In vitro addition of epinephrine, norepinephrine, and carnitine alters palmitate oxidation and esterification in isolated ovine hepatocytes.

Hepatocytes from 4 wethers were used to study the effects of carnitine and increasing concentrations of epinephrine and norepinephrine on palmitate oxidation and esterification. Liver cells were isolated from the wethers and incubated in Krebs-Ringer bicarbonate buffer with 1 mM [14C]-palmitate. Radiolabel incorporation was measured in CO2, acid-soluble products, and esterified products, including triglyceride, diglyceride, and cholesterol esters. Carnitine increased production of CO2 and acid-soluble products from palmitate by 41% and 216%, respectively, but had no effect on conversion of palmitate to esterified products. Epinephrine had a quadratic-increasing effect on palmitate oxidation to CO2, but norepinephrine did not increase palmitate oxidation to CO2. Neither epinephrine nor norepinephrine affected the production of acid-soluble products from palmitate. Increasing concentrations of norepinephrine and epinephrine linearly increased rates of triglyceride formation from palmitate. Increasing norepinephrine concentrations linearly increased diglyceride and cholesterol ester formation from palmitate in the presence of carnitine; epinephrine did not affect diglyceride or cholesterol ester formation. In general, catecholamine treatment had the greatest effect on the formation of esterified products from palmitate, and effects of norepinephrine were more pronounced than epinephrine. Conditions that result in catecholamine release might lead to fat accumulation in the liver.

Effects of in vivo phlorizin treatment and in vitro addition of carnitine, propionate, acetate, and 5-tetradecyloxy-2-furoic acid on palmitate metabolism in ovine hepatocytes.

Modulatory effects of l-carnitine, acetate, propionate, and 5-tetradecyloxy-2-furoic acid (TOFA; an inhibitor of acetyl-CoA carboxylase) on oxidation and esterification of [1-14C]-palmitate were studied in hepatocytes isolated from phlorizin-treated and control wethers. Our hypotheses were that (1) palmitate oxidation would be greater in hepatocytes from sheep injected with phlorizin; (2) l-carnitine would increase palmitate oxidation more in hepatocytes from sheep injected with phlorizin; and (3) acetate and propionate would decrease oxidation in sheep hepatocytes partly through action of acetyl-CoA carboxylase. Palmitate metabolism did not differ between cells from control and those from phlorizin-treated wethers. Carnitine increased oxidation of palmitate to CO2 and acid-soluble products (ASP; mainly ketone bodies) and decreased esterification of palmitate in isolated hepatocytes from both groups of wethers, but the increase in oxidation to ASP was greater in cells from phlorizin-treated wethers. Propionate increased palmitate oxidation to CO2 in phlorizin-treated wethers. Propionate increased oxidation of palmitate to ASP in control wethers but decreased oxidation to ASP in phlorizin-treated wethers. Propionate increased esterification of palmitate to total esterified products and triglyceride, and the effect was larger in phlorizin-treated wethers. Acetate decreased palmitate esterification to total esterified products in control wethers, but the effect was blunted in phlorizin-treated wethers. Acetate did not affect palmitate oxidation. Addition of TOFA increased production of triglyceride from palmitate in the presence of propionate. The lack of interaction between TOFA and propionate indicates that propionate does not inhibit carnitine palmitoyltransferase I via cytosolic generation of methylmalonyl-CoA by acetyl-CoA carboxylase. In conclusion, although in vivo phlorizin treatment did not affect in vitro metabolism of palmitate by isolated ovine hepatocytes, phlorizin increased the stimulatory effect of carnitine on oxidation of palmitate to ASP and the inhibitory effect of propionate on oxidation of palmitate to ASP. Metabolism of acetate and propionate by acetyl-CoA carboxylase did not affect palmitate oxidation or esterification. Results provide additional insight into control of fatty acid metabolism in hepatocytes.

First Evidence for cos2ß>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity.

We present first evidence that the cosine of the CP-violating weak phase 2ß is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2ß=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2ß=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle ß of the CKM Unitarity Triangle is ß=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2ß>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-ß=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.

Thyroid Hürthle cell tumors: research of potential markers of malignancy.

INTRODUCTION: Hurthle cell tumors (HCTs) are rare thyroid neoplasia. To date, capsular and/or vascular invasion are the only findings predicting malignancy. Recently, mutation of 19p13, encoding two proteins involved in cell proliferation and apoptosis (GRIM-19 and p19), has been described. The aim of our study is to evaluate the cellular proliferation index (Ki67), GRIM-19 and p19 expression as diagnostic markers of malignancy in HCT. MATERIALS AND METHODS: Eighty patients with HCT (32 carcinomas, 48 adenomas) whom underwent surgery in our center were included. Samples of both neoplastic lesions and adjacent normal thyroid tissue were analyzed by means of tissue micro-arrays. Correlations between expressions of Ki67, GRIM-19 and p19 and final histology were analyzed. RESULTS: Mean size of the lesion was higher in carcinomas than in adenomas (p = 0.01). GRIM-19 and p19 were significantly underexpressed in Hurthle cells tumors compared to normal tissue (p = 0.0004 and p = 0.0001, respectively). Ki67 and GRIM-19 were, respectively, higher and down-expressed in carcinomas compared to adenomas (p = 0.0004 and p = 0.005, respectively). On multivariate analysis, size correlates with carcinoma diagnosis. Neither GRIM-19 nor Ki67 index was related to size. The expression of p19 was reduced in both adenoma and carcinoma but differences were not statistically significant (p = 0.13). CONCLUSIONS: Our study suggest that Ki67 and GRIM-19 correlate with malignancy in HCT. The expression of p19 is down-regulated in HCT, but it is not diagnostic of carcinoma. Ki67 and GRIM-19 may potentially help as cytological markers of malignancy in HCT.

First Observation of CP Violation in B[over ¯]

We report a measurement of the time-dependent CP asymmetry of B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays, where the light neutral hadron h^{0} is a π^{0}, η, or ω meson, and the neutral D meson is reconstructed in the CP eigenstates K^{+}K^{-}, K_{S}^{0}π^{0}, or K_{S}^{0}ω. The measurement is performed combining the final data samples collected at the ϒ(4S) resonance by the BABAR and Belle experiments at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6} BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6} BB[over ¯] pairs recorded by the Belle detector. We measure the CP asymmetry parameters -η_{f}S=+0.66±0.10(stat)±0.06(syst) and C=-0.02±0.07(stat)±0.03(syst). These results correspond to the first observation of CP violation in B[over ¯]^{0}→D_{CP}^{(*)}h^{0} decays. The hypothesis of no mixing-induced CP violation is excluded in these decays at the level of 5.4 standard deviations.

Response of growing pigs to the inclusion of hybrid rye in low or high-energy diets.

Previous research has shown reduced feed intake and growth rate in pigs fed diets with hybrid rye replacing wheat. A reduction in growth rate caused by reduced feed intake will conceivably be counteracted by increasing the dietary energy level. Our objective, therefore, was to determine the effects of 40% hybrid rye inclusion replacing wheat in diets formulated to be either low or high net energy (NE) on growth, feed intake, energy digestibility, and lesion scores in growing-finishing pigs. We hypothesized that pigs fed 40% hybrid rye would perform better on the high than the low energy diets. A total of 160 pigs (body weight [BW] 70.1 kg) housed in 32 pens, 5 pigs per pen, were fed diets with 0% or 40% hybrid rye (var. 'KWS Bono'; KWS LOCHOW GMBH), either with low (2,350) or high (2,450) kcal NE per kg of diet over two growth phases (phase 1; 70 to 85 kg BW; phase 2; 85 to 130 kg BW). The BW, and feed disappearance were measured on days 0, 8, 17, 28, 42, and 50. Fecal samples obtained in phase 2 (~100 kg BW) were used to calculate apparent total tract digestibility (ATTD) of gross energy (GE). Lesion scores were measured weekly. The ATTD of GE was unaffected by rye inclusion and was reduced in low vs. high NE diets. Overall, (days 0 to 50), pigs fed the low-energy rye diet gained 0.08 kg/d less (P < 0.01) than those fed the high-energy rye diet or the low-energy diet without rye, which was caused by a reduced weight gain during the initial 17 d of the trial. Final BW and overall feed intake were not affected by rye inclusion or NE level. The NE intake was greater (P < 0.05) and feed efficiency (G:F) was reduced (P < 0.05) in pigs fed rye diets compared to those fed diets without rye, whereas there was no effect of NE level on NE intake or G:F. There was no effect of rye inclusion or NE level on lesion scores. In conclusion, pigs can be fed diets including 40% hybrid rye with only minor changes in growth performance. Increasing the NE level of the first phase diet in the grower-finisher barn may be useful to avoid a reduction in growth performance when feeding hybrid rye.

Increasing omega-3 levels through dietary co-extruded flaxseed supplementation negatively affects pork palatability.

To clarify the impact of feeding co-extruded flaxseed on carcass quality and pork palatability, 96 pigs (48 barrows and 48 gilts) were fed three different levels of flaxseed (0%, 5% and 10% of dietary intake) for 76days. Carcass quality and meat quality characteristics of pure loin muscle and ground pork (20% fat) were evaluated. Fat hardness and belly firmness decreased (P<0.001) with increasing co-extruded flaxseed. Pigs fed co-extruded flaxseed levels had higher lean yield (P=0.045) and total lean content (P=0.034). Loin from barrows had higher fat content compared to gilts (P<0.001). Co-extruded flaxseed supplementation increased (P<0.001) omega-3 content in loin and ground pork. Pork flavour intensity and off-flavour intensity scores lowered (P<0.001) with increasing levels of co-extruded flaxseed, being more accentuated (P=0.023) in reheated pork chops from barrows. Diet affected all texture and flavour sensory characteristics (P<0.05) as tissue levels of omega-3 fatty acids increased, likely as a result of increased lipid oxidation.

Greenhouse gases and performance of growing pigs fed wheat-based diets containing wheat millrun and a multi-carbohydrase enzyme.

The objective of this project was to determine the impact of feeding growing pigs with high wheat millrun diets supplemented with a multi-carbohydrase enzyme (amylase, cellulase, glucanase, xylanase, and invertase activities) on nutrient digestibility, growth performance, and greenhouse gas (GHG) output (carbon dioxide, CO2; nitrous oxide, N2O; methane, CH4). Three experiments were conducted utilizing six treatments arranged as a 3 × 2 factorial (0%, 15%, or 30% wheat millrun; with or without enzyme) for the digestibility experiment or as a 2 × 2 factorial (0% or 30% wheat millrun; with or without enzyme) for the performance and GHG experiments. The digestibility, performance, and GHG experiments utilized 48 individually housed pigs, 180 pigs housed 5 per pen, or 96 pigs housed 6 per chamber, respectively. Increasing wheat millrun up to 30% in the diet of growing pigs resulted in decreased energy, nitrogen (N) and phosphorus (P) apparent total tract digestibility and net energy content (P < 0.01). Overall, average daily gain (ADG) and gain to feed ratio were reduced in pigs fed wheat millrun (P < 0.05). Enzyme supplementation had minimal effects on the digestibility or performance parameters measured. Feeding diets with 30% millrun did not affect GHG output (CH4: 4.7 and 4.9; N2O: 0.45 and 0.42; CO2: 1,610 and 1,711 mg/s without or with millrun inclusion, respectively; P > 0.78). Enzyme supplementation had no effect on GHG emissions (CH4: 4.5 and 5.1; N2O: 0.46 and 0.42; CO2: 1,808 and 1,513 mg/s without or with enzymes, respectively; P > 0.51). Overall, the carbohydrase enzyme had minimal effects on parameters measured, regardless of wheat millrun inclusion (P > 0.10). Although energy, N and P digestibility, and ADG were reduced, the inclusion of up to 30% wheat millrun in the diet has no effect on GHG emissions from growing pigs (P > 0.10).

Human neutrophils produce high levels of the interleukin 1 receptor antagonist in response to granulocyte/macrophage colony-stimulating factor and tumor necrosis factor alpha.

Neutrophils, an abundant cell type at sites of inflammation, have the ability to produce a number of cytokines, including interleukin 1 (IL-1), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor alpha (TNF-alpha). In this study, we have examined the ability of human neutrophils to produce the IL-1 receptor antagonist (IL-1Ra), a 17-23-kD protein recently isolated and cloned from macrophages. Since IL-1Ra has been shown to inhibit both the in vitro and in vivo effects of IL-1, its production by large numbers of tissue-invading neutrophils might provide a mechanism by which the effects of IL-1 are regulated in inflammation. Using antibodies that are specific for IL-1Ra and a cDNA probe encoding for this protein, we were able to show that neutrophils constitutively produce IL-1Ra. However, after activation by GM-CSF and TNF-alpha, IL-1Ra was secreted into the extracellular milieu where it constituted the major de novo synthesized product of activated neutrophils. None of a large array of other potent neutrophil agonists were found to affect the production of IL-1Ra by neutrophils. Quantitative measurements by enzyme-linked immunosorbent assay revealed that intracellular IL-1Ra is in eightfold excess of the amount secreted in supernatants when studying nonactivated neutrophils. However, in GM-CSF- and TNF-alpha-activated cells, this difference was reduced to values between four- and fivefold, as virtually all of the de novo synthesized IL-1Ra was secreted. In activated cells, the intracellular content of IL-1Ra was found to be in the 2-2.5-ng/ml range per 10(6) neutrophils, whereas levels reached the 0.5-ng/ml range in supernatants. This would imply that IL-1Ra is produced in excess of IL-1 by a factor of at least 100, an observation that is in agreement with the reported amounts of IL-1Ra needed to inhibit the proinflammatory effects of IL-1. Neutrophils isolated from an inflammatory milieu, the synovial fluid of patients with rheumatoid arthritis, were found to respond to GM-CSF and TNF-alpha in terms of IL-1Ra synthesis, indicating that the in vitro observations made in this study are likely to occur in an inflammatory setting in vivo.

Protective effects of licofelone, a 5-lipoxygenase and cyclo-oxygenase inhibitor, versus naproxen on cartilage loss in knee osteoarthritis: a first multicentre clinical trial using quantitative MRI.

OBJECTIVE: In a multicentre study to explore the effects of licofelone as a disease-modifying osteoarthritis drug in comparison with naproxen in patients with knee osteoarthritis (OA), using MRI and x-ray examination. METHODS: Patients with knee OA (n = 355) were randomised to receive either licofelone (200 mg twice a day) or naproxen (500 mg twice a day). MRI and x-ray examinations were performed at baseline, 6 months (MRI only), 12 and 24 months. MRI was used to assess quantitatively changes in cartilage volume, and x-ray examinations (Lyon-Schuss) to measure changes in the mean and minimum joint space width (JSW) in the medial compartment. Questionnaires probing symptoms were completed. Data were presented as intention to treat (ITT) and according to protocol (ATP). RESULTS: Cartilage volume loss in the global joint and medial and lateral compartments was significantly less in the licofelone than in the naproxen group for ITT at 12 and 24 months and for ATP at all times except in the medial compartment. Patients with medial meniscal extrusion had a greater loss of cartilage volume. In these patients, licofelone markedly reduced the cartilage loss for both ITT and ATP at 12 and 24 months. Although licofelone showed less reduction in the JSW than naproxen, this did not reach significance. All clinical variables were improved at 24 months (p<0.001) for both groups, with a good safety profile. CONCLUSION: Licofelone and naproxen were equally effective in reducing OA symptoms; however, licofelone significantly reduced cartilage volume loss over time, thus having a protective effect in patients with knee OA. This study proves the superiority of quantitative MRI over x-ray examinations in a multicentre clinical trial.

Effects of bedding material and running wheel surface on paw wounds in male and female Syrian hamsters.

The present study investigated the effects of bedding material (pine shavings versus beta chip) and running wheel surfaces (standard metal bars versus metal bars covered with a plastic mesh) on the occurrence of wounds on the paws of male and female Syrian (golden) hamsters, Mesocricetus auratus. Four groups of 10 males and 10 females were each assigned to one of the following treatments: pine/no mesh, pine/mesh, chips/no mesh and chips/mesh. Each hamster paw was observed at 1-3-day intervals for 60 days. A total of 1-3 wounds, separate in time, developed on the paws (mostly the hind ones) of almost all animals. Wounds appeared as small pinpricks, cuts or scabs, mostly on the palms. Females ran 15% less than males, yet their front paws were more commonly affected and their wounds tended to last longer. Hamsters with plastic mesh inside their wheels took longer to develop wounds but once they appeared, the wounds were larger and lasted longer. Hamsters on pine shavings developed fewer wounds and had more wound-free days. Hamsters kept running at high levels and many wounds did not heal during the study, suggesting a need for veterinary intervention.

Effects of supplementing processed straw during late gestation on sow physiology, lactation feed intake, and offspring body weight and carcass quality1.

This study investigated the effects of supplementing late gestation sow diets with processed or unprocessed oat or wheat straw on physiology, early lactation feed intake, and offspring performance. One hundred fifty gestating sows were randomly assigned to 1 of 5 dietary treatments (30 sows per diet) from day 86 of gestation until farrowing. Treatments, arranged as a 2 × 2 factorial plus a control, were a standard gestation diet (control) or control supplemented with 10% wheat or oat straw, processed or unprocessed. Sows were fed a standard lactation diet postfarrowing. The processed straws were produced by high-pressure compaction at 80 °C. On day 101 of gestation (day 15 of the trial), blood samples were collected from a subset of sows (n = 8 per treatment) through ear vein catheters and analyzed for insulin, insulin-like growth factor 1 (IGF-1), prolactin, glucose, and urea concentrations. Fecal samples were collected on days 103 to 104 of gestation to determine nutrient digestibility, and feeding motivation was investigated on day 104. Litter characteristics and sow feed intake were recorded for 7 d postfarrowing. Three piglets per litter were selected at weaning, fed standard diets, and followed to market. Treatment had no effect on feeding motivation, piglet characteristics at birth, estimated milk production, and offspring BW at market or carcass quality. Processed straw improved DM digestibility and energy content and the effect was greater with oat straw (straw × processing effect, P < 0.05). Pre- and postprandial glucose concentrations tended to decrease (P < 0.10) with processing of wheat, but not oat straw, and this effect was more apparent in the preprandial samples. Preprandial prolactin concentration increased with oat but decreased with wheat straw, whereas postprandial IGF-1 and prolactin concentration increased with processing of wheat, but not oat straw (straw × processing, P < 0.05). Sow lactation feed intake improved (P < 0.05) with oat straw supplementation relative to wheat straw. Piglet weaning weight increased (P < 0.05) with oat straw supplementation and processing improved (P < 0.05) nursery exit BW. However, straw supplementation, regardless of processing, had no effect on offspring BW at market or carcass quality. Overall, oat straw supplementation had a greater impact on sow physiology and provided benefits for sows in late gestation, and there was some indication that further benefits could be obtained through mild processing.

Long-term efficacy and safety of lumiracoxib 100 mg: an open-label extension of a 13-week randomized controlled trial in patients with primary osteoarthritis of the knee.

OBJECTIVE: Osteoarthritis (OA) is a chronic condition, accompanied by inflammation and pain, and it is therefore important to demonstrate long-term efficacy and safety of treatment. Here we present data from a 39-week open-label extension to a 13-week randomized, double-blind, double-dummy, parallel-group core study. The objective was to assess the long-term safety and tolerability of lumiracoxib 100 mg once daily (od). METHODS: Patients had originally received lumiracoxib 100 mg od, celecoxib 200 mg od or placebo in the core study. In the extension period, all patients received lumiracoxib 100 mg od. Efficacy variables, overall OA pain intensity (0-100 mm visual analogue scale [VAS]), patient's global assessment of disease activity and physician's global assessment of disease activity (0-100 mm VAS), were assessed at weeks 17, 26, 39 and 52. General safety and tolerability were evaluated by adverse event (AE) reporting and physical examinations and laboratory tests at each visit. RESULTS: Of the 1182 patients completing the core study, 834 patients entered the extension study. Improvements in the three efficacy variables after 3 months were maintained for up to 1 year with lumiracoxib treatment. Lumiracoxib was well tolerated, with most AEs being of mild-to-moderate severity and of the type expected for this patient population and duration of exposure. CONCLUSION: In conclusion, these data suggest that lumiracoxib 100 mg od was effective and well tolerated when treating OA pain of the knee for periods of up to 1 year, making it a useful option for the long-term treatment of OA pain.

Once-daily, controlled-release tramadol and sustained-release diclofenac relieve chronic pain due to osteoarthritis: a randomized controlled trial.

OBJECTIVE: The present study was a randomized, parallel, double-blind comparison between controlled-release (CR) tramadol and sustained-release (SR) diclofenac in patients with chronic pain due to osteoarthritis of the hips and/or knees. METHODS: Patients with at least moderate pain intensity, and having received analgesics over the past three months, underwent a two- to seven-day washout of current analgesics before initiation of 200 mg CR tramadol or 75 mg SR diclofenac. During the eight-week study, patients returned to the clinic biweekly. CR tramadol doses were titrated to a maximum of 200 mg, 300 mg or 400 mg per day. SR diclofenac doses were titrated to 75 mg or 100 mg once daily, or 75 mg twice a day based on pain relief and the presence of side effects. For rescue analgesic, patients took acetaminophen as needed, up to 650 mg three times a day. RESULTS: Forty-five patients on CR tramadol and 52 patients on SR diclofenac were evaluable. Significant improvements from prestudy treatment were shown for visual analogue scale pain (P=0.0001), stiffness (P<0.0005) and physical function (P=0.0001) scores for both treatments. There were no significant differences between the two treatments in the Western Ontario and McMaster Universities subscales, overall pain, pain and sleep, or the clinical effectiveness evaluation. Overall incidence of adverse events was similar in both groups, with more opioid-related adverse events with CR tramadol, and two serious adverse events occurring with the use of SR diclofenac. CONCLUSIONS: CR tramadol is as effective as SR diclofenac in the treatment of pain due to knee or hip osteoarthritis, with the potential for fewer of the serious side effects that characterize nonsteroidal anti-inflammatory drug administration.

A randomized, double-blind, crossover comparison of the efficacy and safety of oral controlled-release tramadol and placebo in patients with painful osteoarthritis.

OBJECTIVE: To compare the efficacy and safety of controlled-release (CR) tramadol (Zytram XL, Purdue Pharma, Canada) and placebo in patients with painful osteoarthritis. METHODS: Patients underwent analgesic washout for two to seven days before random assignment to 150 mg daily of CR tramadol or placebo, and were titrated weekly to 200 mg, 300 mg or a maximum of 400 mg once daily. After four weeks, patients crossed over to the alternate treatment for another four weeks. Plain acetaminophen was provided as a rescue analgesic. All patients who completed the crossover study were eligible to receive open label CR tramadol for six months. RESULTS: Seventy-seven of 100 randomly assigned patients were evaluable for efficacy. CR tramadol resulted in significantly lower visual analogue scale pain intensity scores (37.4+/-23.9 versus 45.1+/-24.3, P=0.0009). Western Ontario and McMaster Universities osteoarthritis index subscale scores for pain (189.0+/-105.0 versus 230.0+/-115.4; P=0.0001) and physical function (632.4+/-361.3 versus 727.4+/-383.4; P=0.0205) were significantly better with CR tramadol. Total pain and disability (22.8+/-14.5 versus 27.2+/-14.8; P=0.0004), and overall pain and sleep (104.7+/-98.0 versus 141.0+/-108.2; P=0.0005) scores in the Pain and Sleep Questionnaire were significantly lower for CR tramadol. Short-form 36 Health Survey scores were significantly better during CR tramadol treatment for the pain index (38.8+/-10.8 versus 35.6+/-9.0; P=0.0100), general health perception (46.5+/-11.2 versus 44.4+/-11.6; P=0.0262), vitality (43.1+/-13.2 versus 40.2+/-13.7; P=0.0255) and overall physical components (40.8+/-8.9 versus 37.8+/-7.7; P=0.0002). CR tramadol treatment was preferred by 55.8% of patients (P=0.0005) versus 20.8% and 23.4% of patients who chose placebo or had no preference, respectively. These improvements were sustained for up to six months, and 86.5% of patients reported at least moderate benefit from CR tramadol during long-term treatment. CONCLUSION: CR tramadol is effective for the management of painful osteoarthritis.

Molecular and Physiological Effects on the Small Intestine of Weaner Pigs Following Feeding with Deoxynivalenol-Contaminated Feed.

We intended to assess how exposure of piglets to deoxynivalenol (DON)-contaminated feed impacted their growth, immune response and gut development. Piglets were fed traditional Phase I, Phase II and Phase III diets with the control group receiving 0.20-0.40 ppm DON (referred to as the Control group) and treatment group receiving much higher level of DON-contaminated wheat (3.30-3.80 ppm; referred to as DON-contaminated group). Feeding a DON-contaminated diet had no impact on average daily feed intake (ADFI) (p < 0.08) or average daily gain (ADG) (p > 0.10) but it did significantly reduce body weight over time relative to the control piglets (p < 0.05). Cytokine analysis after initial exposure to the DON-contaminated feed did not result in significant differences in serum interleukin (IL) IL1ß, IL-8, IL-13, tumor necrosis factor (TNF)-α or interferon (IFN)-γ. After day 24, no obvious changes in jejunum or ileum gut morphology, histology or changes in gene expression for IL-1ß, IL-6, IL-10, TNFα, or Toll-like receptor (TLR)-4 genes. IL-8 showed a trend towards increased expression in the ileum in DON-fed piglets. A significant increase in gene expression for claudin (CLDN) 7 gene expression and a trend towards increased CLDN 2-expression was observed in the ileum in piglets fed the highly DON-contaminated wheat. Because CLDN localization was not negatively affected, we believe that it is unlikely that gut permeability was affected. Exposure to DON-contaminated feed did not significantly impact weaner piglet performance or gut physiology.

Management of acute malignant large-bowel obstruction with self-expanding metal stent.

BACKGROUND: Colorectal stents are being used for palliation and as a "bridge to surgery" in obstructing colorectal carcinoma. The purpose of this study was to review our experience with self-expanding metal stents (SEMS) as the initial interventional approach in the management of acute malignant large bowel obstruction. METHODS: Between February 2002 and May 2006, 67 patients underwent the insertion of a SEMS for an obstructing malignant lesion of the left-sided colon or rectum. RESULTS: In 55 patients, the stents were placed for palliation, whereas in 12 they were placed as a bridge to surgery. Stent placement was technically successful in 92.5% (n = 62), with a clinical success rate of 88% (n = 59). Two perforations that occurred during stent placement we retreated by an emergency Hartmann operation. In intention-to-treat by stent, the peri-interventional mortality was 6% (4/67). Stent migration was reported in 3 cases (5%), and stent obstruction occurred in 8 cases (13.5%). Of the nine patients with stents successfully placed as a bridge to surgery, all underwent elective single-stage operations with no death or anastomotic complication. CONCLUSIONS: Stent insertion provided an effective outcome in patients with malignant colonic obstruction as a palliative and preoperative therapy.

Factors affecting the concentration of sphingomyelin in bovine milk.

Sphingomyelin is a phospholipid located in the outer leaflet of the plasma membrane of most cells and is a component of the milk fat globule membrane. Sphingomyelin and its digestion products participate in several antiproliferative pathways that may suppress oncogenesis. Although milk and dairy products are important sources of sphingomyelin in the human diet, little is known about factors that influence sphingomyelin concentrations in milk fat or whether concentrations can be modified via the nutrition of cows. Sphingomyelin concentrations were determined in milk from Holstein and Jersey cows matched for parity and stage of lactation. Sphingomyelin was more concentrated in milk fat from Holstein cows than in milk fat from Jersey cows (1,044 vs. 839 microg/g of fat). Concentrations in whole milk did not differ because of greater milk fat content for milk from Jerseys. Differences between breeds may be related to the greater fat globule size in milk from Jerseys. Sphingomyelin content in whole milk increased with increasing days in milk because of associated increases in milk fat content. Regardless of breed, primiparous cows had greater amounts of stearic acid and less palmitic acid in sphingomyelin than did older cows. The sphingomyelin concentration in milk fat of cows in a commercial Jersey herd was lower for cows in their fourth or greater parity. Sphingomyelin content in whole milk was greater for cows in late lactation because of greater milk fat content. Feed restriction of multiparous Holstein cows to 37% of ad libitum dry matter intake increased milk fat content but did not affect milk sphingomyelin content or milk fat globule size. Supplementation of the diet with 4% soybean oil did not affect milk composition, sphingomyelin content, or milk fat globule size. Milk was sampled seasonally from 7 herds throughout Illinois during a 2-yr period. Sphingomyelin concentration in milk fat was greatest during summer and least during winter, but whole milk concentrations did not vary across seasons. We conclude that 1) sphingomyelin content of milk fat is greater in milk from Holsteins than that from Jerseys, 2) sphingomyelin content in whole milk increases with stage of lactation, and 3) sphingomyelin content of milk fat is greater during summer. However, efforts to produce milk with a greater sphingomyelin content through altering management and nutrition are unlikely to be successful.

Prepartum nutrition alters fatty acid composition in plasma, adipose tissue, and liver lipids of periparturient dairy cows.

The fatty acyl profile of phospholipids (PL) determines the fluidity of cell membranes and affects cell function. The degree to which long-chain fatty acid (LCFA) composition of PL and triacylglycerols (TG) in liver and total lipids in adipose tissue can be altered by prepartum nutrition in peripartal dairy cows is unclear. Multiparous Holsteins (n = 25) were assigned to 1 of 4 prepartal diets: 1) CA, the control diet fed to meet 120% of energy requirements; 2) CR, a control diet fed to meet 80% of requirements; 3) S, a diet supplemented with mostly saturated free fatty acids (47% 16:0, 36% 18:0, 14% cis-18:1) and fed to meet 120% of requirements; or 4) U, a diet similar to S except that cows were abomasally infused with soybean oil so that the diet plus infused fat would meet 120% of requirements. Diets were fed for 40 d prepartum; all cows received a lactation diet postpartum. Groups CR and U had lower prepartum intakes of dry matter and net energy, but glucose concentrations in plasma were similar among treatments. Cows fed S, U, or CR had greater nonesterified fatty acids in plasma prepartum, but cows fed U had decreased beta-hydroxybutyrate postpartum. Postpartal concentrations of total lipids and glycogen in liver tissue were similar among treatments. Cows in group U had a greater percentage of 18:2 but less 16:0, 18:0, and 20:4 in plasma total lipids than cows fed S. Treatment U increased 18:2 and 18:3 and decreased 18:1 in subcutaneous adipose tissue at 1 d postpartum. Across diets, percentages of 16:0 and trans-18:1 were increased, and 18:0, 20:3, and 20:5 were decreased, in hepatic PL at d 1 postpartum. Significant treatment x time interactions indicated that treatment U increased 18:2 in hepatic PL at the expense of 18:1, 20:3, 20:4, 22:6, and 24:0 on d 1 postpartum, but changes were normalized by d 65 postpartum. The unsaturation index of hepatic PL was lower at d 1 than at d -45 or 65, which implies that hepatic membrane fluidity decreased around parturition. The unsaturation index at d 1 was greater for cows fed S than those fed CA or U. Percentages of 16:0, 18:1, and 22:0 were increased, and 18:0, 20:3, 20:4, 20:5, 24:0, and 26:0 were decreased, in hepatic TG at d 1. Prepartal feed restriction modestly affected tissue LCFA profiles. The LCFA profile of adipose tissue, liver PL, and liver TG can be altered by dietary LCFA supply prepartum; changes in liver are normalized by 65 d postpartum.

Responses to increasing amounts of high-oleic sunflower fatty acids infused into the abomasum of lactating dairy cows.

Increasing the oleic acid (18:1 cis-9) content of milk fat might be desirable to meet consumer concerns about dietary healthfulness and for certain manufacturing applications. The extent to which milk fat could be enriched with oleic acid is not known. Increasing the intestinal supply of polyunsaturated fatty acids decreases dry matter intake (DMI) in cows, but the effects of oleic acid have not been quantified. In a crossover design, 4 multiparous Holstein cows were abomasally infused with increasing amounts (0, 250, 500, 750, or 1,000 g/d) of free fatty acids from high-oleic sunflower oil (HOSFA) or with carrier alone. Continuous infusions (20 to 22 h/d) were for 7 d at each amount. Infusions were homogenates of HOSFA with 240 g/d of meat solubles and 11.2 g/d of Tween 80; controls received carrier only. The HOSFA contained (by wt) 2.4% 16:0, 1.8% 18:0, 91.4% 18:1 cis-9, and 2.4% 18:2. The DMI decreased linearly (range 22.0 to 5.8 kg/d) as the infused amount of HOSFA increased. Apparent total tract digestibilities of dry matter, organic matter, neutral detergent fiber, and energy decreased as the infusion increased to 750 g/d and then increased when 1,000 g/d was infused. Digestibility of total fatty acids increased linearly as infused fatty acids increased. Yields of milk, fat, true protein, casein, and total solids decreased quadratically as infused amounts increased; decreases were greatest when 750 or 1,000 g/d of HOSFA were infused. Concentrations of fat and total solids increased at the higher amounts of HOSFA. The volume mean diameter of milk fat droplets and the diameter below which 90% of the volume of milk fat is contained both increased as HOSFA infusion increased. Concentrations of short-chain fatty acids, 12:0, 14:0, and 16:0 in milk fat decreased linearly as HOSFA increased. The concentration of 18:1 cis-9 (19.4 to 57.4% of total fatty acids) increased linearly as HOSFA infusion increased. Concentrations of 18:1 cis-9 in blood triglyceride-rich lipoproteins increased linearly as infusion increased, whereas contents of 14:0, 16:0, 18:0, total 18:1 trans, and 18:2n-6 decreased linearly. The composition and physical characteristics of milk fat can be altered markedly by an increased intestinal supply of 18:1 cis-9, which could influence processing characteristics and the healthfulness of milk fat. However, an increased supply of free 18:1 cis-9 to the intestine decreased DMI and milk production.