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Significant Depletion (significant + depletion)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	41%

Selected Abstracts

Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2006
Geetu Saxena
This study was designed to investigate the therapeutic potential of meso 2,3-dimercaptosuccinic acid (DMSA) and one of its monoesters, monoisoamyl DMSA (MiADMSA), individually or when administered in combination with an extract of Centella asiatica against experimental lead intoxication in rats. Biochemical variables indicative of alterations in the central nervous system and haem biosynthesis were investigated to determine the toxicity in male Wistar rats. Thirty five rats were exposed to 0.2% lead acetate for 10 weeks, followed by 10 days of treatment with DMSA and MiADMSA (50 mg kg,1, i.p., once daily) alone and in combination with C. asiatica (200 mg kg,1, p.o., once daily). Biochemical variables indicative of oxidative stress and brain biogenic amines, along with lead concentration in blood and brain, were measured. Lead exposure caused a significant depletion of blood and brain ,-aminolevulinic acid dehydratase (ALAD) activity, an important enzyme of the haem biosynthesis pathway, and glutathione (GSH) level. These changes were accompanied by a marked increase in reactive oxygen species (ROS) level, thiobarbituric acid reactive substances (TBARS), ,-aminolevulinic acid synthase (ALAS) and oxidized glutathione (GSSG) activity in blood and brain. Significant depletion of brain noradrenaline (norepinephrine, NE), 5-hydroxytryptamine (5-HT), dopamine (DA) and acetylcholinesterase (AChE) also were observed following lead exposure. Also seen was a significant depletion in brain glutathione peroxidase (GPx), glutathione S-transferase (GST) and monoamine oxidase activity, as well as blood and brain superoxide dismutase (SOD) activity. These biochemical changes were correlated with an increased uptake of lead in blood and brain. Combined administration of MiADMSA and C. asiatica was most effective in reducing these alterations, including biogenic amines, besides reducing body lead burden, compared with individual treatment with MiADMSA. Certain other biochemical variables responded favourably to combination therapy and monotherapy with MiADMSA. Thus, supplementation of C. asiatica during chelation could be recommended for achieving optimum effects of chelation therapy. [source]

Haematological, hepatic and renal alterations after repeated oral or intraperitoneal administration of monoisoamyl DMSA.

JOURNAL OF APPLIED TOXICOLOGY, Issue 6 2002

Abstract Monoisoamyl 2,3-dimercaptosuccinic acid (MiADMSA), a vicinal thiol chelator, is gaining recognition recently as a better chelator than meso 2,3-dimercaptosuccinic acid (DMSA) in decreasing heavy metal burden in tissues because of its lipophilic character. There is, however, little information available on the toxicological properties of this chelator after repeated administration in animals. In the present study, we investigated the dose-dependent effect of MiADMSA on various biochemical parameters suggestive of alterations in haem biosynthesis and hepatic, renal and brain oxidative stress after 21 days of repeated intraperitoneal (i.p.) or oral (p.o.) administration to rats. The concentration of essential metals in blood and soft tissues was determined along with histopathological observations of hepatic and renal tissues. The results suggest that MiADMSA administration had no effect on blood ,-aminolevulinic acid dehydratase activity. However, an increase in zinc protoporphyrin and a decrease in haemoglobin levels were noted in animals given MiADMSA i.p. A moderate increase in serum alkaline phosphatase suggested mild hepatotoxicity at the highest dose (100 mg kg,1, i.p.). This was confirmed by histopathological examinations, which identified basophilic stippling, granulation of the cytoplasm, haemorrhage and congestion. At the highest dose, levels of hepatic thiobarbituric acid reactive substance and oxidized glutathione were increased above those of control values. Levels of hepatic reduced glutathione were decreased. Taken together, these observations point to oxidative stress. In animals administered MiADMSA i.p. there was an increase in the brain malondialdehyde levels at the two higher doses (50 and 100 mg kg,1). Essential metal status revealed a significant effect of MiADMSA (p.o.) in increasing blood zinc while significantly decreasing the kidney zinc level. The most significant adverse effect of MiADMSA was on copper concentration, which showed significant depletion from almost all major organs. Magnesium levels in blood decreased but increased in liver of MiADMSA-administered rats. Histopathological observations of liver and kidneys suggest few moderate lesions. It can be concluded that repeated administration of MiADMSA is compromised with some mild toxic effect, particularly the loss of copper. The effects during oral administration are comparatively less pronounced than by the i.p. route. Copyright © 2002 John Wiley & Sons, Ltd. [source]

Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia

JOURNAL OF NEUROCHEMISTRY, Issue 3 2010
Raghavendra Rao
J. Neurochem. (2010) 114, 728,738. Abstract Hypoglycemia is common during development and is associated with the risk of neurodevelopmental deficits in human infants. The effects of hypoglycemia on the developing hippocampus are poorly understood. The sequential changes in energy substrates, amino acids and phosphocreatine were measured from the hippocampus during 180 min of insulin-induced hypoglycemia (blood glucose < 2.5 mmol/L) in 14-day-old rats using in vivo1H NMR spectroscopy. Hypoglycemia resulted in neuroglycopenia (brain glucose < 0.5 ,mol/g). However, the phosphocreatine/creatine (PCr/Cr) ratio was maintained in the physiological range until approximately 150 min of hypoglycemia, indicating that energy supply was sufficient to meet the energy demands. Lactate concentration decreased soon after the onset of neuroglycopenia. Beyond 60 min, glutamine and glutamate became the major energy substrates. A precipitous decrease in the PCr/Cr ratio, indicative of impending energy failure occurred only after significant depletion of these amino acids. Once glutamate and glutamine were significantly exhausted, aspartate became the final energy source. N -acetylaspartate concentration remained unaltered, suggesting preservation of neuronal/mitochondrial integrity during hypoglycemia. Correction of hypoglycemia normalized the PCr/Cr ratio and partially restored the amino acids to pre-hypoglycemia levels. Compensatory neurochemical changes maintain energy homeostasis during prolonged hypoglycemia in the developing hippocampus. [source]

Ginkgo biloba affords dose-dependent protection against 6-hydroxydopamine-induced parkinsonism in rats: neurobehavioural, neurochemical and immunohistochemical evidences

JOURNAL OF NEUROCHEMISTRY, Issue 1 2005
Muzamil Ahmad
Abstract Ginkgo biloba extract (EGb), a potent antioxidant and monoamine oxidase B (MAO-B) inhibitor, was evaluated for its anti-parkinsonian effects in a 6-hydroxydopamine (6-OHDA) rat model of the disease. Rats were treated with 50, 100, and 150 mg/kg EGb for 3 weeks. On day 21, 2 µL 6-OHDA (10 µg in 0.1% ascorbic acid saline) was injected into the right striatum, while the sham-operated group received 2 µL of vehicle. Three weeks after 6-OHDA injection, rats were tested for rotational behaviour, locomotor activity, and muscular coordination. After 6 weeks, they were killed to estimate the generation of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) content, to measure activities of glutathione- S -transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx), catalase, and superoxide dismutase (SOD), and to quantify catecholamines, dopamine (DA) D2 receptor binding, and tyrosine hydroxylase-immunoreactive (TH-IR) fibre density. The increase in drug-induced rotations and deficits in locomotor activity and muscular coordination due to 6-OHDA injections were significantly and dose-dependently restored by EGb. The lesion was followed by an increased generation of TBARS and significant depletion of GSH content in substantia nigra, which was gradually restored with EGb treatment. EGb also dose-dependently restored the activities of glutathione-dependent enzymes, catalase, and SOD in striatum, which had reduced significantly by lesioning. A significant decrease in the level of DA and its metabolites and an increase in the number of dopaminergic D2 receptors in striatum were observed after 6-OHDA injection, both of which were significantly recovered following EGb treatment. Finally, all of these results were exhibited by an increase in the density of TH-IR fibers in the ipsilateral substantia nigra of the lesioned group following treatment with EGb; the lesioning had induced almost a complete loss of TH-IR fibers. Considering our behavioural studies, biochemical analysis, and immunohistochemical observation, we conclude that EGb can be used as a therapeutic approach to check the neuronal loss following parkinsonism. [source]

Skeletal Growth Acceleration with Growth Hormone Secretagogues in Transgenic Growth Retarded Rats: Pattern-Dependent Effects and Mechanisms of Desensitization

JOURNAL OF NEUROENDOCRINOLOGY, Issue 6 2001
T. Wells
Abstract The transgenic growth retarded (Tgr) rat is the first genetic model of growth hormone (GH) deficiency whose growth can be accelerated with exogenous GH secretagogues (GHSs). In this study, we have demonstrated that GHS-receptor (GHS-R) mRNA expression in the arcuate nucleus of Tgr rats was not significantly different to that in wild-type littermates. We have confirmed that GHS-induced elevation in body weight gain was accompanied by acceleration of skeletal growth, and that the effects of the GHS, GHRP-6, were both dose- and pattern-dependent. The growth response with continuous infusion of GHRP-6 was transient, accompanied by suppression of GH and corticosterone responses to bolus injection of GHRP-6. This desensitization occurred without downregulation of arcuate GHS-R mRNA expression, but was accompanied by elevated periventricular somatostatin mRNA expression. In contrast, pulsatile (3-hourly) infusion of GHRP-6 produced sustained growth and GH responses, which were accompanied by suppression of corticosterone responses and elevated arcuate GH-releasing factor (GRF) mRNA expression. Skeletal growth was further accelerated by coinfusion of GRF, but significant depletion of pituitary GH stores suggested that this growth rate may not be sustainable. These experiments confirm the importance of the Tgr rat for investigating the growth promoting potential of the GHSs in the context of GH-deficient dwarfism, and suggest that elevated somatostatin expression may mediate the suppression of the GRF-GH and hypothalamo-pituitary-adrenal axes following continuous GHRP-6 treatment. [source]

Changes in brain biogenic amines and haem biosynthesis and their response to combined administration of succimers and Centella asiatica in lead poisoned rats

Phase dependence in winter physiological condition of cyclic voles

OIKOS, Issue 4 2007
Otso Huitu
Lack of food resources has been suggested as a factor which limits the growth of cyclic vole populations. During peak phases of the cycle, vole population growth typically ceases during late autumn or early winter, and is followed by a decrease in density over the winter. To investigate whether this decrease is due to increased mortality induced by a depletion of food resources, we studied overwinter food consumption and physiological condition of field voles (Microtus agrestis) in western Finland in both an increase and a decrease phase of a three-year population cycle. The growth rate of vole populations was negatively related both to prevailing vole densities and to densities six months earlier. The condition index of voles, as well as their blood levels of haematocrit, proteins, free fatty acids and immunoglobulin G, were positively related to population growth rate when populations were declining. When populations were increasing, these parameters tended to be negatively related to population growth rate. The overall physiological condition of voles was lower in the winter of the decrease phase as compared to the increase phase. The return rate of voles, a proxy of survival, was also lower in the decrease than in the increase phase of the cycle and positively related to haematocrit levels. Almost 90% of all green vegetation shoots were consumed by voles during the winter of the decrease phase while only two thirds were eaten in the increase phase. Our results suggest that the winter decrease phase of cyclic vole populations is associated with both a deterioration in the physiological condition of voles and a significant depletion of winter food resources. This implies that malnutrition induces poor physiological condition in voles, which in turn may increase mortality either directly through starvation or indirectly through increased susceptibility to predators and pathogens. [source]

Treatment-dependent Loss of Polyfunctional CD8+ T-cell Responses in HIV-infected Kidney Transplant Recipients Is Associated with Herpesvirus Reactivation

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009
O. Gasser
Antiretroviral-therapy has dramatically changed the course of HIV infection and HIV-infected (HIV(+)) individuals are becoming more frequently eligible for solid-organ transplantation. However, only scarce data are available on how immunosuppressive (IS) strategies relate to transplantation outcome and immune function. We determined the impact of transplantation and immune-depleting treatment on CD4+ T-cell counts, HIV-, EBV-, and Cytomegalovirus (CMV)-viral loads and virus-specific T-cell immunity in a 1-year prospective cohort of 27 HIV(+) kidney transplant recipients. While the results show an increasing breadth and magnitude of the herpesvirus-specific cytotoxic T-cell (CTL) response over-time, they also revealed a significant depletion of polyfunctional virus-specific CTL in individuals receiving thymoglobulin as a lymphocyte-depleting treatment. The disappearance of polyfunctional CTL was accompanied by virologic EBV-reactivation events, directly linking the absence of specific polyfunctional CTL to viral reactivation. The data provide first insights into the immune-reserve in HIV+ infected transplant recipients and highlight new immunological effects of thymoglobulin treatment. Long-term studies will be needed to assess the clinical risk associated with thymoglobulin treatment, in particular with regards to EBV-associated lymphoproliferative diseases. [source]

Redox regulation of ascorbic acid transport: Role of transporter and intracellular sulfhydryls

BIOFACTORS, Issue 4 2004
James M. May
Abstract Ascorbic acid is one of the most sensitive cellular defenses against oxidant damage. However, it requires a sodium- and energy-dependent transporter to enter cells against a concentration gradient. To test the hypothesis that ascorbate transport is sensitive to redox stress, we studied changes in transport of the vitamin in response to sulfhydryl modification of the protein and to GSH depletion in cultured endothelial cells. Transport of ascorbic acid, measured as the uptake of radiolabeled ascorbate, was inhibited by the membrane-impermeant sulfhydryl reagents thorin, p -chloromercuribenzene sulfonic acid, and 5,5,-dithiobis-(2-nitrobenzoic acid) in a dose-dependent manner without significant depletion of intracellular GSH. Sulfhydryl reagents capable of penetrating the plasma membrane, including phenylarsine oxide, p -chloromercuribenzoic acid, and N-ethylmaleimide, inhibited transport and lowered cellular GSH. Diamide, which induces disulfide formation, increased ascorbate transport over a narrow concentration range under conditions in which GSH was not depleted. On the other hand, specific depletion of intracellular GSH by several different mechanisms did inhibit transport. Together, these results suggest that the ascorbate transporter is sensitive to redox modulation. This relates in part to sulfhydryl groups exposed on the exofacial ascorbate transporter, and to sulfhydryl groups that are sensitive to changes in the redox state of intracellular GSH. [source]

Simvastatin inactivates ,1-integrin and extracellular signal-related kinase signaling and inhibits cell proliferation in head and neck squamous cell carcinoma cells

CANCER SCIENCE, Issue 6 2007
Ikuko Takeda
The 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors, also called statins, are commonly used as lipid-lowering drugs that inhibit cholesterol biosynthesis. An anticancer effect, as a pleiotropic function of certain statins, has been hypothesized. In the present study, we investigated the effect of simvastatin, one of the natural statins, on cell proliferation, cell cycle, invasive activity, and molecular expressions associated with cell,extracellular matrix adhesion, signal transduction, and DNA synthesis in Tu167 and JMAR cells from head and neck squamous cell carcinoma. The addition of simvastatin resulted in a dose-dependent inhibition of cell growth and migration into the extracellular matrix. Considerable morphological changes occurred after treatment with simvastatin, demonstrating loss of cell adhesion and disruption of actin filaments in cytoplasm. The inhibitory effect of simvastatin on cell proliferation seemed to be associated with cell cycle arrest and increased expression of p21, p27, and activated caspase-3. The expression of ,1-integrin, a counter adhesion for the extracellular matrix, phosphorylated FAK, and phosphorylated ERK was decreased by treatment with simvastatin. The proapoptotic effect of simvastatin was inhibited by treatment with mevalonate. cDNA microarray assay demonstrated that molecular changes resulting from treatment with simvastatin included the up-regulation of cell cycle regulators and apoptosis-inducing factors and the down-regulation of integrin-associated molecules and cell proliferation markers. Of down-regulated genes induced by simvastatin treatment, a significant depletion of thymidylate synthase was confirmed using western blot analysis. These results imply that simvastatin has the potential to be effective for the prevention of the growth and metastasis of cancer cells. (Cancer Sci 2007; 98: 890,899) [source]

Prolonged low-dose thrombolytic therapy: A novel adjunctive strategy in the management of an infected right atrial thrombus

CLINICAL CARDIOLOGY, Issue 7 2002
Sheila Chuang M.D.
Abstract An 81-year-old man presented with a large, infected right atrial thrombus that was refractory to anticoagulants and several courses of antibiotics. The risk of surgical removal of the thrombus, which was associated with a pacemaker electrode, was considered prohibitive. The patient was treated for 7 days with low-dose (40 mg/day) tissue-type plasminogen activator (t-PA). Hemostatic monitoring during infusion revealed (1) aplasma t-PA antigen that was approximately 5% of that achieved during short-course t-PA for acute myocardial infarction, (2) biochemical evidence of prolonged clot lysis, and (3) no significant depletion of fibrinogen or plas-minogen. Nearly complete dissolution of the thrombus was observed. His bacteremia was eradicated by intravenous penicillin despite the presence of the pacemaker lead. This case highlights the benefits of combined antibiotic and thrombolytic therapy and documents for the first time the response of the human hemostatic system to prolonged t-PA infusion and the plasma t-PA levels attained when thrombolytic therapy is administered in this manner. Prolonged courses of fibrinolytic agents may be a good alternative to surgical intervention in selected patients with infected, right-sided intracardiac thrombi. [source]

PHYSIOLOGICAL AND BEHAVIORAL DEVELOPMENT IN DELPHINID CALVES: IMPLICATIONS FOR CALF SEPARATION AND MORTALITY DUE TO TUNA PURSE-SEINE SETS

MARINE MAMMAL SCIENCE, Issue 1 2007
Shawn R. Noren
Abstract Tuna purse-seiners in the eastern tropical Pacific (ETP) capture yellowfin tuna by chasing and encircling herds of associated dolphins. This fishery has caused mortality in 14 dolphin species (20 stocks) and has led to significant depletions of at least three stocks. Although observed dolphin mortality is currently low, set frequency remains high and dolphin stocks are not recovering at expected rates. Mortality of nursing calves permanently separated from their mothers during fishery operations may be an important factor in the lack of population recovery, based on the recent discovery that calves do not accompany 75%,95% of lactating females killed in the purse-seine nets. We assessed age-specific potential for mother,calf separations and subsequent mortality of calves by reviewing and synthesizing published data on physiological and behavioral development in delphinids from birth through 3 yr postpartum. Results indicate that evasive behavior of mothers, coupled with the developmental state of calves, provides a plausible mechanism for set-related mother,calf separations and subsequent mortality of calves. Potential for set-related separation and subsequent mortality is highest for 0,12-mo-old dolphins and becomes progressively lower with age as immature dolphins approach adult stamina and attain independence. [source]