Vitamin D, osteoprotegerin/receptor activator of nuclear factor-kappaB ligand (OPG/RANKL) and inflammation with alendronate treatment in HIV-infected patients with reduced bone mineral density.

OBJECTIVES: The aim of the study was to determine the effect of alendronate (ALN) on inflammatory markers and osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL), and to explore the associations of baseline systemic inflammation and vitamin D status on the bone mineral density (BMD) response to ALN. METHODS: Eighty-two HIV-positive patients with lumbar spine T-score ≤ -1.5 were randomized to ALN 70 mg weekly or placebo for 48 weeks; all received calcium carbonate 500 mg/vitamin D3 200 IU twice daily. Serum C-telopeptide (CTx) and BMD were assessed at baseline and week 48. Stored plasma samples in 70 subjects were assayed for levels of 25-hydroxyvitamin D (25(OH)D), OPG, RANKL, interleukin (IL)-6 and soluble receptors for tumour necrosis factor (TNF)-α 1 and 2 (sTNFR 1 and 2). RESULTS: ALN increased BMD more than placebo at both the lumbar spine (difference ALN - placebo 2.64%; P = 0.011) and the total hip (difference 2.27%; P = 0.016). No within- or between-arm differences in OPG, RANKL or inflammatory markers were observed over 48 weeks. High baseline CTx and sTNFR2 were associated with a more robust BMD response to ALN over 48 weeks at the lumbar spine [difference 5.66%; 95% confidence interval (CI) 3.50, 7.82; P < 0.0001] and total hip (difference 4.99%; 95% CI 2.40, 7.57; P = 0.0002), respectively. Baseline 25(OH)D < 32 ng/mL was associated with larger increases in total hip BMD over 48 weeks, independent of ALN treatment (P = 0.014). CONCLUSIONS: Among HIV-positive patients, higher baseline bone resorption and TNF-α activity were associated with an increased BMD response to ALN. The greater BMD response in those with lower vitamin D reinforces the importance of vitamin D supplementation with bisphosphonate treatment.

Omega-3 fatty acid therapy reduces triglycerides and interleukin-6 in hypertriglyeridemic HIV patients.

OBJECTIVES: Cardiovascular disease and osteoporosis are common in HIV-infected patients and residual systemic inflammation is thought to contribute to both of these disorders. We performed a randomized placebo-controlled trial of omega-3-acid (O3A) ethyl esters in HIV-infected patients with hypertriglyceridaemia, hypothesizing that O3A would decrease serum levels of triglycerides, markers of systemic inflammation, and markers of bone turnover. METHODS: HIV-infected patients (n = 48 recruited at three sites) with CD4 count >200 cells/µL, suppressed viral load, and triglycerides >200 mg/dL were randomized to placebo or 3.6 g/d of O3A. Fasting lipid profiles and markers of inflammation and bone turnover were assessed at baseline and after 8 weeks of treatment. RESULTS: Baseline HIV status, lipid profile, bone metabolism and cardiovascular risk factors were similar between the groups. Inflammatory markers were similar between the treatment groups at baseline, except for interleukin (IL)-6 and tumour necrosis factor (TNF)-α, which were higher in the O3A group. The concentration of triglycerides in patients receiving O3A decreased by a median (interquartile range (IQR)) of -34 (-149, 9.5) mg/dL vs. a median increase of 46.5 (-51, 123) mg/dL in the placebo group (P = 0.01). The median percentage change in IL-6 was greater in the O3A group compared with the placebo group [-39% (-63, 12%) vs. 29% (10, 177%), respectively; P = 0.006]. Similar results were observed for TNF-α, but not other inflammatory or bone turnover markers. CONCLUSIONS: O3A ethyl esters decreased the concentrations of triglycerides, IL-6 and TNF-α in patients with well-controlled HIV infection and hypertriglyceridaemia. Larger studies are required to confirm these findings and investigate their clinical significance.

Effect of dietary boron on physiological responses in growing steers inoculated with bovine herpesvirus type-1.

Thirty-six Angus and Angus×Simmental steers were fed one of three dietary treatments; (1) control (no supplemental B), (2) 5 mg supplemental B/kg, and (3) 15 mg supplemental B/kg for 47 days to determine the effects of dietary boron (B) on disease resistance following an inoculation with bovine herpesvirus type-1 (BHV-1). On day 34 of the study steers were inoculated intranasally with BHV-1. Rectal temperatures began to elevate at day 2, and plasma tumor necrosis factor-α concentrations increased (P<0.05) by day 2 following BHV-1 inoculation. Plasma acute phase proteins were increased (P<0.01) while plasma interferon-γ was decreased (P<0.05) by day 4 post-inoculation. Supplementation of B increased (P<0.001) plasma B concentrations in a dose-responsive manner. However, dietary B did not affect the duration and severity of clinical signs of BHV-1 and had minimal effects on plasma acute phase proteins and cytokines.

Alternative therapies for osteoporosis.

A variety of common complementary and alternative medicine therapies are now being examined for effectiveness in the management of osteoporosis. Short-term studies in postmenopausal women show beneficial effects of soy isoflavone supplementation on bone density, but its long-term effects require clarification. Prospective controlled trials have shown that physical training can increase bone density to varying degrees. Other therapies that have been examined include herbal formulae, essential fatty acids and vitamins A, C, and K, but few data regarding their effectiveness, mechanisms and safety have been published. Further randomized controlled trials are needed.

Effect of breed (Angus vs Simmental) on immune function and response to a disease challenge in stressed steers and preweaned calves.

Two experiments were conducted with feeder steer calves and preweaned calves to determine the effects of breed on immune response. In Exp. 1, newly weaned Angus (n = 24) and Simmental (n = 24) steer calves were blocked by weight within breed and randomly assigned to 12 pens with four calves per pen. The basal diet consisted of 87% corn silage (DM basis) and 13% of a soybean meal-mineral-vitamin supplement. Steers were allowed ad libitum access to feed throughout the study. On d 2 following weaning, calves received an intranasal inoculation of infectious bovine rhinotraecheitis virus (IBRV; 2.7 x 10(8) CCID50). Rectal temperatures in response to the IBRV were higher (P < .05) in Angus calves. On d 9, calves were injected i.m. with 10 mL of a 25% pig red blood cell (PRBC) suspension. Total immunoglobulin (Ig) and IgM titers against PRBC were higher (P < .05) for the Angus calves. Breed did affect cell-mediated immune response to phytohemagglutinin (PHA). In Exp. 2, preweaned (16 Angus and 16 Simmental) calves were selected based on breed, body weight, and sex. On 0 d, all selected calves were injected i.m. with 10 mL of a 25% PRBC suspension. Total Ig and IgG titers against PRBC were higher (P < .05) for Angus calves. On d 28, lymphocytes were isolated from peripheral blood obtained from eight calves per breed. Peripheral lymphocytes from the Angus calves had a greater (P < .07) blastogenic response to 6.25 microg/mL of PHA than lymphocytes from Simmental calves. Results indicate that the immune response of Angus and Simmental calves may differ.

Effect of shipping and chromium supplementation on performance, immune response, and disease resistance of steers.

Forty-eight Angus crossbred steers (263 +/- 2 kg initial BW) were blocked by weight and randomly assigned within weight group to treatment. Treatments consisted of control or .4 mg of supplemental Cr as Cr-nicotinic acid complex/kg of DM. Steers were fed diets containing 90% corn silage (DM basis) and 10% of a soybean meal-mineral-vitamin supplement. After 56 d on the dietary treatment, half of the steers in each treatment were transported 343 km and unloaded in an unfamiliar location. The next day, d 58, shipped steers were returned to the feedlot (50 km). On d 58 after shipped steers were returned to the feedlot, all steers were inoculated with infectious bovine rhinotracheitis virus (IBRV) intranasally. Average daily gain from d 0 to 80 was increased (P < .10) by supplemental Cr. There was a shipping x time interaction for serum cortisol concentrations. Shipping increased (P < .02) serum cortisol on d 58, but 7 d after transport there were no effects of shipping on serum cortisol. Transportation increased (P < .05) the ratio of neutrophils to lymphocytes. Supplemental Cr did not affect rectal temperature after the IBRV challenge or the antibody response to IBRV or porcine red blood cells. Immunoglobulin G antibody response to porcine red blood cells was decreased (P < .09) by shipping. Supplemental Cr as Cr-nicotinic acid improved ADG of growing steers, regardless of whether they had been stressed by shipping. Supplemental Cr did not affect any of the immune responses that were measured.

Effects of copper deficiency and copper deficiency coupled with high dietary iron or molybdenum on phagocytic cell function and response of calves to a respiratory disease challenge.

A study was conducted to determine the effects of supplementing a diet marginally deficient in copper (Cu) with iron (Fe), molybdenum (Mo), or Cu on phagocytic cell function and disease resistance of calves. Thirty-one calves were born to heifers fed a corn silage-based diet containing 4.5 mg of Cu/kg. Treatments consisted of 1) control (CON; no supplemental Cu, Fe, or Mo), 2) 600 mg of Fe added/kg (FE), 3) 5 mg of Mo added/kg (MO), or 4) 10 mg of Cu added/kg of DM (CU). Activity of superoxide dismutase was lower (P < .06) in neutrophils from MO vs CON or CU calves at 170 d of age. bactericidal activity of neutrophils from MO calves tended (P = .15) to be lower compared with those from CU calves at 70 d of age. Calves were inoculated intranasally with live infectious bovine rhinotracheitis virus (IBRV) 2 d after weaning, followed by intratracheal administration of Pasteurella hemolytica 5 d later. Iron- and Cu-supplemented calves exhibited higher (P < .01) body temperatures and lower (P < .06) feed intakes following IBRV inoculation compared with CON and MO calves. Copper-supplemented calves had higher levels of plasma tumor necrosis factor (TNF) than MO calves at weaning (P < .05) and tended to have higher plasma TNF (P = .11) than FE and MO calves 5 d after IBRV inoculation. These data indicate that dietary levels of Mo and Cu can affect body temperature and feed intake responses to disease by affecting TNF and perhaps other cytokines.

Immune response and disease resistance of calves fed chromium nicotinic acid complex or chromium chloride.

Twenty-one Holstein bull calves (< 7 d of age at the initiation of the experiment) fed a milk replacer diet were used to assess the effects of supplemental Cr on immune response. Treatments consisted of milk replacer without supplemental Cr (control) or milk replacer with 0.4 ppm of supplemental Cr from CrCl3 or a Cr-nicotinic acid complex. On d 64, increases in skinfold thickness after an intradermal injection of phytohemagglutinin were measured to evaluate cell-mediated immune response. Calves supplemented with Cr-nicotinic acid complex had a greater response than did controls at 6, 12, 24, and 48 h after injection. Calves supplemented with CrCl3 had a greater response than did controls at 24 and 48 h after injection. In vitro blastogenic responses of lymphocytes to phytohemagglutinin or pokeweed mitogen and antibody response to porcine red blood cells were not affected by treatment. Following a disease challenge with an intranasal dose of infectious bovine rhinotracheitis on d 75, body temperature tended to be lower for calves supplemented with Cr-nicotinic acid complex than for control calves. Calves supplemented with either Cr source had lower serum cortisol concentrations at 5 d after challenge. Chromium supplementation enhanced cell-mediated immune function.

Effect of copper deficiency on tissue, blood characteristics, and immune function of calves challenged with infectious bovine rhinotracheitis virus and Pasteurella hemolytica.

Fourteen Holstein steers, averaging 30 d of age, were fed a semipurified diet (1.5 mg of Cu/kg) supplemented with 0 (-Cu) or 10 mg of Cu/kg of diet (+Cu) for 5 mo. Calves were then challenged by consecutive exposure to aerosol preparations of infectious bovine rhinotracheitis virus (IBRV) and Pasteurella hemolytica on d 0 and 7, respectively, of the 30-d study. Serum ceruloplasmin and plasma copper were higher in +Cu calves throughout the challenge period and increased in +Cu calves after microbial challenge. Heart weights were higher in -Cu calves, although weights of liver, spleen, and thymus were not different between treatments. Copper concentrations in all tissues as well as thymus zinc were higher in +Cu calves. Serum immunoglobulin M tended to be higher in +Cu calves and increased in both treatments after IBRV challenge. Serum IBRV antibody titers were higher in -Cu calves with detectable seroconversion by d 10 postinfection. In contrast, antigen-specific antibodies to P. hemolytica tended to be higher in +Cu calves on d 21. Copper status did not affect blastogenic response, but phytohemagglutinin (PHA)-stimulated blastogenesis was higher in both treatments after IBRV challenge. Repletion of lymphocyte cultures with copper chloride increased proliferative responses to PHA in both +Cu and -Cu calves, and greater responses at all levels of copper (1 to 16 micrograms/mL) were noted in -Cu calves. These results indicate that copper deficiency affects various physiological characteristics that may be important in immunological defense to pathogenic challenge.

Effects of zinc methionine and zinc oxide on performance, blood characteristics, and antibody titer response to viral vaccination in stressed feeder calves.

Ninety steers with an average weight of 214 kg were purchased at 2 feeder calf sales and transported 70 to 100 km. On arrival at the feedlot, steers were weighed and identified, blood was withdrawn, and the steers were vaccinated against bovine herpesvirus-1 (BHV-1) and parainfluenza3 (PI3), using a modified live vaccine, and randomly assigned to treatment groups. Treatments were: control (no supplemental zinc; zinc methionine; and zinc oxide. The control diet contained 26 mg of zinc/kg diet, and zinc was added in treatments 2 and 3 to provide 25 mg of supplemental zinc/kg diet. Neutralizing antibody titers were determined on serum samples taken on days 0 and 14 as a measure of the immune response to BHV-1 and PI3 vaccination. Weight gains for the 28-day study were similar across treatments. Dry matter intake tended to be higher in steers fed supplemental zinc from either source, because steers fed zinc methionine and zinc oxide consumed 5.2 and 4.4% more feed, respectively, than controls. Antibody titers against BHV-1 tended to be higher in steers supplemented with zinc methionine on day 14. Differences between treatments were not found for PI3 titers. Mortalities did not occur and morbidity rate was low.

Selenium effects on glutathione peroxidase and the immune response of stressed calves challenged with Pasteurella hemolytica.

The present study was conducted to determine whether a marginal Se deficiency affects health, blood characteristics and the immune response of calves subjected to stresses associated with weaning, shipping (332 km) and Pasteurella hemolytica inoculation. Treatments were 1) -Se, 2) -Se/P. hemolytica, 3) +Se (.1 mg Se/kg feed) and 4) +Se/P. hemolytica. Previous Se intake was controlled; dams of -Se calves were fed diets marginally deficient in Se (.03 to .05 mg/kg), whereas dams of +Se calves received a s.c. injection of 30 mg Se (as sodium selenite) every 60 d. Calves were inoculated with P. hemolytica intratracheally on d 3 following weaning and transport. Inoculation with P. hemolytica increased (P less than .05) body temperatures, platelet counts, serum IgM concentrations and serum antibody titers and decreased serum albumin concentrations at 4 to 7 d postinoculation. Weight gains for the 21-d study were not affected by Se status, although whole blood and plasma glutathione peroxidase (GSH-Px) were higher (P less than .05) for +Se calves. Plasma GSH-Px increased (P less than .01) in calves showing signs of morbidity. Increases in plasma GSH-Px were correlated positively with body temperature. Serum IgM concentrations were higher (P less than .05) in +Se calves on d 17, but Se-supplemented calves had lower (P less than .05) anti-P. hemolytica titers on d 17 than -Se calves. Selenium status did not affect body temperatures, plasma creatine phosphokinase or serum IgG and albumin concentrations. These results indicate that Se status can affect IgM concentrations following stress.

Effect of dietary selenium and vitamin E on the primary and secondary immune response in lambs challenged with parainfluenza3 virus.

This study was conducted to determine the effect of dietary selenium (Se) and vitamin E (Vit E) on various blood characteristics and the primary and secondary humoral immune response of lambs challenged with parainfluenza3 virus (PI3 V). Treatments included: 1) +Se/+Vit E, 2) -Se/+Vit E, 3) +Se/-Vit E and 4) -Se/-Vit E. The basal diet (-Se/-Vit E) was deficient in Se and Vit E. Sodium selenite (.2 mg Se/kg diet) and alpha-tocopherol acetate (20 mg Vit E/kg diet) were added to +Se and +Vit E diets, respectively, to provide adequate levels of each according to NRC recommendations. Following a 10-wk dietary adaptation and depletion period, lambs in all treatment groups were intratracheally inoculated with PI3 V on d 0 and 35 of the 70-d study. Prior to inoculation, whole blood and plasma glutathione peroxidase (GSH-Px) activities were higher (P less than .01) for +Se lambs. Whole blood and plasma GSH-Px increased (P less than .01) after primary viral inoculation in +Se lambs but not in -Se lambs. Serum immunoglobulin M (IgM) concentrations were enhanced (P less than .05) by Se supplementation on d 14, 35 and 49 of the study. Selenium and (or) Vit E did not affect serum immunoglobulin G (IgG) levels. Serum PI3 V antibody titers increased after inoculation on d 0 and 35 in all treatment groups. Titer levels appeared to increase more substantially for +Se lambs after primary inoculation, but increases were greater (P less than .01) for +Vit E lambs after secondary challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of dietary selenium on the primary and secondary immune response in calves challenged with infectious bovine rhinotracheitis virus.

The present study was conducted to determine if a selenium deficiency affects the primary and secondary humoral immune response of calves challenged with infectious bovine rhinotracheitis virus (IBRV) and to evaluate changes in glutathione peroxidase (GSH-Px) and creatine phosphokinase activities associated with selenium deficiency and viral stress. Treatments included 1) +Se (0.2 mg/kg diet) and 2) -Se (0.03 mg/kg diet). Calves were adapted to their assigned diets during an 84-d depletion period. By d 42 of the depletion period, whole-blood GSH-Px was lower for -Se calves than for +Se calves. Differences between treatments in plasma GSH-Px were observed by d 14. On d 84, Se-dependent GSH-Px activity in liver was higher in +Se calves. After depletion of -Se calves, animals in both treatments were intranasally inoculated with IBRV on d 0 and 35 of the 70-d challenge phase. Whole-blood and plasma GSH-Px increased after IBRV inoculation in +Se calves but not in Se-deficient calves. Serum IgM was higher for +Se calves throughout the challenge phase. Serum IgM increased in both treatments after primary IBRV inoculation but was unaffected by secondary challenge. Serum IgG was not affected by selenium status but increased in both treatments after secondary IBRV challenge. Serum IBRV antibody titers increased after inoculation on d 0 and 35. By d 49, IBRV antibody titers were higher for +Se calves than in Se-deficient calves. These results indicate that selenium deficiency may depress the immune response of calves challenged with a foreign pathogen.