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1.
Molecules ; 25(7)2020 Mar 25.
Article in English | MEDLINE | ID: mdl-32218338

ABSTRACT

Despite previous reports of anti-aging effects of Korean red ginseng (KRG), the underlying mechanisms remain poorly understood. Therefore, this study investigated possible mechanisms of KRG-mediated anti-aging effects in aged mice. KRG significantly inhibited thymic involution in old mice. Interestingly, KRG only increased protein expression, but not mRNA expression, of aging-related genes Lin28a, GDF-11, Sirt1, IL-2, and IL-17 in the thymocytes of old mice. KRG also modulated the population of some types of immune cells in old mice. KRG increased the population of regulatory T cells and interferon-gamma (IFN-γ)-expressing natural killer (NK) cells in the spleen of old mice, but serum levels of regulatory T cell-specific cytokines IL-10 and TGF-ß were unaffected. Finally, KRG recovered mRNA expression of Lin28a, GDF-11, and Sirt1 artificially decreased by concanavalin A (Con A) in both thymocytes and splenocytes of old mice without cytotoxicity. These results suggest that KRG exerts anti-aging effects by preventing thymic involution, as well as modulating the expression of aging-related genes and immune cell subsets.


Subject(s)
Aging/genetics , Aging/immunology , Gene Expression Regulation , Leukocytes/immunology , Panax/chemistry , Animals , Concanavalin A/pharmacology , Cytokines/metabolism , Gene Expression Regulation/drug effects , Leukocytes/drug effects , Mice, Inbred C57BL , Plant Extracts/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Spleen/drug effects , Spleen/immunology , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/metabolism , Thymus Gland/growth & development
2.
J Dev Orig Health Dis ; 11(2): 127-135, 2020 04.
Article in English | MEDLINE | ID: mdl-31475652

ABSTRACT

The thymus undergoes a critical period of growth and development early in gestation and, by mid-gestation, immature thymocytes are subject to positive and negative selection. Exposure to undernutrition during these periods may permanently affect phenotype. We measured thymulin concentrations, as a proxy for thymic size and function, in children (n = 290; aged 9-13 years) born to participants in a cluster-randomized trial of maternal vitamin A or ß-carotene supplementation in rural Nepal (1994-1997). The geometric mean (95% confidence interval) thymulin concentration was 1.37 ng/ml (1.27, 1.47). A multivariate model of early-life exposures revealed a positive association with gestational age at delivery (ß = 0.02; P = 0.05) and higher concentrations among children born to ß-carotene-supplemented mothers (ß = 0.19; P < 0.05). At ∼9-12 years of age, thymulin was positively associated with all anthropometric measures, with height retained in our multivariate model (ß = 0.02; P < 0.001). There was significant seasonal variation: concentrations tended to be lower pre-monsoon (ß = -0.13; P = 0.15), during the monsoon (ß = -0.22; P = 0.04), and pre-harvest (ß = -0.34; P = 0.01), relative to the post-harvest season. All early-life associations, except supplementation, were mediated in part by nutritional status at follow-up. Our findings underscore the known sensitivity of the thymus to nutrition, including potentially lasting effects of early nutritional exposures. The relevance of these findings to later disease risk remains to be explored, particularly given the role of thymulin in the neuroendocrine regulation of inflammation.


Subject(s)
Malnutrition/diet therapy , Prenatal Exposure Delayed Effects/epidemiology , Thymic Factor, Circulating/analysis , Thymus Gland/physiopathology , Adolescent , Child , Child Development , Child, Preschool , Dietary Supplements , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Male , Malnutrition/physiopathology , Maternal Nutritional Physiological Phenomena , Nepal/epidemiology , Nutritional Status/physiology , Pregnancy , Prenatal Exposure Delayed Effects/blood , Prenatal Exposure Delayed Effects/prevention & control , Risk Factors , Rural Population/statistics & numerical data , Seasons , Thymic Factor, Circulating/metabolism , Thymus Gland/growth & development , Treatment Outcome , Vitamin A/administration & dosage , Young Adult , beta Carotene/administration & dosage
3.
Nat Commun ; 10(1): 3031, 2019 07 10.
Article in English | MEDLINE | ID: mdl-31292453

ABSTRACT

Maternal immune dysregulation seems to affect fetal or postnatal immune development. Preeclampsia is a pregnancy-associated disorder with an immune basis and is linked to atopic disorders in offspring. Here we show reduction of fetal thymic size, altered thymic architecture and reduced fetal thymic regulatory T (Treg) cell output in preeclamptic pregnancies, which persists up to 4 years of age in human offspring. In germ-free mice, fetal thymic CD4+ T cell and Treg cell development are compromised, but rescued by maternal supplementation with the intestinal bacterial metabolite short chain fatty acid (SCFA) acetate, which induces upregulation of the autoimmune regulator (AIRE), known to contribute to Treg cell generation. In our human cohorts, low maternal serum acetate is associated with subsequent preeclampsia, and correlates with serum acetate in the fetus. These findings suggest a potential role of acetate in the pathogenesis of preeclampsia and immune development in offspring.


Subject(s)
Acetates/blood , Fetus/immunology , Pre-Eclampsia/immunology , Prenatal Exposure Delayed Effects/immunology , T-Lymphocytes, Regulatory/immunology , Acetates/administration & dosage , Acetates/immunology , Acetates/metabolism , Adult , Animals , Animals, Newborn , Case-Control Studies , Child Development , Child, Preschool , Dietary Supplements , Female , Fetus/cytology , Fetus/diagnostic imaging , Gastrointestinal Microbiome/immunology , Germ-Free Life/immunology , Humans , Immune Tolerance/immunology , Infant , Infant, Newborn , Longitudinal Studies , Maternal-Fetal Exchange/immunology , Mice , Organ Size/immunology , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pregnancy , Prenatal Exposure Delayed Effects/pathology , Prenatal Exposure Delayed Effects/prevention & control , Prospective Studies , Thymus Gland/cytology , Thymus Gland/diagnostic imaging , Thymus Gland/growth & development , Thymus Gland/immunology , Transcription Factors/immunology , Transcription Factors/metabolism , Ultrasonography, Prenatal , Young Adult , AIRE Protein
4.
Anim Sci J ; 90(6): 747-756, 2019 Jun.
Article in English | MEDLINE | ID: mdl-30989748

ABSTRACT

This study was designed to evaluate the potential application of the stems and leaves of Astragalus membranaceus (AMSL) in the poultry industry. Quails were divided into four groups and fed daily with an AMSL-free diet (control) or with 1%, 3%, or 5% (w/w) AMSL-incorporated diets for 35 days. The results showed that supplementing AMSL in the diet, especially at a concentration of 3%, increased daily gain and feed intake during the entire experiment (p < 0.05). The immune organ development of the thymus and bursa of Fabricius was promoted, and the immune system was enhanced by increasing the quantities of IgA and complements C3 and C4 (p < 0.05). The total antioxidant capacity and the activities of glutathione peroxidase and catalase were increased (p < 0.05). Moreover, the 3%-5% AMSL groups regulated the intestinal flora by promoting the proliferation of lactic acid bacteria and inhibiting the growth of coliform bacteria (p < 0.05). In conclusion, feeding incorporated diets with appropriate AMSL levels significantly increased growth performance, strengthened the immune system, improved antioxidative status, and regulated the intestinal microflora of quails, suggesting that AMSL has the potential to serve as a feed additive in the poultry industry.


Subject(s)
Astragalus propinquus , Diet/veterinary , Dietary Supplements , Gastrointestinal Microbiome , Plant Stems , Quail/growth & development , Quail/immunology , Animal Feed , Animals , Antioxidants/metabolism , Bursa of Fabricius/growth & development , Bursa of Fabricius/immunology , Complement C3 , Complement C4 , Immunoglobulin A , Plant Leaves , Quail/metabolism , Quail/microbiology , Thymus Gland/growth & development , Thymus Gland/immunology
5.
J Neuroendocrinol ; 31(4): e12697, 2019 04.
Article in English | MEDLINE | ID: mdl-30773738

ABSTRACT

Stress is among the most frequently self-reported factors provoking epileptic seizures in children and adults. It is still unclear, however, why some people display stress-sensitive seizures and others do not. Recently, we showed that young epilepsy patients with stress-sensitive seizures exhibit a dysregulated hypothalamic-pituitary-adrenal (HPA)-axis. Most likely, this dysregulation gradually develops, and is triggered by stressors occurring early in life (early-life stress [ELS]). ELS may be particularly impactful when overlapping with the period of epileptogenesis. To examine this in a controlled and prospective manner, the present study investigated the effect of repetitive variable stressors or control treatment between postnatal day (PND) 12 and 24 in male mice exposed on PND10 to hyperthermia (HT)-induced prolonged seizures (control: normothermia). A number of peripheral and central indices of HPA-axis activity were evaluated at pre-adolescent and young adult age (ie, at PND25 and 90, respectively). At PND25 but not at PND90, body weight gain and absolute as well as relative (to body weight) thymus weight were reduced by ELS (vs control), whereas relative adrenal weight was enhanced, confirming the effectiveness of the stress treatment. Basal and stress-induced corticosterone levels were unaffected, though, by ELS at both ages. HT by itself did not affect any of these peripheral markers of HPA-axis activity, nor did it interact with ELS. However, centrally we did observe age-specific interaction effects of HT and ELS with regard to hippocampal glucocorticoid receptor mRNA expression, neurogenesis with the immature neurone marker doublecortin and the number of hilar (ectopic) granule cells using Prox1 staining. This lends some support to the notion that exposure to repetitive stress after HT-induced seizures may dysregulate central components of the stress system in an age-dependent manner. Such dysregulation could be one of the mechanisms conferring higher vulnerability of individuals with epilepsy to develop seizures in the face of stress.


Subject(s)
Aging/physiology , Hyperthermia, Induced , Seizures/etiology , Seizures/psychology , Stress, Psychological/physiopathology , Adrenal Glands/growth & development , Animals , Behavior, Animal/physiology , Corticosterone/blood , Female , Hippocampus/chemistry , Hippocampus/growth & development , Male , Mice , Mice, Inbred C57BL , Neurogenesis/physiology , Organ Size , RNA, Messenger/analysis , Receptors, Glucocorticoid/genetics , Seizures/physiopathology , Stress, Psychological/psychology , Thymus Gland/growth & development , Weight Gain
6.
Nutrients ; 10(7)2018 Jul 18.
Article in English | MEDLINE | ID: mdl-30021962

ABSTRACT

Aging is the main factor involved in the onset of degenerative diseases. Dietary protein restriction has been shown to increase the lifespan of rodents and improve metabolic phenotype. Branched-chain amino acids (BCAA) can act as nutrient signals that increase the lifespan of mice after prolonged supplementation. It remains unclear whether the combination of protein restriction and BCAA supplementation improves metabolic and immunological profiles during aging. Here, we investigated how dietary protein levels and BCAA supplementation impact metabolism and immune profile during a 12-month intervention in adult male C57BL/6J mice. We found that protein restriction improved insulin tolerance and increased hepatic fibroblast growth factor 21 mRNA, circulating interleukin (IL)-5 concentration, and thermogenic uncoupling protein 1 in subcutaneous white fat. Surprisingly, BCAA supplementation conditionally increased body weight, lean mass, and fat mass, and deteriorated insulin intolerance during protein restriction, but not during protein sufficiency. BCAA also induced pro-inflammatory gene expression in visceral adipose tissue under both normal and low protein conditions. These results suggest that dietary protein levels and BCAA supplementation coordinate a complex regulation of metabolism and tissue inflammation during prolonged feeding.


Subject(s)
Aging , Amino Acids, Branched-Chain/therapeutic use , Diet, Protein-Restricted , Dietary Proteins/therapeutic use , Dietary Supplements , Gene Expression Regulation, Developmental , Sarcopenia/prevention & control , Adiposity , Amino Acids, Branched-Chain/adverse effects , Amino Acids, Branched-Chain/metabolism , Animals , Cytokines/blood , Diet, Protein-Restricted/adverse effects , Dietary Proteins/adverse effects , Dietary Proteins/metabolism , Dietary Supplements/adverse effects , Gene Expression Profiling , Insulin Resistance , Liver/growth & development , Liver/immunology , Liver/metabolism , Liver/pathology , Male , Mice, Inbred C57BL , Organ Size , Proteomics/methods , Random Allocation , Sarcopenia/immunology , Sarcopenia/metabolism , Sarcopenia/pathology , Spleen/growth & development , Spleen/immunology , Spleen/metabolism , Spleen/pathology , Subcutaneous Fat, Abdominal/growth & development , Subcutaneous Fat, Abdominal/immunology , Subcutaneous Fat, Abdominal/metabolism , Subcutaneous Fat, Abdominal/pathology , Thymus Gland/growth & development , Thymus Gland/immunology , Thymus Gland/metabolism , Thymus Gland/pathology , Weight Gain
7.
Ginekol Pol ; 87(5): 378-83, 2016.
Article in English | MEDLINE | ID: mdl-27304655

ABSTRACT

OBJECTIVES: The aim of our study was to evaluate the association of vitamin D deficiency (VDD) during pregnancy with thymus size in full-term fetuses. MATERIAL AND METHODS: In this prospective study, we evaluated mid-pregnancy serum 25-hydroxyvitamin D3 (25(OH)D3) concentrations. The fetal thymus size was measured by ultrasound in the third trimester. Neonatal 25(OH)D3 levels were evaluated by umbilical cord blood sampling. Correlation of maternal and neonatal vitamin D levels and association between thymus size and both, maternal and neonatal vitamin D concentrations were investigated. RESULTS: Serum 25(OH) D3 concentrations were within the normal range in 48 (29.8%) mothers and 10 (13.1%) new-borns. A strong correlation between mid-pregnancy maternal and neonatal 25(OH)D3 concentration (r = 0.8, p < 0.001) was found. A significant linear correlation was observed between both, maternal and neonatal 25(OH)D3 concentrations and thymus perimeter length (r = 0.45, p = 0.04 and r = 0.43, p < 0.01, respectively). Both, maternal and fetal VDDs were associated with decreased thymus perimeter (p = 0.04, p = 0.03). CONCLUSIONS: Vitamin D deficiency during pregnancy may be associated with smaller fetal thymus. Our data suggest that VDD in pregnancy may lead to systemic inflammatory response in the fetus.


Subject(s)
Pregnancy Complications/blood , Thymus Gland , Vitamin D Deficiency , Vitamin D , Adult , Dietary Supplements , Female , Fetal Blood , Fetal Development/physiology , Humans , Infant, Newborn , Organ Size , Pregnancy , Statistics as Topic , Thymus Gland/growth & development , Thymus Gland/pathology , Vitamin D/blood , Vitamin D/pharmacology , Vitamin D Deficiency/blood , Vitamin D Deficiency/complications , Vitamins/pharmacology
8.
Reprod Fertil Dev ; 28(3): 384-93, 2016 Mar.
Article in English | MEDLINE | ID: mdl-25082148

ABSTRACT

The emerging immune system is vulnerable to insult not only during fetal life, but also through colostrum transfer of maternal factors with immunomodulatory functions. The aim of the present study was to examine the effects of maternal undernutrition during late gestation and/or lactation on colostrum and milk synthesis, as well as on immunological parameters in offspring. Pregnant ewes were fed to 100% of nutrient requirements throughout pregnancy and lactation (Control) or to 50% during lactation (R1) or during the last 20 days of pregnancy and lactation (R2). Colostrum samples were collected 3 and 18h after parturition and thymus glands were obtained from 5-month-old offspring. Lamb birthweight did not differ between groups, whereas growth rate was significantly lower in males in the R1 group and in females in both undernourished groups. There was a significant reduction in lactose percentage in the 18-h colostrum of the R2 group. The IgG concentration, as a percentage of protein, was significantly increased in 3-h colostrum samples of the R2 group. Quantitative polymerase chain reaction analysis revealed a significant increase in the expression of Toll-like receptor (TLR) 2, TLR4 and TLR9 in the thymus gland of female lambs in both undernourished groups. In conclusion, early life nutritional imbalances may impact on immune system function in later life due to programming effects.


Subject(s)
Animal Nutritional Physiological Phenomena , Colostrum/metabolism , Lactation , Malnutrition/physiopathology , Maternal Nutritional Physiological Phenomena , Milk/metabolism , Nutritional Status , Prenatal Exposure Delayed Effects , Age Factors , Animals , Animals, Newborn , Colostrum/immunology , Disease Models, Animal , Female , Gestational Age , Immunoglobulin G/immunology , Immunoglobulin G/metabolism , Lactose/metabolism , Male , Malnutrition/immunology , Malnutrition/metabolism , Milk/immunology , Pregnancy , Sheep , Thymus Gland/growth & development , Thymus Gland/immunology , Thymus Gland/metabolism , Toll-Like Receptors/immunology , Toll-Like Receptors/metabolism , Weight Gain
9.
Zhongguo Zhong Yao Za Zhi ; 39(17): 3363-6, 2014 Sep.
Article in Chinese | MEDLINE | ID: mdl-25522629

ABSTRACT

Ginseng and its effective components are famous for their influence to enhance human immunity, regulate endocrine and antioxidant action. However, the different effects of different components are not clear. In this study, Wistar rats were used to study the effects of main components of ginseng, including total ginsenoside, panaxadiol saponins, panaxtrol saponin and ginseng polysaccharide. The results showed that the effects of panaxadiol saponins and ginseng polysaccharide on improving animal immune organ weight, plasma interleukin 2 (IL-2), interleukin 6 (IL-6), plasma gamma-interferon (IFN-γ), tumor necrosis factor alpha (TNF-α) were better than that of the other groups. Total ginsenoside and panaxtrol saponin can effectively increase the concentration of spleen NK cells (NKC) while panaxadiol saponins and ginseng polysaccharide can significantly increase the concentrations of rat plasma adrenocorticotrophic hormone (ACTH), corticosterone (CORT) and thyroid stimulating hormone (TSH). As for the effect of increasing organization nitric oxide (NO) and superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA), total ginsenoside is better than that of other groups. In brief, different components in ginseng possess different effects on enhancing immunity, regulating endocrine and resisting oxidation. Panaxadiol saponins and ginseng polysaccharide are better in enhancing immune, and total ginsenoside shows advantages in resisting oxidation and stress.


Subject(s)
Ginsenosides/pharmacology , Immune System/drug effects , Panax/chemistry , Polysaccharides/pharmacology , Saponins/pharmacology , Adrenal Glands/drug effects , Adrenal Glands/growth & development , Adrenocorticotropic Hormone/blood , Animals , Brain/drug effects , Brain/metabolism , Corticosterone/blood , Glutathione/metabolism , Immune System/physiology , Interferon-gamma/blood , Interleukin-2/blood , Interleukin-6/blood , Killer Cells, Natural/drug effects , Malondialdehyde/metabolism , Nitric Oxide/metabolism , Organ Size/drug effects , Random Allocation , Rats, Wistar , Spleen/drug effects , Spleen/growth & development , Superoxide Dismutase/metabolism , Thymus Gland/drug effects , Thymus Gland/growth & development , Thyrotropin/blood
10.
Contemp Clin Trials ; 39(2): 269-79, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25269669

ABSTRACT

In recent years, neonatal vitamin A supplementation is considered as an essential infant-survival intervention but the evidence is not conclusive. This randomized controlled clinical trial was conducted to evaluate the effect of vitamin A on immune competence in early infancy. Results would provide a mechanistic basis for understanding the effect of this intervention on infant survival. Within 2 days of birth, infants born at one maternity clinic located in a poor slum area of Dhaka city were supplemented with either 50,000 IU vitamin A or placebo. Live attenuated oral polio vaccine (OPV) and BCG vaccine were provided after supplementation. Infants also receive diphtheria, pertussis, tetanus (TT), hepatitis B (HBV) and Haemophilus influenzae B vaccines (pentavalent combination) along with OPV at 6, 10 and 14 weeks of age. Infant thymus size, anthropometry, feeding practice and morbidity data were collected at regular interval. Infant blood samples were collected to determine T-cell-receptor excision circle (TREC), total, naïve and memory T cells and mucosal targeting lymphocytes including Treg cells. TT-, HBV-, BCG- and OPV-specific T cell blastogenic, cytokine and plasma cell antibody responses were also measured. In 16 mo enrollment period, 306 newborns, equal number of boys and girls, were enrolled. ~95% completed the 4-month follow-up period. Baseline characteristics are presented here. Anthropometry and immune assays with fresh blood samples were completed immediately while stored samples were analyzed in single batches at the end of the trial. Connecting different aspects of immunological data in early infancy will help elucidate immune competence for protecting infection. Trial registration ClinicalTrials.gov: NCT01583972.


Subject(s)
Dietary Supplements , Research Design , Vitamin A/therapeutic use , BCG Vaccine/immunology , Bangladesh , Body Weights and Measures , Diphtheria-Tetanus-Pertussis Vaccine/immunology , Feeding Behavior , Female , Humans , Infant , Infant, Newborn , Male , Poliovirus Vaccine, Oral/immunology , Receptors, Antigen, T-Cell/metabolism , T-Lymphocytes/metabolism , Thymus Gland/growth & development , Vitamin A/administration & dosage
11.
BMC Pediatr ; 14: 92, 2014 Apr 04.
Article in English | MEDLINE | ID: mdl-24708735

ABSTRACT

BACKGROUND: Vitamin A supplementation significantly reduces all-cause mortality when given between 6-59 months of age, but has a null or detrimental effect when given between 1-5 months. Studies of neonatal vitamin A supplementation conducted across Africa and South Asia have produced conflicting findings. These age-pattern variations might result from immunological interactions between vitamin A supplementation and vaccines. Knowledge on the potential immunological sequelae of human neonatal vitamin A supplementation is so scarce that the foremost aim of this study is to seek indicative data on aspects of immunity likely to be affected by neonatal vitamin A supplementation. The objective of this trial is to test whether human neonatal vitamin A supplementation modulates immune function including improved thymic maturation in infancy and improved systemic immune responses to routine immunization. METHODS/DESIGN: In an area of moderate vitamin A deficiency in a peri-urban area of The Gambia, 200 mother-infant pairs were enrolled in a double-blind randomised controlled trial. Within 48 hours of birth, neonates were randomised with stratification by birth weight and sex to receive either an oral dose of 50,000 IU vitamin A or placebo. Expanded Programme of Immunisation birth vaccinations were administered after supplementation, with subsequent vaccinations administered at 8, 12 and 16 weeks of age. A range of immunological outcomes were examined up to 17 weeks of age, with additional morbidity and anthropometry follow-up carried out throughout the first year of life. The primary endpoint of this trial is the frequency of circulating T regulatory (Treg) cells expressing gut homing receptors in infants at 17 week post-supplementation, with secondary outcomes including thymus maturation and B cell immune responses. DISCUSSION: Indicative immunological data from this trial (and its Bangladeshi counterpart), will complement the larger randomised controlled trials (conducted in India, Tanzania and Ghana), on the effectiveness and safety of neonatal vitamin A supplementation in improving infant survival. Combined these trials, in addition to the existing trials, will inform policy. TRIAL REGISTRATION: clinicaltrials.gov NCT01476358.


Subject(s)
Antioxidants/administration & dosage , Dietary Supplements , Vitamin A/analogs & derivatives , B-Lymphocytes/metabolism , Diterpenes , Double-Blind Method , Flow Cytometry , Gambia , Hepatitis B Antibodies/blood , Humans , Immunization Programs , Infant , Infant, Newborn , Intestines/immunology , Receptors, Lymphocyte Homing/metabolism , Retinyl Esters , T-Lymphocytes, Regulatory/metabolism , Thymus Gland/growth & development , Vaccination , Vitamin A/administration & dosage
12.
Int J Biometeorol ; 58(10): 2153-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24676574

ABSTRACT

This research was conducted to investigate the effect of supplementation of zinc (Zn) and ascorbic acid (AA) in heat-stressed broilers. A total of 160-day-old broiler chicks of approximately the same weight and appearance were divided into four treatment groups (control, T1, T2, and T3). Control group was fed a standard diet without any supplementation. T1 was supplemented with Zn at the rate of 60 mg/kg of feed, T2 was supplemented with 300 mg/kg of feed AA, and T3 was supplemented with combination of Zn and AA. From week 3 to 5, heat stress environment was provided at the rate of 12 h at 25 °C, 3 h at 25 to 34 °C, 6 h at 34 °C, and 3 h at 34 to 25 °C daily. The results revealed that feed intake, body weight and feed conversion ratio (FCR), and weight of thymus, spleen, and bursa of Fabricius improved significantly (P < 0.05) in T3 compared to the other treatments. Antibody titer against Newcastle disease (ND), infectious bursal disease (IBD), and infectious bronchitis (IB) increased significantly (P < 0.05) in T2 and T3 groups. However, total leucocytes count, lymphocytes, and monocytes increased (P < 0.05) in all treated groups compared to control. The results indicated that the supplementation of Zn or AA alone or in combination improved the performance and immune status of broilers reared under heat stress.


Subject(s)
Ascorbic Acid/therapeutic use , Dietary Supplements , Heat Stress Disorders/drug therapy , Heat Stress Disorders/immunology , Zinc/therapeutic use , Animals , Antibodies, Viral/blood , Ascorbic Acid/pharmacology , Bursa of Fabricius/drug effects , Bursa of Fabricius/growth & development , Chickens , Drug Therapy, Combination , Eating/drug effects , Heat Stress Disorders/blood , Heat Stress Disorders/veterinary , Infectious bronchitis virus/immunology , Infectious bursal disease virus/immunology , Leukocyte Count , Newcastle disease virus/immunology , Organ Size/drug effects , Spleen/drug effects , Spleen/growth & development , Thymus Gland/drug effects , Thymus Gland/growth & development , Zinc/pharmacology
13.
Inhal Toxicol ; 26(4): 207-21, 2014 Mar.
Article in English | MEDLINE | ID: mdl-24568577

ABSTRACT

A formulation of tobacco extract containing 4% nicotine (TE) and similar nicotine formulation containing vehicle and 4% nicotine (NF) were evaluated using animal inhalation assays. Two 4-h inhalation exposures at 1 and 2 mg/L aerosol exposure concentrations, respectively, of the tobacco extract with 4% nicotine formulation showed that the LC50 was greater than 2 mg/L, the maximum concentration tested. All inhalation exposures were conducted using the capillary aerosol generator (CAG). Increasing aerosol TPM concentrations (0, 10, 50, 200, 1000 mg/m(3) TE and 0, 50, 200, 500, 1000 mg/m(3) NF) were generated via the CAG and used to expose groups of male and female rats for 4-h per day for 14 days. In life monitors for potential effects included clinical observations, weekly body weights and food consumption. Post mortem evaluations included gross tissue findings, hematology, clinical chemistry, serum plasma and nicotine levels, absolute and normalized organ and tissue weights, and histopathology of target organs. Treatment-related changes were observed in body weights, hematology, clinical chemistry, organ weights and histopathological findings for TE at the 200 and 1000 mg/m(3) exposure levels, and in the 500 and 1000 mg/m(3) exposure groups for NF. Under the conditions of these studies, the no-observed-adverse-effect level in the rat was approximately 50 mg/m(3) for the TE aerosol-exposed groups, and approximately 200 mg/m(3) in the NF aerosol-exposed groups.


Subject(s)
Nicotiana , Nicotine/toxicity , Plant Extracts/toxicity , Administration, Inhalation , Animals , Body Weight/drug effects , Cotinine/blood , Eating/drug effects , Female , Larynx/drug effects , Larynx/pathology , Male , Nicotine/blood , Nicotine/pharmacokinetics , No-Observed-Adverse-Effect Level , Organ Size/drug effects , Rats , Rats, Sprague-Dawley , Spleen/drug effects , Spleen/growth & development , Spleen/pathology , Thymus Gland/drug effects , Thymus Gland/growth & development , Thymus Gland/pathology , Toxicity Tests, Acute , Toxicity Tests, Subacute
14.
Int J Biometeorol ; 58(5): 741-52, 2014 Jul.
Article in English | MEDLINE | ID: mdl-23525898

ABSTRACT

A study was conducted using 360 broiler chickens to evaluate the effects of dietary vitamin E (0, 125 and 250 mg/kg), selenium (Se, 0, 0.5 and 1 mg/kg), or their different combinations on immune response and blood biological parameters of broilers raised under either thermoneutral (TN, 23.9 °C constant) or heat stress (HS, 23.9 to 37 °C cycling) conditions. Humoral immunity was assessed by intravenous injection of 7% sheep red blood cell (SRBC) followed by evaluation of serum for antibody titers in primary and secondary responses. Heterophil to lymphocyte (H/L) ratio also determined as an indicator of stress. Furthermore, at the end of the experiment, birds were bled for determination of some biological parameters. There was a significant reduction in body weight and feed intake, but the feed conversion ratio increased when the birds were exposed to HS (P<0.05). Body weight and feed intake were not influenced significantly by dietary vitamin E and Se (P>0.05), whereas feed conversion was improved significantly by 125 mg/kg vitamin E (P<0.05). The liver and lymphoid organ weights as well as IgM and IgG, antibody titers for primary and secondary antibody responses to SRBC were reduced significantly under HS (P<0.05). Heat stress also resulted in a significant increase in H/L ratio (P<0.05). Dietary vitamin E resulted in improvement of primary and secondary antibody responses both in TN and HS broilers (P<0.05). The HS birds also showed an improved antibody titer in secondary response with high concentration of Se (P<0.05). Vitamin E and Se had interactive effects on anti-SRBC titers; however, no consistent differences were found between dietary levels during the study. The H/L ratio decreased by feeding vitamin E at both levels either under HS or TN conditions (P < 0.05). The serum concentrations of glucose, triglycerides, total cholesterol, and LDL-cholesterol were increased but serum HDL-cholesterol decreased in HS broilers (P<0.05).


Subject(s)
Antioxidants/pharmacology , Heat Stress Disorders/blood , Heat Stress Disorders/immunology , Selenium/pharmacology , Vitamin E/pharmacology , Animal Feed , Animals , Antibodies/immunology , Blood Glucose/analysis , Chickens , Diet , Eating , Erythrocytes/immunology , Heat Stress Disorders/veterinary , Immunity, Humoral/drug effects , Lipids/blood , Liver/drug effects , Liver/growth & development , Lymphocytes/immunology , Organ Size/drug effects , Sheep , Spleen/drug effects , Spleen/growth & development , Temperature , Thymus Gland/drug effects , Thymus Gland/growth & development
15.
J Med Food ; 16(7): 663-8, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23875906

ABSTRACT

Crude polysaccharides (PSs) were isolated from the fruit pulp of jackfruit, and their chemical composition determined and evaluated for an immune regulatory activity in mice. The PSs were isolated from water extracts of jackfruit pulp (JFP) using the ethanol precipitation method. The resulting precipitates were further purified by dialysis and protein depletion by the Sevage method. The phenol-sulfuric method was used to determine the content of the PSs. The composition of PSs was determined by the Sephadex-G200 column chromatography and high-performance liquid chromatography methods. The thymus index and macrophage phagocytic function methods in mice were used to evaluate the immune regulatory activity of JFP-PSs. The JFP-PSs content in jackfruit was about 21% (w/w) and the yield of crude PSs was 3.91%. The single molecular mass weight PS was the main constituent of JFP-PSs. The major monosaccharide residues were rhamnose, glucose, galactose, and arabinose. The JFP-PSs enhanced the thymus weight index and the phagocytic rate after 30 days of subchronic p.o. administration to mice at 4.5 mg/kg. The JFP contains single molecular PS and JFP-PS has immune-stimulating activities in mice. These data suggest that at least some of the traditional uses of JFP can be ascribed to its immunomodulatory effects.


Subject(s)
Artocarpus/chemistry , Immune System/drug effects , Immunologic Factors/administration & dosage , Plant Extracts/administration & dosage , Polysaccharides/administration & dosage , Animals , Fruit/chemistry , Immunologic Factors/chemistry , Immunologic Factors/isolation & purification , Macrophages/drug effects , Macrophages/immunology , Male , Mice , Molecular Weight , Organ Size/drug effects , Phagocytosis/drug effects , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Polysaccharides/chemistry , Polysaccharides/isolation & purification , Thymus Gland/drug effects , Thymus Gland/growth & development , Up-Regulation/drug effects
16.
Regul Toxicol Pharmacol ; 67(2 Suppl): S10-29, 2013 Nov 01.
Article in English | MEDLINE | ID: mdl-23247261

ABSTRACT

The repeat-dose and developmental toxicities of certain petroleum refinery streams are related to their polycyclic aromatic compound (PAC) content (Feuston et al., 1994). Building on this foundation, and working within the context of the US EPA High Production Volume (HPV) Chemical Challenge Program, we: (1) characterized relationships between PAC content and repeat-dose and developmental toxicities of high boiling petroleum substances (HBPS), and (2) developed statistical models that can be used to predict critical effects of similar untested substances. Data from 39 dermal toxicity studies of HBPS were used to develop statistical models to predict the dose-response relationships between the weight percent concentration of each of their 1-7 aromatic ring classes and 4 repeat-dose and 3 developmental endpoints (absolute thymus weight, hemoglobin count, platelet count, liver to body weight, live fetus count, fetal weight, and percent resorptions). The correlations between the observed and model-predicted values are >0.90. The predictive ability of the models was tested via a series of evaluation or corroboration methods. As is shown in the paper, using only compositional data of untested HBPS, the models can be used to predict the effect at a given dose or the dose that causes an effect of a stipulated magnitude.


Subject(s)
Models, Statistical , Petroleum/toxicity , Polycyclic Aromatic Hydrocarbons/toxicity , Animals , Dose-Response Relationship, Drug , Female , Fetal Development/drug effects , Fetal Resorption , Hemoglobins/analysis , Litter Size , Liver/drug effects , Liver/growth & development , Mice , Organ Size/drug effects , Platelet Count , Polycyclic Aromatic Hydrocarbons/chemistry , Pregnancy , Rats , Rats, Sprague-Dawley , Thymus Gland/drug effects , Thymus Gland/growth & development , Toxicity Tests , Transition Temperature
17.
BMC Pregnancy Childbirth ; 12: 107, 2012 Oct 11.
Article in English | MEDLINE | ID: mdl-23057665

ABSTRACT

BACKGROUND: Recent observational research indicates that immune development may be programmed by nutritional exposures early in life. Such findings require replication from trials specifically designed to assess the impact of nutritional intervention during pregnancy on infant immune development. The current trial seeks to establish: (a) which combination of protein-energy (PE) and multiple-micronutrient (MMN) supplements would be most effective; and (b) the most critical periods for intervention in pregnancy and infancy, for optimal immune development in infancy. METHODS/DESIGN: The ENID Trial is a 2 x 2 x 2 factorial randomized, partially blind trial to assess whether nutritional supplementation to pregnant women (from < 20 weeks gestation to term) and their infants (from 6 to 12 months of age) can enhance infant immune development. Eligible pregnant women from the West Kiang region of The Gambia (pregnancy dated by ultrasound examination) are randomized on entry to 4 intervention groups (Iron-folate (FeFol = standard care), multiple micronutrients (MMN), protein-energy (PE), PE + MMN). Women are visited at home weekly for supplement administration and morbidity assessment and seen at MRC Keneba at 20 and 30 weeks gestation for a detailed antenatal examination, including ultrasound. At delivery, cord blood and placental samples are collected, with detailed infant anthropometry collected within 72 hours. Infants are visited weekly thereafter for a morbidity questionnaire. From 6 to 12 months of age, infants are further randomized to a lipid-based nutritional supplement, with or without additional MMN. The primary outcome measures of this study are thymic development during infancy, and antibody response to vaccination. Measures of cellular markers of immunity will be made in a selected sub-cohort. Subsidiary studies to the main trial will additionally assess the impact of supplementation on infant growth and development to 24 months of age. DISCUSSION: The proposed trial is designed to test whether nutritional repletion can enhance early immune development and, if so, to help determine the most efficacious form of nutritional support. Where there is evidence of benefit from a specific intervention/combination of interventions, future research should focus on refining the supplements to achieve the optimal, most cost-effective balance of interventions for improved health outcomes.


Subject(s)
Dietary Fats/administration & dosage , Dietary Proteins/administration & dosage , Micronutrients/therapeutic use , Nutritional Support/methods , Thymus Gland/growth & development , Adult , Child Development , Dietary Supplements , Female , Fetal Development , Folic Acid/therapeutic use , Gambia , Humans , Immune System/embryology , Immune System/growth & development , Infant , Infant, Newborn , Iron/therapeutic use , Pregnancy , Rural Health Services , Thymus Gland/embryology
18.
Endocrine ; 41(2): 338-41, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22212440

ABSTRACT

To investigate the adrenal effect of a phytosterol (PS) additive, 80 male Japanese quail were divided into four sub-groups and fed 0, 40, 400, and 4,000 ppm of PS, respectively, for 21 days. Subsequently, 50% of the birds from each dosage group were subjected to a 6-day adrenal function test, whereby they were injected with long-lasting adrenocorticotropin (ACTH). The remaining quail in each PS dosage group were raised under normal conditions. The groups receiving 400 and 4000 ppm PS exhibited decreased serum levels of LDL-cholesterol with and without ACTH stimulation (P < 0.01). No amount of dose of PS changed serum corticosterone (CORT) under normal conditions (P > 0.05). Enhancement of CORT was observed on the 2nd and the 6th days of the ACTH challenge in birds receiving 400 ppm (P < 0.05). Average ACTH-induced CORT levels in the 400 ppm group were higher than in the 0 ppm group (P < 0.01). Our results demonstrated that PS can boost ACTH-induced CORT levels in male Japanese quail.


Subject(s)
Adrenal Glands/physiology , Adrenocorticotropic Hormone/metabolism , Anticholesteremic Agents/adverse effects , Dietary Supplements/adverse effects , Phytosterols/adverse effects , Adrenal Cortex Function Tests , Adrenal Glands/growth & development , Animals , Body Weight , Cholesterol, LDL/blood , Corticosterone/blood , Coturnix , Male , Organ Size , Thymus Gland/growth & development
19.
Br J Nutr ; 107(6): 858-66, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21787453

ABSTRACT

The present study was conducted to investigate the effects of dietary yeast (Saccharomyces cerevisiae) cell walls (YCW) from the yeast extract industry on performance and immune function of cyclosporine A (CSA)-treated, immunosuppressed broiler chickens. A total of 240 day-old male broilers were allocated randomly into four treatments: (1) non-challenged control; (2) non-challenged control+0·3 % YCW; (3) CSA-challenged group; (4) CSA-challenged+0·3 % YCW. On days 1-4 and 22-25 of age, broilers were subcutaneously injected with CSA or sterile saline. The results showed that supplementation of YCW significantly improved daily weight gain (DWG) during the starter (days 1-21, P < 0·01), finisher (days 22-42, P < 0·01) and overall (days 1-42, P < 0·05) periods compared with the control birds, but had no effect on feed conversion ratio (FCR, P>0·05). Compared with the CSA-treated birds, YCW alleviated the decrease of DWG (P < 0·01) and increase of FCR (P < 0·05) caused by CSA challenge at different periods and cumulatively. On days 21 and 42, YCW mitigated the CSA-induced decrease of peripheral blood lymphocyte blastogenic response (P < 0·01). In addition, YCW improved the relative weights of the bursa of Fabricius (P < 0·01) and thymus (P < 0·01) and up-regulated the splenic expression of pro-inflammatory cytokines IL-1ß (P < 0·01) and IL-6 (P < 0·01) on day 42 compared with the CSA-treated birds. These results indicate that YCW supplementation has beneficial effects in attenuating the immunosuppressive effects of CSA challenge, therefore improving growth performance of broiler chickens.


Subject(s)
Cell Wall/metabolism , Chickens/growth & development , Chickens/immunology , Dietary Supplements , Immunity, Cellular , Immunosuppression Therapy/veterinary , Yeast, Dried/therapeutic use , Animals , Avian Proteins/genetics , Avian Proteins/metabolism , Bursa of Fabricius/cytology , Bursa of Fabricius/growth & development , Bursa of Fabricius/immunology , Cells, Cultured , Cyclosporine , Energy Intake , Immunosuppression Therapy/adverse effects , Interleukins/genetics , Interleukins/metabolism , Lymphocytes/cytology , Lymphocytes/immunology , Male , Organ Size , Poultry Diseases/immunology , Poultry Diseases/prevention & control , RNA, Messenger/metabolism , Spleen/cytology , Spleen/growth & development , Spleen/immunology , Spleen/metabolism , Thymus Gland/cytology , Thymus Gland/growth & development , Thymus Gland/immunology , Up-Regulation , Weight Gain , Yeast, Dried/metabolism
20.
Poult Sci ; 91(1): 74-88, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22184431

ABSTRACT

There is interest in the enrichment of poultry meat with long-chain n-3 polyunsaturated fatty acids in order to increase the consumption of these fatty acids by humans. However, there is concern that high levels of n-3 polyunsaturated fatty acids may have detrimental effects on immune function in chickens. The effect of feeding increasing levels of fish oil (FO) on immune function was investigated in broiler chickens. Three-week-old broilers were fed 1 of 4 wheat-soybean basal diets that contained 0, 30, 50, or 60 g/kg of FO until slaughter. At slaughter, samples of blood, bursa of Fabricius, spleen, and thymus were collected from each bird. A range of immune parameters, including immune tissue weight, immuno-phenotyping, phagocytosis, and cell proliferation, were assessed. The pattern of fatty acid incorporation reflected the fatty acid composition of the diet. The FO did not affect the weight of the spleen, but it did increase thymus weight when fed at 50 g/kg (P < 0.001). Fish oil also lowered bursal weights when fed at 50 or 60 g/kg (P < 0.001). There was no significant effect of FO on immune cell phenotypes in the spleen, thymus, bursa, or blood. Feeding 60 g/kg of FO significantly decreased the percentage of monocytes engaged in phagocytosis, but it increased their mean fluorescence intensity relative to that of broilers fed 50 g/kg of FO. Lymphocyte proliferation was significantly decreased after feeding broiler chickens diets rich in FO when expressed as division index or proliferation index, although there was no significant effect of FO on the percentage of divided cells. In conclusion, dietary n-3 polyunsaturated fatty acids decrease phagocytosis and lymphocyte proliferation in broiler chickens, highlighting the need for the poultry industry to consider the health status of poultry when poultry meat is being enriched with FO.


Subject(s)
Chickens/immunology , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Unsaturated/pharmacology , Fish Oils/pharmacology , Animals , Blood Chemical Analysis/veterinary , Body Weight , Bursa of Fabricius/drug effects , Bursa of Fabricius/growth & development , Chickens/blood , Chickens/metabolism , Chromatography, Gas/veterinary , Dose-Response Relationship, Drug , Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/metabolism , Fatty Acids, Unsaturated/administration & dosage , Fatty Acids, Unsaturated/metabolism , Fish Oils/administration & dosage , Fish Oils/metabolism , Flow Cytometry/veterinary , Leukocytes/drug effects , Lymphocyte Subsets/drug effects , Male , Organ Size , Spleen/drug effects , Spleen/growth & development , Thymus Gland/drug effects , Thymus Gland/growth & development
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