Biomedical subjects

Y Deng

Publications and source records attributed to Y Deng.

At least 37 records · Page 2Linked to original sources

PubMed2001

Vanadium, molybdenum, and sodium triethanolamine complexes derived from an assembly system containing tetrathiometalate and triethanolamine.

The reaction system composed of triethanolamine (TEA) and tetrathiovanadate in the presence of MeONa (MeOLi) or NaNH2 was studied to afford vanadium and alkali metal TEA complexes. Complexes [M subsetV6O6[N(CH2CH2O)2(CH2CH2OH)]6]2S6 (M = Na (1), Li (2)) contain two cyclic V((IV)) [12]metallacrown-6 cations linked by a polysulfide S6(2-) anion. Also separated from the reaction system is a novel sodium TEA complex [[Na(TEA)]2S6]n (3), in which parallel coordination chains [Na(TEA)+]n are connected by O-H...S hydrogen bonds forming 3-D network structure. Variable-temperature conductance of 3 was determined to display semiconductor feature. The desulfurization of VS4(3-) was observed to form S6(2-) anion and/or S8 molecule in the synthetic reactions of 1-3. A striking contrast was noted that MoS4(2-) did not desulfurize in the similar reaction to that of VS4(3-) with TEA, and a Na/TEA complex containing MoS4(2-), (Et4N)2[Na2(mu-TEA)2(CH3OH)2](MoS4)2 (4), was obtained instead. The S...H-O and O...H-O hydrogen bonds play an important role in forming the one- or three-dimensional structures for all these complexes by the linkages between clusters and chains. The IR spectrum indicates the structural similarity of complexes 1 and 2. For complex 4, the Mo=S stretch vibration at 468 cm(-1) showing widening and slight red-shift and the slight movement of the 1H NMR signals of TEA ligand to downfield are considered to be the influence of the S...H-O hydrogen bonds. Variable temperature magnetic susceptibility data were collected for complex 1. The effect magnetic moment per V6 unit varies gradually from 4.04 muB at 300 K to 6.24 muB at 5 K, exhibiting ferromagnetic interaction. Heisenberg-type vector-coupling model and molecular field approximation were used to treat the interaction between the paramagnetic sites and gave a good fitting result: J = 3.97 cm(-1), J' = 1.99 cm(-1), g = 1.99, F = 3.64 x 10(-3). Density functional calculation was also performed to complex 1 and its Li, K analogues. The lowest total bonding energy of -874.001 eV was obtained for [Na subsetV6(mu3-O)6] complex containing six unpaired electrons, indicating the stability of a V6 system with six independent spins S = 1/2. When the alkali metal ion is inserted into the [V6(mu3-O)6] cavity, the positive values of the bonding interaction (E(b)) indicate that the insertion depresses the total energy and that complexes 1 and 2 together with K+ complex may exist. However, the lowest E(b) value of the K+ complex implies its instability.

Journal Article↗

PubMed2001

Adrenomedullin increases fluid extravasation from the splenic circulation of the rat.

1. We studied the effect of adrenomedullin (ADM) on fluid efflux from the splenic vasculature into extravascular spaces. 2. Splenic arterial infusion of ADM (1, 3 and 9 ng min(-1); n = 9, 11 and 10, respectively) caused a dose-dependent increase in intrasplenic fluid efflux (+0.6 +/- 0.3 (saline) vs. +2.0 +/- 0.3 ml min(-1) (9 ng min(-1) ADM), P < 0.05), and in splenic (venous minus arterial) haematocrit (+0.8 +/- 0.1 (saline, n = 6) vs. +3.1 +/- 0.3 % (9 ng min(-1) ADM, n = 7), P < 0.05). There was no change in splenic weight (0.99 +/- 0.02 (saline, n = 6) vs. 0.99 +/- 0.02 g (9 ng min(-1) ADM, n = 7), P > 0.05). 3. There was no change in MAP before (97.5 +/- 2.2 mmHg), during (98.4 +/- 3.4 mmHg), or after (100.2 +/- 2.2 mmHg) intrasplenic infusion of ADM (9 ng min(-1)) (n = 11, P < 0.05). 4. ADM (9 ng min(-1)) caused an increase in intrasplenic microvascular pressure (11.3 +/- 0.3 (saline, n = 5) vs. 13.0 +/- 0.3 mmHg (9 ng min(-1) ADM, n = 6), P < 0.05). 5. ADM (1 x 10(-11) to 1 x 10(-6) M) induced greater vasorelaxation of isolated preconstricted splenic resistance arteries than veins (maximal relaxation: 60 +/- 0.9 (artery, n = 9) vs. 43 +/- 1.7 % (vein, n = 8), P < 0.05). L-NMMA (10(-4) M) partially inhibited the ADM-induced relaxation in splenic arteries (maximal relaxation: 38 +/- 3 (ADM + L-NMMA, n = 5) vs. 60 +/- 3 % (ADM + D-NMMA, n = 5), P < 0.05). 6. It is concluded that ADM increases fluid efflux from the splenic vasculature by differentially reducing pre- vs. post-capillary resistance, thus increasing intrasplenic microvascular pressure.

Adrenomedullin↗

PubMed2001

Atrial natriuretic factor increases splenic microvascular pressure and fluid extravasation in the rat.

The spleen is an important site of atrial natriuretic factor (ANF)-induced fluid extravasation into the systemic lymphatic system. The mechanism underlying this process was studied in a blood-perfused (1 ml min(-1)) rat spleen using the double occlusion technique. To ensure that our observations were spleen specific, a similar protocol was repeated in the hindquarters. Rat ANF(1-28), infused into the splenic artery of anaesthetized male rats, caused a dose-dependent (0.3-59 pmol min(-1)) increase in microvascular pressure from 11.3 +/- 0.7 to 14.9 +/- 0.5 mmHg and in post-capillary resistance from 7.2 +/- 0.6 to 10.1 +/- 1.1 mmHg ml(-1). ANF elicited no change in splenic pre-capillary resistance or in hindquarter haemodynamics. Intrasplenic ANF (6.5 pmol min(-1)) caused a sustained increase in intrasplenic fluid efflux from 0.1 +/- 0.1 to 0.3 +/- 0.1 ml min(-1), and in capillary filtration coefficient (Kf) from 1.2 +/- 0.5 to 2.4 +/- 0.6 ml mmHg-1 min-1 (100 g tissue)-1. Mechanical elevation of splenic intravascular pressure (from 11.3 +/- 0.7 to 22.4 +/- 0.2 mmHg) significantly increased intrasplenic fluid extravasation (from 0.4 +/- 0.3 to 1.4 +/- 0.3 ml min(-1)). The natriuretic peptide receptor-C (NPRC)-specific agonist C-ANF(4-23) (12.5 and 125 pmol min(-1)) did not alter splenic intravascular pressure or pre-/post-capillary resistance. The ANF antagonist A71915 (8.3 and 83 pmol min-1), which blocks ANF-stimulated cGMP production via natriuretic peptide receptor-A (NPRA), inhibited the ANF-induced changes in splenic microvascular pressure and post-capillary resistance. It is concluded that ANF enhances the extravasation of isoncotic fluid from the splenic vasculature both by raising intrasplenic microvascular pressure (increased post-capillary resistance) and by increasing filtration area. The constrictive activity of ANF on the splenic vasculature is mediated through NPRA.

Animals↗

PubMed2001

Separation and determination of flavonoids and other phenolic compounds in cranberry juice by high-performance liquid chromatography.

A HPLC method was developed for the separation and determination of flavonoid and phenolic antioxidants in cranberry juices. Free flavonoid and phenolic compounds were fractionated into neutral and acidic groups by means of a solid-phase extraction method, followed by subsequent HPLC separations. Combined flavonoids and phenolics were hydrolyzed by acid before HPLC analysis. This developed method provides a fast and high resolution of individual flavonoid and phenolic compounds. In cranberry fruit, flavonoids and phenolic acids exist predominantly in combined forms, such as glycosides and esters. A total of 400 mg of total flavonoids and phenolic compounds/l of sample was found in a freshly squeezed cranberry juice, which was distributed as about 44% of phenolic acids and 56% of flavonoids. Benzoic acid was the major phenolic compound. Major flavonoids in the freshly squeezed cranberry juice were quercetin and myricetin.

Chromatography, High Pressure Liquid↗

PubMed2001

Chip-based quantitative capillary electrophoresis/mass spectrometry determination of drugs in human plasma.

A chip-based capillary electrophoresis/mass spectrometry (CE/MS) system is described for the on-chip separation and coupled electrospray detection of selected small drug molecule compounds. These studies include the quantitative determination of carnitine and acetylcarnitine in analytical standard solutions as well as imipramine and desipramine in fortified human plasma samples. A clinical human plasma sample was also analyzed following the normal administration of desipramine to a volunteer, and the parent drug was determined using the described chipbased CE/MS technique. In each instance, stable isotope-incorporated internal standards were used. The chip-based CE system was microfabricated from glass and coupled to a micro ion spray device constructed in-house. The atmospheric pressure ionization system employed in this work was a PE Sciex API III tandem triple quadrupole system operated in the selected ion monitoring (SIM) mode. The results from the work reported here demonstrate the feasibility for carrying out rapid (30 s) chipbased quantitative CE/MS determinations of samples containing small-molecule compounds. Using SIM CE/ MS techniques, the described API III quadrupole system provided acceptable ion current electropherograms from subpicomole levels of the targeted compounds loaded onto the chip. The corresponding electropherograms for the standard solution of carnitines at the 1-500 microg/mL level were obtained via SIM CE/MS techniques (R2 > 0.99). In addition, analyses of fortified samples of imipramine desipramine were measured relative to their corresponding d3 internal standards to obtain calibration curves ranging from 5 to 500 microg/mL in human plasma (R2 > 0.99). The intra-assay precision ranged from 4.1 to 7.3% RSD. The intra-assay accuracy ranged from 94.0 to 104%. These results demonstrate the feasibility for on-chip CE separation and electrospray mass spectrometric determination in applications for bioanalytical measurements for these important compounds in synthetic mixtures and human plasma extracts.

Acetylcarnitine↗

PubMed2001

2-Bromoethylamine as a potent selective suicide inhibitor for semicarbazide-sensitive amine oxidase.

Semicarbazide-sensitive amine oxidase (SSAO) catalyzes the deamination of methylamine and aminoacetone to produce toxic aldehydes, i.e. formaldehyde and methylglyoxal, as well as hydrogen peroxide and ammonia. An increase of SSAO activity was detected by different laboratories in patients suffering from vascular disorders, i.e. diabetes and myocardial infarction. The enzyme has been suggested to play a role in vascular endothelial damage and atherogenesis. To date, there are no selective SSAO inhibitors. In the present study, 2-bromoethylamine (2-BrEA) was found to be a highly effective and selective inhibitor of SSAO obtained from different sources. The inhibition was irreversible and time dependent. It was competitive when the enzyme was not preincubated with the inhibitor, but became noncompetitive after incubation of the enzyme with 2-BrEA. The aldehyde trapping agent o-phenylenediamine was capable of preventing 2-BrEA-induced inhibition of SSAO activity. An aldehyde product was detected to be an initial product of 2-BrEA after it was incubated with SSAO. The inhibition, therefore, is mechanism-based. The SSAO inhibitory effects of eight structural analogues of 2-BrEA were assessed. It was concluded that a bromine atom at the beta position is quite important for exerting high potency of SSAO inhibition. The inhibition of SSAO activity by 2-BrEA was also demonstrated in vivo. It increased the urinary excretion of methylamine, an endogenous substrate for SSAO, in mice. 2-BrEA can be employed as a very useful tool in the investigation of SSAO.

Amine Oxidase (Copper-Containing)↗

PubMed2001

Chip-based capillary electrophoresis/mass spectrometry determination of carnitines in human urine.

A chip-based capillary electrophoresis/mass spectrometry (CE/MS) system is described for the CE separation and on-line electrospray detection of carnitine and selected acylcarnitines from mixtures of analytical standards as well as extracts of fortified human urine. Chip-based CE/MS experiments in two different laboratories were carried out using a triple-quadrupole mass spectrometer and a quadrupole time-of-flight (QTOF) mass spectrometer, respectively. The glass chips used with both systems were comparably equipped with a microfabricated capillary electrophoresis (CE) channel but with different electrosprayers. The quadrupole chip-based CE/MS experiments employed a miniature coupled microsprayer, which allowed coupling of the microelectrospray process via a micro liquid junction at the exit of the CE capillary channel. Selected ion monitoring (SIM) CE/MS experiments were employed for all of the quadrupole CE/MS work. The QTOF CE/MS full-scan single MS and MS/MS experiments were carried out in another laboratory using accurate mass measurement TOF mass spectrometry techniques. The electrospray process that was employed with the QTOF system differed in that an inserted nanoelectrospray capillary needle was carefully affixed into a flat-bottomed hole that was aligned with the CE channel exit orifice. SIM CE/MS using the described quadrupole system provided acceptable ion current electropherograms from fmole levels from analytical standard solutions of carnitine and acylcarnitines that were manually injected (loaded) onto the chip. In addition, the corresponding electropherograms for human urine fortified with the target carnitine and acylcarnitines at a 10-20 microg/mL (35-124 microM) level were obtained via SIM CE/MS techniques. The measured CE separation efficiency for the SIM CE/MS electropherograms was determined to be 2860 plates (peak width at half-height method or N = 5.54(T/WO.5(2)), and carnitine and three acylcarnitines were separated in less than 48 s. In contrast, using quadrupole-TOF technologies, the same samples could be diluted by a factor of 2-4 to obtain a comparable detector response for the target compounds. In the full-scan, single mass analyzer mode (m/z 150-500), the CE separation efficiency was measured to be 2600 plates, but mass measurement accuracy was less than 5.0 ppm for the quaternary cations. In the CE/MS/MS mode, full-scan collision-induced dissociation (CID) mass spectra were obtained with a mass accuracy of < or =10 ppm for the higher mass ions and < or =27 ppm for the lower mass product ions. These results demonstrate the feasibility for on-chip CE separation and electrospray mass spectrometric detection for these important compounds in synthetic mixtures, as well as in human urine extracts.

Carnitine↗

PubMed2001

High-speed liquid chromatography/tandem mass spectrometry using a monolithic column for high-throughput bioanalysis.

With the ever-increasing workload from a variety of in vitro and in vivo screening procedures, new analytical methodologies to perform bioanalysis in an accurate and high-throughput manner are in great demand. In this work, monolithic columns were used instead of conventional particulate HPLC columns to perform chromatographic separations. Because the pressure drop on a monolithic column was considerably lower than that on a particulate column, a high flow rate (6 mL/min) was used for a 4.6 x 50 mm monolithic column with a total backpressure of about 61 bar measured using acetonitrile/water (50:50). The capability of using a regular column length at high flow rates, combined with the extremely small dependency of separation efficiency on linear flow velocity, allowed for the generation of sufficient chromatographic resolving power in a significantly reduced runtime. As demonstrated in this work, a plasma extract of a mixture of tempazepam, tamoxifen, fenfluramine, and alprozolam were baseline separated within a total analysis time of one minute. An average peak width at half maximum of approximately one second was noted using a generic broad gradient. It was also found that the separation efficiency and signal/noise (S/N) ratios for this separation remained almost constant at flow rates of 1, 3, and 6 mL/min, respectively. The ruggedness of the separation was evaluated by injecting 600 plasma extracts containing the replicates of a standard curve of the above mixture during an overnight run. The chromatographic retention time, separation quality, peak response and sensitivity were highly reproducible throughout the run. This high-speed liquid chromatography/tandem mass spectrometry (LC/MS/MS) system has been used routinely in the authors' laboratory to support drug discovery programs.

Acetonitriles↗

PubMed2001

Multiple-sprayer tandem mass spectrometry with parallel high flow extraction and parallel separation for high-throughput quantitation in biological fluids.

In this work, an on-line four-column high-flow parallel extraction device was set up and interfaced to a four-column parallel separation system with a four-sprayer tandem mass spectrometric detector. This system allowed for the direct and simultaneous sampling, extraction, separation, and detection of four samples in biological fluids, resulting in significantly increased throughput. The performance of this system was evaluated using rat plasma samples spiked with methotrexate as a test compound. The results showed that the relative standard deviation for responses across the four parallel channels was less than 10% for a concentration range from 10 to 2500 nM, resulting in comparable sensitivity (slope of curve) for the analyte on all channels. A ruggedness test was performed using a mixed set of new and used extraction columns and the relative standard deviation in analyte response was found to be below 15%. The inter-channel crosstalk was measured to be about 0.1%. A comparison between the data generated on this system and on a conventional system for a rat pharmacokinetic study showed no more than 20% difference in measured concentrations. This parallel system is a viable tool for high-throughput bioanalysis in a drug discovery environment.

Animals↗

PubMed2001

Size effects of realgar particles on apoptosis in a human umbilical vein endothelial cell line: ECV-304.

Regulation of endothelial cell apoptosis is a critical modulator of normal and pathological angiogenesis. Inorganic arsenic, especially arsenic trioxide, has been demonstrated to induce clinical remission in patients with acute promyelocytic leukemia as well as those with several solid cancers. So, in this study, we examined the in vitro effect of realgar(As2S2), used to treat human diseases for centuries in traditional Chinese medicine, on cell survival and apoptosis in a human umbilical vein endothelial cell (HUVEC) line: ECV-304. Four different suspensions of realgar particles with diameters from 100-500 nm containing equivalent doses were investigated to determine their size effects. After 2, 4, 6 and 8 h, realgar particles of diameters 100 nm and 150 nm obviously reduced ECV-304 cell survival, which was evidenced by a reduction of cell viability in the MTT assay, whereas cells exhibited slight viability reduction in response to treatment with realgar particles of diameters 200 nm and 500 nm. Significant apoptosis was identified by morphological observation, flow cytometry assay and DNA gel electrophoresis in the ECV-304 cells by the presence of realgar particles of diameters 100 nm and 150 nm. It is demonstrated that particles of realgar with average diameters from 100 nm to 150 nm can induce ECV-304 cell apoptosis. These results suggest that particles of realgar smaller than 150 nm may provide a less toxic agent for anti-neoplasia by suppressing angiogenesis.

Acridine Orange↗

PubMed2001

The binding ability analysis of the normal VLDL receptor and its mutant.

The ligand-binding domain of VLDL receptor contains eight imperfectly similar repeats. To discuss the contribution of each repeat to ligand binding, the RT-PCR technique was used to clone the VLDLR-cDNA from the heart muscle of Chinese people. Two recombinants were further constructed, which contained the full-length cDNA of VLDLR and the mutant lacking repeats 1-5. CHO cell line was transfected with two recombinants. The expression of VLDLR gene could be detected by RT-PCR from the CHO cells transfected with pCD-VR. The results of binding experiments showed that the ability of the CHO cells transfected with the full-length cDNA of VLDL-R binding DiI-labeled beta-VLDL was higher than that of the CHO cells transfected with the mutant. Our findings indicated that human VLDL-R gene could be expressed effectively on CHO cells, and the receptor was almost inactivated when repeats 1-5 were deleted.

Animals↗

PubMed2001

Effect of pressure on intracardiac backscatter from microbubbles.

The backscatter from sonicated albumin microbubbles (Albunex) was analyzed using acoustic densitometry in an in vitro pulsatile heart model to evaluate the effects of pressure on the backscatter from Albunex, and the cardiac cyclic changes of intracardiac backscatter from sonicated albumin microbubbles in 16 healthy persons were analyzed. It was found that the Albunex microbubbles were compressed in systole and decompressed in diastole, causing corresponding changes of backscatter in cardiac cycle. Although the intensities of backscatter in diastole and systole were related to the concentration of microbubbles, the concentration of microbubbles had no effect on the difference of end-diastolic and end-systolic backscatter. The difference of the backscatter was highly correlated with end-systolic pressure (r = 0.96, P = 0.001). In human studies, we also observed same intracardiac cyclic changes of backscatter from sonicated albumin microbubbles. Our study indicates that it is possible to evaluate the intracardiac pressure non-invasively by analyzing the intracardiac backscatter from the microbubbles with acoustic densitometry.

Acoustics↗

PubMed2001

Changes in soil organic carbon storage under grassland as evidenced by changes in sulphur input-output budgets.

Information about temporal changes in soil organic carbon (C) pools may be obtained indirectly from changes in input-output budgets of organically combined nutrients such as sulphur (S). Sulphur budgets were therefore evaluated for Northern Ireland (NI) for the period 1940-1990, inclusive. These budgets indicated that the land or soil had acted first as a sink but then as a source for S, and that reserves of soil S built up between 1940 and 1965 were totally depleted by the mid-1980s. Pooled data from six long-term soil-monitoring sites on undisturbed grassland suggested that negative S budgets from the late-1970s onwards had been due to the net mineralization of soil organic matter and thus were indicative of net losses of organic C from surface soil horizons. There was some evidence that the decline in rainfall and fertiliser S inputs from the mid-1960s may have precipitated the breakdown of soil organic matter.

Animal Feed↗

PubMed2001

Photo-induction of an NADPH dehydrogenase which functions as a mediator of electron transport to the intersystem chain in the cyanobacterium Synechocystis PCC6803.

Illumination of the dark-incubated cells of Synechocystis PCC6803 caused recovery of both respiratory activity of oxygen uptake and PS I-cyclic electron flow, which was monitored by the dark reduction of P700(+) in the presence of DCMU after a 50 ms pulse light (MT) under background far-red light, but the effects were much smaller in those of the mutant M55, which has an ndh-B defective gene. Activity of an NADPH-NBT oxidoreductase with a higher molecular mass (around 380 kDa), which was only found in wild type but not in M55, became evident after the dark-incubated cells were exposed to the light. Immuno-blotting analysis indicated that the NADPH-NBT oxidoreductase contains the NdhB subunit of NDH. The expression of NdhB decreased in dark-incubated cells and increased upon transfer of the cells back to light. These results indicate that an NADPH-specific NDH participates in the light-regulated cyclic electron transport around Photosystem I as well as in respiratory electron transport to the intersystem chain in Synechocystis 6803.

Journal Article↗

PubMed2001

Role of immunologic factors and cyclooxygenase 2 in persistent postinfective enteric muscle dysfunction in mice.

BACKGROUND & AIMS: Chronic abdominal symptoms develop in some patients after acute enteric infection. This study examined mechanisms underlying smooth muscle hypercontractility that persists after acute infection in mice. METHODS: Euthymic and athymic National Institutes of Health (NIH) Swiss mice were infected with Trichinella spiralis and studied 4 weeks postinfection (PI). Isometric tension was assessed in longitudinal muscle. Cytokine and cyclooxygenase (COX)-2 messenger RNA was determined in the muscularis externa by reverse-transcription polymerase chain reaction. COX-2 protein was identified by immunohistochemistry and prostaglandin E(2) was measured by enzymatic immunoassay. Studies were performed in euthymic and athymic NIH Swiss mice 28 days PI and in the presence or absence of treatment with corticosteroid or COX inhibitors. RESULTS: Muscle hypercontractility was evident in euthymic mice but was attenuated in athymic mice or in steroid-treated euthymic mice 28 days PI. Expression of Th2 cytokines interleukins 4, 5, and 13 was increased during the acute infection but not thereafter. COX-2 was localized to muscle and its enzymatic activity remained significantly increased in the muscle on day 28 PI. Selective COX-2 inhibition in vitro reduced the sustained increase in tension generation. CONCLUSIONS: These findings show that COX-2 activation in resident cells of the muscularis externa contributes to the muscle hypercontractility that persists after infection.

Adrenal Cortex Hormones↗

PubMed2001

Use of contact testing in the characterization and design of all-ceramic crownlike layer structures: a review.

Ceramic-based crowns, particularly molar crowns, can fail prematurely from accumulation of fracture and other damage in continual occlusal contact. Damage modes depend on ceramic types (especially microstructures), flaw states, loading conditions, and geometric factors. These damage modes can be simulated and characterized in the laboratory with the use of Hertzian contact testing on monolayer, bilayer, and trilayer structures to represent important aspects of crown response in oral function. This article reviews the current dental materials knowledge base of clinically relevant contact-induced damage in ceramic-based layer structures in the context of all-ceramic crown lifetimes. It is proposed that simple contact testing protocols that make use of sphere indenters on model flat, ceramic-based layer structures-ceramic/polymer bilayers (simulating monolithic ceramic crowns on dentin) and ceramic/ceramic/polymer trilayers (simulating veneer/core all-ceramic crowns on dentin)-can provide useful relations for predicting critical occlusal loads to induce lifetime-threatening fracture. It is demonstrated that radial cracking from the lower core layer surface is the dominant failure mode for ceramic layer thicknesses much below 1 mm. Such an approach may be used to establish a scientific, materials-based foundation for designing next-generation crown layer structures.

Bite Force↗

PubMed2001

Critical role for signal transducer and activator of transcription factor 6 in mediating intestinal muscle hypercontractility and worm expulsion in Trichinella spiralis-infected mice.

Intestinal nematode infections in rats or mice are accompanied by intestinal muscle hyper contractility that may contribute to parasite expulsion from the gut. Previous studies demonstrated that both the expulsion of nematode parasites and the associated muscle hyper contractility are dependent on CD4(+) T helper cells. Nevertheless, the precise immunological mechanism underlying changes in intestinal muscle function remains to be determined. In this study, we investigated the role of interleukin 4 (IL-4) and signal transducer and activator of transcription factor 6 (STAT6) in the development of intestinal muscle hypercontractility and worm expulsion by infecting IL-4 and STAT6-deficient mice with Trichinella spiralis. Worm expulsion was almost normal in IL-4-deficient mice but substantially delayed in STAT6-deficient mice. Consistent with delayed worm expulsion, we also observed a marked attenuation of carbachol-induced muscle contraction in STAT6-deficient mice but only a moderate decrease in muscle hypercontractility in IL-4-deficient mice. In addition, we also observed severe impairment of T helper type 2 cytokine responses and intestinal mucosal mastocytosis in STAT6-deficient mice, although some degree of intestinal tissue eosinophilia was evident in these animals. These results are consistent with the hypothesis that STAT6-dependent changes in intestinal muscle function contribute to host protection in nematode infection.

Animals↗

PubMed2001

IL-12 gene transfer alters gut physiology and host immunity in nematode-infected mice.

Immune responses elicited by nematode parasite infections are characterized by T helper 2 (Th2) cell induction. The immunologic basis for changes in intestinal physiology accompanying nematode infection is poorly understood. This study examined whether worm expulsion and associated goblet cell hyperplasia and muscle contractility share a similar immune basis by shifting the response from Th2 to Th1 using interleukin-12 (IL-12) overexpression. We used a single administration of recombinant adenovirus vector expressing IL-12 (Ad5IL-12) in Trichinella spiralis-infected mice. Ad5IL-12 administered 1 day after infection prolonged worm survival and inhibited infection-induced muscle hypercontractility and goblet cell hyperplasia. This was correlated with upregulated interferon-gamma (IFN-gamma) expression and downregulated IL-13 expression in the muscularis externa layer. We also observed increased IFN-gamma production and decreased IL-4 and IL-13 production from in vitro stimulated spleen and mesenteric lymph node cells of infected Ad5IL-12-treated mice. These results indicate that transfer and overexpression of the IL-12 gene during Th2-based nematode infection shifts the immune response toward Th1 and delays worm expulsion. Moreover, the immune response shift abrogated the physiological responses to infection, attenuating both muscle hypercontractility and goblet cell hyperplasia. These findings strongly indicate that worm expulsion, muscle hypercontractility, and goblet cell hyperplasia share a common immunologic basis and may be causally linked.

Adenoviridae↗