Changes in the expression of α-tocopherol-related genes in liver and mammary gland biopsy specimens of peripartum dairy cows.

Blood α-tocopherol (α-Toc) concentrations decline gradually throughout the prepartum period, reaching the nadir after calving in dairy cows. The 6 α-Toc-related molecules [α-Toc transfer protein (TTPA); afamin; scavenger receptor class B, Type I; ATP-binding cassette transporter A1; tocopherol-associated protein (SEC14L2); and cytochrome P450 family 4, subfamily F, polypeptide 2 (CYP4F2)] are expressed in liver and other peripheral tissues. These molecules could regulate α-Toc transport, blood concentrations, and metabolism of α-Toc. Therefore, the aim of this study was to evaluate the changes in the expression of α-Toc-related genes in liver and mammary gland tissues of dairy cows around calving, which have remained elusive until now. In experiment (Exp.) 1, 28 multiparous Holstein cows were used (from -5 to 6 wk relative to parturition) to monitor the changes in dietary α-Toc intake, blood concentrations of α-Toc, and lipoproteins; in Exp. 2, 7 peripartum Holstein cows were used (from -4 to 4 wk relative to parturition) for liver tissue biopsy; and in Exp. 3, 10 peripartum Holstein cows were used (from -8 to 6 wk relative to parturition) to carry out the mammary gland tissue biopsy and milk sampling. In Exp. 1, the serum α-Toc concentrations declined gradually with decreasing amount of α-Toc intake and plasma high-density lipoprotein concentrations toward calving time. However, in the early lactation period after calving, serum α-Toc concentrations remained at a lower concentration despite the recovery of α-Toc intake and plasma high-density lipoprotein concentrations. In Exp. 2, just after calving, the TTPA, SEC14L2, afamin, and albumin mRNA expression levels in the liver were temporarily downregulated, and the hepatic mRNA levels of endoplasmic reticulum stress-induced unfolded protein response markers and acute-phase response marker increased at calving. In Exp. 3, the concentrations of α-Toc in colostrum were greater than those in precolostrum (samples were collected at wk -1 relative to parturition) and mature milk. The expression of TTPA, SEC14L2, and CYP4F2 mRNA in bovine mammary gland tissue was detected. However, TTPA and SEC14L2 mRNA expressions showed the opposite trends: the expression levels of TTPA mRNA peaked whereas SEC14L2 mRNA reached a nadir at calving. These results indicate that the expression of α-Toc-related genes involved in specific α-Toc transfer and metabolism in the liver and mammary gland are altered during calving. Moreover, these changes might be associated with the maintenance of lower serum α-Toc concentrations after calving.

Postweaning changes in the expression of chemerin and its receptors in calves are associated with the modification of glucose metabolism.

Chemerin, originally known as a chemoattractant derived from adipose tissue and the liver, has been reported to have regulatory functions in gluconeogenesis, peripheral insulin sensitivity, and insulin secretion. This study was conducted to assess the postweaning changes in expression of this cytokine and its physiological role in the modification of glucose metabolism associated with weaning. Eighteen tissue samples were collected from Holstein calves (90 d of age; n = 4) to investigate the tissue distributions of chemerin and its receptors genes. was highly expressed in the liver, and secreted chemerin protein was found in the plasma. Among the receptors of chemerin, and were ubiquitously expressed whereas was predominantly expressed in the liver. The changes in glucose metabolism and expression of these genes after weaning were assessed by comparing suckling calves (n = 6) and weaned calves (n = 8) of Japanese Black cattle. No significant difference was observed in plasma glucose levels between suckling and weaned calves (P = 0.22), whereas the plasma level of total ketone bodies was significantly higher in weaned calves (P < 0.01). Plasma levels of insulin and cortisol did not differ between suckling and weaned calves. The mRNA levels of certain key enzymes involved in hepatic gluconeogenesis were also altered; for instance, level was lower in postweaning calves (P < 0.05) and () level tended to be higher after weaning (P = 0.08). However, was not altered after weaning. The plasma levels of hepatic stress indicators were also changed, with aspartate transaminase, alanine transaminase, and lactate dehydrogenase being significantly elevated in postweaning calves (P < 0.05). Chemerin protein in liver tissue was less abundant in weaned calves (P < 0.05), although there were no changes in its transcript levels. The abundance of plasma chemerin protein did not change after weaning (P = 0.95). In summary, these data indicate that as a consequence of weaning, which causes physiological stress and alters hepatic metabolism, chemerin protein expression within the liver is downregulated, indicating that chemerin plays a role in the upregulation of hepatic expression via its inhibitory effect on hepatic gluconeogenesis.

Clinical Significance of the Champagne Bottle Neck Sign in the Extracranial Carotid Arteries of Patients with Moyamoya Disease.

BACKGROUND AND PURPOSE: The champagne bottle neck sign represents a rapid reduction in the extracranial ICA diameters and is a characteristic feature of Moyamoya disease. However, the clinical significance of the champagne bottle neck sign is unclear. We investigated the relationship between the champagne bottle neck sign and the clinical and hemodynamic stages of Moyamoya disease. MATERIALS AND METHODS: We analyzed 14 patients with Moyamoya disease before revascularization (5 men, 9 women; age, 43.2 ± 19.3 years). The ratio of the extracranial ICA and common carotid artery diameters was determined using carotid ultrasonography or cerebral angiography; a ratio of < 0.5 was considered champagne bottle neck sign-positive. The clinical disease stage was determined using the Suzuki angiographic grading system. CBF and cerebral vasoreactivity also were measured. RESULTS: The ICA/common carotid artery ratio (expressed as median [interquartile range]) decreased as the clinical stage advanced (stages I-II, 0.71 [0.60-0.77]; stages III-IV, 0.49 [0.45-0.57]; stages V-VI, 0.38 [0.34-0.47]; P < .001). Lower ICA/common carotid artery ratio tended to occur in symptomatic versus asymptomatic arteries (0.47 [0.40-0.53] versus 0.57 [0.40-0.66], respectively; P = .06). Although the ICA/common carotid artery ratio was not related to cerebral perfusion, it decreased as cerebral vasoreactivity decreased (P < .01). All champagne bottle neck sign-positive arteries were classified as Suzuki stage ≥III, 73% were symptomatic, and 89% exhibited reduced cerebral vasoreactivity. In contrast, all champagne bottle neck sign-negative arteries were Suzuki stage ≤III, 67% were asymptomatic, and all showed preserved cerebral vasoreactivity. CONCLUSIONS: The champagne bottle neck sign was related to advanced clinical stage, clinical symptoms, and impaired cerebral vasoreactivity. Thus, detection of the champagne bottle neck sign might be useful in determining the clinical and hemodynamic stages of Moyamoya disease.

Expression of α-tocopherol-associated genes and α-tocopherol accumulation in Japanese Black (Wagyu) calves with and without α-tocopherol supplementation.

The aim of the study was to clarify 1) the distribution of 6 α-tocopherol (α-Toc)-associated gene expressions in 20 major tissues, including metabolic, reproductive, endocrine, immune, and digestive and absorptive tissues, in relation to α-Toc status and 2) the change in expression patterns of the genes induced when α-Toc was orally administered to Japanese Black (JB) calves. This study examined weaned male JB calves ( = 10), of which 5 calves were orally administered α-Toc for 2 wk (30 IU·kg BW·d; TOC group). The others did not receive the α-Toc supplement and were the control (CONT) group. The 20 tissues and venous blood (serum) were sampled on the final day. In both groups, the mean mRNA expression levels for α-Toc transfer protein, afamin (AFM), ATP-binding cassette transporter A1, and tocopherol-associated protein were greatest in the liver ( < 0.05), whereas scavenger receptor class B, Type I (SR-BI) mRNA was greatest in the adrenal gland ( < 0.05). The gene for cytochrome P450 family 4, subfamily F, polypeptide 2 was most highly expressed in the liver, testes, and adrenal gland. The α-Toc content was greatest ( < 0.05) in the testes of the 20 sampled tissues in the CONT group. However, the levels in the testes and jejunum were similar and greater ( < 0.05) than the levels in the other 18 tissues in the TOC group. The mean increase in α-Toc levels after oral α-Toc administration (mean α-Toc content for the TOC group divided by the CONT group content) were greater ( < 0.05) in the jejunum (40.7-fold) and duodenum and liver (26.3- and 23.1-fold) than in the serum (7.8-fold). In the liver, α-Toc administration significantly increased ( < 0.05) the AFM and SR-BI mRNA expression levels. The results show that the liver may play an important role in the regulation of α-Toc disposition, but other peripheral tissues that accumulate large amounts of α-Toc could moderate the local α-Toc status and functions, as inferred from the high expressions of the α-Toc-associated genes in JB calves.

Impact of delivery models on understanding genomic risk for type 2 diabetes.

BACKGROUND: Genetic information, typically communicated in-person by genetic counselors, can be challenging to comprehend; delivery of this information online--as is becoming more common--has the potential of increasing these challenges. METHODS: To address the impact of the mode of delivery of genomic risk information, 300 individuals were recruited from the general public and randomized to receive genomic risk information for type 2 diabetes mellitus in-person from a board-certified genetic counselor or online through the testing company's website. RESULTS: Participants were asked to indicate their genomic risk and overall lifetime risk as reported on their test report as well as to interpret their genomic risk (increased, decreased, or same as population). For each question, 59% of participants correctly indicated their risk. Participants who received their results in-person were more likely than those who reviewed their results on-line to correctly interpret their genomic risk (72 vs. 47%, p = 0.0002) and report their actual genomic risk (69 vs. 49%, p = 0.002). CONCLUSIONS: The delivery of personal genomic risk through a trained health professional resulted in significantly higher comprehension. Therefore, if the online delivery of genomic test results is to become more widespread, further evaluation of this method of communication may be needed to ensure the effective presentation of results to promote comprehension.

Genome-wide association study of degenerative bony changes of the temporomandibular joint.

OBJECTIVES: To identify susceptibility genes underlying degenerative bony changes of the temporomandibular joint (TMJ). MATERIALS AND METHODS: Bony changes of the TMJ condylar head were diagnosed by examination of panoramic radiographs and/or magnetic resonance images and/or computed tomography images. We conducted a genome-wide association study (GWAS) of 146 cases with TMJ degeneration and 374 controls from East Asian populations using an Illumina HumanOmniExpress BeadChip. After rigorous quality-control filtering, approximately 550,000 single nucleotide polymorphisms (SNPs) were used for tests of associations with disease status. RESULTS: Forty-one SNPs at 22 independent loci showed association signals at P < 1 × 10(-4). The SNP rs878962, which maps on an intron of TSPAN9 on chromosome 12, showed the strongest association (combined OR = 1.89, 95% confidence interval = 1.43-2.50, P = 8.1 × 10(-6)). According to in silico predictions of the 41 SNPs, two intronic SNPs of APOL3 (rs80575) and MRC2 (rs2460300) may fall within regulatory elements and affect DNA-protein interactions. We could not replicate SNPs located on genes that have been reported to be associated with temporomandibular disorder or temporomandibular osteoarthritis in previous studies at P < 1 × 10(-4). CONCLUSIONS: Our GWAS identified 22 independent loci showing suggestive association signals with degenerative bony changes of the TMJ. These loci provide good candidates for future follow-up studies.

The potential impact of pharmacogenetic testing on medication adherence.

Poor medication adherence is a well-known problem, particularly in patients with chronic conditions, and is associated with significant morbidity, mortality and health-care costs. Multi-faceted and personalized interventions have shown the greatest success. Pharmacogenetic (PGx) testing may serve as another tool to boost patients' confidence in the safety and efficacy of prescribed medications. Here, we consider the potential impact (positively or negatively) of PGx testing on medication-taking behavior.

A high-protein diet induces dissociation between plasma concentrations of growth hormone and ghrelin in wethers.

High-carbohydrate or high-fat diets have been demonstrated to change ghrelin concentrations in plasma; however, there remains a need to clarify the effects of dietary protein on the interaction between circulating GH and ghrelin concentrations in the ruminant. In this study, we investigated the postprandial changes in plasma concentrations of GH and ghrelin and their interactions when wethers were fed either a high-protein (HP; 40% CP) or a low-protein (LP; 10% CP) diet for 2 wk. The wethers were divided into 2 groups and fed once a day for 2 wk in a randomized crossover design. Each diet contained the same level of ME. Blood was collected from the animals at specific times over 24 h to measure hormones and metabolites. Feeding once a day caused a prompt reduction in the GH and ghrelin concentrations regardless of the type of diet that the wethers consumed. The preprandial concentrations (P = 0.04), area under the curve (AUC; P = 0.04), and incremental AUC (iAUC; P = 0.06) for ghrelin in HP-fed wethers were or tended to be greater than those in LP-fed wethers although concentrations for GH were the same for both diets (P = 0.23). In addition, the time it took for the postprandial ghrelin concentrations to recover to the preprandial concentrations was greater in HP-fed wethers than in LP-fed wethers although this was not true for GH concentrations. Similarly, as for ghrelin, postprandial increase (P < 0.001) and AUC (P = 0.03) for insulin concentration was greater in the HP-fed wethers than in the LP-fed wethers. From these findings, we concluded that dietary proteins (or some other derived metabolites) may dissociate the interaction between plasma concentrations of GH and ghrelin in wethers.

Primary care physicians' knowledge of and experience with pharmacogenetic testing.

It is anticipated that as the range of drugs for which pharmacogenetic testing becomes available expands, primary care physicians (PCPs) will become major users of these tests. To assess their training, familiarity, and attitudes toward pharmacogenetic testing in order to identify barriers to uptake that may be addressed at this early stage of test use, we conducted a national survey of a sample of PCPs. Respondents were mostly white (79%), based primarily in community-based primary care (81%) and almost evenly divided between family medicine and internal medicine. The majority of respondents had heard of PGx testing and anticipated that these tests are or would soon become a valuable tool to inform drug response. However, only a minority of respondents (13%) indicated they felt comfortable ordering PGx tests and almost a quarter reported not having any education about pharmacogenetics. Our results indicate that primary care practitioners envision a major role for themselves in the delivery of PGx testing but recognize their lack of adequate knowledge and experience about these tests. Development of effective tools for guiding PCPs in the use of PGx tests should be a high priority.

Survey of genetic counselors and clinical geneticists' use and attitudes toward pharmacogenetic testing.

Pharmacogenetic (PGx) testing aims to improve therapeutic outcomes through tailoring treatment based on a patient's genetic risk for non-response and/or an adverse event. Given their expertise, geneticists could facilitate the use of PGx testing; however, the preparedness and perceived role of the clinical genetics community is unclear. To assess the attitudes, preparedness, and perceived roles of geneticists in the delivery of PGx testing, we conducted a survey of 1500 randomly selected board-certified genetic counselors and clinical geneticists in the United States [response rate: 37.8% (n = 516)]. Twelve percent of genetic counselors and 41% of clinical geneticists indicated that they had ordered or coordinated patient care for PGx testing, a seemingly high proportion at this early stage of adoption. Almost all respondents had some education on pharmacogenetics, although only 28% of counselors and 58% of clinical geneticists indicated they felt well-informed about PGx testing. About half of counselors (52%) and clinical geneticists (46%) felt they would play 'some' role in the delivery of PGx testing; 17 and 19%, respectively, felt that they would play 'no' or 'a little' role. At this early stage of PGx testing, the role of geneticists and genetic counselors is unclear. However, their experience may aid in readying PGx testing and informing delivery strategies into clinical practice.

Survey of US public attitudes toward pharmacogenetic testing.

To assess public attitudes and interest in pharmacogenetic (PGx) testing, we conducted a random-digit-dial telephone survey of US adults, achieving a response rate of 42% (n=1139). Most respondents expressed interest in PGx testing to predict mild or serious side effects (73±3.29 and 85±2.91%, respectively), guide dosing (91%) and assist with drug selection (92%). Younger individuals (aged 18-34 years) were more likely to be interested in PGx testing to predict serious side effects (vs aged 55+ years), as well as Whites, those with a college degree, and who had experienced side effects from medications. However, most respondents (78±3.14%) were not likely to have a PGx test if there was a risk that their DNA sample or test result could be shared without their permission. Given differences in interest among some groups, providers should clearly discuss the purpose of testing, alternative testing options (if available) and policies to protect patient privacy and confidentiality.

Practical ethics: establishing a pathway to benefit for complex pharmacogenomic tests.

Pharmacogenomic tests offer a promising strategy to improve the safety and efficacy of drug treatment. Compelling examples, such as HLA-B*5701 testing to identify patients at risk for abacavir-associated hypersensitivity, are already changing clinical care. However, the level of evidence required to establish clinical utility is often the subject of debate. Determining the most efficient and effective pathway to benefit for a given test is therefore both a practical and an ethical concern.

Public perspectives on returning genetics and genomics research results.

BACKGROUND: The debate about returning research results has revealed different perspectives among researchers, participants and advisory groups with participants generally interested in obtaining their results. Given this preference, policies regarding return of individual research results may affect whether a potential subject chooses to participate in a study. Public attitudes, particularly those of African-Americans, toward this issue have been understudied. METHODS: In 2008-2009, we convened 10 focus groups in Durham, N.C. to explore attitudes about returning research results and how different policies might influence their likelihood to participate in genetic/genomic studies. Transcripts were complimented by a short anonymous survey. Of 100 participants, 73% were female and 76% African-American with a median age of 40-49 years. RESULTS: Although there was general interest in obtaining genetics research results, particularly individual results, discussants recognized many potential complexities. The option to obtain research results (individual or summary) was clearly valued and lack thereof was potentially a deterrent for genetic/genomic research enrollment. CONCLUSIONS: Providing the option to learn research results may help strengthen relationships between investigators and participants and thereby serve as a positive influencing factor for minority communities. Consideration of the broader implications of returning research results is warranted. Engaging diverse publics is essential to gain a balance between the interests and burdens of participants and investigators.

Public perspectives regarding data-sharing practices in genomics research.

BACKGROUND: Genomics research data are often widely shared through a variety of mechanisms including publication, meetings and online databases. Re-identification of research participants from sequence data has been shown possible, raising concerns of participants' privacy. METHODS: In 2008-09, we convened 10 focus groups in Durham, N.C. to explore attitudes about how genomic research data were shared amongst the research community, communication of these practices to participants and how different policies might influence participants' likelihood to consent to a genetic/genomic study. Focus groups were audio-recorded and transcripts were complemented by a short anonymous survey. Of 100 participants, 73% were female and 76% African-American, with a median age of 40-49 years. RESULTS: Overall, we found that discussants expressed concerns about privacy and confidentially of data shared through online databases. Although discussants recognized the benefits of data-sharing, they believed it was important to inform research participants of a study's data-sharing plans during the informed consent process. Discussants were significantly more likely to participate in a study that planned to deposit data in a restricted access online database compared to an open access database (p < 0.00001). CONCLUSIONS: The combination of the potential loss of privacy with concerns about data access and identity of the research sponsor warrants disclosure about a study's data-sharing plans during the informed consent process.

Factors influencing uptake of pharmacogenetic testing in a diverse patient population.

BACKGROUND: The successful integration of pharmacogenetic (PGx) testing into clinical care will require attention to patient attitudes. In this study, we aimed to identify the major reasons why patients would or would not consider PGx testing and whether these factors differed by race, socioeconomic and insurance status, and medical history. METHODS: We developed and conducted a survey within the adult patient population of the Duke Family Medicine Center. RESULTS: Of 75 completed surveys (65% African-American), 77% indicated they were 'very likely' or 'somewhat likely' to take a PGx test. Respondents who had experienced a side effect were significantly more likely to indicate they would take a PGx test and expressed greater interest in learning more about testing than those who had not. Drug safety and effectiveness were the major reasons to have PGx testing. Privacy concerns and lack of insurance coverage for testing were the major reasons to decline testing. CONCLUSIONS: We found no differences in interest in PGx tests by race or socioeconomic status, but found stronger interest from those with a history of side effects and private insurance. While the overall support of PGx testing is encouraging, greater reassurance of medical privacy and development of educational resources are needed.

The potential of a placebo/nocebo effect in pharmacogenetics.

Pharmacogenetic testing holds great promise to improve health outcomes and reduce adverse drug responses through enhanced selection of therapeutic agents. Since drug responses can be manipulated by verbal suggestions, it is of particular interest to understand the potential impact of pharmacogenetic test results on drug response. Placebo and nocebo-like effects may be possible due to the suggestive nature of pharmacogenetic information that a drug will or will not likely lead to improved health outcomes. For example, pharmacogenetic testing could provide further reassurance to patients that a given drug will be effective and/or cause minimal side effects. However, pharmacogenetic information could adversely affect drug response through negative expectations that a drug will be less than optimally effective or cause an adverse response, known as a nocebo-like effect. Therefore, a patient's perceived value of testing, their understanding of the test results, and the manner in which they are communicated may influence therapeutic outcome. As such, physicians should consider the potential effect of pharmacogenetic test results on therapeutic outcome when communicating results to patients. Studies are needed to investigate the impact of pharmacogenetic information of therapeutic outcome.

Changes in cardiac structure and function among elite judoists resulting from long-term judo practice.

AIM: The aim of this study was to investigate the character of changes in cardiac structure and function among elite judoists due to long-term judo practice. METHODS: A group of male (N = 20, average age: 22.1) and female (N = 15, average age: 19.4) athletes practising judo for about 10 years was subjected to echocardiographic tests carried out during rest (aorta diameter [AoD], diastolic dimension of the left ventricle [Dd], thickness of the interventricular septum [IVST], the thickness of the posterior wall of the left ventricle [LVPWT]), and to measurement of cardiovascular system's action parameters (heart rate [HR], stroke volume [SV], cardiac output [Q], blood pressure [BP]). Moreover, control non trained subjects were also studied, women (N = 30, average age: 19.1) and men (N = 30, average age: 21.4). In order to determine aerobic efficiency, the authors measured the maximal oxygen uptake (VO2max) using the direct method. The anaerobic capacity was estimated on the basis of the maximal anaerobic power, and the volume of the performed work was calculated by means of the 30s Wingate test. RESULTS: Echocardiographic test values imply that changes in heart morphology induced by long term judo training, such as increase diastolic dimension of the left ventricle, thickness of the interventricular septum and left ventricular posterior wall, resemble more the changes observed in endurance athletes than changes observed in strength athletes. CONCLUSION: The obtained data indicated that judo training improves both aerobic and anerobic performance and these changes were associated with changes in heart structure and function as compared to non trained control.

Changes in hepatic key enzymes of dairy calves in early weaning production systems.

The objective of the present study was to describe plasma hormonal and metabolite profile and mRNA expression levels and activities of the enzymes pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), and acetyl-coenzyme A (CoA) carboxylase in the liver of male Holstein calves before (1 and 3 wk of age) and after (8, 13, and 19 wk of age) weaning at 6 wk of age. The mean plasma concentration of acetate and beta-hydroxybutyrate increased, and that of plasma lactate and nonesterified fatty acids decreased with week, particularly after weaning. Plasma glucose concentration was lowest at 8 wk of age. The mean plasma concentration of insulin and glucagon did not change with time, and that of cortisol was greatest at 1 wk of age. In the liver, enzyme activity of PC was greatest at 1 wk of age and decreased with time. There was a significant relationship between the activity and the mRNA level for PC. Activity of PEPCK also decreased with week. Acetyl-CoA carboxylase activity tended to decrease with week, and activity at 13 wk of age was lower than that at other times. Expression of PC mRNA, but not that of PEPCK and acetyl-CoA carboxylase alpha, decreased with week. We conclude that the hepatic gluconeogenic enzymes and acetyl-CoA carboxylase activities tend to decrease with age, reflecting changes in plasma metabolites in early weaning production systems.

Changes of activity and mRNA expression of urea cycle enzymes in the liver of developing Holstein calves.

Urea is an important reutilizable nitrogen source for the ruminant and is mainly synthesized through the urea cycle in the liver. The cycle is undertaken by 5 enzymes: carbamoyl phosphate synthetase (CPS), ornithine transcarbamoylase (OTC), arginino-succinate synthetase (AS), argininosuccinate lyase (AL), and arginase. The purpose of this study was to investigate changes in the activity of the enzymes and mRNA expression, given that previous observations have indicated an increase in plasma urea concentrations with age in Holstein calves. First, plasma concentrations of metabolites and hormones were determined in calves at 1, 3, 8, 13, and 19 wk of age (n = 4, weaned at 6 wk of age). The plasma concentration of urea drastically increased after weaning (P < 0.001). The plasma concentration of glucose was lowest at 8 wk. The plasma concentration of IGF-I gradually increased with age, although those of NEFA, glucagon, and cortisol decreased (P < 0.001). Concentrations of triglyceride, alpha-amino nitrogen, growth hormone, and insulin did not change significantly with age of the calf. Next, using the liver tissues taken from calves at 2, 13, and 19 wk of age (n = 4 to 6 at each time point, weaned at 6 wk of age), we measured the activity and mRNA expression of the enzymes by biochemical methods and quantitative reverse transcription-PCR, respectively. The activities of CPS (P < 0.001), OTC (P = 0.001), and AS (P = 0.015) increased with age, whereas AL (P = 0.003) decreased. Although mRNA expression was decreased with age for AL (P = 0.002) and arginase (P = 0.007), no significant change was observed for CPS, OTC, or AS mRNA expression. We conclude that the increased urea production in the liver may be explained not only by an increase in the activities of the urea cycle enzymes, but also by increased ammonia production by rumen fermentation and gluconeogenesis from amino acids around weaning time.

Different responses in postprandial plasma ghrelin and GH levels induced by concentrate or timothy hay feeding in wethers.

Ghrelin and growth hormone (GH) play a key role in regulating energy balance, metabolic hormone secretion and food intake. Ghrelin and GH responses to dietary compositions have not yet been fully clarified, although there may be significant relationships between dietary compositions and ghrelin and GH responses. In the present study, therefore, we assessed whether dietary compositions influence postprandial plasma ghrelin and GH levels in wethers. Four wethers were respectively fed concentrate (C) or timothy hay (R) for 14 days. The levels of total digestive nutrients (TDN) and crude protein (CP) were adjusted to be at the same level. The basal ghrelin in both groups was rapidly and significantly decreased after feeding. Although the decline of ghrelin levels in C was greater and shorter than that in R, no significant difference was observed in the area under the curve (AUC) or in the incremental area. The plasma GH levels were also rapidly and significantly decreased after feeding in both groups and a significant difference was observed between the two groups for AUC of GH. Interestingly, the circadian changes in the plasma ghrelin levels were close to those in the GH levels in C, but this was not the case in R. These data suggest that dietary compositions influence postprandial plasma ghrelin and GH levels, and that these differences may be caused by several factors, including nutrients and ruminal fermentation.