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1.
Animal ; 17(5): 100805, 2023 May.
Article in English | MEDLINE | ID: mdl-37149993

ABSTRACT

The physiological consequences of overstocking require more investigation, and no research has explored whether dietary supplements could mitigate the anticipated negative physiological effects. OmniGen AF (OG, Phibro Animal Health Corporation, Teaneck, NJ, USA) is a nutritional supplement that has been shown to support the immune system of cattle following internal and environmental stressors. This study aimed to determine if a 45-day period of OG feed supplementation would influence whole blood leukocyte messenger RNA abundance, energy metabolism and glucocorticoid concentration, during a two-week period of overstocking. Two stocking density treatments (control: one headlock and lying stall per cow; overstocked: 0.5 headlocks and 0.5 lying stalls per cow) and two diet treatments (control: no added supplement; and OG: 56 g/cow per day) were investigated. Four pens of 15 cows were fed their assigned diet (two pens per diet; control stocking density) for 45 days after which each stocking density treatment was applied for a 14-day period using a cross-over design; this study design was replicated twice. During each 14-day period, blood was collected on day four to measure whole blood leukocyte messenger RNA abundance (cluster of differentiation 80, interleukin 8 receptor-beta, interleukin 10 receptor-beta and L-selectin) and fecal samples were collected every two days to measure fecal cortisol metabolite concentration (11,17-dioxoandrostanes). At the end of each 14-day period, eight cows from each pen were selected for an intravenous glucose tolerance test; glucose, insulin and non-esterified fatty acids were measured. There were no effects of diet or stocking density on leukocyte messenger RNA abundance. Fecal cortisol metabolite concentrations were highest for overstocked cows on the control diet on day four of the stocking density treatment; however, by day 10, overstocked cows fed OG had the highest fecal cortisol metabolite concentrations. Overstocked cows, regardless of diet, had an attenuated insulin response during the glucose tolerance test, represented by a lower area under the curve estimate. Cows fed OG but not overstocked, had a lower non-esterified fatty acid nadir during the glucose challenge, compared to all the other treatments. In conclusion, overstocking prompts a physiological stress response and alters energy metabolism by decreasing the insulin response to an intravenous glucose challenge. Feeding OG during overstocking delayed the increase in fecal cortisol metabolites by several days; however, it is unclear if this altered glucocorticoid response benefited the cow, as OG had no effect on insulin responses or immune parameters.


Subject(s)
Glucocorticoids , Hydrocortisone , Female , Cattle , Animals , Glucocorticoids/pharmacology , Glucocorticoids/metabolism , Lactation/physiology , Milk/metabolism , Diet/veterinary , Dietary Supplements , Leukocytes/metabolism , Insulin/metabolism , Glucose/metabolism , Energy Metabolism , Animal Feed
2.
J Dairy Sci ; 104(11): 11580-11592, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34454748

ABSTRACT

The continuous trend for a narrowing margin between feed cost and milk prices across dairy farms in the United States highlights the need to improve and maintain feed efficiency. Yeast culture products are alternative supplements that have been evaluated in terms of milk performance and feed efficiency; however, less is known about their potential effects on altering rumen microbial populations and consequently rumen fermentation. Therefore, the objective of this study was to evaluate the effect of yeast culture supplementation on lactation performance, rumen fermentation profile, and abundance of major species of ruminal bacteria in lactating dairy cows. Forty mid-lactation Holstein dairy cows (121 ± 43 days in milk; mean ± standard deviation; 32 multiparous and 8 primiparous) were used in a randomized complete block design with a 7-d adaptation period followed by a 60-d treatment period. Cows were blocked by parity, days in milk, and previous lactation milk yield and assigned to a basal total mixed ration (TMR; 1.6 Mcal/kg of dry matter, 14.6% crude protein, 21.5% starch, and 38.4% neutral detergent fiber) plus 114 g/d of ground corn (CON; n = 20) or basal TMR plus 100 g/d of ground corn and 14 g/d of yeast culture (YC; n = 20; Culture Classic HD, Cellerate Yeast Solutions, Phibro Animal Health Corp.). Treatments were top-dressed over the TMR once a day. Cows were individually fed 1 × /d throughout the trial. Blood and rumen fluid samples were collected in a subset of cows (n = 10/treatment) at 0, 30, and 60 d of the treatment period. Rumen fluid sampled via esophageal tubing was analyzed for ammonia-N, volatile fatty acids (VFA), and ruminal bacteria populations via quantitative PCR amplification of 16S ribosomal DNA genes. Milk yield was not affected by treatment effects. Energy balance was lower in YC cows than CON, which was partially explain by the trend for lower dry matter intake as % body weight in YC cows than CON. Cows fed YC had greater overall ruminal pH and greater total VFA (mM) at 60 d of treatment period. There was a contrasting greater molar proportion of isovalerate and lower acetate proportion in YC-fed cows compared with CON cows. Although the ruminal abundance of specific fiber-digesting bacteria, including Eubacterium ruminantium and Ruminococcus flavefaciens, was increased in YC cows, others such as Fibrobacter succinogenes were decreased. The abundance of amylolytic bacteria such as Ruminobacter amylophilus and Succinimonas amylolytica were decreased in YC cows than CON. Our results indicate that the yeast culture supplementation seems to promote some specific fiber-digesting bacteria while decreasing amylolytic bacteria, which might have partially promoted more neutral rumen pH, greater total VFA, and isovalerate.


Subject(s)
Lactation , Rumen , Animal Feed/analysis , Animals , Cattle , Diet/veterinary , Dietary Supplements , Digestion , Eubacterium , Female , Fermentation , Fibrobacter , Milk , Pregnancy , Rumen/metabolism , Ruminococcus , Saccharomyces cerevisiae , Succinivibrionaceae
3.
J Dairy Sci ; 104(10): 10727-10743, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34253357

ABSTRACT

Feeding yeast culture fermentation products has been associated with improved feed intake and milk yield in transition dairy cows. These improvements in performance have been further described in terms of rumen characteristics, metabolic profile, and immune response. The objective of this study was to evaluate the effects of a commercial yeast culture product (YC; Culture Classic HD, Phibro Animal Health) on performance, blood biomarkers, rumen fermentation, and rumen bacterial population in dairy cows from -30 to 50 d in milk (DIM). Forty Holstein dairy cows were enrolled in a randomized complete block design from -30 to 50 DIM and blocked according to expected calving day, parity, previous milk yield, and genetic merit. At -30 DIM, cows were assigned to either a basal diet plus 114 g/d of ground corn (control; n = 20) or a basal diet plus 100 g/d of ground corn and 14 g/d of YC (n = 20), fed as a top-dress. Cows received the same close-up diet from 30 d prepartum until calving [1.39 Mcal/kg of dry matter (DM) and 12.3% crude protein (CP)] and lactation diet from calving to 50 DIM (1.60 Mcal/kg of DM and 15.6% CP). Blood samples and rumen fluid were collected at various time points from -30 to 50 d relative to calving. Cows fed YC compared with control showed a trend for increased energy-corrected milk (+3.2 kg/d). Lower somatic cell counts were observed in YC cows than in control. We detected a treatment × time interaction in nonesterified fatty acids (NEFA) that could be attributed to a trend for greater NEFA in YC cows than control at 7 DIM, followed by lower NEFA in YC cows than control at 14 and 30 DIM. In the rumen, YC contributed to mild changes in rumen fermentation, mainly increasing postpartal valerate while decreasing prepartal isovalerate. This was accompanied by alterations in rumen microbiota, including a greater abundance of cellulolytic (Fibrobacter succinogenes) and lactate-utilizing bacteria (Megasphaera elsdenii). These results describe the potential benefits of supplementing yeast culture during the late pregnancy through early lactation, at least in terms of rumen environment and performance.


Subject(s)
Rumen , Saccharomyces cerevisiae , Animals , Biomarkers/metabolism , Cattle , Diet/veterinary , Dietary Supplements , Female , Fermentation , Fibrobacter , Lactation , Milk , Pregnancy , Rumen/metabolism
4.
J Anim Sci ; 93(6): 3055-65, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26115291

ABSTRACT

The objective of this study was to determine the impact of stocker production systems differing in growth rate on rumen fermentation characteristics and utilization of substrates for fatty acid synthesis in intramuscular (IM), subcutaneous (SC), and perirenal (PR) adipose tissues. Angus steers were assigned to 4 stocker cattle production systems in 2 consecutive years: 1) 1.0 kg/d of 40% CP cottonseed meal­based supplement while grazing dormant native range (CON), 2) ground corn/soybean meal­based supplement while grazing dormant native range fed at 1% of BW (CORN), 3) grazing wheat pasture at a high stocking rate to achieve a low rate of BW gain (LGWP), and 4) grazing wheat pasture at a low stocking rate for a high rate of BW gain (HGWP). Eight ruminally cannulated steers were used to determine rumen fermentation characteristics. Steers were harvested during the stocker phase at similar age (different carcass weight) in Exp. 1 (3 steers/treatment) or at similar carcass weight in Exp. 2 (4 steers/treatment). Adipose tissues were analyzed for mRNA expression of genes involved in glucose (solute carrier family 2, member 4 [GLUT4], glucose-6-phosphate dehydrogenase [G6PDH], phosphofructokinase, muscle [PFKM], and pyruvate kinase 2, muscle [PK2]), lactate (lactate dehydrogenase B [LDHB]), and acetate (acetyl-CoA synthetase, cytosol [ACSS2]) utilization for fatty acid synthesis. The acetate:propionate ratio was least (P < 0.05) for HGWP steers, intermediate for CORN and LGWP steers, and greatest for CON steers. At similar age, LGWP and HGWP steers tended (F-test; P < 0.15) to have greater (P < 0.10) G6PDH and ACSS2 mRNA expression than CON and CORN steers in SC and PR but not IM adipose tissue. Expression of PFKM and PK2 mRNA tended (F-test; P < 0.15) to be greater (P < 0.10) in HGWP than CON and LGWP steers in IM but not SC or PR adipose tissue. At similar HCW, expression of GLUT4 and G6PDH mRNA were greater (P < 0.10) in SC adipose tissue of LGWP and HGWP steers compared with CON and CORN steers but not in IM and PR adipose tissue. Expression of LDHB mRNA was lesser (P < 0.10) in SC adipose tissue but greater (P < 0.10) in PR adipose tissue of LGWP and HGWP steers compared with CON and CORN steers. These results indicate a shift toward glucose utilization in SC adipose tissue but a shift towards lactate utilization in PR adipose tissue. These results suggest that diet and changes in VFA profile can influence substrates utilized for fatty acid synthesis, but diet has a greater effect in SC than IM adipose tissue.


Subject(s)
Adipogenesis/genetics , Adipose Tissue/metabolism , Cattle/physiology , Fatty Acids/metabolism , Rumen/metabolism , Acetates/metabolism , Adipogenesis/physiology , Animal Feed/analysis , Animals , Edible Grain , Fermentation/physiology , Gene Expression Regulation/physiology , Glucose/metabolism , Herbivory , Housing, Animal , Lactic Acid/metabolism , Male , RNA, Messenger/metabolism , Weight Gain/physiology
5.
J Anim Sci ; 92(4): 1462-72, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24663156

ABSTRACT

The objective of this study was to determine the impact of stocker production systems differing in growth rate on differential adipogenic and lipogenic gene expression of intramuscular (IM), subcutaneous (SC), and perirenal (PR) adipose tissues. Angus steers were assigned to 4 stocker cattle production systems in 2 consecutive years: 1) cottonseed meal-based supplement while grazing dormant native range (CON), 2) ground corn/soybean meal-based supplement while grazing dormant native range (CORN), 3) grazing wheat pasture at a high stocking rate for a low rate of BW gain (LGWP), and 4) grazing wheat pasture at a low stocking rate for a high rate of BW gain (HGWP). Steers were harvested during the stocker phase at similar age (different carcass weight) in Exp. 1 (3 steers/treatment) or at similar carcass weight in Exp. 2 (4 steers/treatment). Adipose tissues were analyzed for mRNA expression of adipogenic (peroxisome proliferator activated receptor γ [PPARγ], sterol regulatory element binding factor 1 [SREBF1], CAATT/enhancer binding protein ß, and delta-like homolog 1) and lipogenic (glycerol-3-phosphate dehydrogenase [GPDH], fatty acid synthase [FASN], and diacylglycerol acyltransferase 2 [DGAT2]) genes. Multivariate analysis was used to evaluate the expression of adipogenic or lipogenic genes collectively. There was not a treatment × adipose tissue interaction (F-test, P > 0.15) when steers were harvested at similar age, but a treatment × adipose tissue interaction (F-test, P < 0.05) was evident when steers were harvested at similar carcass weight. At similar carcass weight, treatment had no effect (P > 0.10) on the canonical variate of adipogenic or lipogenic mRNA expression in IM adipose tissue, but faster rates of gain of LGWP and HGWP steers increased (P < 0.10) the canonical variate of adipogenic and lipogenic mRNA expression in SC and PR adipose tissue compared with CON and CORN steers. Strong positive correlations (P < 0.05) of PPARγ, SREBF1, GPDH, FASN, and DGAT2 mRNA expression with the canonical variate indicate that these genes strongly influenced differences between treatments and adipose tissues. These results suggest that contrary to our hypothesis rate of gain has little influence on differentiation and lipid synthesis of IM adipose tissue at similar carcass weight but faster rates of gain increase differentiation and lipid synthesis of SC and PR adipose tissue even at similar carcass weight.


Subject(s)
Adipose Tissue/metabolism , Cattle/physiology , Gene Expression Regulation/physiology , Muscle, Skeletal/metabolism , Weight Gain/physiology , Animals , Male
6.
Brain Res ; 1546: 1-8, 2014 Feb 10.
Article in English | MEDLINE | ID: mdl-24365206

ABSTRACT

The ability of melatonin treatment of aged animals to partially restore the pattern of gene expression characterizing the younger animal has been frequently reported. The current study examines the effect of melatonin upon age-related changes of some key proteins relevant to the aging process. Male B6C3F1 mice, aged 5.5 months and 23.4 months were used as a model for aging and half of each group received a diet supplemented with 40-ppm (w/w) melatonin for 9.3 weeks. Protein components of the globus pallidus were studied including glial fibrillary acidic protein (GFAP), NF-κB, protein disulfide isomerase (PDI), and Nissl staining. Some age-related changes were in an upward direction (GFAP and NF-κB), while others were depressed with age (PDI and intensity of Nissl staining). However, in either case, melatonin treatment of aged mice generally altered these parameters so that they came to more closely resemble the levels found in younger animals. The extent of this reversal to a more youthful profile, ranged from complete (for NF-κB) to very minor (for Nissl staining and PDI). Overall, these findings are in accord with prior data on the effect of melatonin on cortical gene expression and confirm the value of melatonin as a means of retarding events associated with senescence.


Subject(s)
Aging/drug effects , Dietary Supplements , Globus Pallidus/drug effects , Melatonin/pharmacology , Aging/metabolism , Animals , Glial Fibrillary Acidic Protein/metabolism , Globus Pallidus/cytology , Globus Pallidus/metabolism , Male , Melatonin/administration & dosage , Mice , NF-kappa B/metabolism , Protein Disulfide-Isomerases/metabolism
7.
J Anim Sci ; 91(9): 4322-35, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23851994

ABSTRACT

Two experiments were conducted to examine the effect of growth rate to similar age or BW on fat deposition in stocker cattle grazing dormant native range (DNR) or winter wheat pasture (WP). In each experiment, fall-weaned Angus steers were randomly allotted to 1 of 4 stocker production programs: 1) control, 1.02 kg/d of a 40% CP cottonseed meal-based supplement during grazing of DNR (CON); 2) corn/soybean meal-based supplement fed at 1% of BW during grazing of DNR (CORN); 3) grazing WP at a high stocking rate to achieve a low rate of BW gain (LGWP); and 4) grazing WP at a low stocking rate to achieve a high rate of BW gain (HGWP). In Exp. 1, a subset of steers (3 steers per treatment) was harvested after winter grazing (138 d) at similar age. The remaining WP steers were transitioned into the finishing phase, whereas DNR steers were allowed to graze the same native range pastures for another 115 d without supplementation before entering the feedyard. In Exp. 2, steers grazed their respective pastures until each treatment reached an estimated HCW of 200 kg (262, 180, 142, and 74 d, respectively, for the CON, CORN, LGWP, and HGWP treatments), at which time a subset of steers (4 steers per treatment) were selected for intermediate harvest before finishing. In both experiments, the remaining steers were fed a finishing diet to a common 12th-rib fat thickness of 1.27 cm. In Exp. 1, winter grazing ADG was 0.19, 0.52, 0.68, and 1.37 ± 0.03 kg/d; and in Exp. 2, winter/summer grazing ADG was 0.46, 0.61, 0.83, and 1.29 ± 0.02 kg/d, respectively for CON, CORN, LGWP, and HGWP treatments. At intermediate harvest in Exp. 1, HGWP steers had greater (P < 0.01) 12th-rib fat thickness and marbling scores, compared with the other treatments. However, in Exp. 2, LGWP steers had greater (P < 0.01) marbling scores compared with HGWP steers, which were greater than DNR steers. At final harvest in Exp. 1, LGWP steers had greater (P < 0.01) 12th-rib fat thickness and smaller LM area, compared with the other treatments; however, there were no differences (P = 0.99) in final marbling scores. In Exp. 2, CON steers had lower (P < 0.05) 12th-rib fat thickness and tended (P = 0.10) to have greater marbling scores, compared with the other treatments. These data suggest that changes in the partitioning of fat among depots during the stocker phase may not be reflected after finishing when steers are fed to a common 12th-rib fat thickness.


Subject(s)
Adiposity , Body Composition , Cattle/physiology , Meat/analysis , Weight Gain , Age Factors , Animal Feed/analysis , Animal Husbandry , Animal Nutritional Physiological Phenomena , Animals , Body Weight , Cattle/growth & development , Diet/veterinary , Dietary Supplements/analysis , Male , Random Allocation
8.
J Anim Sci ; 91(5): 2355-66, 2013 May.
Article in English | MEDLINE | ID: mdl-23463558

ABSTRACT

Two experiments were conducted to examine the effect of rate of BW gain during the stocker phase on visceral organ mass and body composition of growing-finishing cattle that had grazed dormant native range (DNR) or winter wheat pasture (WP). In each experiment, fall-weaned steers were allotted randomly to 1 of these stocker production programs: 1) control, 1.02 kg · steer(-1) · d(-1) of a 40% CP cottonseed meal-based supplement during grazing of DNR (CON); 2) corn/soybean meal-based supplement fed at 1% of BW during grazing of DNR (CORN); 3) grazing WP at a high stocking rate to achieve a reduced rate of BW gain (LGWP); and 4) grazing WP at a low stocking rate to achieve an increased rate of BW gain (HGWP). In Exp. 1, 3 steers per treatment were harvested after winter grazing (138 d). The remaining WP steers were transitioned into a finishing phase and DNR steers were allowed to graze the same pastures for another 115 d before entering a feedyard. In Exp. 2, steers grazed respective pastures until each treatment reached an estimated HCW of 200 kg (262, 180, 142, and 74 d, respectively, for CON, CORN, LGWP, and HGWP treatments), at which time 4 steers per treatment were randomly selected for intermediate harvest before finishing. At the end of the finishing period, 4 additional steers from each treatment were randomly selected for final carcass measurements. All steers were fed to a common 12th rib fat thickness of 1.27 cm. After winter grazing in Exp. 1, HGWP steers had the greatest (P < 0.01) mesenteric/omental fat, total viscera, total splanchnic tissue mass, and carcass and empty body fat, compared with the other treatments. In Exp. 2 at intermediate harvest, WP steers had greater (P < 0.03) mesenteric/omental fat, total viscera, and total splanchnic tissue mass, compared with CORN steers, with CON steers being intermediate. Also, the WP steers had greater (P < 0.02) carcass and empty body fat, compared with CORN steers, with CON steers being intermediate. At final harvest in Exp. 2, LGWP steers had the least total viscera and total splanchnic tissue mass, compared with the other treatments. However, there were no differences (P > 0.53) among treatments for carcass or empty body fat. Stocker systems using WP or DNR result in cattle with differences in body fat and visceral organ mass before finishing; this may influence feedlot efficiency, even though there were no differences in body fat and visceral organ mass at the end of the finishing period.


Subject(s)
Body Composition , Cattle/growth & development , Diet/veterinary , Weight Gain , Animal Husbandry , Animals , Body Weight , Male , Organ Size , Random Allocation
9.
J Anim Sci ; 91(5): 2264-77, 2013 May.
Article in English | MEDLINE | ID: mdl-23463572

ABSTRACT

Fifty-five normal-weaned Angus steers (268 ± 22 kg; 265 ± 16 d of age) were used to evaluate the effects of starch- vs. fiber-based energy supplements for stocker cattle grazing low-quality dormant native range on growth performance, body composition, and adipose tissue development of different fat depots. Steers were randomly allotted to 4 treatments: 1.02 kg·steer(-1)·d(-1) of a 40% CP cottonseed meal-based supplement (CON), corn/soybean meal-based supplement fed at 1% of BW (CORN), soybean hull/soybean meal-based supplement fed at 1% of BW (SBH), or dried distillers grains with solubles fed at 1% of BW (DDGS). All supplements were individually fed 5 d/wk during the 121-d winter grazing phase. After winter grazing, 3 steers per treatment were harvested to determine body composition and carcass characteristics, and collect subcutaneous (SC) and perirenal (PR) adipose tissue samples. The remaining steers grazed cool-season grass pastures for 74 d without supplementation before finishing. Steers were fed a common finishing diet for 113 d before harvest, at which time carcass characteristics were collected at a commercial abattoir. Energy supplementation increased (P < 0.01) winter grazing ADG compared with CON steers, and CORN steers had greater (P < 0.01) ADG than SBH and DDGS steers. Energy supplementation increased (P < 0.04) mesenteric/omental fat mass but did not influence (P > 0.13) 12th rib fat thickness or marbling score at intermediate harvest compared with CON steers. The mRNA expression of genes involved in lipogenesis and markers of adipogenesis were greater (P < 0.05) in PR adipose tissue of energy-supplemented steers compared with CON steers but not in SC adipose tissue. Fiber-supplemented steers had greater (P < 0.01) mRNA expression of fatty acid synthase and fatty acid binding protein 4 compared with CORN steers in PR adipose tissue but not SC adipose tissue. At final harvest, energy-supplemented steers had greater (P < 0.05) KPH and yield grade than CON steers, but no differences (P = 0.75) in marbling score were observed. Neither energy supplementation nor type of energy supplement influenced intramuscular fat deposition in stocker cattle grazing dormant native range. These data suggest that the total energy intake and stage of animal maturity during grazing supplementation were not great enough to influence marbling deposition.


Subject(s)
Adipose Tissue/metabolism , Animal Feed/analysis , Body Composition , Cattle/physiology , Dietary Carbohydrates/metabolism , Energy Intake , Gene Expression Regulation , Animals , Cattle/genetics , Cattle/growth & development , Diet/veterinary , Dietary Carbohydrates/administration & dosage , Dietary Fiber/administration & dosage , Dietary Fiber/metabolism , Dietary Supplements/analysis , Male , Polymerase Chain Reaction/veterinary , Starch/administration & dosage , Starch/metabolism
10.
J Neuroimmunol ; 182(1-2): 22-31, 2007 Jan.
Article in English | MEDLINE | ID: mdl-17070935

ABSTRACT

Melatonin modulates the expression of a number of genes related to inflammation and immunity. Declining levels of melatonin with age may thus relate to some of the changes in immune function that occur with age. mRNA expression levels in murine CNS were measured using oligonucleotide microarrays in order to determine whether a dietary melatonin supplement may modify age-related changes in the response to an inflammatory challenge. CB6F1 male mice were fed 40-ppm melatonin for 9 weeks prior to sacrifice at 26.5 months of age, and compared with age-matched untreated controls and 4.5-month-old controls. A subset of both young and old animals was injected i.p. with lipopolysaccharide (LPS). After 3 h, total RNA was extracted from whole brain (excluding brain stem and cerebellum), and individual samples were hybridized to Affymetrix Mouse 430-2.0 arrays. Data were analyzed in Dchip and GeneSpring. Melatonin treatment markedly altered the response in gene expression of older animals subjected to an LPS challenge. These changes in general, caused the response to more closely resemble that of young animals subjected to the same LPS challenge. Thus melatonin treatment effects a major shift in the response of the CNS to an inflammatory challenge, causing a transition to a more youthful mRNA expression profile.


Subject(s)
Aging/physiology , Brain/drug effects , Lipopolysaccharides/pharmacology , Melatonin/pharmacology , Aging/metabolism , Animals , Dietary Supplements , Drug Synergism , Gene Expression/drug effects , Injections, Intraperitoneal , Male , Melatonin/administration & dosage , Mice , Mice, Inbred Strains , Microarray Analysis , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism
11.
Diabetes ; 53(11): 2804-14, 2004 Nov.
Article in English | MEDLINE | ID: mdl-15504960

ABSTRACT

Clinical studies indicate that significant loss of functional islet mass occurs in the peritransplant period. Islets are injured as a result of detrimental effects of brain death, pancreas preservation, islet isolation, hypoxia, hyperglycemia, and immune-mediated events. In addition, recent studies demonstrated that islets are injured as a result of their exposure to blood and of activation of intrahepatic endothelial and Kupffer cells, resulting in inflammation and thrombosis. Activated protein C (APC) is an anticoagulant enzyme that also exerts anti-inflammatory and antiapoptotic activities by acting directly on cells. Here, we report that exogenous administration of recombinant murine APC (mAPC) significantly reduced loss of functional islet mass after intraportal transplantation in diabetic mice. Animals given mAPC exhibited better glucose control, higher glucose disposal rates, and higher arginine-stimulated acute insulin release. These effects were associated with reduced plasma proinsulin, intrahepatic fibrin deposition, and islet apoptosis early after the transplant. In vitro and in vivo data demonstrated that mAPC treatment was associated with a significant reduction of proinflammatory cytokine release after exposure of hepatic endothelial cells to islets. mAPC treatment also prevented endothelial cell activation and dysfunction elicited by intrahepatic embolization of isolated islets inherent to pancreatic islet transplantation (PIT). This study demonstrates multiple remarkable beneficial effects of mAPC for PIT and suggests that APC therapy may enhance the therapeutic efficacy of PIT in diabetic patients.


Subject(s)
Islets of Langerhans Transplantation/physiology , Islets of Langerhans/drug effects , Protein C/pharmacology , Animals , Arginine/pharmacology , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/surgery , Enzyme Activation , Insulin/metabolism , Insulin Secretion , Islets of Langerhans/anatomy & histology , Mice , Mice, Inbred C57BL , Recombinant Proteins/pharmacology , Transplantation, Isogeneic/physiology
12.
Ann N Y Acad Sci ; 1035: 197-215, 2004 Dec.
Article in English | MEDLINE | ID: mdl-15681809

ABSTRACT

Slowing the functional decline in the aging brain is not only relevant to nonpathological senescence but also to a broad range of neurodegenerative diseases. Although disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are not found in the young adult, they gradually manifest with increasing age. AD, in particular, is an increasing major public health concern as the population ages; therapies that delay disease onset will markedly reduce overall disease prevalence. Aging of the brain has been repeatedly associated with cumulative oxidative damage to macromolecules and to abnormal levels of inflammatory activity. Melatonin has attained increasing prominence as a candidate for ameliorating these changes occurring during senescence. Recent research has focused on supplementation with dietary melatonin designed to elucidate the specific key intracellular targets of age-related inflammatory events, and the optimal means of affording protection of these targets. This report summarizes the progress made in this area.


Subject(s)
Aging/drug effects , Brain/drug effects , Melatonin/administration & dosage , Neurodegenerative Diseases/drug therapy , Aging/physiology , Animals , Brain/physiopathology , Cytokines/metabolism , Gene Expression Regulation/drug effects , Gene Expression Regulation/physiology , Humans , Inflammation/drug therapy , Inflammation/etiology , Neurodegenerative Diseases/complications , Oxidative Stress/drug effects
13.
J Gerontol A Biol Sci Med Sci ; 56(12): B520-3, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11723144

ABSTRACT

Senescence is a complex and multifactorial process that may predispose organisms to altered responses to environmental stressors. The cytokine interleukin-6 (IL-6) is expressed by a variety of cells and is one of the earliest mediators of the acute inflammatory response. In this study, the level of IL-6 mRNA in younger (7 months) and old (23 months) mice was determined in the tissue of several organs with or without stimulation with lipopolysaccharide (LPS). Whereas younger animals had a basal expression of IL-6 mRNA in all organs, this was undetectable in the old animals. In contrast, when the mice were injected with LPS, in a majority of the organ tissues there was a robust stimulation of IL-6 mRNA in the old mice whereas the younger animals had a more variable response. These data indicate that the aging process may predispose animals to an exaggerated and potentially harmful inflammatory response.


Subject(s)
Aging/metabolism , Interleukin-6/genetics , Lipopolysaccharides/pharmacology , RNA, Messenger/metabolism , Animals , Male , Mice , Mice, Inbred Strains , Tissue Distribution
14.
Neurobiol Aging ; 22(4): 629-34, 2001.
Article in English | MEDLINE | ID: mdl-11445263

ABSTRACT

Aging is a pleiotropic process involving genetic and environmental factors. Recently it has been demonstrated that dietary constituents may affect senescence. In the present study, adult (3 month-old) mice were fed diets supplemented with ubiquinone (coenzyme Q(10)), alpha-lipoic acid, melatonin or alpha-tocopherol for a six-month period to determine if antioxidants may reverse or inhibit the progression of certain age-associated changes in cerebral mitochondrial electron transport chain (ETS) enzyme activities. The control consisted of a group of mice maintained on a basal diet for the same period. The activity of cytochrome c oxidase (Complex IV) increased with age but melatonin supplementation restored the activity to levels of 3 month-old animals. The activity of succinate dehydrogenase (Complex II) showed no age-related changes. However, this enzyme complex was elevated, in animals supplemented with coenzyme Q(10), alpha-lipoic acid and alpha-tocopherol, above corresponding values obtained with basal diet. NADH-ubiquinone oxidoreductase (Complex I) and ubiquinol:ferricytochrome-c oxidoreductase (Complex III) activities remained unchanged.


Subject(s)
Aging/metabolism , Antioxidants/pharmacology , Cerebral Cortex/metabolism , Electron Transport/physiology , Melatonin/pharmacology , Animals , Electron Transport Complex I , Electron Transport Complex II , Electron Transport Complex III/metabolism , Electron Transport Complex IV/metabolism , Male , Mice , Mice, Inbred C3H , Mice, Inbred C57BL , Mitochondria/drug effects , Mitochondria/enzymology , Multienzyme Complexes/metabolism , NADH, NADPH Oxidoreductases/metabolism , Oxidoreductases/metabolism , Succinate Dehydrogenase/metabolism , Thioctic Acid/pharmacology , Ubiquinone/pharmacology , Vitamin E/pharmacology
15.
Aust Health Rev ; 11(4): 277-83, 1988.
Article in English | MEDLINE | ID: mdl-10293100

ABSTRACT

This review of Australian and international research on the effects of shift work on nurses reveals that there is neither a wide nor a growing body of information on shift work in nursing. Shift work in nursing has been the subject of only three substantial studies overseas, and none in Australia. Although research indicates that there are negative physiological, psychological and social consequences associated with shift work, it is not possible at the current time to favour any single shift or roster system, particularly in nursing where empirical research is wanting.


Subject(s)
Nursing Staff, Hospital/psychology , Personnel Management/standards , Personnel Staffing and Scheduling/standards , Work Schedule Tolerance , Work , Australia , Evaluation Studies as Topic
17.
Anaesthesia ; 36(10): 970-4, 1981 Oct.
Article in English | MEDLINE | ID: mdl-7304888

ABSTRACT

The Sheffield Regional Hospital Board, which became the Trent Regional Health Authority in 1974, initiated a scheme for training of Senior House Officers in anaesthesia in 1962; between 1962 and 1972, 73 graduates passed through the scheme of whom 29 (40%)* held consultant posts at the time of the review (mid 1979), another 8 (11%)* were senior registrars and on the way to consultant status. None of the 16 overseas graduates had achieved consultant status although one was a senior registrar. Twenty-six (35-6%)* of the 73 doctors (15(20-5%)* United Kingdom or Republic of Ireland graduates and 11 (15-1%)* from overseas) are thought to have left the practice of anaesthesia although some of these were not traced and may indeed be practising, and some of the females have indicated an intention to return to the specialty when their children are older.


Subject(s)
Anesthesiology , Anesthesiology/education , Consultants , Education, Medical, Graduate , Female , Foreign Medical Graduates , Humans , Ireland , Male , United Kingdom , Workforce
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