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1.
J Phys Condens Matter ; 31(50): 505505, 2019 12 18.
Article in English | MEDLINE | ID: mdl-31476747

ABSTRACT

High-performance permanent magnets (PM) are compounds with outstanding intrinsic magnetic properties. Most PMs are obtained from a favorable combination of rare earth metals (RE = Nd, Pr, Ce) with transition metals (TM = Fe, Co). Amongst them, CeFe11Ti claims considerable attention due to its large Curie temperature, saturation magnetization, and significant magnetocrystalline anisotropic energy. CeFe11Ti has several potential applications, in particular, in the development of electric motors for future automatic electrification. In this work, we shed some light on the mictrostructure of this compound by performing periodic hybrid-exchange density functional theory (DFT) calculations. We use a combined approach of atom-centered local orbitals, plane waves and full-potential linear muffin-tin orbital (LMTO) for our computations. The electronic configuration of the atoms involved in different steps of formation of the crystal structure of CeFe11Ti gives an explanation on the effect of Ce and Ti on its magnetic properties. While Ti stabilizes the structure, atomic orbitals of Ce hybridizes with Fe atomic orbitals to a significant extent and alters the electronic bands. Our calculations confirm a valence of 3+ for Ce, which has been deemed crucial to obtain a large magnetocrystalline anisotropy. In addition, we analyze several spin configurations, with the ferromagnetic configuration being most stable. We compare and contrast our data to those available and provide an insight for further development of optimized high-performance PMs. Moreover, we compute the Magnetocrystalline Anisotropy of this compound by means of two approaches: the Force Theorem and a full-potential LMTO method.

2.
Comp Biochem Physiol C Toxicol Pharmacol ; 157(3): 287-97, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23402931

ABSTRACT

Alcohol consumption by women during pregnancy often induces fetal alcohol spectrum disorder (FASD) in children who have serious central nervous system (CNS), cardiovascular, and craniofacial defects. Prevention of FASD, other than women abstaining from alcohol drinking during pregnancy, is not known. A limitation of the use of synthetic anti-alcoholic drugs during pregnancy led us to investigate herbal products. In particular, many plants including Asian ginseng (Panax ginseng) have therapeutic potential for the treatment of alcoholism. We used Japanese ricefish (medaka) (Oryzias latipes), an animal model of FASD, for identifying herbal medicines that can attenuate ethanol toxicity. Fertilized eggs in standard laboratory conditions were exposed to ginseng (PG) root extract (0-2 mg/mL) either 0-2 (group A) or 1-3 (group B) day post fertilization (dpf) followed by maintenance in a clean hatching solution. The calculated IC50 as determined 10 dpf in A and B groups were 355.3±1.12 and 679.7±1.6 µg/mL, respectively. Simultaneous exposure of embryos in sub-lethal concentrations of PG (50-200 µg/mL) and ethanol (300 mM) for 48 h disrupted vessel circulation and enhanced mortality. However, PG (100 µg/mL) may partially protect trabecular cartilage (TC) deformities in the neurocranium in B group embryos induced by ethanol (300 mM). To understand the mechanism, embryonic ethanol concentration was measured at 2 dpf and adh5, adh8, aldh2, aldh9a, catalase, GST, and GR mRNAs were analyzed at 6 dpf. It was observed that although ethanol is able to reduce adh8 and GST mRNA contents, the simultaneous addition of PG was unable to alter ethanol level as well as mRNA contents in these embryos. Therefore, antagonistic effects of PG on ethanol toxicity are mediated by a mechanism which is different from those regulating ethanol metabolism and oxidative stress.


Subject(s)
Ethanol/toxicity , Fetal Alcohol Spectrum Disorders/prevention & control , Oryzias/embryology , Panax , Plant Extracts/pharmacology , Animals , Catalase/genetics , Disease Models, Animal , Dose-Response Relationship, Drug , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/enzymology , Enzymes/genetics , Female , Gene Expression Regulation, Developmental/drug effects , Humans , Pregnancy , Teratogens/toxicity
3.
Biochem Biophys Res Commun ; 286(5): 1082-6, 2001 Sep 07.
Article in English | MEDLINE | ID: mdl-11527411

ABSTRACT

Alcohol dehydrogenase (ADH) is the primary enzyme responsible for metabolism of ethanol to acetaldehyde. One class of ADH has been described in fish, and has been found to be structurally similar to mammalian class III ADH (glutathione-dependent formaldehyde dehydrogenase) but functionally similar to class I ADH (primarily responsible for ethanol metabolism). We have cloned a cDNA by RT-PCR from zebrafish (Danio rerio) liver representing the zebrafish ADH3 gene product, with a coding region of 1131 nucleotides. The deduced amino acid sequences share 90% identity to ADH3 from the marine fish Sparus aurata, and 82 and 81% identity to the mouse and human sequences, respectively. Using a quantitative competitive RT-PCR assay, ADH3 mRNA was detected at all timepoints analyzed and was lowest between 8 and 24 h postfertilization. Thus, differential ADH3 expression may be at least partly responsible for temporal variations in the sensitivity of zebrafish embryos to developmental alcohol exposure.


Subject(s)
Alcohol Dehydrogenase/biosynthesis , Alcohol Dehydrogenase/chemistry , Amino Acid Sequence , Animals , Binding, Competitive , Cytosol , DNA, Complementary/metabolism , Embryo, Nonmammalian/metabolism , Glutathione/metabolism , Humans , Kinetics , Larva/metabolism , Liver/metabolism , Molecular Sequence Data , Phylogeny , Protein Isoforms , RNA/metabolism , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Time Factors , Zebrafish
4.
Mol Cell Endocrinol ; 182(1): 39-48, 2001 Aug 20.
Article in English | MEDLINE | ID: mdl-11500237

ABSTRACT

Previous in-vitro investigations of rat granulosa cells (GC) have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits estrogen secretion and FSH-induced aromatase activity. Although TCDD exerted no effect on basal aromatase enzyme activity, TCDD did reduce steady-state aromatase mRNA levels in GC using competitive RT-PCR. TCDD is hypothesized to induce these changes through aromatic hydrocarbon receptor(AHR)-mediated gene transcription and the modulation of the estrogen receptor (ER)-signaling pathway. In this study we show that rat GC express mRNA for AHR and the AHR nuclear translocator (ARNT) as well as biomarkers of TCDD action, CYP1A1 and CYP1B1 mRNA. Basal CYP1A1 and ER-alpha mRNAs were present only in trace amounts. By relative RT-PCR analysis we showed that CYP1A1 and CYP1B1 mRNA were induced significantly by TCDD at 6 h and that induction of CYP1A1 was maintained throughout the experiment. Using competitive RT-PCR, we observed no significant change in the mRNA levels of ARNT between control and TCDD-treated GC. Both AHR and ER-beta mRNA levels increased significantly at 48 h with TCDD compared with controls. Since ER-beta mRNA was not increased significantly until 48 h in culture, we suggest that in rat GC, the observed ER-beta mRNA increase by TCDD might be a result of CYP1A1/CYP1B1 catalyzed estrogen metabolism and aromatase mRNA inhibition via AHR.


Subject(s)
Aryl Hydrocarbon Hydroxylases , Polychlorinated Dibenzodioxins/pharmacology , RNA, Messenger/drug effects , Receptors, Estrogen/genetics , Animals , Cell Culture Techniques , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Cytochrome P-450 CYP1B1 , Cytochrome P-450 Enzyme System/genetics , Cytochrome P-450 Enzyme System/metabolism , Enzyme Induction/drug effects , Estrogen Receptor beta , Estrogens/metabolism , Female , Granulosa Cells/drug effects , Granulosa Cells/enzymology , Granulosa Cells/metabolism , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Receptors, Estrogen/drug effects
5.
Comp Biochem Physiol C Toxicol Pharmacol ; 129(3): 265-73, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11461841

ABSTRACT

We investigated whether carbofuran (CF), a carbamate pesticide, at sub-lethal concentration had any adverse effects on reproductive function of the Indian catfish, Heteropneustes fossilis. 17beta-Estradiol content of serum and ovary of pre-spawning (P) and spawning (S) fish was reduced after sub-lethal concentration of carbofuran treatment (0.5-2 mg/ml, 30 days). After 30 days of CF treatment, the serum and ovarian vitellogenin levels of fish at the P stage were also reduced but remained unaltered in the S stage. The staining intensity of the pituitary gonadotrophs of the pre-spawning fish was significantly higher in CF-treated fish compared to controls suggesting the inability of the pituitary gonadotrophs to release gonadotropin following CF treatment. CF thus acts as an antiestrogenic, endocrine-disrupting agent in fish, possibly targeting the pituitary-gonad axis.


Subject(s)
Carbofuran/toxicity , Catfishes/metabolism , Estrogen Receptor Modulators/toxicity , Insecticides/toxicity , Ovary/drug effects , Pituitary Gland/drug effects , Animals , Estradiol/blood , Female , Ovary/metabolism , Pituitary Gland/metabolism , Vitellogenins/blood
6.
Mol Cell Endocrinol ; 164(1-2): 5-18, 2000 Jun.
Article in English | MEDLINE | ID: mdl-11026553

ABSTRACT

We investigated the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in prepubertal (PP) and adult (A) rat granulosa cells (GC) in vitro by examining the changes in estrogen secretion, aromatase enzyme activity and mRNAs for steroidogenic enzymes P450scc, 3beta-HSDI, P450arom; and for components of the AHR signaling pathway-CYP1A1, aromatic hydrocarbon receptor (AHR), and the AHR nuclear translocator protein (ARNT). In PP and A rat GC, TCDD (3.1 nM) reduced estrogen secretion at 48 h without altering aromatase enzyme activity. Addition of FSH (50 ng/ml) increased aromatase activity in GC with or without TCDD. FSH-induced aromatase activity was significantly reduced by TCDD (3.1 nM) at 48 h. Semi-quantitative RT-PCR showed a significant increase in CYP1A1 mRNA both at 24 and 48 h with TCAP, while a significant reduction in P450scc and P450arom mRNA was observed with competitive RT-PCR. All steroidogenic enzyme mRNAs were significantly lower in adults than in PP GC. We conclude that in rat GC, TCDD modulates the level of cytochrome P450 enzymes involved in the steroid biosynthetic cascade. This effect may be attributable to AHR interaction with dioxin-responsive elements present in the genes encoding these enzymes.


Subject(s)
Cytochrome P-450 Enzyme System/genetics , Gene Expression Regulation, Enzymologic/drug effects , Granulosa Cells/physiology , Polychlorinated Dibenzodioxins/pharmacology , Teratogens/pharmacology , Animals , Cells, Cultured , Cytochrome P-450 Enzyme System/biosynthesis , Female , Polymerase Chain Reaction/methods , RNA, Messenger/analysis , Rats , Rats, Sprague-Dawley
7.
Article in English | MEDLINE | ID: mdl-10904858

ABSTRACT

Different doses of vitamin B12 (0.25, 0.5, 1, 2 and 4 micrograms/g, injected intraperitoneally for three consecutive days) altered the activities of mitochondrial-alpha-glycerophosphate dehydrogenase (alpha-GPD) and NADP-dependent cytosolic malic enzyme (ME) in the brain of singi fish. The alpha-GPD activity increased at doses of 0.5, 1, 2 and 4 micrograms/g vitamin B12. A dose of 0.5 microgram/g vitamin B12 induced less activity than higher doses. ME activity increased with 1, 2 and 4 micrograms/g of vitamin B12/g. The mitochondrial and cytosolic protein content remained unchanged after vitamin B12 administration. Cycloheximide treatment inhibited the vitamin B12-induced increase in alpha-GPD and ME activity. Thus, vitamin B12 is involved in the induction of some enzymes in fish brain.


Subject(s)
Brain/enzymology , Catfishes , Glycerolphosphate Dehydrogenase/metabolism , Malate Dehydrogenase/metabolism , Vitamin B 12/pharmacology , Animals , Brain/drug effects , Cycloheximide/pharmacology , Cytosol/drug effects , Cytosol/enzymology , Glycerolphosphate Dehydrogenase/drug effects , Malate Dehydrogenase/drug effects , Mitochondria/drug effects , Mitochondria/enzymology
8.
Arch Environ Contam Toxicol ; 38(3): 371-6, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10667936

ABSTRACT

Polychlorinated biphenyls (PCBs) and dioxins are known to cause disruptions in circulating hormone concentrations, which may influence fertility and normal fetal development. Structure activity relationships have been determined for individual congeners, but it is unclear what impacts occur due to exposure to complex mixtures of chemicals found in the environment. Most laboratory studies of PCB exposure have used commercial mixtures in high doses, which may not be representative of environmental concentrations of individual congeners, nor accurately represent complex interactions of multiple contaminants. The present study investigated endocrine alterations in rats associated with the consumption of lake trout collected from three specific locations in the Great Lakes. Composite fish samples were analyzed for PCBs, organochlorines, and mercury and ranged from 415 ppb to 1,275 ppb for individual contaminants. Fillet composites were fed to timed-pregnant Long-Evans rats as 30% of their diet. Concentrations of total thyroxine and estrogen were not significantly different in offspring of dosed dams from that of controls. However, aromatase activity was lowered in all dosed groups as compared with controls. This may represent a lowered expression of the CYP 19 gene in exposed rats or may be due to the presence of one or more substances in the contaminants that are capable of altering the affinity of the aromatase enzyme for its normal endogenous substrate. It is also possible that the number of maturing follicles in the lake trout-fed rats may be fewer than controls, which would result in an overall reduction in the enzyme activity. Data regarding the endocrine effects of environmental contaminant mixtures found in fish from the Great Lakes Basin are still controversial. Additionally, information is scarce with respect to the F1 generation of laboratory animals following environmental maternal exposures, therefore, we investigated the reproductive-endocrine alterations in rat offspring associated with the consumption of lake trout (Salvelinus namaycush) collected from three areas in the Great Lakes.


Subject(s)
Endocrine System/drug effects , Environmental Pollutants/adverse effects , Food Contamination , Trout , Animals , Aromatase/metabolism , Diet , Female , Metals, Heavy/adverse effects , Polychlorinated Biphenyls/adverse effects , Pregnancy , Prenatal Exposure Delayed Effects , Rats , Rats, Long-Evans , Reproduction/drug effects
9.
Mar Environ Res ; 50(1-5): 147-51, 2000.
Article in English | MEDLINE | ID: mdl-11460681

ABSTRACT

Natural resistance-associated macrophage protein (Nramp) genes in rainbow trout, Oncorhynchus mykiss, were identified and characterized. The greatest mRNA level encoding these genes was in the developing ovary of rainbow trout. We evaluated the response of these genes to a certain aromatic hydrocarbon receptor (AHR) agonist. Adult rainbow trout were treated with beta-naphthoflavone (BNF) (50 and 100 mg/kg) for 48 h. Using reverse-transcriptase polymerase chain reaction with ovary and head kidney RNA and specific alpha and beta Nramp primers, a 400 bp Nramp-alpha- and a 400 bp Nramp-beta-specific cDNA were obtained. There were no changes in the alpha and beta Nramp mRNA levels in the ovary following BNF administration. CYP1A1 mRNA was increased in the ovary and kidney, suggesting the presence of AHR in rainbow trout ovary, while the AHR agonist produced no effect on Nramp mRNAs.


Subject(s)
Carrier Proteins/genetics , Cation Transport Proteins , Gene Expression Regulation/drug effects , Iron-Binding Proteins , Membrane Proteins/genetics , Oncorhynchus mykiss/genetics , Water Pollutants, Chemical/toxicity , beta-Naphthoflavone/toxicity , Animals , Cytochrome P-450 CYP1A1/biosynthesis , Cytochrome P-450 CYP1A1/metabolism , Female , Kidney/drug effects , Kidney/metabolism , Male , Oncorhynchus mykiss/metabolism , Ovary/drug effects , Ovary/metabolism , RNA, Messenger/metabolism , Receptors, Aryl Hydrocarbon/metabolism , Reverse Transcriptase Polymerase Chain Reaction/veterinary
10.
Neuroradiology ; 39(7): 499-503, 1997 Jul.
Article in English | MEDLINE | ID: mdl-9258927

ABSTRACT

Pituitary abscesses, rare lesions, may be divided into primary and secondary types. Primary pituitary abscesses occur within a previously healthy gland, while secondary abscesses arise within an existing lesion, such as an adenoma, craniopharyngioma, or Rathke's cleft cyst. Secondary abscesses share radiologic characteristics with the lesions from which they arise. There has been no review of the MRI characteristics of primary pituitary abscesses. We report two cases and review the literature. The typical primary pituitary abscess gives the same or slightly lower signal than brain on T1-weighted images, and could be mistaken for a solid mass or presumed to represent a pituitary adenoma. Contrast-enhanced images are useful, demonstrating absence of central enhancement, suggesting a fluid or necrotic center. In one of our cases, meningeal enhancement was obvious; this has not been reported previously and may be diagnostic, when associated with a rim-enhancing pituitary mass.


Subject(s)
Brain Abscess/diagnosis , Candidiasis/diagnosis , Magnetic Resonance Imaging , Pituitary Diseases/diagnosis , Staphylococcal Infections/diagnosis , Adenoma/diagnosis , Adenoma/surgery , Adult , Brain/pathology , Brain Abscess/surgery , Candidiasis/surgery , Diagnosis, Differential , Female , Humans , Pituitary Diseases/surgery , Pituitary Gland/pathology , Pituitary Neoplasms/diagnosis , Pituitary Neoplasms/surgery , Sinusitis/diagnosis , Sinusitis/surgery , Staphylococcal Infections/surgery
11.
Circulation ; 93(7): 1396-402, 1996 Apr 01.
Article in English | MEDLINE | ID: mdl-8641029

ABSTRACT

BACKGROUND: Experimental production of glucose intolerance has been associated with increased diastolic stiffness of the left ventricle, accompanied by interstitial fibrosis. Because carbohydrate metabolism is altered in hypertension, we undertook the present study to assess the relation of diastolic dysfunction in hypertension to plasma glucose and insulin concentrations. The latter are also affected by obesity. To facilitate this analysis, we studied moderately obese hypertensives. Elucidation of these relations was then sought in diabetic subjects. METHODS AND RESULTS: Subjects undergoing catheterization for chest pain were included in the study when significant coronary disease was not present. In groups 1 (lean), 2 (obese), 3 (lean hypertensive), and 4 (obese hypertensives), intraventricular pressures and volumes were determined. Fasting plasma glucose, insulin, hemoglobinAIC, and glucose tolerance were assessed. Basal ejection fraction and end-systolic wall stress were normal in the four groups. Chamber stiffness was significantly elevated in the hypertensives and was higher in group 4 than in group 3 (P < .05). Diastolic dysfunction was correlated with fasting blood glucose (r = .69, P < .006) but not with plasma insulin or left ventricular mass. Chamber stiffness was also increased in diabetics, with a larger effect in the obese. CONCLUSIONS: Hypertension is associated with increased diastolic stiffness of the left ventricle, which is enhanced by moderate obesity, and abnormal carbohydrate metabolism. Experimentally and in humans, hypertension is associated with interstitial fibrosis of mycardium, the presumed basis for the diastolic dysfunction. Chamber stiffness in group 4 hypertensives was similar to that in the lean diabetics but less than that in the obese diabetics. Although the latter exhibited a correlation with plasma hemoglobinAIC, the large rise in stiffness suggests a potential role for growth factors in further alteration of myocardial composition.


Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/physiopathology , Hypertension/physiopathology , Insulin/blood , Ventricular Dysfunction, Left/physiopathology , Chest Pain/etiology , Coronary Angiography , Diabetes Mellitus, Type 2/complications , Diastole , Female , Humans , Hypertension/blood , Hypertension/complications , Hypertrophy, Left Ventricular/etiology , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged , Obesity/complications , Obesity/physiopathology , Ventricular Dysfunction, Left/etiology , Ventricular Function, Left
14.
J Diabetes Complications ; 9(2): 74-80, 1995.
Article in English | MEDLINE | ID: mdl-7599351

ABSTRACT

In this study, human platelets were used as a cellular model for exploring cytosolic free Ca (Cai) regulation in non-insulin-dependent diabetes mellitus (NIDDM). Cai levels were monitored in resting and thrombin-stimulated platelets from obese females with NIDDM; obese, nondiabetic women, and nonobese, nondiabetic women. All subjects were black. Significant and marked elevation of basal Cai levels was observed in platelets from the diabetic subjects when no aspirin was used during platelet isolation. However, no significant differences were observed in Cai between aspirin-treated platelets from women with NIDDM and platelets from nondiabetic women. The rate of the Cai return to basal level after thrombin stimulation was significantly lower in platelets from the diabetic subjects, suggesting an abnormality in platelet Ca extrusion or sequestration in NIDDM. Platelet Cai levels positively correlated with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL/HDL) and fasting blood glucose. These findings suggest abnormalities in platelet Cai homeostasis in NIDDM that are influenced by the serum lipid profile and perhaps glucose.


Subject(s)
Black People , Blood Platelets/metabolism , Calcium/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus/blood , Obesity/blood , Thrombin/pharmacology , Adult , Analysis of Variance , Aspirin/pharmacology , Blood Glucose/analysis , Blood Platelets/drug effects , Cholesterol/blood , Cohort Studies , Cytosol/metabolism , Female , Humans , In Vitro Techniques , Insulin/blood , Kinetics , Lipoproteins/blood , Middle Aged , Platelet Aggregation , Reference Values , Triglycerides/blood
15.
Diabetes Care ; 17(4): 297-304, 1994 Apr.
Article in English | MEDLINE | ID: mdl-8026285

ABSTRACT

OBJECTIVE--To determine the prevalence of incipient and overt nephropathy in African-American subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic. Contributory factors, such as blood pressure (BP), duration and age at onset of diabetes, hyperglycemia, hyperlipidemia, and body mass index (BMI) also were evaluated. RESEARCH DESIGN AND METHODS--We recruited 116 African-American subjects with NIDDM for this cross-sectional, descriptive, and analytical study. BP, BMI, 24-h urine albumin excretion, creatinine clearance, serum creatinine, lipids, and GHb levels were measured. Albumin excretion rate (AER) was calculated, and subjects were divided into three groups: no nephropathy (AER < 20 micrograms/min), incipient nephropathy (AER 20-200 micrograms/min), and overt nephropathy (AER > 200 micrograms/min). Frequency of hypertension and nephropathy was analyzed by chi 2 testing, group means were compared using analysis of variance, and linear correlations were performed between AER and other variables. Multiple regression analysis was used to examine the association of these variables while controlling for the effects of other variables. RESULTS--Increased AER was present in 50% of our subjects; 31% had incipient and 19% had overt nephropathy. Hypertension was present in 72.4%; nephropathy, particularly overt nephropathy, was significantly more prevalent in the hypertensive group. Mean BP and diastolic blood pressure (dBP) were higher in the groups with incipient and overt nephropathy, and systolic blood pressure (sBP) was increased in overt nephropathy. Men with either form of nephropathy had higher sBP, dBP, and mean BP, whereas only women with overt nephropathy had increased sBP and mean BP. Subjects with incipient or overt nephropathy had a longer duration of diabetes, and those with overt nephropathy had a younger age at onset of diabetes. By multiple regression analysis, AER correlated with younger age at diabetes onset, but not with diabetes duration. No correlation with age, lipid levels, or GHb was noted. BMI correlated with AER. CONCLUSIONS--Incipient and overt nephropathy were observed frequently in these African-American subjects with NIDDM. Albuminuria correlated with BP, younger age at diabetes onset, and BMI. Association of albuminuria and increased cardiovascular mortality may place 50% of inner-city African-American patients with NIDDM at risk for developing cardiovascular complications.


Subject(s)
Black or African American , Diabetes Mellitus, Type 2/physiopathology , Diabetic Nephropathies/epidemiology , Adult , Age Factors , Age of Onset , Aged , Aged, 80 and over , Albuminuria , Black People , Blood Pressure , Body Mass Index , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cross-Sectional Studies , Diabetes Mellitus, Type 2/blood , Diabetic Nephropathies/blood , Diabetic Nephropathies/physiopathology , Diastole , Female , Humans , Male , Middle Aged , Prevalence , Systole , Triglycerides/blood
16.
Article in English | MEDLINE | ID: mdl-7905804

ABSTRACT

1. The role of protein kinase C (PKC) in B-naphthoflavone (BNF) induction of CYP1A1 in rainbow trout hepatocytes was investigated. 2. Primary cultures of rainbow trout hepatocytes treated with BNF for 24 hr showed an increase in microsomal 7-ethyoxyresorufin-O-deethylase (EROD) activity compared to cells treated with vehicle (DMSO) only. 3. Increases in EROD activities were proportional to increased concentrations of BNF from 1 to 10 nM reaching a plateau at higher concentrations (20-100 nM) of BNF. 4. Western blot analysis using specific antibody (LM4b) against CYP1A1 showed that changes in microsomal CYP1A1 protein paralleled that of EROD activity. 5. The induction of EROD activity by BNF required both protein and RNA synthesis since the process was blocked by both cycloheximide and actinomycin D. 6. Pretreatment of hepatocytes with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) led to a dose dependent suppression of BNF-induced EROD activity and CYP1A1 content. TPA alone had no effect on hepatic EROD activity and CYP1A1 protein level. 7. Pretreatment with sn-1,2 didecanoylglycerol, a PKC activator, had no effect on BNF-induced EROD activity in these cells. 8. Pretreatment of cells with staurosporine, a PKC inhibitor, effectively blocked BNF-induced EROD activity. 9. PKC may play a role in the induction of CYP1A1 gene expression in fish liver by BNF.


Subject(s)
Cytochrome P-450 Enzyme System/biosynthesis , Liver/enzymology , Oncorhynchus mykiss/metabolism , Protein Kinase C/physiology , Alkaloids/pharmacology , Animals , Benzoflavones/pharmacology , Blotting, Western , Cells, Cultured , Cytochrome P-450 CYP1A1 , Diglycerides/pharmacology , Enzyme Induction/drug effects , Oxidoreductases/biosynthesis , Protein Kinase C/antagonists & inhibitors , Staurosporine , Tetradecanoylphorbol Acetate/pharmacology , beta-Naphthoflavone
17.
In Vitro Cell Dev Biol Anim ; 29A(8): 643-8, 1993 Aug.
Article in English | MEDLINE | ID: mdl-8397184

ABSTRACT

Short-term culture of rainbow trout (Onchorhynchus mykiss) hepatocytes was used to examine the effect of dexamethasone (DEX) on microsomal CYP 1A1 protein content and 7-ethoxyresorufin-O-deethylase (EROD) activity in vitro. Hepatocytes prepared by controlled collagenase digestion and plated at a density of 0.25 x 10(6) cells/cm2 in plastic culture dishes precoated with trout skin extract (7.6 micrograms skin protein/cm2) to facilitate cell attachment were maintained at 16 degrees C. Cells were treated with DEX (10(-9) to 10(-7) M) or vehicle (dimethyl sulfoxide, DMSO) at 24 h. Microsomal CYP 1A1 protein content and EROD activities were measured at 72 h. Both CYP 1A1 protein as measured by Western blots using CYP 1A1 specific anti-sera and EROD activity were significantly lower in DEX (10(-8) to 10(-7) M)-treated hepatocytes compared to untreated (control) or DMSO-treated cells. The effect was dose dependent in that a gradual decrease of CYP 1A1 protein and EROD activities were seen with increasing doses of DEX (10(-8) to 10(-7) M). DEX at 10(-9) M was ineffective. Concomitant addition of 10(-6) M RU486, a type II specific glucocorticoid receptor antagonist, to hepatocytes treated with 10(-7) M DEX abolished the DEX effect. RU486 at 10(-8) M was ineffective. Spironolactone (10(-8) to 10(-6) M), a type I specific glucocorticoid receptor antagonist, did not counteract the DEX effect. RU486 or spironolactone (10(-6) M) alone had no effect on CYP 1A1 under similar conditions. DEX thus down regulates CYP 1A1 in fish cultured hepatocytes and this regulation is mediated through the type II glucocorticoid receptor(s).


Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Dexamethasone/pharmacology , Electron Transport Complex IV/biosynthesis , Liver/enzymology , Microsomes, Liver/enzymology , Oxidoreductases/metabolism , Animals , Blotting, Western , Cell Nucleus/enzymology , Cells, Cultured , Culture Techniques/methods , Cytochrome P-450 CYP1A1 , Enzyme Induction , Kinetics , Liver/cytology , Liver/drug effects , Microsomes, Liver/drug effects , Mifepristone/pharmacology , Mitochondria, Liver/enzymology , Receptors, Glucocorticoid/antagonists & inhibitors , Receptors, Glucocorticoid/physiology , Trout
18.
Fish Physiol Biochem ; 10(5): 419-24, 1993 Mar.
Article in English | MEDLINE | ID: mdl-24214380

ABSTRACT

Three consecutive days of injections of triiodothyronine (T3)(0.038, 0.075, 0.15 and 1.54 nmoles/g) significantly elevated the acetylcholinesterase (AchE) activity in the brain of Singi fish, Heteropneustes fossilis (Bloch). The higher doses of 0.075, 0.15 and 1.54 nmoles of T3/g induced a greater increase in enzyme activity than 0.038 nmoles/g. A T3 dose of 0.019 nmoles/g was found to be ineffective. The T3 action on AchE activity was blocked by cycloheximide. Thiourea treatment for 30 days decreased the AchE activity below the control level. This reduced level of the enzyme activity was brought back even above the control level by T3 injections. It is, therefore, suggested that thyroid hormone is involved in the sustenance of AchE activity in fish brain.

19.
Am J Hypertens ; 5(12 Pt 1): 863-8, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1337457

ABSTRACT

This study evaluated the effect of chronic hyperglycemia on erythrocyte membrane Ca and Na/K-ATPase activities in streptozotocin-induced diabetic rats. The activity of Ca-ATPase was significantly lower in diabetic than in normal rats. Good glycemic control by insulin restored the Ca-ATPase activity to normal. By contrast, diltiazem, a calcium entry blocker, had no effect on the enzyme activity. Calmodulin stimulated Ca-ATPase activity in all groups of rats. Na/K-ATPase activity was not altered in diabetic rats, and no effects of either insulin or diltiazem treatments were observed. The results suggest that erythrocyte Ca-ATPase activity is decreased in diabetic rats and is normalized by good glycemic control.


Subject(s)
Blood Glucose/analysis , Calcium-Transporting ATPases/blood , Calcium/antagonists & inhibitors , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/drug therapy , Diltiazem/therapeutic use , Erythrocytes/enzymology , Sodium-Potassium-Exchanging ATPase/blood , Animals , Blood Glucose/drug effects , Blood Glucose/physiology , Calmodulin/pharmacology , Diabetes Mellitus, Experimental/enzymology , Diltiazem/pharmacology , Glycated Hemoglobin/analysis , Male , Rats , Rats, Wistar , Streptozocin , Time Factors
20.
Hypertension ; 20(4): 549-54, 1992 Oct.
Article in English | MEDLINE | ID: mdl-1328048

ABSTRACT

In this investigation we correlated platelet Na-H antiport parameters with blood pressure and serum lipids in a sample population of non-insulin-dependent diabetic obese, nondiabetic obese, and nondiabetic nonobese black women. Parameters of the Na-H antiport were examined in aspirin-treated platelets. These parameters were not altered in resting or in thrombin-stimulated platelets of diabetic patients. The activity index of platelet Na-H antiport after thrombin stimulation was positively correlated with the blood pressure (systolic blood pressure, r = 0.5320 and p = 0.0001; diastolic blood pressure, r = 0.5123 and p = 0.0017). Lower high density lipoprotein cholesterol levels were associated with an alkaline shift in the cytosolic pH set point for activation of the Na-H antiport. Highly significant correlations were also observed between the total cholesterol/high density lipoprotein cholesterol ratio and the cytosolic pH set point for activation of the Na-H antiport. These correlations were independent of diabetes or the body mass index. Together, these observations indicate that parameters of platelet Na-H antiport are altered with an increase in blood pressure and a decrease in serum high density lipoprotein cholesterol.


Subject(s)
Blood Platelets/metabolism , Carrier Proteins/metabolism , Diabetes Mellitus, Type 2/physiopathology , Obesity/physiopathology , Adult , Analysis of Variance , Biological Transport, Active , Black People , Blood Glucose/analysis , Blood Pressure , Body Mass Index , Diabetes Mellitus, Type 2/blood , Female , Humans , Insulin/blood , Lipids/blood , Middle Aged , Obesity/blood , Sodium-Hydrogen Exchangers
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