Effects of ambient temperature and rumen-protected fat supplementation on growth performance, rumen fermentation and blood parameters during cold season in Korean cattle steers.

OBJECTIVE: This study was performed to evaluate whether cold ambient temperature and dietary rumen-protected fat (RPF) supplementation affect growth performance, rumen fermentation, and blood parameters in Korean cattle steers. METHODS: Twenty Korean cattle steers (body weight [BW], 550.6±9.14 kg; age, 19.7±0.13 months) were divided into a conventional control diet group (n = 10) and a 0.5% RPF supplementation group (n = 10). Steers were fed a concentrate diet (1.6% BW) and a rice straw diet (1 kg/d) for 16 weeks (January 9 to February 5 [P1], February 6 to March 5 [P2], March 6 to April 3 [P3], and April 4 to May 2 [P4]). RESULTS: The mean and minimum indoor ambient temperatures in P1 (-3.44°C, -9.40°C) were lower (p<0.001) than those in P3 (5.87°C, -1.86°C) and P4 (11.18°C, 4.28°C). The minimum temperature in P1 fell within the moderate cold-stress (CS) category, as previously reported for dairy cattle, and the minimum temperatures of P2 and P3 were within the mild CS category. Neither month nor RPF supplementation affected the average daily gain or gain-to-feed ratio (p>0.05). Ruminal ammonia nitrogen concentrations were higher (p<0.05) in cold winter than spring. Plasma cortisol concentrations were lower (p<0.05) in the coldest month than in the other months. Serum glucose concentrations were generally higher in colder months than in the other months but were unaffected by RPF supplementation. RPF supplementation increased both total cholesterol (p = 0.004) and high-density lipoprotein (HDL) concentrations (p = 0.03). CONCLUSION: Korean cattle may not be significantly affected by moderate CS, considering that the growth performance of cattle remained unchanged, although variations in blood parameters were observed among the studied months. RPF supplementation altered cholesterol and HDL concentrations but did not affect growth performance.

Effects of heat stress and rumen-protected fat supplementation on growth performance, rumen characteristics, and blood parameters in growing Korean cattle steers.

OBJECTIVE: This study was performed to evaluate whether hot temperature and rumen-protected fat (RPF) supplementation affect growth performance, rumen characteristics, and serum metabolites in growing stage of Korean cattle steers. METHODS: Twenty Korean cattle steers (230.4±4.09 kg of body weight [BW], 10.7±0.09 months of age) were divided into a conventional control diet group (n = 10) and a 0.8% RPF supplementation group (n = 10). Steers were fed 1.5% BW of a concentrate diet and 4 kg of tall fescue hay for 16 weeks (July 10 to August 6 [P1], August 7 to September 3 [P2], September 4 to October 1 [P3], October 2 to 30 [P4], of 2015). RESULTS: The mean temperature-humidity index (THI) was higher (p<0.001) in P1 (76.8), P2 (76.3), and P3 (75.9) than in P4 (50.9). The mean THI of P1-3 were within the alert heat stress (HS) category range according to previously reported categories for feedlot cattle, and the mean THI of P4 was under the thermo-neutral range. Neither month nor RPF supplementation affected (p>0.05) average daily gain and gain to feed ratio. Month and RPF supplementation affected concentrations of glucose, albumin, and high-density lipoprotein (HDL); those of albumin and glucose tended to decrease (p<0.10), but HDL concentration increased (p<0.01) by RPF supplementation. Neither month nor RPF affected (p>0.05) ruminal pH, NH3-N, and volatile fatty acid concentrations, whereas the C2:C3 ratio was affected (p<0.05) by month. CONCLUSION: Korean cattle may not have been significantly affected by alert HS during the growing stage. Growth performance was higher during hotter months, although some changes in blood metabolites were observed. The RPF supplementation affected some blood lipids and carbohydrate metabolites but did not affect growth performance.

Comparison of reducing sugar content, sensory traits, and fatty acids and volatile compound profiles of the longissimus thoracis among Korean cattle, Holsteins, and Angus steers.

OBJECTIVE: This study was performed to compare fat content, reducing sugar contents, sensory traits, and fatty acid (FA) and volatile compound profiles in longissimus thoracis (LT) among Korean cattle (KC), Holstein (HO), and Angus (AN) steers. METHODS: Twelve LT samples (about 500 g each) of KC with an average age of 31±0.42 months, an average carcass weight of 431±12.5 kg, and a quality grade (QG) of 1+ were obtained from the joint livestock products market. Twelve LT samples of HO cattle with an average age of 24±0.54 months, an average carcass weight of 402±7.81 kg, and a QG of 2 were also obtained from the same market. Twelve LT samples of AN steers with an average age of about 20 months and a QG of choice were purchased from a beef delivery company. After slaughter, samples were kept at 4°C for 42 days and prepared for immediate analysis or stored at appropriate conditions. The chemical composition, color, pH, shear force, collagen content, reducing sugars, sensory evaluation, FA composition, and volatile compound content for each LT sample were analyzed. RESULTS: The LT of KC had the highest (p<0.05) fat content, the highest reducing sugar content, and the highest scores in the sensory evaluation (flavor, tenderness, juiciness, and overall acceptance). All the sensory traits were positively correlated (p<0.001) with intramuscular fat and reducing sugar content. Several FAs and volatile compound profiles varied among the breeds. KC LT had the highest (p<0.05) concentrations of acetaldehyde, 3-methyl butanal, and 3-hydroxy-2-butanone, and these volatile compounds were positively correlated (p<0.05) with all the sensory traits. CONCLUSION: Variations in fat content and reducing sugar contents and FA and volatile compound profiles may contribute to differences in the sensory quality of LT among breeds.

Genetic, management, and nutritional factors affecting intramuscular fat deposition in beef cattle - A review.

Intramuscular fat (IMF) content in skeletal muscle including the longissimus dorsi muscle (LM), also known as marbling fat, is one of the most important factors determining beef quality in several countries including Korea, Japan, Australia, and the United States. Genetics and breed, management, and nutrition affect IMF deposition. Japanese Black cattle breed has the highest IMF content in the world, and Korean cattle (also called Hanwoo) the second highest. Here, we review results of research on genetic factors (breed and sex differences and heritability) that affect IMF deposition. Cattle management factors are also important for IMF deposition. Castration of bulls increases IMF deposition in most cattle breeds. The effects of several management factors, including weaning age, castration, slaughter weight and age, and environmental conditions on IMF deposition are also reviewed. Nutritional factors, including fat metabolism, digestion and absorption of feed, glucose/starch availability, and vitamin A, D, and C levels are important for IMF deposition. Manipulating IMF deposition through developmental programming via metabolic imprinting is a recently proposed nutritional method to change potential IMF deposition during the fetal and neonatal periods in rodents and domestic animals. Application of fetal nutritional programming to increase IMF deposition of progeny in later life is reviewed. The coordination of several factors affects IMF deposition. Thus, a combination of several strategies may be needed to manipulate IMF deposition, depending on the consumer's beef preference. In particular, stage-specific feeding programs with concentrate-based diets developed by Japan and Korea are described in this article.

Muscle-specific deletion of signal transducer and activator of transcription 5 augments lipid accumulation in skeletal muscle and liver of mice in response to high-fat diet.

PURPOSE: Growth hormone (GH) controls liver metabolism through the transcription factor signal transducer and activator of transcription 5 (STAT5). However, it remains to be fully understood to what extent other GH/STAT5 target tissues contribute to lipid and glucose metabolism. This question was now addressed in muscle-specific STAT5 knockout (STAT5 MKO) mice model. METHODS: Changes in lipid and glucose metabolism were investigated at physiological and molecular levels in muscle and liver tissues of STAT5 MKO mice under normal diet or high-fat diet (HFD) conditions. RESULTS: STAT5 MKO mice exhibited an increased intramyocellular lipid (IMCL) accumulation in the quadriceps in HFD group. Decreased lipolytic hormone-sensitive lipase transcript levels may contribute to the increased IMCL accumulation in STAT5 MKO mice. STAT5 MKO induced hepatic lipid accumulation without deregulated STAT5 signaling. The upregulation of lipoprotein lipase and Cd36 mRNA levels, an increased trend of very low-density lipoprotein receptor mRNA levels, and elevated circulating concentrations of free fatty acid, triglyceride, and total cholesterol support the increase in hepatic lipid accumulation. CONCLUSIONS: STAT5 MKO in conjunction with a HFD deregulated both lipid and glucose metabolism in skeletal muscle, and this deregulation induced hepatic fat accumulation via increased circulating glucose, FFA, and TG concentrations. Our study emphasizes that muscle-specific STAT5 signaling is important for balancing lipid and glucose metabolism in peripheral tissues, including muscle and liver and that the deregulation of local STAT5 signaling augments HFD-induced lipid accumulation in both muscle and liver.

Effects of ambient temperature and dietary glycerol addition on growth performance, blood parameters and immune cell populations of Korean cattle steers.

OBJECTIVE: This study was performed to evaluate whether ambient temperature and dietary glycerol addition affect growth performance, and blood metabolic and immunological parameters, in beef cattle. METHODS: Twenty Korean cattle steers (405.1±7.11 kg of body weight [BW], 14.2±0.15 months of age) were divided into a conventional control diet group (n = 10) and a 2% glycerol- added group (n = 10). Steers were fed 1.6% BW of a concentrate diet and 0.75% BW of a timothy hay diet for 8 weeks (4 weeks from July 28th to August 26th and 4 weeks from August 27th to September 26th). Blood was collected four times on July 28th, August 11th, August 27th, and September 26th. RESULTS: The maximum indoor ambient temperature-humidity index in August (75.8) was higher (p<0.001) than that in September (70.0), and in August was within the mild heat stress (HS) category range previously reported for dairy cattle. The average daily gain (ADG; p = 0.03) and feed efficiency (p<0.001) were higher in hotter August than in September. Glycerol addition did not affect ADG and feed efficiency. Neither month nor glycerol addition affected blood concentrations of cortisol, triglyceride, or non-esterified fatty acid. Blood concentrations of cholesterol, low-density lipoprotein, high-density lipoprotein, glucose, and albumin were lower (p<0.05) on August 27th than on September 26 th, and blood phosphorus, calcium and magnesium concentrations were also lower on August 27th than on September 27th. Glycerol addition did not affect these blood parameters. Percentages of CD4+ T cells and CD8+ T cells were higher (p<0.05) on July 28th than on August 27th and September 26th. The blood CD8+ T cell population was lower in the glycerol supplemented-group compared to the control group on July 28th and August 27th. CONCLUSION: Korean cattle may not be significantly affected by mild HS, considering that growth performance of cattle was better in hotter conditions, although some changes in blood metabolic and mineral parameters were observed.

Effects of castration on expression of lipid metabolism genes in the liver of korean cattle.

Castration induces the accumulation of body fat and deposition of intramuscular fat in Korean cattle, resulting in improved beef quality. However, little is known about the metabolic adaptations in the liver following castration. To understand changes in lipid metabolism following castration, hepatic expression levels of lipid metabolism genes were compared between Korean bulls and steers. Steers had higher (p<0.001) hepatic lipids contents and higher (p<0.01) mRNA levels of lipogenic acetyl-CoA carboxylase. This differential gene expression may, in part, contribute to increased hepatic lipid content following the castration of bulls. However, we found no differences in the hepatic expression levels of genes related to triglyceride synthesis (mitochondrial glycerol-3-phosphate acyltransferase, diacylglycerol O-acyltransferase 1 and 2) and fatty acid (FA) oxidation (carnitine palmitoyltransferase 1A, C-4 to C-12 straight chain acyl-CoA dehydrogenase, very long chain acyl-CoA dehydrogenase) between bulls and steers. No differences in gene expression for very-low-density lipoprotein (VLDL) secretion, including apolipoprotein B mRNA and microsomal triglyceride transfer protein (MTTP) protein, were observed in the liver although MTTP mRNA levels were higher in steers compared to bulls. In conclusion, FA synthesis may contribute to increased hepatic lipid deposition in steers following castration. However, hepatic lipid metabolism, including triglyceride synthesis, FA oxidation, and VLDL secretion, was not significantly altered by castration. Our results suggest that hepatic lipid metabolism does not significantly contribute to increased body fat deposition in steers following castration.

Comparison of Carcass and Sensory Traits and Free Amino Acid Contents among Quality Grades in Loin and Rump of Korean Cattle Steer.

This study was performed to compare carcass traits, sensory characteristics, physiochemical composition, and contents of nucleotides, collagen, and free amino acids among quality grades (QG) and to understand the association between QG and above parameters in loin and rump of Korean cattle steer. Loin and rump samples were obtained from 48 Korean cattle steers with each of four QG (QG 1++, 1+, 1, and 2; average 32 months of age). Carcass weight and marbling score (MS) were highest in QG 1++, whereas texture score measured by a meat grader was highest in QG 2. A correlation analysis revealed that MS (r = 0.98; p<0.01) and fat content (r = 0.73; p<0.01) had strong positive correlations with QG and that texture had a strong negative correlation (r = -0.78) with QG. Fat content in loin was highest but protein and moisture contents were lowest in QG 1++. Our results confirmed that a major determinant of QG is the MS; thus, intramuscular fat content. The International Commission on Illumination L*, a*, and b* values in loin were highest in QG 1++. Numeric values of shear force in loin were lowest in QG 1++, whereas those of tenderness, juiciness, and overall acceptability tended to be highest in QG 1++ without statistical significance. QG was strongly correlated with juiciness (r = 0.81; p<0.01) and overall acceptability (r = 0.87; p<0.001). All sensory characteristics were higher (p<0.05) in loin than those in rump. Adenosine-5'-monophosphate (AMP) and inosine-5'-monophosphate (IMP) contents in both loin and rump did not differ among QGs. No nucleotide (AMP, IMP, inosine, hypoxanthine) was correlated with any of the sensory traits. Total, soluble, and insoluble collagen contents in loin were higher in QG 1++ than those in QG 1. All three collagens had lower content in loin than that in rump. All three collagens were positively correlated with tenderness, juiciness, and overall acceptability. Glutamic acid content did not significantly differ among the four QGs in either loin or rump. In conclusion, it is confirmed that QG is associated with sensory traits but nucleotide contents in beef may not be a major factor determining meat palatability in the present study.

Melatonin improves functional outcome via inhibition of matrix metalloproteinases-9 after photothrombotic spinal cord injury in rats.

BACKGROUND: Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9 play an important role in secondary inflammatory reaction and blood-central nervous system (CNS) barrier disruption after spinal cord injury (SCI). Theoretically, it is expected that early blockade of activation of MMPs can provide neuro-protective effects from secondary tissue damage and improve functional neurological outcomes. The aim of this study was to investigate the expression and the activity of MMP-2 and MMP-9, and to determine the regulatory effect of melatonin on MMP expression and activity after photochemically induced SCI in rats. METHODS: Female Sprague-Dawley rats weighing between 250 and 300 g (age 8 weeks) received focal ischemia by photothrombosis using Rose Bengal (RB). The injured animals were divided into two groups; one group received 50 mg/kg of melatonin intraperitoneally, starting 1 h after injury and at 12 h intervals for 7 days, while animals in the control group received weight-adjusted doses of a saline vehicle. In each group, the expressions and activities of MMP-2 and MMP-9 were assessed by Western blot and gelatin zymography at various times from 6 h to 3 days. The locomotor function was assessed using the Basso-Beattie-Bresnahan (BBB) scale at 3 days after SCI and then once per week for 4 weeks. The animals were killed at 28 days after the injury, and the histopathology of the lesions was assessed. FINDINGS: The expressions and activities of MMP-9 were increased at 6, 24, 48, and 72 h after SCI in the control group. In the melatonin-treated group, the expression of MMP-9 was significantly decreased at 24, 48, and 72 h after SCI compared with the control group, and the activity of MMP-9 was significantly reduced at 72 h after SCI. In contrast, there were no significant changes in the MMP-2 level in both groups during the experimental period. Melatonin treatment following photochemically induced SCI in rats significantly ameliorated the functional deficits. On histopathologic examination, the lesion size in the spinal cord after photothrombotic insult was significantly reduced by melatonin administration. CONCLUSIONS: This study showed that the up-regulation of MMP-9 correlated with the secondary damage after SCI in rats. The results of this study suggest that the ability of melatonin to reduce secondary tissue damage is intimately related to the reduction of MMP-9 expression, resulting in functional improvement.

Effects of synchronization of carbohydrate and protein supply in total mixed ration with korean rice wine residue on ruminal fermentation, nitrogen metabolism and microbial protein synthesis in holstein steers.

Three Holstein steers in the growing phase, each with a ruminal cannula, were used to test the hypothesis that the synchronization of the hourly rate of carbohydrate and nitrogen (N) released in the rumen would increase the amount of retained nitrogen for growth and thus improve the efficiency of microbial protein synthesis (EMPS). In Experiment 1, in situ degradability coefficients of carbohydrate and N in feeds including Korean rice wine residue (RWR) were determined. In Experiment 2, three total mixed ration (TMR) diets having different rates of carbohydrate and N release in the rumen were formulated using the in situ degradability of the feeds. All diets were made to contain similar contents of crude protein (CP) and neutral detergent fiber (NDF) but varied in their hourly pattern of nutrient release. The synchrony index of the three TMRs was 0.51 (LS), 0.77 (MS) and 0.95 (HS), respectively. The diets were fed at a restricted level (2% of the animal's body weight) in a 3×3 Latin-square design. Synchronizing the hourly supply of energy and N in the rumen did not significantly alter the digestibility of dry matter, organic matter, crude protein, NDF or acid detergent fiber (ADF) (p>0.05). The ruminal NH3-N content of the LS group at three hours after feeding was significantly higher (p<0.05) than that of the other groups; however, the mean values of ruminal NH3-N, pH and VFA concentration among the three groups were not significantly different (p>0.05). In addition, the purine derivative (PD) excretion in urine and microbial-N production (MN) among the three groups were not significantly different (p>0.05). In conclusion, synchronizing dietary energy and N supply to the rumen did not have a major effect on nutrient digestion or microbial protein synthesis (MPS) in Holstein steers.

Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells.

Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

Quercetin reduces the elevated matrix metalloproteinases-9 level and improves functional outcome after cerebral focal ischemia in rats.

BACKGROUND: Blood-brain barrier (BBB) disruption mediated by matrix metalloproteinase (MMPs) activation is a critical event during cerebral ischemia. The inhibition of MMP might be a potential approach to protect against secondary injury. The present study was designed to determine the effects of quercetin on BBB disruption and MMP activity, in a focal ischemia model induced by photothrombosis, in rats. METHODS: Adult male Sprague-Dawley rats received focal ischemia by photothrombosis. The injured animals were divided into two groups: one group received 25 µmol/kg of quercetin intraperitoneally, starting 1 h after injury with continued treatment at 12-h intervals for 3 days, while animals in the control group received weight-adjusted doses of a saline vehicle. The effects of quercetin on BBB disruption, brain edema, MMP activities, and neurological deficits were determined. FINDINGS: Quercetin treatment markedly reduced ischemia-induced up-regulation of MMP-9 at 24 and 48 h after ischemic injury. No significant change in MMP-2 activity was observed throughout the experimental period. Post-ischemic increase in BBB permeability and brain edema were significantly reduced in the quercetin-treated group compared to the vehicle-treated ischemia control. Quercetin treatment significantly improved the functional outcomes assessed by the accelerating rotarod test. CONCLUSIONS: The results of this study demonstrated that quercetin attenuated BBB disruption during focal ischemia through inhibitory effects on MMP-9 activity. These results suggest that quercetin might have a potential role in the protection against neuronal injury in patients with focal ischemic stroke.

Early activation of matrix metalloproteinase-9 is associated with blood-brain barrier disruption after photothrombotic cerebral ischemia in rats.

BACKGROUND: The activation of matrix metalloproteinases (MMPs) is a critical event for disruption of the blood-brain barrier (BBB) during cerebral ischemia. Among the MMPs, MMP-2, and MMP-9 expression were reported to be significantly elevated after the onset of ischemia. The aim of this study was to investigate which one is more significant for BBB disruption in the photothrombotic cerebral ischemia. MATERIALS AND METHODS: Male Sprague-Dawley rats weighing 250-300 g received focal cerebral ischemia by photothrombosis. MMP-2 and MMP-9 activities were assessed by gelatin zymography at various times from 2 h to 7 days. The BBB integrity was assessed using Evans blue dye with a spectrophotometric assay. FINDINGS: The Evans blue extravasation was increased within 2 h after cerebral ischemia, and was maximal at 12 and 24 h after the injury, and then gradually decreased. MMP-9 protein activity was detected as early as 2 h after the focal ischemic event; it rapidly increased at 6 h after ischemia, and reached a maximum level 48 h after the ischemic event. Thereafter, the MMP-9 level abruptly decreased and returned to the baseline at 72 h after the insult. By contrast, the MMP-2 protein activity was up-regulated at 6 h after the focal ischemic insult, and reached a maximum level at 72 h after the event. The elevated MMP-2 levels persisted for 7 days after the injury. CONCLUSIONS: The early activation of MMP-9 was correlated with the increase in the permeability of the BBB. Our findings suggest that MMP-9 is the key factor involved in BBB disruption and subsequent brain injury after photothrombotic cerebral ischemia in rats.

Deletion of liver-specific STAT5 gene alters the expression of bile acid metabolism genes and reduces liver damage in lithogenic diet-fed mice.

Signal transducers and activators of transcription 5 (STAT5) mediates growth hormone signals, which may control hepatic cholesterol uptake and bile acid metabolism. Deregulation of liver cholesterol homeostasis and bile acid metabolism may cause liver damage and cholesterol gallstone development. The purpose of this study was to understand the role of local STAT5 signaling in cholesterol and bile acid metabolism using liver-specific STAT5 knock-out (STAT5 LKO) mice on a normal diet and a cholesterol- and bile acid-containing lithogenic diet. STAT5 LKO mice showed significant down-regulation of STAT5 and insulin-like growth factor-1 genes. STAT5 gene deletion had a minor effect on cholesterol metabolism, as evidenced by a minor change in circulating cholesterol levels and no changes in expression of hepatic low-density lipoprotein receptor and cholesterol synthesis genes in STAT5 LKO mice. In contrast, bile acid synthesis and uptake genes were profoundly down-regulated and bile acid detoxification genes were up-regulated in STAT5 LKO mice. In STAT5 fl/fl mice, a lithogenic diet induced liver damage, as evidenced by moderate increases in liver ballooning, inflammation and fibrosis. However, STAT5 deletion ameliorated the degree of liver damage induced by the lithogenic diet. In STAT5 LKO mice, a lithogenic diet did not alter the incidence or severity of cholesterol gallstones. In conclusion, local STAT5 signaling does not have a significant role in cholesterol metabolism. In contrast, hepatic STAT5 signaling has significant roles in regulating transcription of genes for synthesis, transport and detoxification of bile acids, but it has only a minor role in bile acid metabolism.

Effects of road transportation on metabolic and immunological responses in Holstein heifers.

This study examined the effects of road transportation on metabolic and immunological responses in dairy heifers. Twenty Holstein heifers in early pregnancy were divided into non-transported (NT; n = 7) and transported (T; n = 13) groups. Blood was collected before transportation (BT), immediately after transportation for 100 km (T1) and 200 km (T2), and 24 h after transportation (AT). The T heifers had higher (P < 0.05) blood cortisol and non-esterified fatty acid concentrations after T1 and T2 than did NT heifers. By contrast, the T heifers had lower (P < 0.05) serum triglyceride concentrations after T1 and T2 than had the NT heifers. The serum cortisol and triglyceride concentrations returned (P > 0.05) to the BT concentrations at 24 h AT in the T heifers. The granulocyte-to-lymphocyte ratio and the percentage of monocytes were higher (P < 0.05) after T2 in the T heifers than in the NT heifers, suggesting that transportation stress increased the numbers of innate immune cells. T heifers had higher (P < 0.01) plasma haptoglobin concentrations than NT heifers 24 h AT. In conclusion, transportation increased cortisol secretion and was correlated with increased metabolic responses and up-regulation of peripheral innate immune cells in dairy heifers.

Liver-specific deletion of the signal transducer and activator of transcription 5 gene aggravates fatty liver in response to a high-fat diet in mice.

Growth hormone (GH) signal is mediated by signal transducer and activator of transcription 5 (STAT5), which controls hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) is clinically associated with a deficiency in GH. This study was performed to understand the role of local STAT5 signaling on hepatic lipid and glucose metabolism utilizing liver-specific STAT5 gene deletion (STAT5 LKO) mice under both normal diet and high-fat diet (HFD) feeding conditions. STAT5 LKO induced hepatic steatosis under HFD feeding, while this change was not observed in mice on normal diet. STAT5 LKO caused hyperglycemia, hyperinsulinemia, hyperleptinemia and elevated free fatty acid and cholesterol concentrations under HFD feeding but induced only hyperglycemia on normal diet. At the molecular level, STAT5 LKO up-regulated the expression of genes involved in lipid uptake (CD36), very low-density lipoprotein receptor (VLDLR), lipogenic stearoyl-CoA desaturase and adipogenic peroxisome proliferator-activated receptor gamma, in both diet groups. In response to HFD feeding, further increases in CD36 and VLDLR expression were found in STAT5 LKO mice. In conclusion, our study suggests that low STAT5 signaling on normal diet predisposes STAT5 LKO mice to early development of fatty liver by hyperglycemia and activation of lipid uptake and adipogenesis. A deficiency in STAT5 signaling under HFD feeding deregulates hepatic and body glucose and lipid metabolism, leading to the development of hepatic steatosis. Our study indicates that low STAT5 signaling, due to low GH secretion, may increase a chance for NAFLD development in elderly people.

[Treatment of proximal humeral fractures with percutaneous locking plate fixation through lateral deltoid approach].

OBJECTIVE: To investigate the effects of locking plate fixation through lateral deltoid approach for proximal humeral fracture combined with micro-invasive percutaneous plating (MIPPO) technique. METHODS: From April 2009 to March 2012,26 patients with proximal humeral fractures were treated with proximal humeral locking system plate fixation through lateral deltoid approach, including 17 males and 9 females with an average age of 58 years old ranging from 28 to 76 years old. The time from injury to operation was 3 to 10 days (averaged 5.6 days). According to Neer typing for the proximal humeral fractures, 7 cases had 2 parts of fracture,15 had 3 parts of fracture,and 4 had 4 parts of fracture. The Neer score for shoulder function was evaluated. RESULTS: All patients were followed up,and the duration ranged from 10 to 21 months (averaged 13.6 months). All patients were achieved bony union,the average healing time was 12.5 weeks (ranged from 10 to 21 weeks). No humeral head necrosis and axillary nerve injury occurred. According to Neer scoring system,the total score was 88.36 +/- 7.82, pain 30.82 +/- 3.24, function 23.76 +/- 5.71, activity 17.59 +/- 5.36, anatomical position 7.03 +/- 2.39; the result was excellent in 18 cases, good in 5 cases, fair in 2 cases, poor in 1 case. CONCLUSION: Lateral deltoid approach combined with locking plate fixation for treatment of proximal humeral fracture has advantages of small invasion,less blood lossing, short operative time, stable fixation, high rate of fracture healing, and satisfactory functional recovery.

Rutin improves functional outcome via reducing the elevated matrix metalloproteinase-9 level in a photothrombotic focal ischemic model of rats.

BACKGROUND: Blood-brain barrier (BBB) disruption mediated by proteases plays a pivotal role in neural tissue damage after acute ischemic stroke. In an animal stroke model, the activation of matrix metalloproteinases (MMPs), especially MMP-9, was significantly increased and it showed potential association with blood-brain barrier (BBB) disruption and cerebral edema. Theoretically, it is expected that early blockade of expression and activation of MMP-9 after ischemic stroke provides neuroprotective effects from secondary neural tissue damage. This study was aimed to determine the ability of rutin to influence MMP-9 expression, activity and BBB disruption using a photothrombotic focal ischemic model in rats. METHODS: Adult male Sprague-Dawley rats, weighing between 250 and 300 g (aged 8 weeks) received focal cerebral ischemia by photothrombosis using Rose Bengal (RB) and cold light. Injured animals were divided into two groups; one group received 50mg/kg of rutin intraperitoneally, starting 1h after injury and at 12h intervals for 3 days, while animals in the control group received weight-adjusted doses of saline vehicle over the same period. In each group, the expressions and activities of MMP-9 were assessed by Western blot and gelatin zymography at 6, 24, 48, and 72 h after photothrombotic insult. The effects of rutin on BBB disruption and functional outcomes were also determined. RESULTS: Western blot and zymographic analysis showed up-regulated MMP-9 expression and activity in the ischemic cortex. The expression and activity of MMP-9 were significantly elevated at 6h after photothrombotic insult, which remained up-regulated for at least until 72 h after injury. In the rutin-treated group, MMP-9 expression and activity were significantly attenuated at 6, 24, and 48 h compared to the control group. Relative to the control group, BBB permeability was significantly reduced in the rutin-treated group. The results of the rotarod test revealed that rutin treatment significantly improved functional outcomes. CONCLUSIONS: Rutin treatment starting 1h after injury attenuated BBB disruption during photothrombotic focal ischemia, which was partly, at least, achieved through inhibitory effects on MMP-9 expression and activity. The results of this study suggest that rutin might be useful in clinical trials aimed to improve the outcome of patients suffering from acute ischemic stroke.

Melatonin reduced the elevated matrix metalloproteinase-9 level in a rat photothrombotic stroke model.

BACKGROUND: The accumulation of toxic free radicals plays a pivotal role in the early molecular cascades of blood-brain barrier (BBB) disruption mediated by matrix metalloproteinases (MMPs) activation in ischemic stroke. Theoretically, it is expected that early blockade of activation of MMPs may provide protective effects from secondary neural tissue damage. The present study was designed to determine the ability of melatonin to influence MMP-9 activity and BBB disruption, in a focal ischemia rat model induced by photothrombosis. METHODS: Adult, male, 8-week Sprague-Dawley rats weighing 230-300 g received focal cerebral ischemia by photothrombosis using Rose Bengal (RB). The injured animals were divided into two groups. One group received 50mg/kg of melatonin intraperitoneally, starting 1h after injury and at 12h intervals for 3 days. The control group received weight-adjusted doses of saline vehicle. In each group, MMP-9 expression and activity were assessed by Western blot and gelatin zymography, respectively, at various times. The effects of melatonin on BBB disruption and brain edema were also determined. RESULTS: MMP-9 activity and expression were significantly elevated at 24h in the ischemic cortex, which remained up-regulated at least until 72 h after injury. Melatonin treatment significantly attenuated MMP-9 activity and expression at 24, 48, and 72 h after ischemic injury. Relative to control group, BBB permeability was significantly reduced in the melatonin-treated group. The water content was decreased by melatonin treatment, although there was no statistically significant difference. CONCLUSIONS: Melatonin treatment starting 1h after injury attenuated BBB disruption during focal ischemia, which is at least partly due to inhibition of MMP-9 activity. Melatonin might have a potential role in clinical trials aimed to improve the outcome of patients suffering cerebral ischemia.

A mouse model of photochemically induced spinal cord injury.

OBJECTIVE: A mouse model of spinal cord injury (SCI) could further increase our basic understanding of the mechanisms involved in injury and repair of the nervous system. The purpose of this study was to investigate whether methods used to produce and evaluate photochemical graded ischemic SCI in rats, could be successfully adapted to mice, in a reliable and reproducible manner. METHODS: Thirty female imprinting control region mice (weighting 25-30 g, 8 weeks of age) were used in this study. Following intraperitoneal injection of Rose bengal, the translucent dorsal surface of the T8-T9 vertebral laminae of the mice were illuminated with a fiber optic bundle of a cold light source. The mice were divided into three groups; Group 1 (20 mg/kg Rose bengal, 5 minutes illumination), Group 2 (20 mg/kg Rose bengal, 10 minutes illumination), and Group 3 (40 mg/kg Rose bengal, 10 minutes illumination). The locomotor function, according to the Basso-Beattie-Bresnahan scale, was assessed at three days after the injury and then once per week for four weeks. The animals were sacrificed at 28 days after the injury, and the histopathology of the lesions was assessed. RESULTS: The mice in group 1 had no hindlimb movement until seven days after the injury. Most mice had later recovery with movement in more than two joints at 28 days after injury. There was limited recovery of one joint, with only slight movement, for the mice in groups 2 and 3. The histopathology showed that the mice in group 1 had a cystic cavity involving the dorsal and partial involvement of the dorsolateral funiculi. A larger cavity, involving the dorsal, dorsolateral funiculi and the gray matter of the dorsal and ventral horns was found in group 2. In group 3, most of the spinal cord was destroyed and only a thin rim of tissue remained. CONCLUSION: The results of this study show that the photochemical graded ischemic SCI model, described in rats, can be successfully adapted to mice, in a reliable and reproducible manner. The functional deficits are correlated an increase in the irradiation time and, therefore, to the severity of the injury. The photothrombotic model of SCI, in mice with 20 mg/kg Rose bengal for 5 minutes illumination, provides an effective model that could be used in future research. This photochemical model can be used for investigating secondary responses associated with traumatic SCI.