycine. This study was conducted with young pigs to test the hypothesis that milk-fed neonates require dietary glycine supplementation for maximal growth. Fourteen-day-old piglets were allotted randomly into one of four treatments (15 piglets/treatment), representing supplementation with 0, 0.5, 1 or 2% glycine (dry matter basis) to a liquid milk replacer. Food was provided to piglets every 8 h (3 times/day) for 2 weeks. Milk intake (32.0-32.5 g dry matter/kg body weight per day) did not differ between control and glycine-supplemented piglets. Compared with control piglets, dietary supplementation with 0.5, 1 and 2% glycine increased (P < 0.05) plasma concentrations of glycine and serine, daily weight gain, and body weight without affecting body composition, while reducing plasma concentrations of ammonia, urea, and glutamine, in a dose-dependent manner. Dietary supplementation with 0.5, 1 and 2% glycine enhanced (P < 0.05) small-intestinal villus height, glycine transport (measured using Ussing chambers), mRNA levels for GLYT1, and anti-oxidative capacity (indicated by increased concentrations of reduced glutathione and a decreased ratio of oxidized glutathione to reduced glutathione). These novel results indicate, for the first time, that glycine is a nutritionally essential amino acid for maximal protein accretion in milk-fed piglets. The findings not only enhance understanding of protein nutrition, but also have important implications for designing improved formulas to feed human infants, particularly low birth weight and preterm infants.

Effect of glycine supplementation on growth performance, body composition and salinity stress of juvenile Pacific white shrimp, Litopenaeus vannamei fed low fishmeal diet

An 8-week feeding trial was conducted to evaluate the optimum dietary glycine level in low fishmeal diet for juvenile Pacific white shrimp, Litopenaeus vannamei. Six practical diets (44.4% protein, 8.8% lipid) were formulated to contain graded levels (2.26, 2.33, 2.44, 2.58, 2.67 and 2.74%) of l-glycine. Each diet was randomly assigned to triplicate groups of 30 shrimps (approximately 0.61g) and the shrimps were fed 4 times a day to apparent satiation. The results indicated that the weight gain and specific growth rate were significantly increased with the supplementation of glycine. The highest weight gain and specific growth rate were observed at 2.56% dietary glycine, and then decrease with a further increase in dietary glycine. Hepatosomatic index, protein productive value and condition factor were also significantly influenced by the dietary glycine levels and show a similar trend to those of growth performance. There were no significant differences observed in feed efficiency, protein efficiency ratio and survival among all treatments. Mg, Ca and Fe concentrations in whole body were significantly increased with the supplementation of glycine. Non-essential amino acid, essential amino acid and arginine ratio in muscle were significantly affected by the dietary glycine levels. Dietary glycine levels higher than 2.44% significantly increased the survival of shrimps after 2h and 3h of acute salinity change, and T-SOD activity and Na+/K+-ATPase activity in hematological and hepatopancreas before and after acute salinity change are also significantly affected by the dietary glycine levels. Analysis by second-order regression of weight gain indicated that the optimal dietary glycine level was 2.54% of the dry diet (5.7% of the dietary protein and 6.66% of the dietary amino acids).

Dietary glycine and blood pressure: the International Study on Macro/Micronutrients and Blood Pressure

Available data have indicated independent direct relations of dietary animal protein and meat to the blood pressure (BP) of individuals. In this study, we aimed to assess whether BP is associated with the intake of dietary amino acids higher relatively in animal than in vegetable protein (alanine, arginine, aspartic acid, glycine, histidine, lysine, methionine, and threonine). The study was a cross-sectional epidemiologic study that involved 4680 persons aged 40-59 y from 17 random population samples in the People's Republic of China, Japan, the United Kingdom, and the United States. BP was measured 8 times at 4 visits; dietary data (83 nutrients and 18 amino acids) were from four 24-h dietary recalls and two 24-h urine collections. Dietary glycine and alanine (the percentage of total protein intake) were considered singly related directly to BP; with these 2 amino acids together in regression models (from model 1, which was controlled for age, sex, and sample, to model 5, which was controlled for 16 possible confounders), glycine, but not alanine, was significantly related to BP. Estimated average BP differences associated with a 2-SD higher glycine intake (0.71 g/24 h) were 2.0-3.0-mm Hg systolic BP (z = 2.97-4.32) stronger in Western than in East Asian participants. In Westerners, meat was the main dietary source of glycine but not in East Asians (Chinese: grains/flour and rice/noodles; Japanese: fish/shellfish and rice/noodles). Dietary glycine may have an independent adverse effect on BP, which possibly contributes to direct relations of animal protein and meat to BP.

Dietary glycine+serine responses of male broilers given low-protein diets with different concentrations of threonine

1. The objective of this study was to determine the optimum glycine+serine (Gly+Ser) concentration in low-crude protein (CP) diets that have adequate or high concentrations of dietary threonine (Thr) for broiler chickens in the initial growth phase. 2. Treatments consisted of four concentrations of dietary Gly+Ser (18.4; 19.8; 21.2 and 22.6 g/kg) and two concentrations of dietary Thr (9.3 and 10.7 g/kg, corresponding to 100 and 115% of the required Thr, respectively). 3. At 21d, interactions were observed between dietary Gly+Ser and Thr concentrations for the feed conversion ratio, creatine content in the pectoral muscles and serum concentrations of uric acid. There was a quadratic effect of the concentrations of Gly+Ser in the diets with 9.3 g Thr/kg on the feed conversion ratio and creatine content in the pectoral muscles, with an optimisation concentration of 20.8 and 21.1 g Gly+Ser/kg, respectively. 4. Diets containing 10.7 g Thr/kg negatively affected the feed conversion ratio, relative breast weight, creatine content in the pectoral muscles, serum concentrations of uric acid and ammonia in poultry compared to diets containing 9.3 g Thr/kg. 5. The need for Gly+Ser in diets with low-protein concentration (190 g CP/kg) and adequate concentration of Thr (9.3 g/kg) is 20.8 g/kg for broilers in the 1- to 21-d phase.

Glycine reduces platelet aggregation

It has been demonstrated that a wide variety of white blood cells and macrophages (i.e. Kupffer cells, alveolar and peritoneal macrophages and neutrophils) contain glycine-gated chloride channels. Binding of glycine on the receptor stimulates Cl(-) influx causing membrane hyperpolarization that prevents agonist-induced influx of calcium. Since platelet-aggregation is calcium-dependent, this study was designed to test the hypothesis that glycine would inhibit platelet aggregation. Rats were fed diets rich of glycine for 5 days, while controls received isonitrogenous valine. The bleeding time and ADP- and collagen-induced platelet aggregation were measured. Dietary glycine significantly increased bleeding time about twofold compared to valine-treated controls. Furthermore, the amplitude of platelet aggregation stimulated with ADP or collagen was significantly decreased in whole blood drawn from rats fed 2.5 or 5 % dietary glycine by over 50 %. Addition of glycine in vitro (1-10 mM) also blunted rat platelet aggregation in a dose-dependent manner. Strychnine, a glycine receptor antagonist, abrogated the inhibitory effect of glycine on platelet-aggregation in vitro suggesting the glycine works via a glycine receptor. Glycine also blunted aggregation of human platelets. Further, the glycine receptor was detected in both rat and human platelets by western blotting. Based on these data, it is concluded that glycine prevents aggregation of platelets in a dose-dependent manner via mechanisms involving a glycine receptor.

Alleviation of body weight loss by dietary methionine is independent of insulin‐like growth factor‐I in protein‐starved young chickens

It is well known that in protein-starved chickens, small amounts of amino acid supplement, especially methionine, reduces nitrogen excretion and thereby improves nitrogen balance. On the other hand, excess intake of methionine causes growth depression and the growth-depressive effect of excess methionine can be alleviated by consumption of dietary glycine. Insulin-like growth factor-I (IGF-I) is one of various growth-promoting factors relating to the efficiency of animal production and is known to be very sensitive to changes in nutritional status. In the present study, the interactive effect of glycine on nitrogen sparing effect of methionine in protein-starved chickens was examined. In addition, the relation of IGF-I and its specific binding protein to the nitrogen sparing effect of supplemented methionine was also investigated. Two-days refeeding of methionine supplemented to protein-free diet could promptly alleviate body weight loss in protein-starved chickens, and the alleviation of body weight loss by methionine was not improved by glycine supplements. Moreover, such acute alleviation of body weight loss by dietary methionine was independent of the change in plasma IGF-I concentration.

Dietary glycine supplementation mimics lifespan extension by dietary methionine restriction in Fisher 344 rats

Dietary methionine (Met) restriction (MR) extends lifespan in rodents by 30–40% and inhibits growth. Since glycine is the vehicle for hepatic clearance of excess Met via glycine N-methyltransferase (GNMT), we hypothesized that dietary glycine supplementation (GS) might produce biochemical and endocrine changes similar to MR and also extend lifespan. Seven-week-old male Fisher 344 rats were fed diets containing 0.43% Met/2.3% glycine (control fed; CF) or 0.43% Met/4%, 8% or 12% glycine until natural death. In 8% or 12% GS rats, median lifespan increased from 88 weeks (w) to 113 w, and maximum lifespan increased from 91 w to 119 w v CF. Body growth reduction was less dramatic, and not even significant in the 8% GS group. Dose-dependent reductions in several serum markers were also observed. Long-term (50 w) 12% GS resulted in reductions in mean (±SD) fasting glucose (158 ± 13 v 179 ± 46 mg/dL), insulin (0.7 ± 0.4 v 0.8 ± 0.3 ng/mL), IGF-1 (1082 ± 128 v 1407 ± 142 ng/mL) and triglyceride (113 ± 31 v 221 ± 56 mg/dL) levels compared to CF. Adiponectin, which increases with MR, did not change in GS after 12 w on diet. We propose that more efficient Met clearance via GNMT with GS could be reducing chronic Met toxicity due to rogue methylations from chronic excess methylation capacity or oxidative stress from generation of toxic by-products such as formaldehyde. This project received no outside funding.

Role of Oil Vehicle on Hepatic Cell Proliferation in PCB-Treated Rats

We report the role of dietary glycine and the type of oil used as a vehicle in the hepatotoxicity of control rats and rats treated with 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153). In our first experiment, glycine or valine (as control) was fed in an unrefined diet at 5% for the entire study duration (5 days) to inhibit Kupffer cell activity. PCB-153 (100 or 300 μmol/kg) dissolved in medium chain triglyceride (MCT) oil, was injected intraperitoneally 2 days before euthanasia; the peroxisome proliferator Wy-14,643 was included as a positive control. MCT oil decreased cell proliferation by approximately 50%. PCB-153 slightly increased hepatic cell proliferation, but dietary glycine did not reduce cell proliferation. Because of the inhibition of cell proliferation in rats receiving MCT oil compared with rats receiving no injection, we hypothesized that MCT oil may have been inhibiting the hepatocyte proliferation in PCB-153-treated rats. We therefore performed another experiment using 3 types of oil as a vehicle for PCB-153: MCT oil, corn oil, and olive oil. Rats were injected with PCB-153 (300 μmol/kg) or one of the vehicles, again 2 days before euthanasia. MCT oil again decreased the hepatocyte proliferation by approximately 50%. In rats receiving PCB-153, hepatocyte proliferation was slightly higher than their respective vehicle controls for corn oil and olive oil but not for MCT oil. These studies show that the oil vehicle is important in cell proliferation after PCB exposure, with MCT oil appearing to be protective.

Glycine soya diet synergistically enhances the suppressive effect of tamoxifen and inhibits tamoxifen-promoted hepatocarcinogenesis in 7,12-dimethylbenz[α]anthracene-induced rat mammary tumor model

There is increasing interest in phytoestrogens as potential alternatives to synthetic selective estrogen receptor modulators (SERMs) in the prevention and therapy of breast cancer. The present study is aimed at determining whether dietary glycine soya (Glycine max seeds; GS), which is rich in phytoestrogens, can enhance the anti breast cancer efficacy of the SERM tamoxifen (TAM) and the effect of TAM and GS, either alone or in combination, on DMBA-initiated hepatocarcinogenesis in rat. For determination of enhancing effect, rats bearing palpable 7, 12-dimethylbenz[α] anthracene (DMBA)-induced mammary tumors were treated with TAM (10mgkg−1/day) while being fed AIN-93G diet with or without added GS (3×104mgkg−1), and the tumor growth was monitored up to 5weeks of treatment. For determining the effect on hepatocarcinogenesis, DMBA-initiated rats were exposed to TAM and dietary GS as above for 6weeks during promotion stage in a medium-term bioassay, and the development of placental form of glutathione-S-transferase (GST-P)-expressing preneoplastic liver lesions was quantified. Exposure to both TAM and dietary GS enhanced the anti tumor efficacy of TAM via a combination of tumor cell apoptosis (determined by TUNEL) and inhibition of tumor cell proliferation (determined by PCNA immunostaining) and suppressed the growth of GST-P-positive liver lesions. The findings show that dietary GS enhances the therapeutic efficacy of TAM against mammary tumors and minimizes TAM’s hepatocarcinogenesis promotion potential.

Dietary glycine protects from chemotherapy-induced hepatotoxicity

Hepatotoxic side effects of neoadjuvant chemotherapy for colorectal liver metastases increase perioperative morbidity and mortality. Glycine protects liver from injury in various animal models. Thus, this study was designed to assess its effect on liver after chemotherapy. Sprague-Dawley rats (200-220 g) were fed a synthetic diet containing 5% glycine for 5 days. Subsequently, chemotherapy (FOLFIRI: irinotecan, folinic acid and fluorouracil, or FOLFOX: oxaliplatin, folinic acid and fluorouracil) was administered at standard doses. Transaminases, histology, immunohistochemistry and in vivo microscopy were used to index liver injury, to monitor intrahepatic microperfusion and activation of Kupffer cells. Glycine significantly decreased transaminases after chemotherapy to 25-50% of control values (p < 0.05). Microvesicular steatosis was significantly reduced from 18.5 ± 3.4 and 57.1 ± 8.6% in controls to 9.5 ± 1.8 and 37.7 ± 4.4% after FOLFIRI and FOLFOX, respectively. Furthermore, phagocytosis of latex beads was reduced by about 50%, while leukocyte adherence in central and midzonal subacinar zones decreased to 60-80% after glycine (p < 0.05). Glycine significantly reduced expression of inducible nitric oxide synthase after chemotherapy, while hepatic microcirculation was increased (p < 0.05). This study shows for the first time that glycine reduces chemotherapy-induced liver injury. The underlying mechanisms most likely include Kupffer cells and an improved intrahepatic microperfusion.

The epithelial glycine transporter GLYT1: protecting the gut from inflammation

The epithelial glycine transporter GLYT1: protecting the gut from inflammation

EFFECTS OF DIETARY GLYCINE BETAINE ON BLOOD CHARACTERISTICS AND PORK QUALITY

ABSTRACT This study was conducted to determine the effects of dietary glycine betaine on pork quality and blood characteristics. A total of 80 female pigs (Landrace × Yorkshire × Duroc) were randomly allotted into one of four experimental diet groups. Each group of pigs fed with a commercial diet (control) added with 0.2 g glycine betaine (T1), 0.4 g glycine betaine (T2) and 0.6 g glycine betaine (T3)/kg diet during 40 days. Glycine betaine concentrations in plasma and loin muscle were significantly increased by dietary glycine betaine; however, triglyceride concentration in serum was decreased by dietary glycine betaine. Creatine phosphokinase concentrations in plasma had no significant difference among the dietary groups. Redness (a*) was significantly higher in T2 and T3; however, at the first and seventh days of storage, redness (a*) was not significantly different between dietary groups. Shear force was significantly higher in dietary glycine betaine groups at the first day of storage. Cholesterol content was significantly lower in T2 and T3, whereas T1 was not significantly different compared with the control group. In fatty acid composition, the ratio of saturated fatty acids was increased, whereas unsaturated fatty acids were decreased by dietary glycine betaine.PRACTICAL APPLICATIONSGlycine betaine is an amino acid (trimethylglycine) present in most organisms, and is an obligatory intermediate in the catabolism of choline. Glycine betaine has been reported to affect some aspects of pork qualities. As a result of this study, dietary glycine betaine should improve meat redness and reduce cholesterol. However, dietary glycine betaine did not influence creatine phosphokinase levels in plasma. These results will be helpful to the pork industry and meat scientists for improving meat qaulity.

Roles of Glycinergic and Gamma‐aminobutyric‐ergic Mechanisms in the Micturition Reflex in Rats

The micturition reflex is one of the autonomic reflexes mediated by the spinobulbospinal reflex pathway that passes through the pontine micturition center. In the central nervous system, glutamate is a major excitatory amino acid, while glycine and gamma-aminobutyric acid (GABA) are major inhibitory neurotransmitters and act to inhibit the micturition reflex at supraspinal and/or spinal sites. Glycine and GABA have additive or synergistic inhibitory effects on bladder activity. Hypofunction of glycinergic/GABAergic mechanisms in the lumbosacral spinal cord induces voiding dysfunctions, such as detrusor overactivity (DO) or detrusor-sphincter dyssynergia (DSD) after spinal cord injury (SCI) or bladder outlet obstruction in rats. Intrathecal, intravenous, or dietary glycine inhibits both bladder and urethral activity in normal and spinal cord injury (SCI) rats. Therefore, glycine might be a useful agent for the treatment of DO. Intrathecal muscimol and baclofen (GABA(A) and GABA(B) agonists, respectively) also inhibit non-voiding bladder contractions by suppressing C-fiber bladder afferents in SCI rats. They also improve DSD by suppressing Onuf's nucleus and C-fiber bladder afferents. Baclofen is approved for the treatment of DO in SCI patients, but this agent has not been widely used because the therapeutic window of the drug is modest and the dose is limited by side-effects. Glutamic acid decraboxylase (GAD), the GABA synthesis enzyme, gene delivery by using non-replicating herpes simplex virus (HSV) vectors inhibits DO by suppressing C-fiber bladder afferents without affecting voiding contraction in SCI rats. Therefore, GAD gene therapy can restore urine storage function without affecting voiding function; it would be more beneficial than drug therapy for the treatment of urinary problems in SCI patients.

Effects of dietary glycine supplementation and fish meal on inflammatory responses in broiler chicks

1. The effect of dietary protein source and glycine (Gly) supplementation on inflammatory responses was investigated using broiler chicks. Birds (7 d of age) were fed on a maize–soybean meal based (CS) diet with or without 20 g fish meal (FM)/kg and/or 10 g Gly/kg for 14 d. 2. Inflammatory responses were assessed by determining changes in the plasma concentrations of nitrate plus nitrite (NO x ), caeruloplasmin (Cer) and α-1 acid glycoprotein (AGP), and changes in the expression of mRNA encoding substances related to the inflammatory response, such as interleukin (IL)-1 β and −6, tumour necrosis factor like ligand (TL)1A, inducible nitrite synthase (iNOS), interferon(IFN)-γ, following lipopolysaccharide (LPS) injection. 3. IL-1 β and TL1A mRNA expression in chicks fed on the FM diet was higher than in chicks fed on the CS diet. 4. Supplementing the CS diet with Gly resulted in smaller increases in the plasma concentrations of NO x , Cer and AGP after LPS injection than were observed for chicks fed on the CS diet alone. In addition, 2 h after LPS challenge the expression of encoding inflammatory response-related substances was lower in the spleens of those chicks fed on the Gly-supplemented diet than in those fed the CS diet. 5. Supplementation of the FM diet with Gly reduced the plasma AGP concentration and IL-1 β and TL1A expression. 6. These results suggest that modulation of inflammatory responses by dietary Gly supplementation is affected by dietary composition; Gly supplementation has different effects on the cytokine responses dependent on the diet.