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At least 379 records · Page 21Linked to original sources
PubMed2000

Polysulphated glycosaminoglycan treatments can mitigate decreases in stiffness of articular cartilage in a traumatized animal joint.

A single, blunt impact to the rabbit patellofemoral joint has been shown to decrease the stiffness of retropatellar cartilage and increase the thickness of the underlying bone. Polysulphated glycosaminoglycan treatments, on the other hand, have been shown to inhibit the degradation of articular cartilage and possibly increase synthesis of collagen and glycosaminoglycans in experimental studies on diseased joints. The aim of the current study was to examine the effect of early treatments with polysulphated glycosaminoglycans on cartilage using an in vivo post-trauma animal model. The study used 24 Flemish Giant rabbits in three groups: control, impacted, and impacted with treatment. Treatment consisted of intramuscular injections the day of insult and every 4 days thereafter for 6 weeks. At 30 weeks after trauma, mechanical tests were performed on the retropatellar cartilage to determine its mechanical stiffness. The patellae were also grossly evaluated for surface lesions on the retropatellar cartilage and histologically processed to measure the thickness of the subchondral bone. The rabbits that received no treatment had a statistically significant decrease in stiffness (modulus) for the cartilage of the impacted patellae compared with that of the contralateral, unimpacted patellae and compared with the cartilage of rabbits in the control group. The degradation in mechanical stiffness, however, was not observed in patellae of rabbits in the group receiving treatment. There was also a significant increase in the underlying thickness of the subchondral plate on the impacted patellae compared with that on the contralateral, unimpacted sides for rabbits in both the treated and nontreated groups. In conclusion, the polysulphated glycosaminoglycan treatments minimized a decrease in mechanical stiffness (modulus) of retropatellar articular cartilage 30 weeks after trauma. The mechanism by which the mechanical stiffness of the cartilage was preserved is unknown.

Animals↗
PubMed2005

Mitigation of susceptibility-induced signal loss in neuroimaging using localized shim coils.

Correction of magnetic field distortions is essential for obtaining accurate brain blood-oxygen-level-dependent functional magnetic resonance imaging (fMRI) activation maps. The present work introduces an active shimming method that utilizes the magnetic field generated by resistive shim coils placed in the mouth to locally homogenize the magnetic field in the inferior portion of the frontal lobe, where the field is most seriously distorted. The shimming field can be optimized in situ patient by patient for the region of interest of the scanner operator's choice. The method at 1.5 T is shown to be effective in reducing field inhomogeneity and in recovery of fMRI signal. For example, in a region of interest approximately of 149 cm3, a coil of simple geometry can reduce the root mean square of the magnetic field by more than 50% and the recovered signal increases the extent of activation detected in a breath-holding fMRI experiment.

Artifacts↗
PubMedDate not supplied

Current United States Department of Agriculture-Agricultural Research Service research on understanding agrochemical fate and transport to prevent and mitigate adverse environmental impacts.

Environmentally and economically viable agriculture requires a variety of cultivation practices and pest management options as no one system will be appropriate for every situation. Agrochemicals are some of the many pest control tools used in an integrated approach to pest management. They are applied with the intent of maximizing efficacy while minimizing off-site movement; however, their judicious use demands a practical knowledge of their fate and effects in agricultural and natural ecosystems. Agrochemical distribution into environmental compartments is influenced by the physical and chemical properties of the agrochemical and environmental conditions, ie soil type and structure, and meteorological conditions. Agricultural Research Service (ARS) researchers working in the area of agrochemical fate have focused on accurately describing those processes that govern the transport, degradation and bioavailability of these chemicals under conditions reflecting actual agronomic practices. Results from ARS research concerning the environmental fate and effects of agrochemicals have led to the development of science-based management practices that will protect vulnerable areas of the ecosystem. The new challenge is to identify these vulnerable areas and the temporal and spatial variations prior to use of the chemical by predicting how it will behave in environmental matrices, and using that information, predict its transport and transformation within an air- or watershed. With the development of better predictive tools and GIS (Geographic Information System)-based modeling, the risks of agricultural management systems can be assessed at the watershed and basin levels, and management strategies can be identified that minimize negative environmental impacts.

Agrochemicals↗
PubMed2003

Mitigation of thyroxine-induced hyperglycaemia by two plant extracts.

Extracts of Trigonella foenum-graecum (TFG) seed and Allium sativum (AS) bulb were evaluated for their efficacy to ameliorate l-thyroxine (l-T4) induced hyperglycaemia in rats. Simultaneously, the serum cholesterol concentration, a supporting parameter for thyroid function, was also estimated. Thyroxine treatment in rats (300 microg/kg b. wt./day) increased the levels of both the thyroid hormones, namely thyroxine (T4) and tri-iodothyronine (T3) with a concomitant elevation in serum glucose concentration and a reduction in serum cholesterol level. Administration of TFG (220 mg/kg/day) and AS (500 mg/kg/day) extracts in hyperthyroid animals decreased the serum glucose concentration as well as the serum thyroid hormones. For comparison, propyl thiouracil (PTU), an antithyroid compound, was used as the standard at a daily dose of 10 mg/kg. The reductions in serum glucose and thyroid hormone concentrations in the plant extract treated groups were comparable to that in PTU treated animals. Our findings indicate that TFG seed and AS bulb extracts may prove to be effective in the treatment of thyroxine-induced hyperglycaemia.

Alanine Transaminase↗
PubMed1975

Mitigation of caffeine-induced teratogenicity in mice by prior chronic caffeine ingestion.

Pregnant A/J female mice, which had drunk tap water or a 0.05% caffeine solution for 8-19 weeks after weaning, were each injected sc with 150 or 250 mg/kg caffeine once on day 13 of gestation. After 150 mg/kg caffeine the frequencies at term of fetal death, external malformation, and subcutaneous hematomas were significantly lower in the caffeine- than water-drinking group. After 250 mg/kg caffeine the frequency of fetal death but not of malformations and hematomas was lower in the group with caffeine pretreatment. These findings were explained by assuming that long-term ingestion of caffeine induced and increased rate of degradation of caffeine administered during pregnancy.

Abnormalities, Drug-Induced↗
PubMed1997

Role for CD40-mediated activation of c-Rel and maintenance of c-myc RNA levels in mitigating anti-IgM-induced growth arrest.

CD40 crosslinking on B cells activates NF-kappaB and stress-activated protein kinase (SAPK) pathways. Since CD40 crosslinking rescues WEHI 231 B cells from anti-IgM-induced apoptosis, those pathways were likely candidates to be involved. Indeed, both signaling cascades predominated in anti-IgM-treated WEHI 231 cells, treated concurrently with anti-CD40 to rescue them from apoptosis. Crosslinking of CD40 activated the NF-kappaB proteins c-Rel and p50, but had no influence on their cytoplasmic steady state level. However, in contrast to-and even in the presence of-anti-IgM-mediated signals, engagement of CD40 resulted in a prolonged nuclear translocation of c-Rel, thereby allowing the formation of active NF-kappaB complexes. Consistent with this, the upstream regulatory element of the c-myc promoter, known to be regulated by NF-kappaB, was differently regulated after BCR ligation vs BCR plus CD40 crosslinking. The level of c-myc RNA was rapidly downregulated after BCR engagement, but persistent in the presence of CD40 signaling.

Animals↗
PubMed1997

Mitigating effects of interleukin 11 on consecutive courses of 5-fluorouracil-induced ulcerative mucositis in hamsters.

Ulcerative mucositis is a painful, debilitating and dose-limiting toxicity of cancer chemotherapy. Current treatment is largely palliative and no adequate preventive treatment exists. Recently, we reported that recombinant human(rh) interleukin 11 (IL-11) favourably modified the course of mucositis following a single stomatotoxic regimen of 5-fluorouracil in hamsters. Although potentially beneficial, the clinically relevant issue of mucositis and myelosuppression during multicourse chemotherapy treatment was not addressed. The present study was undertaken to evaluate the effect of rhIL-11 on two consecutive courses of mucositis and myelosuppression in hamsters. Ulcerative mucositis was induced using a standardized protocol consisting of 5-fluorouracil (60 mg/kg) on days 1 and 2 followed by superficial irritation of the buccal mucosa on day 4. Animals treated with 100 microg of rhIL-11 for 12 consecutive days following each regimen of chemotherapy experienced a reduction in the incidence, severity, and duration of mucositis, a reduction in weight loss, and less morbidity and mortality relative to control animals. Bone marrow cellularity and function was not adversely affected by rhIL-11 treatment. The present study is consistent with the potential use of rhIL-11 treating patients at risk of developing ulcerative mucositis while undergoing intensive multicourse chemotherapy treatment.

Animals↗
PubMed1999

Interleukin 10 mitigates the development of the zymosan-induced multiple organ dysfunction syndrome in mice.

We investigated the effect of interleukin 10 on the development of zymosan-induced multiple organ dysfunction syndrome (MODS) and on plasma concentrations and production capacity of tumour necrosis factor (TNF)-alpha by peritoneal cells. Groups of C57BL/6 mice received a single intraperitoneal injection with zymosan, a cell wall component of Saccharomyces cerevisiae, at day 0. Daily doses of human recombinant interleukin 10 (IL-10: 10 or 50 microg/kg) were given intraperitoneally either starting directly before administration of zymosan (day 0), or 5 or 8 days after administration of zymosan. The animals were monitored for survival, condition, body weight and temperature. On day 12 all surviving animals were killed to obtain plasma, organs and peritoneal cells. Plasma concentrations of TNF-alpha and lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells were measured; organ weights were registered as an indicator for organ damage. IL-10 improves survival and clinical condition and also reduces organ damage, but only at the highest dose used and only when started simultaneously with the administration of zymosan. Circulating TNF-alpha concentrations 12 days after zymosan are not affected by any of the IL-10 schedules used. However, lipopolysaccharide-stimulated production of TNF-alpha by peritoneal cells is increased, in a dose- and time-dependent fashion. The anti-inflammatory cytokine IL-10 is able to attenuate the development of MODS in this model, but only when given simultaneously with zymosan, and in high dosages.

Animals↗
PubMed1993

Decrease in glycation of lens proteins by lysine and glycine by scavenging of glucose and possible mitigation of cataractogenesis.

The amino acid lysine has been reported to delay cataractogenesis by 'some unknown mechanism'. Lysine and glycine were found to react with glucose at physiological pH and temperature and undergo non-enzymic glycation. The formation of glycated lysine was shown by paper and thin-layer chromatography, HPLC and using an authentic sample of epsilon-fructosyl lysine. Confirmation was made by studies on incorporation of U-[14C]glucose into lysine and glycine. The extent of glycation of lysine was 15.5% in 96 hr and rose to 20% in 20 days. Lysine and glycine alone of varying concentrations lowered the extent of glycation of lens proteins significantly in glucose-treated homogenates of normal lens from humans and goats. Scavenging of intracellular glucose and thereby protecting the lens proteins from excessive glycation appears to be the mechanism of action by which lysine and glycine could exercise beneficial effect on cataract.

Animals↗
PubMed1996

Bacterial alkaloids mitigate seizure-induced hippocampal damage and spatial memory deficits.

Studies of human patients with temporal lobe epilepsy and animal models of epilepsy have established relationships between seizures, excitotoxic hippocampal damage, and memory impairment. We report that bacterial alkaloids, recently shown to mimic actions of neurotrophic factors in cell culture, attenuate seizure-induced damage to hippocampal neurons and memory impairment in adult rats when administered subcutaneously. Intrahippocampal administration of convulsant doses of kainic acid (KA) to adult rats resulted in degeneration of neurons in CA3, CA1, and hilus. Rats administered KA exhibited (24 h later) deficits in performance on both goal latency and probe trial tasks in Morris water maze (MWM) tests of visuospatial memory. Seizure-induced damage to hippocampal neurons was significantly reduced, to varying extents, in rats administered the bacterial alkaloids K252a, K252b, or staurosporine (daily injections of 4 micrograms/kg body weight) prior to KA administration. The KA-induced deficits in MWM goal latency performance were abrogated in rats administered K252a or K252b, and K252a and staurosporine completely prevented seizure-induced impairment on the MWM probe trial. The alkaloids did not suppress electroencephalographic seizure activity, suggesting a dissociation between synchronization of activity and synaptically mediated excitotoxic injury to hippocampal neurons. Each alkaloid caused an increase in levels of protein tyrosine phosphorylation as determined by Western blot analysis of hippocampal tissue. Our data indicate that these bacterial alkaloids have potent antiexcitotoxic activities which may have clinical utility in epilepsy and other disorders that involve excitotoxic damage.

Alkaloids↗
PubMed1979

Mitigation of experimental allergic encephalomyelitis by cathepsin D inhibition.

Intraperitoneal treatment with the enzyme inhibitor, pepstatin, of BSVS mice, guinea pigs and Lewis rats which were sensitized with guinea pig spinal cord and pertussis vaccine resulted in complete or partial suppression of paralysis dependent on the species studied and alterations of histological signs of experimental allergic encephalomyelitis (EAE). The effect was dose-dependent but had no relationship to the age of the experimental animal at the time of the experiment.

Animals↗
PubMed1978

The mitigating effect of dietary antioxidants on chemically-induced carcinogenesis.

The effect of a dietary antioxidant mixture on 3-methylcholanthrene mediated carcinogenesis in hairless mice was investigated. The antioxidant mixture significantly reduced the frequency of premalignant lesions and their subsequent development into tumors. The similarities in response of chemical and UV light-carcinogenesis to these antioxidants suggest some congruity in the mechanisms of the carcinogenic process.

Animals↗
PubMed1999

Oxidative stress during selenium deficiency in seedlings of Trigonella foenum-graecum and mitigation by mimosine. Part I. Hydroperoxide metabolism.

Oxidative stress during selenium (Se) deficiency in the seedlings of Trigonella foenum-graecum grown for 72 h was investigated and the response to supplemented levels of Se (0.5-1 ppm) and mimosine (0.05-1 mM) was evaluated. Beneficial effects of Se was maximal at 0.75 ppm. Mimosine, a toxic amino acid, was also found to be beneficial to the growth of the seedlings exposed up to 0.2 mM. When compared to the stressed seedlings, mitochondrial oxygen uptake from seedlings of Se (0.75 ppm) group and mimosine (0.2 mM) group exhibited threefold enhancement in state 3 respiration rate and a controlled state 4 rate, with respiratory control ratios of 5-8. Upon supplementation at the optimal levels, superoxide dismutase (SOD) activities were enhanced fourfold with Se and eightfold with mimosine in the mitochondria. The soluble activity in mimosine groups increased twofold, but only by 75% in Se groups. Peroxidase activity registered a significant increase by threefold in mitochondria and fourfold in soluble fraction in both Se and mimosine groups. Exposure to Se or mimosine exhibited a differential response in the mitochondrial catalase and ascorbate peroxidase (Asc-Px) activities. In the Se groups, both catalase and Asc-Px in mitochondria decreased by 50-60%, which was contrasted by 60% increase in Asc-Px activity and 40% in catalase activity in mimosine groups. Supplementation with either Se or mimosine evoked similar responses of increases with respect to soluble catalase by twofold to threefold and Asc-Px by 90%. The results of the present study reveal (1) the prevalence of oxidative stress in T. foenum-graecum during Se deficiency, (2) enhanced mitochondrial functional efficiency mediated by Se and mimosine independently, and (3) an antioxidative role for mimosine during Se deficiency. The study demonstrates for the first time that mimosine, a naturally occurring toxic amino acid, could be a beneficial growth factor in concentrations between 0.1 and 0.2 mM.

Ascorbate Peroxidases↗