Biomechanical analysis of load distribution in porcine hip joints at different acetabular coverages.

BACKGROUND: Developmental dysplasia of the hip causes secondary osteoarthritis. Finite element analysis suggests high hip joint contact pressure in patients with hip dysplasia and a reduction in contact pressure after periacetabular osteotomy. However, few biomechanical studies have examined the load distribution in the hip joint. This study aimed to investigate the biomechanical properties of load distribution in porcine hip joints at different acetabular coverages. METHODS: Six porcine hip joints were analyzed using three models: 1) neutral coverage, 2) 15° under-coverage (defined as dysplasia model), and 3) 15° over-coverage created by varying the acetabular coverage. The load distribution was assessed using a pressure-mapping sensor system after applying a loading force of 100 N to the hip joint. RESULTS: In the dysplasia model, the load was concentrated at the acetabular rim; in the neutral and over-coverage models, it was dispersed. The average contact pressure was significantly higher in the dysplasia model than in the neutral coverage model ([0.42 vs. 0.3 MPa]; p = 0.004). The contact area was significantly smaller in the dysplasia model than in the neutral coverage model ([250.7 vs. 345.0 mm2]; p = 0.004). No significant differences were observed in contact pressure or area between the neutral and over-coverage models. CONCLUSIONS: Insufficient acetabular coverage in the dysplasia model demonstrated higher contact pressure and smaller contact area than the neutral model. Conversely, the contact pressure and area in the over-coverage model did not differ significantly from those in the normal model. Therefore, surgeons should note that acetabular coverage overcorrection has limited effect; normalization is crucial during periacetabular osteotomy.

Zymosan and lipopolysaccharide decrease gene expression of neuronal nitric oxide synthase in peripheral organs in chicks.

Nitric oxide (NO) is gaseous bioactive molecule that is synthesized by NO synthase (NOS). Inducible NOS (iNOS) expression occurs in response to pathogenic challenges, resulting in the production of large amounts of NO. However, there is a lack of knowledge regarding neuronal NOS (nNOS) and endothelial NOS (eNOS) in birds during pathogenic challenge. Therefore, the present study was conducted to determine the influence of intraperitoneal (IP) injection of zymosan (cell wall component of yeast) and lipopolysaccharide (LPS, a cell wall component of gram-negative bacteria) on NOS expression in chicks (Gallus gallus). Furthermore, the effect of NOS inhibitors on the corresponding behavioral and physiological parameters was investigated. Zymosan and LPS injections induced iNOS mRNA expression in several organs. Zymosan had no effect on eNOS mRNA expression in the organs investigated, whereas LPS increased its expression in the pancreas. Zymosan and LPS decreased nNOS mRNA expression in the lung, heart, kidney, and pancreas. The decreased nNOS mRNA expression in pancreas was probably associated with the NO from iNOS provided that such effect was reproduced by IP injection of sodium nitroprusside, which is a NO donor. Furthermore, pancreatic nNOS mRNA expression decreased following subcutaneous injection of corticosterone. Furthermore, IP injections of a nonspecific NOS inhibitor, NG-nitro-L-arginine methyl ester, and an nNOS-specific inhibitor, 7-nitroindazole, resulted in the significant decreases in food intake, cloacal temperature, and feed passage via the digestive tract in chicks. Collectively, the current findings imply the decreased nNOS expression because of fungal and bacterial infections, which affects food intake, body temperature, and the digestive function in birds.

Analysis of survivorship following periacetabular osteotomy for hip dysplasia based on three-dimensional acetabular coverage.

Periacetabular osteotomy (PAO) is an established procedure for correcting acetabular coverage and preventing osteoarthritis progression in hip dysplasia. However, it is unclear how acetabular coverage changes three-dimensionally after PAO and how it affects survival. Therefore, this study aimed to investigate the change in three-dimensional acetabular coverage preoperatively and postoperatively and identify demographic, clinical and radiographic factors associated with conversion to total hip arthroplasty (THA) and radiographic osteoarthritis progression after PAO. We retrospectively reviewed 46 consecutive patients (66 hips) who underwent PAO, using preoperative and postoperative radiographs and pelvic computed tomography (CT). Three-dimensional acetabular coverage based on CT data was investigated. Kaplan-Meier survival analysis was performed, and hazard ratios were calculated using univariate Cox regression models to identify the risk factors associated with conversion to THA and radiographic osteoarthritis progression after PAO as the endpoints. Radiographic osteoarthritis progression was defined as a minimum joint space of <2.0 mm. The mean follow-up was 10.7 years. Post-PAO, acetabular coverage gradually increased from the anterosuperior to the superior to the posterosuperior direction. The survival rate after PAO was 98.0% at 10 years. Less postoperative superior acetabular coverage, with a hazard ratio of 0.93, was significantly associated with conversion to THA and radiographic osteoarthritis progression after PAO (P = 0.03). In this study, poor superior acetabular coverage after PAO was a significant risk factor for conversion to THA and radiographic progression of osteoarthritis. Therefore, surgeons should attempt to prioritize the correction of the superior acetabular coverage when performing PAO.

Effect of platelet-activating factor on food intake, cloacal temperature, voluntary activity and crop emptying rate in chicks.

Platelet-activating factor (PAF) plays a significant role in several leucocyte functions, including platelet aggregation and inflammation. Additionally, PAF has a role in the behavioral and physiological changes in mammals. However, the effect of PAF has not been well studied in birds. Therefore, the study aimed to determine if PAF affects feeding behavior, voluntary activity, cloacal temperature, and feed passage through the digestive tract in chicks (Gallus gallus). We also studied the involvement of PAF in the innate immune system induced by lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria. Both intraperitoneal (IP) and intracerebroventricular (ICV) injections of PAF significantly decreased food intake. IP injection of PAF significantly decreased voluntary activity and slowed the feed passage from the crop, whereas ICV injection had no effect. Conversely, ICV injection of PAF significantly increased the cloacal temperature, but IP injection had no effect. The IP injection of LPS significantly reduced the mRNA expression of lysophosphatidylcholine acyltransferase 2, an enzyme responsible for PAF production in the heart and pancreas. On the other hand, LPS significantly increased the mRNA expression of the PAF receptor in the peripheral organs. The present study shows that PAF influences behavioral and physiological responses and is related to the response against bacterial infections in chicks.

Possible role of neuropeptide Y on zymosan- and lipopolysaccharide-induced change in gastrointestinal feed passage via the medulla oblongata in chicks.

Zymosan is a fungi-derived pathogen-associated molecular pattern. It activates the immune system and induces the reduction of feed passage rate in the gastrointestinal tract of vertebrates including birds. However, the mechanism mediating the zymosan-induced inhibition of feed passage in the gastrointestinal tract remains unknown. Since the medulla oblongata regulates the digestive function, it is plausible that the medulla oblongata is involved in the zymosan-induced inhibition of feed passage. The present study was performed to identify the genes that were affected by zymosan within the medulla oblongata of chicks (Gallus gallus) using an RNA sequencing approach. We found that mRNAs of several bioactive molecules including neuropeptide Y (NPY) were increased with an intraperitoneal (IP) injection of zymosan. The increase of mRNA expression of NPY in the medulla oblongata was also observed after the IP injection of lipopolysaccharide, derived from gram-negative bacteria. These results suggest that medullary NPY is associated with physiological changes during fungal and bacterial infection. Furthermore, we found that intracerebroventricular injection of NPY and its receptor agonists reduced the feed passage from the crop. Additionally, the injection of NPY reduced the feed passage from the proventriculus to lower digestive tract. NPY also suppressed the activity of duodenal activities of amylase and trypsin. The present study suggests that fungi- and bacteria-induced activation of the immune system may activate the NPY neurons in the medulla oblongata and thereby reduce the digestive function in chicks.

D-Galactosamine Causes Liver Injury Synergistically with Lipopolysaccharide but not Zymosan in Chicks.

The pathogen-associated molecular patterns (PAMPs) lipopolysaccharide (LPS) and zymosan, derived from gram-negative bacteria and fungi, respectively, activate the innate immune system and cause injury to multiple organs, including the liver and intestine, in mammals. In rodents, PAMP-induced injury has been demonstrated to be potentiated by co-administration of D-galactosamine (D-GalN) in rodents. However, whether PAMPs and D-GalN collectively cause organ injury in birds remains unclear. The present study aimed to measure the effects of intraperitoneal injection of D-GalN with LPS or zymosan on parameters related to hepatic injury in chicks (Gallus gallus). Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities were not affected by intraperitoneal injection of D-GalN alone. Although these activities were not affected by LPS injection alone, they were increased by combining LPS with D-GalN. In contrast, plasma AST, ALT, and LDH activities were not affected by zymosan, both alone and with D-GalN. The expression of mRNAs for interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS) in the liver was significantly increased by the combination of LPS and D-GalN. In contrast, combining zymosan with D-GalN significantly increased iNOS mRNA expression, irrespective of hepatic injury. These results suggest that IL-6 may be the cause and/or result of hepatic injury in chicks. Additionally, chicks are tolerant to the hepatic effects of D-GalN, LPS, or zymosan alone.

Possible role of corticosterone on behavioral, physiological, and immune responses in chicks.

Glucocorticoids are one of steroid hormone and have a variety of functions including stress response, carbohydrate metabolism, and modulation of immune system in vertebrates. Corticosterone is the main glucocorticoid in birds, although the precise role of the glucocorticoid during immune challenge is not fully understood. Therefore, the purpose of the present study was to determine if a single subcutaneous injection of corticosterone could affect inflammation-related gene expressions in the spleen and liver of chicks (Gallus gallus). In addition, the effects of corticosterone injection on the food intake, cloacal temperature, formation of conditioned visual aversion, and plasma constituents were also measured. Corticosterone did not affect the food intake or cloacal temperature and did not cause conditioned visual aversion in chicks. The corticosterone injection was associated with a significant decrease in gene expression of several pro-inflammatory cytokines including inducible nitric oxide synthase and cyclooxygenase-2 in the spleen and liver at 1 and 3 h post-injection. Corticosterone increased the plasma glucose and uric acid concentrations and the antioxidant capacity. In summary, the present study suggests that corticosterone is likely not associated with food intake, cloacal temperature or the development of aversive sensation, but suppresses the synthesis of inflammation-associated bioactive molecules and increases the antioxidant capacity in chicks.

Administration of prosaposin-derived neurotrophic factor to neural tube defects facilitates regeneration and restores neurological functions.

Neural tube defects (NTDs) cause fetal and pediatric deaths or lifelong neurological disabilities. No effective treatment is currently available for NTDs. We attempted to elucidate the pathogenesis of NTDs and propose a therapeutic strategy. Intra-amniotic treatment with prosaposin-derived 18-mer peptide (PS18) protected the spinal cord from secondary damage and rescued neurological function in an established chicken model of spina bifida aperta (SBA), the severe type of NTDs. PS18 promoted the formation of a neuroectodermal covering over the defective neural tube within 24-h after treatment, enhanced the regeneration/restoration process, and decreased apoptotic activity in the developing spinal cord. PS18 reduced the SBA wound and almost completely formed the spinal cord. SBA chicks that received PS18 exhibited relatively normal walking and sensorimotor responses, and reduced pain-associated behavior in postnatal life. In conclusion, PS18 is a promising therapeutic agent for NTDs and may be useful for treating other types of spinal cord injuries.

Biomolecules Triggering Altered Food Intake during Pathogenic Challenge in Chicks.

Food intake is regulated by several complicated synergistic mechanisms that are affected by a variety of internal and external influences. Some of these factors include those that are released from pathogens such as bacteria, fungi, and viruses, and most of these factors are associated with suppression of the chick's food intake. Although chicks are well-known to decrease their food intake when they experience a pathogenic challenge, the mechanisms that mediate this type of satiety are poorly understood. One of the goals of our research group has been to better understand these mechanisms in chicks. We recently provided evidence that pathogen-associated molecular patterns, which are recognized by pattern-recognition receptors such as Toll-like receptors, likely contribute to satiety in chicks that are experiencing a pathogenic challenge. Additionally, we identified several inflammatory cytokines, including interleukin-1ß, tumor necrosis factor-like cytokine 1A, prostaglandins, and nitric oxide, that likely contribute to satiety during a pathogenic challenge. This review summarizes the current knowledge on pathogen-induced satiety in chicks mainly accumulated through our recent research. The research will give good information to improve the loss of production during infection in poultry production in the future.

Effect of ornithokinin on feeding behavior, cloacal temperature, voluntary activity and crop emptying rate in chicks.

Bradykinin is a well-studied bioactive peptide associated with several physiological functions, including vasodilation and inflammation, in mammals. However, its avian homolog, ornithokinin, has received less research attention in birds. Therefore this study aimed to investigate the effect of intraperitoneal (IP) and intracerebroventricular (ICV) injections of ornithokinin on feeding behavior, cloacal temperature, voluntary activity, crop emptying rate, and blood constituents in chicks (Gallus gallus). We also investigated the effect of lipopolysaccharide (LPS), a cell wall component of gram-negative bacteria, on ornithokinin-associated gene expression was also investigated to determine whether activation of the ornithokinin system is induced by bacterial infection. Both IP and ICV injections of ornithokinin significantly decreased feed intake, cloacal temperature, voluntary activity, and crop emptying rate in chicks, but they did not affect the plasma concentration of corticosterone. Additionally, LPS significantly increased the expression of ornithokinin B2 receptor mRNA in several organs. Hence, ornithokinin is associated with a range of physiological responses in chicks and may be related to their response to bacterial infection.

Effect of lithium chloride on food intake, cloacal temperature, voluntary activity, and crop-emptying rate in chicks.

Infections frequently accompany with non-specific symptoms such as anorexia and hyperthermia. In addition, there may be unpleasant sensations such as visceral discomfort during infection. Lipopolysaccharide (LPS), a Gram-negative bacteria cell wall component, is known to induce the unpleasant sensation of conditioned taste aversion in mammals. However, the relationship between unpleasant sensations and changes in behavior and physiological conditions has not been investigated extensively in birds. Lithium chloride (LiCl) is a compound that induces unpleasant sensations, including visceral discomfort, although its effects on behavior and physiological conditions have also not been investigated extensively in birds. Thus, the present study was aimed to investigate the effect of an intraperitoneal (IP) injection of LiCl on conditioned visual aversion, food intake, cloacal temperature, voluntary activity, crop-emptying rate, and blood constituents in chicks (Gallus gallus). We also examined the effect of IP injections of LPS and zymosan, a cell wall component of fungus, on conditioned visual aversion formation. First, IP injection of LiCl was confirmed to induce conditioned visual aversion in chicks. An IP injection of LiCl significantly decreased food intake, voluntary activity, and crop-emptying rate but did not affect the temperature. In addition, the injection of LiCl significantly increased plasma corticosterone concentration, indicating that LiCl serves as a stressor in chicks. Finally, IP injections of LPS and zymosan were found to induce conditioned visual aversion in chicks. Collectively, these results suggest that LiCl induces conditioned aversion, anorexia, hypoactivity, and inhibition of crop-emptying in chicks. In addition, LPS and zymosan would induce unpleasant sensations in chicks.

Poly I:C and R848 facilitate nitric oxide production via inducible nitric oxide synthase in chicks.

Nitric oxide (NO) is a gaseous bioactive molecule associated with many physiological functions including vasodilation and neurotransmission. NO also plays an important role in immune responses during viral infections in mammals. However, there is a paucity of knowledge regarding the involvement of NO in viral infections in birds. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) injection of poly I:C and R848 (resiquimod), which are analogues of virus component, affects NO production in chicks (Gallus gallus) as a bird model. The involvement of inducible NO synthase (iNOS) in poly I:C- and R848-induced anorexia and corticosterone release was also investigated. These virus analogues significantly increased plasma NO metabolites (NOx) concentrations. IP injection of poly I:C and R848 significantly increased iNOS mRNA expression in several organs including the liver. On the other hand, poly I:C and R848 significantly decreased mRNA expressions of endothelial NOS and neural NOS in several organs, indicating that induction of iNOS might be responsible for increased NOx levels in plasma. This finding was further confirmed by using a selective iNOS inhibitor, S-methylisothiourea sulfate (SMT), which abolished the poly I:C- and R848-induced increase in plasma NOx concentration. In addition, SMT partly attenuated the poly I:C- and R848-induced increase in plasma corticosterone concentration, suggesting that corticosterone release induced by these virus analogues may be partly mediated by iNOS. Collectively, the present results suggest that viral infections facilitate NO production by inducing iNOS. The liver would play an important role in the NO production because the response in iNOS mRNA expression to poly I:C and R848 was remarkable. The present results also suggest that NO is associated with corticosterone release in birds under viral infection.

Effect of sodium nitroprusside on feeding behavior, voluntary activity, and cloacal temperature in chicks.

Nitric oxide (NO) is a well-known gaseous signaling molecule that is involved in a variety of physiological and pathological processes in vertebrates. The role of NO in physiological responses of birds has been investigated primarily using NOS inhibitors. Therefore, the effect of the absence of NO is well characterized. However, there is little knowledge on the effects of abundant NO in birds, which is the case in birds that have infections. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) and intracerebroventricular (ICV) injections of sodium nitroprusside (SNP), a NO donor, affected feed intake, voluntary activity, cloacal temperature, crop emptying rate, and blood constituents in domesticated chicks (Gallus gallus) as model birds. We found that both IP and ICV injections of SNP significantly decreased feed intake while there was little effect on voluntary activity. Cloacal temperature was temporarily, but significantly, decreased by both types of injection of SNP. Additionally, both IP and ICV injections of SNP significantly decreased the crop emptying rate. The IP injection of SNP significantly increased the plasma concentrations of NO2/NO3, which are metabolites of NO, and corticosterone, and decreased the plasma glucose concentrations, while the ICV injection had no effect. The IP injection of SNP also showed the tendency to increase the nitrotyrosine level, to increase superoxide dismutase activity, and to decrease catalase activity in the plasma. These results suggest that under specific situations which produce abundant NO such as infection, NO would induce anorexia, hypothermia, inhibition of feed passage, and activation of the hypothalamus-pituitary-adrenal axis in chicks.

Periprosthetic fragility fracture of the femur after primary cementless total hip arthroplasty.

OBJECTIVES: Periprosthetic bone fragility due to stress shielding (SS) can be a risk factor of periprosthetic fracture after cementless total hip arthroplasty (THA). We aimed to obtain epidemiological information on periprosthetic fragility fracture of the femur (PPFF) after THA. METHODS: We retrospectively reviewed the medical records of 1062 hips that had undergone cementless THA. We evaluated the epidemiological data as well as the features of PPFFs. RESULTS: Of the 1062 hips, 8 (0.8%) were diagnosed with PPFFs. The survival rates, with the occurrence of PPFF as the end point, were 99.2% and 97.6% at 10 and 16 years postoperatively, respectively. When patients were classified as having either mild or severe SS on radiographs 5 years postoperatively, there was no significant difference in the survival rate, with PPFF as the end point. CONCLUSIONS: In our cases, the incidence of PPFF after cementless THA was 0.8%.

Patient body mass index modifies the association between waiting time for hip fracture surgery and in-hospital mortality: A multicenter retrospective cohort study.

BACKGROUND: Patient body mass index (BMI) plays an important role in stress exposure, especially in elderly patients with hip fracture. However, how BMI modifies the relationship between the waiting time for surgery and mortality remains unclear. METHODS: We investigated the association between waiting time and mortality using a nationwide multicenter database of patients undergoing hip fracture surgery. The primary outcome was in-hospital mortality and secondary outcomes were complications. We performed prespecified subgroup analysis with stratification by BMI. RESULTS: Overall, 305,846 patients (mean age, 83.5; standard deviation [SD], 8.2); women, 79.5% (n = 243,214) were included in our study. A cubic spline curve revealed two inflection points in the association between waiting time and mortality, and we statistically divided patients into three groups accordingly: the reference group (80,110 patients [26.2%] who waited 1 day for surgery), the delayed group (184,778 patients [60.4%] who waited 2-6 days for surgery), and the extremely delayed group (40,958 patients [13.4%] who waited more than 6 days for surgery). Multivariable logistic regression models showed that the odds of mortality in the delayed group was 14% higher than that in the reference group (adjusted odds ratio [aOR], 1.14; p = 0.002), whereas the odds of mortality in the extremely delayed group was 52% higher than that of the reference group (aOR, 1.52; p < 0.001). Patients with lower BMI were more negatively affected by delayed surgery compared to patients with normal BMI (p for interaction = 0.002). Respiratory disorders were most frequent and the spline curve was accordant with in-hospital mortality. CONCLUSION: Patients underwent surgery within 1 day, particularly with lower BMI, had a lower mortality than normal BMI. To optimize limited health care resource, patient's BMI should be considered for hip fracture management, and further investigation in prospective study should be needed to address causal relationship. LEVEL OF EVIDENCE: Therapeutic Level III.

Role of nitric oxide on zymosan-induced inhibition of crop emptying in chicks.

Zymosan, a component of yeast cell walls, reduces feed passage through the digestive tract in chicks (Gallus gallus), although the mechanism mediating this effect is poorly understood. Nitric oxide (NO) is associated with a variety of biological actions including effects on the immune system. In addition, it has been suggested that NO is involved in relaxation of the digestive tract and affects feed passage in mammals. It is therefore possible that NO might be related to zymosan-induced reduction of feed passage in chicks. However, the role of NO on the effect of zymosan feed passage has not been clarified yet. Thus, the purpose of the present study was to investigate whether NO is associated with zymosan-induced alteration of feed passage in chicks. Intraperitoneal (IP) injection of zymosan significantly increased plasma nitrate and nitrite (NOx) concentrations at 6 h after injection. Zymosan-induced elevation of plasma NOx concentration was abolished by co-injection of S-methylisothiourea (SMT), a selective inhibitor for inducible NO synthase (iNOS), indicating that zymosan facilitated the induction of iNOS. Furthermore, because zymosan increased iNOS mRNA expression in the digestive tract, NO is likely associated with the effect of zymosan on the digestive tract. IP injection of NO donors significantly decreased crop emptying rate, suggesting that NO functions as an inhibitor of crop emptying. This result implied that zymosan stimulates NO production by the induction of iNOS in the digestive tract and thereby inhibits crop emptying rate. However, the co-injection of SMT did not attenuate the inhibitory effect of zymosan on crop emptying. The present study provides evidence that some changes in the digestive tract caused by zymosan are mediated by iNOS-induced NO in chicks, but NO does not mediate the effect of zymosan on feed passage through the crop.

Early recovery of basic mobility under femoral nerve block after hip fracture surgery - A propensity score matched pilot study.

BACKGROUND: Previous studies have shown better pain reduction utilizing femoral nerve block (FNB) in patients who underwent hip fracture surgery. However, few studies have focused on the recovery of physical function after FNB, and most studies excluded patients with dementia. We investigated the association between FNB performed in the operating room and the recovery of physical function after hip fracture surgery, including patients with dementia. METHODS: A total of 103 patients with a mean age of 87.4 years who underwent hip fracture surgery under spinal anesthesia between July 2015 and December 2017 (46 patients receiving a single injection of FNB and 57 standard care) were enrolled. Patients with FNB versus standard care were matched by a propensity score to adjust for patient characteristics. An anesthesiologist performed FNB with 20ml of 0.2% ropivacaine, and the standard care group received intravenous 1000 mg acetaminophen or 50mg flurbiprofen once after surgery. After matching, 78 patients were analyzed. Our primary outcome was 3-day cumulated ambulation score (CAS, 0-18 points) and secondary outcomes were 1-day CAS on postoperative day 1-3 and length of hospital stay. We also stratified patient groups based on the presence of dementia and fracture type. RESULTS: Patients undergoing FNB had significantly better 3-day CAS compared to standard care (mean [SD], 8.72 [3.42] vs 7.33 [2.62]; mean difference, 1.38 [95%CI; 0.03 - 2.74]; p = 0.048) and 1-day CAS on postoperative day two (mean [SD], 3.10 [1.39] vs 2.56 [0.94]; mean difference, 0.54 [0.01 - 1.07]; p = 0.049). Length of hospital stay did not significantly differ among the two groups (p = 0.65). Larger positive effect was likely to be seen for patients with a femoral neck fractures and for those without dementia. CONCLUSIONS: Patients who underwent surgery with spinal anesthesia plus FNB had better ambulatory status early after hip fracture surgery compared to patients not offered FNB. The beneficial association between FNB and ambulatory status was likely to be observed especially in patients with femoral neck fracture and without dementia.

Prostaglandin E2-induced anorexia involves hypothalamic brain-derived neurotrophic factor and ghrelin in chicks.

Central administration of prostaglandin E2 (PGE2) is associated with potent anorexia in rodents and chicks, although hypothalamic mechanisms are not fully understood. The objective of the present study was to identify hypothalamic nuclei and appetite-related factors that are involved in this anorexigenic effect, using chickens as a model. Intracerebroventricular injection of 2.5, 5, and 10 nmol of PGE2 suppressed food and water intake in broiler chicks in a dose-dependent manner. c-Fos immunoreactivity was increased in the paraventricular nucleus (PVN) at 60 min post injection of 5 nmol of PGE2. Under the same treatment condition, hypothalamic expression of melanocortin receptor 3 and ghrelin mRNAs increased, whereas neuropeptide Y receptor sub-type 5 and tropomyosin receptor kinase B (TrkB) mRNAs decreased in PGE2-treated chicks. In the PVN, chicks injected with PGE2 had more brain-derived neurotrophic factor (BDNF), ghrelin, and c-Fos mRNA but less corticotrophin-releasing factor receptor 1 (CRFR1), CRFR2, and TrkB mRNA expression. In conclusion, PGE2 injection resulted in decreased food and water intake that likely involves BDNF and ghrelin originating in the PVN. Because the anorexigenic effect is so potent and hypothalamic mechanisms are similar in chickens and rodents, a greater understanding of the role of PGE2 in acute appetite regulation may have implications for treating eating and metabolic disorders in humans.

Influence of Dietary Metformin on the Growth Performance and Plasma Concentrations of Amino Acids and Advanced Glycation End Products in Two Types of Chickens.

Glycation is a non-enzymatic reaction inducing the bonding of glucose to amino acids and proteins. Glycated amino acids are not useful for protein synthesis, suggesting that glycation reduces the utilization of amino acids. Metformin (MF) is well known as a therapeutic drug for type II diabetes that inhibits glycation. It is possible that treatment with MF raises the utilization of amino acids by the inhibition of glycation, thereby improving the growth performance of chickens. In the present study, therefore, we investigated the influence of dietary MF on the growth performance, and plasma concentrations of free amino acids and N ε -(Carboxymethyl)lysine (CML), which is an advanced glycation end product, in layer (Experiment 1) and broiler (Experiment 2) chickens. From 7 d of age, chicks were allowed free access to one of the experimental diets containing MF at 3 supplementation levels (0, 150, and 300 mg/kg diet) for 14 days. Body weight and feed intake were measured every week. At the end of the experiments, blood and breast muscle (M. pectoralis major) were collected for further analysis. Dietary MF did not affect weight gain, feed intake, or feed efficiency in both layer and broiler chickens. Dietary MF at the level of 150 mg/kg diet increased breast muscle weight in both layer and broiler chickens. Dietary MF increased plasma concentrations of branched chain amino acids and decreased concentrations of CML in layer chickens, although it did not affect plasma concentrations of glucose. The present study suggested that dietary MF might have the potency to increase breast muscle weight of layer chickens with an increment in plasma concentrations of branched-chain amino acids.

Behavioral and physiological responses to peripheral injection of flagellin in chicks.

Flagellin (Flg) is a globular protein, found in bacterial flagella, that serves as a pathogen-associated molecular pattern and also serves as a toll-like receptor-5 (TLR5) ligand in vertebrates. Most ligands for TLRs are involved in non-specific effects such as anorexia and hypoactivity in an animal infected by bacteria. However, there is little knowledge on the effects of Flg in birds. Therefore, the purpose of the present study was to determine if intraperitoneal (IP) injection of Flg affects food intake, voluntary activity, cloacal temperature, crop emptying rate, blood constituents, and splenic gene expression of cytokines in chicks (Gallus gallus). The effect of Flg22, an N-terminus fragment of Flg, was also investigated. IP injection of 10 µg Flg significantly increased the splenic gene expression of interleukin-8, interferon-γ (IFN-γ), and tumor necrosis factor-like cytokine-1A, suggesting that Flg activated the innate immune system in chicks. The injection of Flg significantly decreased food intake, voluntary activity, blood glucose concentration, and crop emptying rate, and increased cloacal temperature and plasma concentrations of nitrite, nitrate, and corticosterone. However, the injection of Flg22 only affected the splenic gene expression of IFN-γ, indicating that the full-length of Flg is required for its action. These results suggest that Flg, a ligand for TLR5, is related to non-specific symptoms including anorexia, hypoactivity, increase in body temperature, disturbance of food passage in the digestive tract, and the activation of hypothalamic-pituitary-adrenal axis during bacterial infection in chicks.