lipid-a has been researched along with Body-Weight* in 11 studies
1 review(s) available for lipid-a and Body-Weight
1 trial(s) available for lipid-a and Body-Weight
10 other study(ies) available for lipid-a and Body-Weight
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MPL and CpG combination adjuvants promote homologous and heterosubtypic cross protection of inactivated split influenza virus vaccine.
Annual vaccination is not effective in conferring cross-protection against antigenically different influenza viruses. Therefore, it is of high priority to improve the cross protective efficacy of influenza vaccines. We investigated the adjuvant effects of monophosphoryl lipid A (MPL) and oligodeoxynucleotide CpG (CpG) on promoting homologous protection and cross-protection after vaccination of C57BL/6 and BALB/c mice with inactivated split virus. Combination adjuvant effects of MPL and CpG on improving homologous and cross protective vaccine efficacy were evident as shown by higher levels of homologous and cross-reactive binding IgG and hemagglutination inhibiting antibodies. Combination adjuvant effects on enhancing the protective efficacy against homologous and heterosubtypic virus were demonstrated by less weight loss, lower airway inflammatory disease, and better control of viral loads as well as prevention of inflammatory cytokines and cellular infiltrates. Overall, the findings in this study suggest that a combination adjuvant of different toll-like receptor ligands exhibits a unique pattern of innate and adaptive immune responses, contributing to improved homologous and heterosubtypic cross-protection by inactivated split virion influenza vaccination. Topics: Adjuvants, Immunologic; Animals; Antibodies, Viral; Body Weight; Cross Protection; Cytokines; Disease Models, Animal; Humans; Immunoglobulin G; Influenza Vaccines; Influenza, Human; Lipid A; Mice, Inbred BALB C; Mice, Inbred C57BL; Oligodeoxyribonucleotides; Vaccines, Inactivated; Vaccines, Subunit; Viral Load | 2018 |
Pharmacological TLR4 Inhibition Protects against Acute and Chronic Fat-Induced Insulin Resistance in Rats.
To evaluate whether pharmacological TLR4 inhibition protects against acute and chronic fat-induced insulin resistance in rats.. For the acute experiment, rats received a TLR4 inhibitor [TAK-242 or E5564 (2x5 mg/kg i.v. bolus)] or vehicle, and an 8-h Intralipid (20%, 8.5 mg/kg/min) or saline infusion, followed by a two-step hyperinsulinemic-euglycemic clamp. For the chronic experiment, rats were subcutaneously implanted with a slow-release pellet of TAK-242 (1.5 mg/d) or placebo. Rats then received a high fat diet (HFD) or a low fat control diet (LFD) for 10 weeks, followed by a two-step insulin clamp.. Acute experiment; the lipid-induced reduction (18%) in insulin-stimulated glucose disposal (Rd) was attenuated by TAK-242 and E5564 (the effect of E5564 was more robust), suggesting improved peripheral insulin action. Insulin was able to suppress hepatic glucose production (HGP) in saline- but not lipid-treated rats. TAK-242, but not E5564, partially restored this effect, suggesting improved HGP. Chronic experiment; insulin-stimulated Rd was reduced ~30% by the HFD, but completely restored by TAK-242. Insulin could not suppress HGP in rats fed a HFD and TAK-242 had no effect on HGP.. Pharmacological TLR4 inhibition provides partial protection against acute and chronic fat-induced insulin resistance in vivo. Topics: Animals; Body Weight; Diet, High-Fat; Glucose; Insulin Resistance; Lipid A; Lipids; Liver; Male; Obesity; Rats, Long-Evans; Rats, Wistar; Sulfonamides; Toll-Like Receptor 4 | 2015 |
Body weight and waist circumference as predictors of vitamin D deficiency in patients with type 2 diabetes and cardiovascular disease.
Vitamin D deficiency is a well-established risk factor for bone disease, but emerging data suggest that altered vitamin D homeostasis may play a role in the development of type 2 diabetes mellitus (T2DM), dyslipidemia hypertension, and other cardiovascular diseases (CVD). The aim of this study was to investigate the prevalence of vitamin D deficiency in patients with T2DM with/without CVD, to correlate it with anthropometric and metabolic parameters and to determine the predictors of vitamin D deficiency.. A total of 88 patients with T2DM (49 male/39 female, aged 61.0 +/- 0.9 yrs, body mass index (BMI) 29.9 +/- 0.4 kg/m2) and 67 patients (44 male/23 female, aged 63.6 +/- 1.0 yrs, BMI 29.2 +/- 0.5 kg/m2) with T2DM and CVD (myocardial infarction in 57 patients and angina pectoris in 10 patients) were included in this study. These patients were compared with 87 healthy subjects (35 male/52 female, aged 52.8 +/- 1.4 yrs, BMI 27.2 +/- 0.5 kg/m2). Weight, height, waist circumference and BMI were recorded in all patients. Also, total cholesterol, triglycerides, hemoglobin A1c (HbA1c) and 25-hydroxy-vitamin D [25(OH)D] levels were measured in all. According to 25(OH)D level, all subjects were divided into three categories: severe vitamin D deficiency (< or = 15 ng/mL), vitamin D insufficiency (15-20 ng/mL) and vitamin D sufficiency (?20 ng/mL). We correlated vitamin D levels with anthropometric and metabolic status and determined the predictors of vitamin D deficiency.. Severe vitamin D deficiency was registered in 16.1% healthy subjects, in 21.6% patients with T2DM and in 26.9% patients with T2DM and CVD. Patients with T2DM who were vitamin D deficient had increased weight, waist circumference, cholesterol and triglyceride levels when compared with patients with T2DM who had sufficient vitamin D level. 25(OH)D levels correlated with BMI and waist circumference in all subjects, but did not correlate with metabolic parameters (lipids, HbA1c). The best predictors of vitamin D level in all subjects were weight, waist circumference and BMI.. The high prevalence of vitamin D deficiency in patients with T2DM and particularly in patients with T2DM and CVD suggests that supplementation with vitamin D may be beneficial although there is still not sufficient evidence for recommending prescribing vitamin D. Topics: Body Mass Index; Body Weight; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Lipid A; Male; Middle Aged; Risk Factors; Vitamin D Deficiency; Waist Circumference | 2013 |
Evaluation of the intramuscular administration of Cervarix™ vaccine on fertility, pre- and post-natal development in rats.
Cervarix™ is a prophylactic human papillomavirus (HPV)-16/18 vaccine for the prevention of cervical cancer. It contains GSK Biologicals' proprietary Adjuvant System AS04. The objective of this study was to investigate the effects of Cervarix™ and of AS04 on female fertility and pre- and post-natal development in Sprague Dawley rats. Female rats were injected with vaccine, AS04, or saline 30 days before mating and on Gestation Days 6, 8, 11 and 15. Each dose of vaccine was one-fifth the human dose volume. Treatment of rats with vaccine or AS04 was not associated with any systemic toxicity and had no impact on female fertility. There were no adverse effects on pre- or post-natal development of litters from treated rats, as judged by fetal evaluation at Gestation Day 20, and growth and survival of pups to postnatal Day 25. These results support the use of the vaccine in the targeted human population. Topics: Alphapapillomavirus; Aluminum Hydroxide; Animals; Animals, Newborn; Body Weight; Embryo, Mammalian; Embryonic Development; Female; Fertility; Fetal Development; Injections, Intramuscular; Lactation; Lipid A; Longevity; Maternal Exposure; Papillomavirus Vaccines; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Toxicity Tests | 2011 |
Low-dose intraperitoneal Freund's adjuvant: toxicity and immunogenicity in mice using an immunogen targeting amyloid-beta peptide.
Complete Freund's adjuvant (CFA) is effective for potentiating immune responses in mice when administered subcutaneously, and is often more potent when given intraperitoneally (i.p.). However, the the potential toxicity of i.p. administration in mice has led investigators and Institutional Animal Care and Use committees to increasingly view the use of CFA i.p. with reservation. We evaluated whether an 80% reduction in the dose of CFA administered i.p. to mice, compared to the i.p. doses used in a previous analysis, could abrogate the untoward effects associated with its use, while still maintaining adjuvanticity. Using a novel immunogen targeting the N-terminus of the 42-amino acid amyloid-beta peptide, we compared low dose CFA administered i.p., with three other commonly used adjuvants given i.p.: alum, incomplete Freunds adjuvant (IFA) and monophoshoryl lipid A + trehalose dicorynomycolate (MPL + TDM). The results of the study showed that, though the reduction in intraperitoneal dose of CFA mitigated transient weight loss and leukocytosis observed previously with higher doses of i.p. CFA, all mice administered CFA or IFA i.p. developed abdominal adhesions and granulomatous peritonitis. Mice from all adjuvant groups, however, appeared to tolerate the respective adjuvants well and excellent comparative immunogenicity was observed in mice immunized with the Freunds and MPL + TDM adjuvants. Consequently, we conclude that though a high-titered, humoral response may be generated using low dose CFA administered i.p., the accompanying toxicity remains significant, and thus alternative adjuvants and/or routes should be considered. Topics: Adjuvants, Immunologic; Alum Compounds; Alzheimer Vaccines; Amyloid beta-Peptides; Animals; Antibodies; Body Weight; Cord Factors; Female; Freund's Adjuvant; Injections, Intraperitoneal; Leukocyte Count; Lipid A; Mice; Mice, Inbred C57BL; Models, Animal; Spleen | 2006 |
Evaluation of the Mtb72F polyprotein vaccine in a rabbit model of tuberculous meningitis.
Using a rabbit model of tuberculous meningitis, we evaluated the protective efficacy of vaccination with the recombinant polyprotein Mtb72F, which is formulated in two alternative adjuvants, AS02A and AS01B, and compared this to vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) alone or as a BCG prime/Mtb72F-boost regimen. Vaccination with Mtb72F formulated in AS02A (Mtb72F+AS02A) or Mtb72F formulated in AS01B (Mtb72F+AS01B) was protective against central nervous system (CNS) challenge with Mycobacterium tuberculosis H37Rv to an extent comparable to that of vaccination with BCG. Similar accelerated clearances of bacilli from the cerebrospinal fluid, reduced leukocytosis, and less pathology of the brain and lungs were noted. Weight loss of infected rabbits was less extensive for Mtb72F+AS02A-vaccinated rabbits. In addition, protection against M. tuberculosis H37Rv CNS infection afforded by BCG/Mtb72F in a prime-boost strategy was similar to that by BCG alone. Interestingly, Mtb72F+AS01B induced better protection against leukocytosis and weight loss, suggesting that the polyprotein in this adjuvant may boost immunity without exacerbating inflammation in previously BCG-vaccinated individuals. Topics: Adjuvants, Immunologic; Animals; Bacterial Proteins; Body Weight; Central Nervous System; Disease Models, Animal; Drug Combinations; Drug Evaluation, Preclinical; Immunity, Active; Immunization, Secondary; Lipid A; Lung; Mycobacterium bovis; Mycobacterium tuberculosis; Rabbits; Recombinant Proteins; Saponins; Tuberculosis Vaccines; Tuberculosis, Meningeal | 2006 |
Essential role of inducible nitric oxide synthase in monophosphoryl lipid A-induced late cardioprotection: evidence from pharmacological inhibition and gene knockout mice.
Monophosphoryl lipid A (MLA), a nontoxic analogue of endotoxin, is a pharmacological agent that is known to have anti-ischemic effects. Mechanisms involved with the cardioprotection are still unclear. A role for inducible nitric oxide synthase (iNOS) was recently proposed. We tested this hypothesis using S-methylisothiourea (SMT), one of the specific pharmacological inhibitors of iNOS, as well as iNOS gene knockout mice.. Adult male ICR or B6,129 mice were pretreated with either MLA 35 or 350 microg/kg IP (MLA35 or MLA350) or vehicle 24 hours before global ischemia/reperfusion, which was carried out in a Langendorff isolated perfused heart model (n=8 to 9 per group). Another group of MLA350 mice received SMT 3 mg/kg IP 30 minutes before heart perfusion. Ventricular contractile function and heart rate were not different between the groups during the preischemia and reperfusion periods (P>0.05). Preischemic basal coronary flow was significantly increased in all MLA350 but not MLA35 mice. Myocardial infarct size was reduced significantly, from 26.9+/-2.9% of risk area in vehicle-treated mice to 13.5+/-2.4% in the MLA350 group (mean+/-SEM, P<0.05). This reduction in infarct size was accompanied by augmented nitrite/nitrate accumulation, from 0.23+/-0. 05 nmol/mg protein in the vehicle group to 0.97+/-0.27 nmol/mg protein in MLA350 mice (P<0.01). Infarct size increased significantly, to 22.2+/-2.8% after treatment with SMT in the MLA350 group. Furthermore, MLA350 failed to reduce infarct size in iNOS knockout mice (25.5+/-3.6%).. These results demonstrate a direct association of infarct size reduction with increased NO production with MLA350. An obligatory role for iNOS in mediating the cardioprotective effect induced by MLA was confirmed with the pharmacological inhibition and gene knockout mice. Topics: Animals; Body Weight; Cardiotonic Agents; Coronary Circulation; Enzyme Inhibitors; Heart Rate; Hemodynamics; In Vitro Techniques; Isothiuronium; Lipid A; Male; Mice; Mice, Inbred ICR; Mice, Knockout; Myocardial Contraction; Myocardial Infarction; Myocardial Ischemia; Myocardial Reperfusion; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Organ Size; Ventricular Function | 1999 |
Monophosphoryl lipid A preserves myocardial contractile function following multiple, brief periods of coronary occlusion in dogs.
The effects of a 1- or 24-hour pretreatment regimen with monophosphoryl lipid A (MLA, 35 micrograms/kg i.v.) on myocardial stunning produced by repetitive coronary occlusions were studied in barbital-anesthetized dogs. Regional segment function (%SS) and myocardial blood flow were measured by sonomicrometry and the radioactive microsphere technique, respectively. In controls, six 5-min periods of coronary occlusion interpersed with 10-min periods of reperfusion and ultimately followed by 2 h of reperfusion produced regional segment dysfunction. Pretreatment with MLA for 1 h prior to the first occlusion period had no effect on %SS, however, pretreatment with MLA 24 h prior to the first occlusion period resulted in a significant (p < 0.05) improvement in the recovery of %SS at all reperfusion periods as compared to the control group. In addition, segment dysfunction during each occlusion period was significantly less severe in animals receiving a 24-hour pretreatment with MLA as compared to the controls. These results are the first to demonstrate that MLA, a lipid A derivative of endotoxin, preserves contractile function of ischemic myocardium in an in vivo canine model and that its cardio-protection is time dependent. Topics: Animals; Arterial Occlusive Diseases; Blood Gas Analysis; Body Weight; Coronary Circulation; Coronary Disease; Dogs; Female; Hemodynamics; Hydrogen-Ion Concentration; Hypertrophy, Left Ventricular; Lipid A; Male; Microspheres; Myocardial Contraction; Myocardial Reperfusion Injury; Organ Size | 1995 |
Synthetic lipid A with endotoxic and related biological activities comparable to those of a natural lipid A from an Escherichia coli re-mutant.
A synthetic compound (506), beta (1-6) D-glucosamine disaccharide 1,4'-bisphosphate, which is acylated at 2'-amino and 3'-hydroxyl groups with (R)-3-dodecanoyloxytetradecanoyl and (R)-3-tetradecanoyloxytetradecanoyl groups, respectively, and has (R)-3-hydroxytetradecanoyl groups at 2-amino and 3-hydroxyl groups, exhibited full endotoxic activities identical to or sometimes stronger than those of a reference lipid A from an Escherichia coli Re-mutant (strain F515). Endotoxic activities tested include pyrogenicity and leukopenia-inducing activity in rabbits, body weight-decreasing toxicity in normal mice, lethal toxicity in galactosamine-sensitized mice and chicken embryos, and the preparation and provocation of the local Shwartzman reaction in rabbits. Compound 406, a synthetic counterpart of a biosynthetic precursor of lipid A molecule, showed by contrast only weak activities in all of the above assay systems except for the lethality in galactosamine-loaded mice. This finding strongly suggests that the presence of acyloxyacyl groups at the C-2' and C-3' positions of the disaccharide backbone is one of the most important determinant structures of the lipid A molecule for exhibition of strong biological activities characteristic of lipopolysaccharide and its lipid A moiety. The activities of the corresponding 4'-monophosphate (compound 504) and 1-monophosphate (505) analogs were considerably less than those of the parent molecule 506 and the reference F515 lipid A. Regarding other biological activities, not only compound 506 but also compounds 504, 505, and 406 showed definite activities, sometimes comparable to those of F515 lipid A and other reference natural products. These are the activation of Tachypleus tridentatus amoebocyte clotting enzyme cascade and human complement via the classical pathway, mitogenic and polyclonal B-cell activation of murine splenocytes, stimulation of peritoneal macrophages in a guinea pig, enhancement of migration of human blood polymorphonuclear leukocytes, and induction of a serum factor that is cytostatic and cytocidal to L-929 cells in Mycobacterium bovis BCG-primed mice. Relative potencies of test synthetic compounds depended on the assay systems and varied from one system to another. Dephospho-compound 503 lacked most of the biological activities that were definitely observed with phosphorylated compounds, probably because of its insolubility. This study demonstrates the successful chemical synthesis of an E. coli-type Topics: Adjuvants, Immunologic; Animals; Body Weight; Chemotaxis, Leukocyte; Complement Activation; Endotoxins; Escherichia coli; Fever; Glycoproteins; Leukopenia; Limulus Test; Lipid A; Lymphocyte Activation; Macrophage Activation; Mice; Mice, Inbred Strains; Shwartzman Phenomenon; Structure-Activity Relationship; Tumor Necrosis Factor-alpha | 1985 |
Hepatic drug-metabolizing enzyme system and endotoxin tolerance: structural requirement of LPS in induction of an early tolerance.
The alteration of hepatic drug-metabolizing enzyme activities in mice given Salmonella endotoxin by single or multiple intraperitoneal injections was investigated. An essentially the same biphasic, early and late phase, endotoxin tolerance was observed in the animals receiving a single injection of endotoxin or repetitive daily injections. The results of reciprocal cross tolerance tests using lipopolysaccharide and free lipid A preparations derived from Salmonella minnesota, Salmonella typhimurium, E. coli, Pseudomonas aeruginosa, and Chromobacterium violaceum suggested that lipid A moiety plays an important role in the induction of early endotoxin tolerance to endotoxin response. Topics: Animals; Body Weight; Cytochrome P-450 Enzyme System; Drug Tolerance; Endotoxins; Lipid A; Lipopolysaccharides; Liver; Male; Mice; Polysaccharides, Bacterial; Salmonella | 1984 |