Biomedical subjects

H Zhang

Publications and source records attributed to H Zhang.

At least 379 records · Page 21Linked to original sources

PubMed2001

Histone deacetylase activity represses gamma interferon-inducible HLA-DR gene expression following the establishment of a DNase I-hypersensitive chromatin conformation.

Expression of the retinoblastoma tumor suppressor protein (Rb) is required for gamma interferon (IFN-gamma)-inducible major histocompatibility complex class II gene expression and transcriptionally productive HLA-DRA promoter occupancy in several human tumor cell lines. Treatment of these Rb-defective tumor cell lines with histone deacetylase (HDAC) inhibitors rescued IFN-gamma-inducible HLA-DRA and -DRB mRNA and cell surface protein expression, demonstrating repression of these genes by endogenous cellular HDAC activity. Additionally, Rb-defective, transcriptionally incompetent tumor cells retained the HLA-DRA promoter DNase I-hypersensitive site. Thus, HDAC-mediated repression of the HLA-DRA promoter occurs following the establishment of an apparent nucleosome-free promoter region and before transcriptionally productive occupancy of the promoter by the required transactivators. Repression of HLA-DRA promoter activation by HDAC activity likely involves a YY1 binding element located in the first exon of the HLA-DRA gene. Chromatin immunoprecipitation experiments localized YY1 to the HLA-DRA gene in Rb-defective tumor cells. Additionally, mutation of the YY1 binding site prevented repression of the promoter by HDAC1 and partially prevented activation of the promoter by trichostatin A. Mutation of the octamer element also significantly reduced the ability of HDAC1 to confer repression of inducible HLA-DRA promoter activation. Treatment of Rb-defective tumor cells with HDAC inhibitors greatly reduced the DNA binding activity of Oct-1, a repressor of inducible HLA-DRA promoter activation. These findings represent the first evidence that HDAC activity can repress IFN-gamma-inducible HLA class II gene expression and also demonstrate that HDAC activity can contribute to promoter repression following the establishment of a DNase I-hypersensitive chromatin conformation.

Butyrates↗

PubMed2001

Mice with a targeted deletion of the tetranectin gene exhibit a spinal deformity.

Tetranectin is a plasminogen-binding, homotrimeric protein belonging to the C-type lectin family of proteins. Tetranectin has been suggested to play a role in tissue remodeling, due to its ability to stimulate plasminogen activation and its expression in developing tissues such as developing bone and muscle. To test the functional role of tetranectin directly, we have generated mice with a targeted disruption of the gene. We report that the tetranectin-deficient mice exhibit kyphosis, a type of spinal deformity characterized by an increased curvature of the thoracic spine. The kyphotic angles were measured on radiographs. In 6-month-old normal mice (n = 27), the thoracic angle was 73 degrees +/- 2 degrees, while in tetranectin-deficient 6-month-old mice (n = 35), it was 93 degrees +/- 2 degrees (P < 0.0001). In approximately one-third of the mutant mice, X-ray analysis revealed structural changes in the morphology of the vertebrae. Histological analysis of the spines of these mice revealed an apparently asymmetric development of the growth plate and of the intervertebral disks of the vertebrae. In the most advanced cases, the growth plates appeared disorganized and irregular, with the disk material protruding through the growth plate. Tetranectin-null mice had a normal peak bone mass density and were not more susceptible to ovariectomy-induced osteoporosis than were their littermates as determined by dual-emission X-ray absorptiometry scanning. These results demonstrate that tetranectin plays a role in tissue growth and remodeling. The tetranectin-deficient mouse is the first mouse model that resembles common human kyphotic disorders, which affect up to 8% of the population.

Animals↗

PubMed2001

Insulin control of glycogen metabolism in knockout mice lacking the muscle-specific protein phosphatase PP1G/RGL.

The regulatory-targeting subunit (RGL), also called GM) of the muscle-specific glycogen-associated protein phosphatase PP1G targets the enzyme to glycogen where it modulates the activity of glycogen-metabolizing enzymes. PP1G/RGL has been postulated to play a central role in epinephrine and insulin control of glycogen metabolism via phosphorylation of RGL. To investigate the function of the phosphatase, RGL knockout mice were generated. Animals lacking RGL show no obvious defects. The RGL protein is absent from the skeletal and cardiac muscle of null mutants and present at approximately 50% of the wild-type level in heterozygotes. Both the level and activity of C1 protein are also decreased by approximately 50% in the RGL-deficient mice. In skeletal muscle, the glycogen synthase (GS) activity ratio in the absence and presence of glucose-6-phosphate is reduced from 0.3 in the wild type to 0.1 in the null mutant RGL mice, whereas the phosphorylase activity ratio in the absence and presence of AMP is increased from 0.4 to 0.7. Glycogen accumulation is decreased by approximately 90%. Despite impaired glycogen accumulation in muscle, the animals remain normoglycemic. Glucose tolerance and insulin responsiveness are identical in wild-type and knockout mice, as are basal and insulin-stimulated glucose uptakes in skeletal muscle. Most importantly, insulin activated GS in both wild-type and RGL null mutant mice and stimulated a GS-specific protein phosphatase in both groups. These results demonstrate that RGL is genetically linked to glycogen metabolism, since its loss decreases PP1 and basal GS activities and glycogen accumulation. However, PP1G/RGL is not required for insulin activation of GS in skeletal muscle, and rather another GS-specific phosphatase appears to be involved.

Animals↗

PubMed2001

Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose-related fashion.

High concentrations of neutrophil defensins from airway and blood have been reported in patients with inflammatory lung diseases, but their exact role is unclear. We investigated the direct effect of defensins on the lungs of mice. Intratracheal instillation of purified defensins (5-30 mg/kg) induced a progressive reduction in peripheral arterial O(2) saturation, increased lung permeability, and enhanced the lung cytochrome c content. These indexes of acute lung dysfunction were associated with an increased total cell number and a significant neutrophil influx into the lung [5.1 +/- 0.04% in control vs. 48.6 +/- 12.7% in the defensin (30 mg/kg) group, P < 0.05]. Elastase concentrations in the bronchoalveolar lavage (BAL) fluids increased from 38 +/- 11 ng/ml (control) to 80 +/- 4 ng/ml (defensins, P < 0.05). Five hours after defensin instillation, concentrations of tumor necrosis factor-alpha and macrophage inflammatory protein-2 in BAL fluid were significantly increased. High levels of monocyte chemoattractant protein-1 in BAL fluid and plasma were also found after defensin stimulation. We conclude that intratracheal instillation of defensins causes acute lung inflammation and dysfunction, suggesting that high concentrations of defensins in the airways may play an important role in the pathogenesis of inflammatory lung diseases.

Animals↗

PubMed2001

Direct and indirect bacterial killing functions of neutrophil defensins in lung explants.

Studies of the antimicrobial activity of neutrophil defensins have mostly been carried out in microbiological media, and their effects on the host defense in physiological conditions are unclear. We examined 1) the antibacterial activity of defensins in physiological media with and without lung tissue present, 2) the effect of defensins on hydrogen peroxide (H(2)O(2)) production by lung tissue that had been exposed to bacteria, and 3) the effect of diphenyleneiodonium (DPI), an inhibitor of reactive oxygen species formation, on the antibacterial activity of defensins in the presence of lung tissue. Defensins were incubated with Escherichia coli or Pseudomonas aeruginosa in the absence or presence of primary cultured mouse lung explants. Defensins reduced bacterial counts by approximately 65-fold and approximately 25-fold, respectively, at 48 h; bacterial counts were further decreased by approximately 600-fold and approximately 12,000-fold, respectively, in the presence of lung tissue. Defensins induced H(2)O(2) production by lung tissue, and the rate of killing of E. coli by defensins was reduced by approximately 2,500-fold in the presence of 10 microM DPI. We conclude that defensins exert a significant antimicrobial effect under physiological conditions and that this effect is enhanced in the presence of lung tissue by a mechanism that involves the production of reactive oxygen species.

Animals↗

PubMed2001

Alpha1-adrenoceptor subtypes on rat afferent arterioles assessed by radioligand binding and RT-PCR.

We utilized [3H]prazosin saturation and competition radioligand binding studies to characterize the expression of alpha1-adrenoceptors in preglomerular vessels. mRNA for adrenoceptor subtypes was assayed using RT-PCR. The vessels were isolated using an iron oxide-sieving method. [3H]prazosin bound to a single class of binding sites (Kd 0.087 +/- 0.012 nM, Bmax 326 +/- 56 fmol/mg protein). Phentolamine displaced [3H]prazosin (0.2 nM) with a pK(i) of 8.37 +/- 0.09. Competition with the selective alpha1A-adrenoceptor antagonist 5-methylurapidil fit a two-site model (pK(i) 9.38 +/- 0.21 and 7.04 +/- 0.15); 59 +/- 3% of the sites were high-affinity, and 41 +/- 3% were low-affinity binding sites. Competition with the alpha1D-adrenoceptor antagonist 8-(2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl)-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (BMY-7378) fit a one-site model with low affinity (pK(i) 6.83 +/- 0.03). The relative contents of alpha1A-, alpha1B-, and alpha1D-adrenoceptor mRNAs were 64 +/- 5, 25 +/- 5, and 11 +/- 1%, respectively. Thus there was a very good correlation between mRNA and receptor binding for the subtypes. These data indicate a predominance of the alpha1A-adrenoceptor subtype in rat renal resistance vessels, with smaller densities of alpha1B- and alpha1D-adrenoceptors.

Animals↗

PubMed2001

AMPA and NMDA receptors regulate responses of neurons in the rat's inferior colliculus.

The contribution of N-methyl-D-aspartate (NMDA) and AMPA receptors to auditory responses in the rat's inferior colliculus was examined by recording single-unit activity before, during, and after local iontophoretic application of receptor-specific antagonists. Tone bursts and sinusoidal amplitude modulated sounds were presented to one ear, and recordings were made from the contralateral central nucleus of inferior colliculus (ICC). The receptor specific antagonists, (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP) for NMDA receptors and 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX) for AMPA receptors, were released at the recording site through a multi-barreled pipette. For most neurons, either CPP or NBQX alone resulted in a reversible reduction in the number of action potentials evoked by tonal stimulation. For neurons with an onset response pattern, NBQX either completely eliminated or greatly reduced the number of action potentials. CPP also reduced the number of action potentials but had a less pronounced effect than NBQX. For neurons with a sustained firing pattern, NBQX reduced the total number of action potentials, but had a preferential effect on the early part (first 10-20 ms) of the response. CPP also resulted in a reduction in the total number of action potentials, but had a more pronounced effect on the later part (>20 ms) of the response. These results indicate that both AMPA and NMDA receptors contribute to sound evoked excitatory responses in the ICC. They have a selective influence on early and late components of tone-evoked responses. Both receptor types are involved in generating excitatory responses across a wide range of sound pressure levels as indicated by rate level functions obtained before and during drug application. In addition, both CPP and NBQX reduced responses to sinusoidal amplitude modulated sounds. The synchrony of firing to the modulation envelope as measured by vector strength at different rates of modulation was not greatly affected by either CPP or NBQX in spite of the decrease in firing rate.

Acoustic Stimulation↗

PubMed2001

Genetic suppression of seizure susceptibility in Drosophila.

Despite the frequency of seizure disorders in the human population, the genetic and physiological basis for these defects has been difficult to resolve. Although many genetic defects that cause seizure susceptibility have been identified, the defects involve disparate biological processes, many of which are not neural specific. The large number and heterogeneous nature of the genes involved makes it difficult to understand the complex factors underlying the etiology of seizure disorders. Examining the effect known genetic mutations have on seizure susceptibility is one approach that may prove fruitful. This approach may be helpful both in understanding how different physiological processes affect seizure susceptibility and in identifying novel therapeutic treatments. In this study, we have taken advantage of Drosophila, a genetically tractable system, to identify factors that suppress seizure susceptibility. Of particular interest has been a group of Drosophila mutants, the bang-sensitive (BS) mutants, which are much more susceptible to seizures than wild type. The BS phenotypic class includes at least eight genes, including three examined in this study, bss, eas, and sda. Through the generation of double-mutant combinations with other well-characterized Drosophila mutants, the BS mutants are particularly useful for identifying genetic factors that suppress susceptibility to seizures. We have found that mutants affecting Na+ channels, mle(napts) and para, K+ channels, Sh, and electrical synapses, shak-B(2), can suppress seizures in the BS mutants. This is the first demonstration that these types of mutations can suppress the development of seizures in any organism. Reduced neuronal excitability may contribute to seizure suppression. The best suppressor, mle(napts), causes an increased stimulation threshold for the giant fiber (GF) consistent with a reduction in single neuron excitability that could underlie suppression of seizures. For some other double mutants with para and Sh(KS133), there are no GF threshold changes, but reduced excitability may also be indicated by a reduction in GF following frequency. These results demonstrate the utility of Drosophila as a model system for studying seizure susceptibility and identify physiological processes that modify seizure susceptibility.

Animals↗

PubMed2001

DNA amplification associated with double minutes originating from chromosome 19 in mouse hepatocellular carcinoma.

DNA amplification is associated with genomic instability, the main characteristic of cancer cells, and it frequently involves protooncogenes. Double minute chromosomes (DM) and homogeneously stained regions (HSR) are cytological manifestations of DNA amplification. Gain of chromosome 19 is a recurrent alteration in mouse hepatocellular carcinoma (HCC). In one tumor cell line established from HCC developed in myc transgenic mice, DM derived from chromosome 19 were identified by spectral karyotyping and confirmed by fluorescence in situ hybridization (FISH). A probe generated by PCR from microdissected DM was localized by FISH on normal and HCC-derived cell lines on DM and chromosome 19 at two sites separated by several medium size G-bands. This organization of DM containing amplified sequences from separate loci of the same chromosome, indicates a complex mechanism of DNA amplification, possibly involving more than one gene. DM or HSR were not previously identified in mouse HCC and adult human HCC. The recognition of these loci could lead to the cloning of new genes or identification of known genes important in development or progression of HCC.

Animals↗

PubMed2001

Nitric oxide differentially regulates induction of type II nitric oxide synthase in rat vascular smooth muscle cells versus macrophages.

We studied effects of nitric oxide (NO) released by different NO donors on induction of inducible NO synthase (iNOS) in rat aortic smooth muscle cells (RASMC) and rat macrophage cell line NR8383. iNOS protein expression induced by a CM (interleukin-1beta 250 U/mL, interferon-gamma 150 U/mL, and tumor necrosis factor-alpha 150 U/mL) was not affected by the NO donor SNAP (0.2 to 1 mmol/L) in RASMC at 24 hours of incubation but was dose-dependently decreased by SNAP in macrophages (maximal 60% inhibition). A fully functional -3.2-kb rat iNOS promoter was transfected into RASMC and macrophages. The CM-induced promoter activity in transfected macrophages was inhibited by SNAP (maximal 67% inhibition), but this inhibitory effect by SNAP was not observed in transfected RASMC. Electrophoretic mobility-shift assays demonstrated that nuclear factor-kappaB (NF-kappaB) binding patterns were different in 2 cell types and that the ratio of p50:p65 subunits was significantly lower in macrophages than in RASMC. Furthermore, NF-kappaB activity was not affected by SNAP in RASMC but was reduced by SNAP in macrophages. Another putative NO donor, NOR3 (1 mmol/L), completely inhibited iNOS induction by CM in RASMC, but this was accompanied by severe cytotoxicity, which resulted in cell death. Similar concentrations of SNAP did not exhibit cytotoxicity in RASMC, whereas macrophages demonstrated 88% viability compared with cells without SNAP. NO synthase inhibitor N(g)-monomethyl-L-arginine significantly inhibited CM-induced nitrite production in both cell types and stimulated iNOS protein expression in macrophages but did not affect iNOS expression in RASMC. These data strongly suggest that NO may affect transcriptional regulation of iNOS differently in RASMC versus macrophages, possibly by means of regulation of NF-kappaB activation.

Animals↗

PubMed2001

Angiotensin II relaxes microvessels via the AT(2) receptor and Ca(2+)-activated K(+) (BK(Ca)) channels.

Angiotensin II (Ang II) is one of the most potent vasoconstrictor substances, yet paradoxically, Ang II may dilate certain vascular beds via an undefined mechanism. Ang II-induced vasoconstriction is mediated by the AT(1) receptor, whereas the relative expression and functional importance of the AT(2) receptor in regulating vascular resistance and blood pressure are unknown. We now report that Ang II induces relaxation of mesenteric microvessels and that this vasodilatory response was unaffected by losartan, an AT(1) receptor antagonist, but was inhibited by PD123,319, a selective antagonist of AT(2) receptors. In addition, reverse transcriptase-polymerase chain reaction studies revealed high amounts of AT(2) receptor mRNA in smooth muscle from these same microvessels. Ang II-induced relaxation was inhibited by either tetraethylammonium or iberiotoxin, suggesting involvement of the large-conductance, calcium- and voltage-activated potassium (BK(Ca)) channel. Subsequent whole-cell and single-channel patch-clamp studies on single myocytes demonstrated that Ang II increases the activity of BK(Ca) channels. As in our tissue studies, the effect of Ang II on BK(Ca) channels was inhibited by PD123,319, but not by losartan. In light of these consistent findings from tissue physiology, molecular studies, and cellular/molecular physiology, we conclude that Ang II relaxes microvessels via stimulation of the AT(2) receptor with subsequent opening of BK(Ca) channels, leading to membrane repolarization and vasodilation. These findings provide evidence for a novel endothelium-independent vasodilatory effect of Ang II.

Angiotensin II↗

PubMed2001

Long-term antioxidant administration attenuates mineralocorticoid hypertension and renal inflammatory response.

We previously reported increased monocyte/macrophage infiltration, reactive oxygen species accumulation, and nuclear factor-kappaB (NF-kappaB) activation in mineralocorticoid (deoxycorticosterone acetate [DOCA]) hypertensive rats. We tested the hypothesis that prolonged antioxidant administration inhibits superoxide accumulation, lowers blood pressure, and reduces NF-kappaB activation in DOCA-salt hypertensive rats. DOCA rats exhibited a significant increase in systolic blood pressure compared with sham rats. Aortic rings from DOCA rats exhibited increased superoxide (O(2)(-)) production compared with sham rats. In addition, the treatment of DOCA rats with pyrrolidinedithiocarbamate (PDTC) or 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (Tempol) caused a significant decrease in systolic blood pressure and aortic superoxide accumulation. Monocyte/macrophage infiltration was also significantly decreased in DOCA rats treated with PDTC or Tempol compared with untreated DOCA rats. NF-kappaB-binding activity was significantly greater in untreated DOCA rats than in either sham rats or PDTC- or Tempol-treated DOCA rats. Also, DOCA rats treated with Tempol exhibited no significant difference in NF-kappaB-binding activity compared with sham. These results suggest that antioxidants attenuate systolic blood pressure, suppress renal NF-kappaB-binding activity, and partly alleviate renal monocyte/macrophage infiltration in DOCA-salt hypertension.

Animals↗

PubMed2001

The novel C. elegans gene sop-3 modulates Wnt signaling to regulate Hox gene expression.

We describe the properties of a new gene, sop-3, that is required for the regulated expression of a C. elegans Hox gene, egl-5, in a postembryonic neuroectodermal cell lineage. Regulated expression of egl-5 in this cell lineage is necessary for development of the sensory rays of the male tail. sop-3 encodes a predicted novel protein of 1475 amino acids without clear homologs in other organisms. However, the sequence contains motifs consisting of homopolymeric runs of amino acids found in several other transcriptional regulators, some of which also act in Hox gene regulatory pathways. The genetic properties of sop-3 are very similar to those of sop-1, which encodes a component of the transcriptional Mediator complex, and mutations in the two genes are synthetic lethal. This suggests that SOP-3 may act at the level of the Mediator complex in regulating transcription initiation. In a sop-3 loss-of-function background, egl-5 is expressed ectopically in lineage branches that normally do not express this gene. Such expression is dependent on the Hox gene mab-5, as it is in branches where egl-5 is normally expressed. Ectopic egl-5 expression is also dependent on the Wnt pathway. Thus, sop-3 contributes to the combinatorial control of egl-5 by blocking egl-5 activation by MAB-5 and the Wnt pathway in inappropriate lineage branches.

Amino Acid Sequence↗

PubMed2001

Effects of two saponins extracted from the polygonatum Zanlanscianense pamp on the human leukemia (HL-60) cells.

Two saponins, methyl protodioscin and dioscin, were extracted from the root of Polygonatum Zanlanscianense Pamp. One of them, dioscin exerted significant inhibitory effects on the growth of the human leukemia cell HL-60, inducing differentiation and apoptosis. HL60 cells were induced mainly along the granulocytic lineage. In addition, we have found that dioscin affects many cancer cells. These studies may have important significance in treating related cancers.

Apoptosis↗

PubMed2001

Ethnic and environmental differences in various markers of dietary intake and blood pressure among Chinese Han and three other minority peoples of China: results from the WHO Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study.

Our aim was to examine differences in dietary intake and blood pressure (BP) and their associations in four different ethnic Chinese populations, the Han, the Uygur, the Kazak and Tibetan subjects. This study used a sub-database of the Chinese sample of the WHO-Cardiovascular Diseases and Alimentary Comparison (CARDIAC) Study. The WHO-CARDIAC Study was a multicenter cross-sectional study. In each center, 100 men and 100 women aged 48-56 years were selected at random from the local population. Various markers of dietary intake and their relation with BP were studied. The results of the present study indicated the following. 1) There were significant differences in mean BP and prevalence rates of hypertension, with both being higher in the Kazak and Tibetan subjects than in Han and Uygur subjects. 2) The highest mean body mass index (BMI) was observed in the Kazak subjects, while the highest 24-h urinary sodium (Na) and sodium to potassium (Na/K) ratio excretion were observed in the Tibetan subjects. There were also significant differences in other factors, such as magnesium, 3-methylhistidine (3MH) (a biological marker of animal protein intake) and taurine (a biological marker of seafood intake) excretion levels among the four ethnic peoples. 3) In general, BMI, Na and/or Na/K ratios were positively, and 3MH/creatinine and taurine/creatinine ratios were negatively associated with BP. 4) After adjustment for age, sex and potassium, subjects with obesity (BMI > or =26 kg/m2) had significantly higher relative risk of being hypertensive (HT) than those with BMI<26 kg/m2 in the Han, Uygur and Kazak populations; and subjects with elevated sodium excretion (Na > or =244 mmol/day) had significantly higher relative risk of being HT than those with Na<244 mmol/day in the Han, Uygur and Tibetan populations. In conclusion, mean BP and prevalence rates of hypertension were significantly different among the four ethnic groups. These differences are likely to be due, at least in part, to the differences in several diet-related factors, which in turn are associated with culture and environmental differences. Different health promotion strategies might thus be emphasized in different populations.

Blood Pressure↗

PubMed2001

Oligonucleotide inhibition of Fas as a potential treatment strategy in human liver disease.

Fas (CD95 or APO-1) is a member of tumor necrosis factor receptor (TNFR) family. Upon activation, by either binding with Fas ligand or self-aggregation, Fas signaling leads to cell apoptosis. Fas is believed to play a role in T-cell- and B-cell-mediated cytotoxicity and depletion; however, Fas is also constitutively expressed in many tissues, including liver. While the function of Fas in normal liver is unclear, many studies have demonstrated that Fas expression in liver is up-regulated under certain inflammatory conditions. A number of clinical reports also indicate that Fas expression and apoptosis are correlated with damage in liver during progression of several hepatic diseases. Therefore Fas may represent an attractive therapeutic target to control excessive or abnormal apoptosis in liver. One approach to regulate Fas expression in vivo is to use antisense oligonucleotides. This class of compound have been shown to be effective inhibitors of gene expression in many organs, including liver, and we have demonstrated protection of liver from apoptotic injury in animals by treatment with antisense oligonucleotides that inhibit Fas. In this article, we describe the evidence of a role for Fas in mediating some forms of liver disease and we review how antisense oligonucleotides can be used to prevent or control this pathology.

Journal Article↗

PubMed2001

Estrogen inhibits lipopolysaccharide-induced tumor necrosis factor-alpha release from murine macrophages.

During their reproductive years, female have a lower risk for atherosclerosis as compared with age-matched males, although the mechanisms behind this are not clearly understood. Cytokines, including TNF-alpha play an important role in the pathogenesis of atherosclerosis. We therefore evaluated whether or not there was any difference between 17 beta-estradiol and testosterone in modulating TNF-alpha release from murine bone marrow-derived macrophages (BMM) in vitro. Cells were incubated with or without physiological concentrations (10(-10)-10(-8) M) of 17 beta-estradiol or testosterone for 48 h, followed by an additional 6 h in the absence or presence of lipopolysaccharide (LPS; 10 micrograms/ml). The amount of TNF-alpha released into the culture medium was determined with radioimmunoassay. We found that 17 beta-estradiol or testosterone alone did not affect TNF-alpha release from BMM as compared to untreated controls. Preincubation with 17 beta-estradiol significantly inhibited LPS-induced TNF-alpha release by 18.15% (p < 0.05). 25.28% (p < 0.05) and 40.83% (p < 0.01) for 10(-10), 10(-9) and 10(-8) M of 17 beta-estradiol, respectively, as compared to LPS alone. In contrast, testosterone tested for 3 concentrations did not significantly effect TNF-alpha release induced by LPS. The results indicate that 17 beta-estradiol, but not testosterone, inhibits TNF-alpha release from LPS-stimulated macrophages, which may be one of the mechanisms by which estrogen protects against atherosclerosis.

Animals↗

PubMed2001

Changes of serum selenium in pregnant women with gestational diabetes mellitus.

Gestational diabetes is one of the most common diseases in pregnancy. In the present work, the possible relationship between serum selenium concentration and gestational diabetes was investigated. Blood samples of 234 pregnant women were collected, including 98 subjects with impaired glucose tolerance (IGT), 46 subjects with gestational diabetes mellitus (GDM), and 90 normal pregnant women (NPW). An additional 17 samples of normal women of fertile age (NW) were collected for comparison. The hydride generation atomic fluorescence spectrometry was used for selenium determination. The mean serum selenium levels obtained for each group were 0.0741 +/- 0.0167 mg/L for NPW, 0.0631 +/- 0.0132 mg/L for IGT, 0.0635 +/- 0.0120 mg/L for GDM, and 0.108 +/- 0.0170 mg/L for NW. Serum selenium levels were significantly lower in pregnant woman with IGT (p < 0.001) and GDM (p < 0.001) than in NPW. Furthermore, an inverse correlation between the serum selenium concentration and the gestational period was also observed. Selenium supplementation during gestation for pregnant women, especially with IGT and GDM, should be considered.

Adult↗