Biomedical subjects

D Cui

Publications and source records attributed to D Cui.

At least 19 recordsLinked to original sources

PubMed2001

Microcirculatory changes in right lobe grafts in living-donor liver transplantation: a near-infrared spectrometry study.

BACKGROUND: A continuing shortage of cadaveric liver even for adult patients has motivated not a few centers to proceed to living-donor liver transplantation using right lobe grafts. One of controversies is potential congestion in the graft anterior segment by the deprivation of the middle hepatic vein. METHODS: Hepatic tissue oxygenation and hemoglobin concentration were investigated with a near-infrared spectroscopy in the course of harvesting and implantation in living-donor liver transplantation. Twenty adult recipients of right lobe graft were involved in the study. The aim of the analysis was to detect tissue congestion or ischemia. RESULTS: No significant change in mean hepatic tissue oxygenation and hemoglobin was noted in the right lobe during donor operation even after hepatic parenchymal transection, although some trend for relative congestion, i.e., increased tissue hemoglobin, compared with the left lobe was observed. After graft reperfusion in the recipient, both mean hepatic tissue oxygen saturation and hemoglobin decreased significantly in the anterior segment, which was accompanied by increased heterogeneity of tissue hemoglobin and oxygenation. Increased heterogeneity of oxygenation and decreased tissue hemoglobin were observed also in the posterior segment. CONCLUSIONS: The anterior segment in right lobe living-donor liver transplantation is sensitive to ischemia, rather than congestion, at least in the immediate phase after graft reperfusion. The anterior segment seems to be also more prone to circulatory disturbance than the other part of the graft.

Adult↗

PubMed2001

Orphanin FQ: an endogenous antagonist of rat brain dopamine transporter.

Orphanin FQ, also known as nociceptin (NC),is a well-known ligand for opioid receptor-like ORLI receptor. This heptadecapeptide was identified as potently inhibiting the uptake of rat dopamine transporter (rDAT) which is stably expressed in CHO cells (designated D8 cells). Further kinetic analysis proved that this occurs through competitive inhibition with an IC50 of about 1.9 microM. Orphanin FQ also inhibits [3H]dopamine uptake by rat striatal synaptosomes, which confirmed the effect of orphanin FQ on D8 cells. Orphanin FQ was also found to inhibit GABA transporter type I (GATI) but not the serotonin transporter. These results suggest that orphanin FQ is an endogenous antagonist of dopamine transport and that it affects locomotion and other activities at least partly by inhibiting dopamine transporter and directly affecting dopamine transmission or by inhibiting GABA transporter to indirectly change dopaimne transmission.

Animals↗

PubMed2001

Voltammetric determination of cadmium(II) using a chemically modified electrode.

An 1-(pyridylazo)-2-naphthol modified glassy carbon electrode has been investigated as sensor for the measurement of trace levels of Cd2+. Cd2+ is deposited on the surface of a PAN modified glassy carbon electrode at -1.10 V (vs. SCE) via forming Cd2+-PAN and subsequent reduction at the electrode. In the following step, Cd-PAN is oxidized, and voltammograms are recorded by scanning the potential in a positive direction. Calibration plots were found to be linear in the range 2 x 10(-8) mol/L to 8 x 10(-7) mol/L. The detection limit was 5 x 10(-10) mol/L, and the coefficient of variation, determined on one single electrode at a concentration of 5 x 10(-7) mol/L, was calculated to be 3.2% (n = 5). Using this new kind of modified electrode, trace levels of Cd(II) in water samples were determined; the average recovery was calculated to be 98.78%.

Cadmium↗

PubMed2001

Peptide derived from insulin with regulatory activity of dopamine transporter.

A nonapeptide derived from the C terminus of the insulin B chain, H(2)N-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala-COOH, was found to strongly inhibit dopamine (DA) uptake by rat dopamine transporter (DAT) stably expressed in CHO cells (designated D8 cells). The kinetic experiments on D8 cells gave a curve typical of competitive inhibition with an IC(50)=6.9 microM. This inhibitory effect was also confirmed by experiments on striatal synaptosomes. The rat administered with the nonapeptide unilaterally into substantia nigra showed dose-dependent velocity and duration of the round movement contralateral to the nonapeptide-injected side. In addition, the nonapeptide dose-dependently reduced the binding of the tritium-labeled cocaine analog (-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (WIN35,428) to DAT of D8 cells, which suggests that the nonapeptide may inhibit the transport activity of DAT in the way as cocaine does. Meanwhile, the peptide DOI (insulin with 8 amino acid residues deleted at the C terminus of the B chain) shows a significantly stimulating effect on DAT uptake activity in D8 cells. So insulin is proposed as a kind of neuropeptide precursor in the brain and insulin-derived peptides may be involved in the process of regulating the DA system, and these peptides may be developed into new medicines for disorders concerning the DA system such as Parkinson's disease and cocaine addiction.

Aminobutyrates↗

PubMed2001

Crystal structure of the complex of concanavalin A and tripeptide.

The X-ray structure analysis of a cross-linked crystal of concanavalin A soaked with the tripeptide molecule as the probe molecule showed electron density corresponding to full occupation in the binding pocket. The site lies on the surface of concanavalin A and is surrounded by three symmetry-related molecules. The crystal structure of the tripeptide complex was refined at 2.4-A resolution to an R-factor of 17.5%, (Rfree factor of 23.7%), with an RMS deviation in bond distances of 0.01 A. The model includes all 237 residue of concanavalin A, 1 manganese ion, 1 calcium ion, 161 water molecules, 1 glutaraldehyde molecule, and 1 tripeptide molecule. This X-ray structure analysis also provides an approach to mapping the binding surface of crystalline protein with a probe molecule that is dissolved in a mixture of organic solvent with water or in neat organic solvent but is hardly dissolved in aqueous solution.

Binding Sites↗

PubMed2001

Crystal structure of the complex of concanavalin A and hexapeptide.

The X-ray structure analysis of a cross-linked crystal of concanavalin A soaked with a hexapeptide molecule as a probe molecule showed an electron density corresponding to full occupation in the binding pocket. The site lies on the surface of concanavalin A and is surrounded by three symmetry-related molecules. The crystal structure of the hexapeptide complex was refined at 1.93-A resolution, to an R-factor of 19% (Rfree factor of 25%), with an RMS deviation in bond distances of 0.01 A. The model includes all 237 residues of concanavalin A, one manganese ion, one calcium ion, 95 water molecules, one glutaraldehyde molecule, one isopropanol molecule, and one hexapeptide molecule. This X-ray structure analysis also provides an approach to mapping the binding surface of crystalline protein with a probe molecule that is dissolved in the mixture of organic solvent with water or in neat organic solvent but is hardly dissolved in aqueous solution.

Binding Sites↗

PubMed2001

Useful polyclonal antibodies against synthetic peptides corresponding to immunoglobulin light chain constant region for immunohistochemical detection of immunoglobulin light chain amyloidosis.

For the immunohistochemical detection of immunoglobulin (Ig) light chain amyloidosis on formalin-fixed, paraffin-embedded tissue sections, we prepared polyclonal antibodies against synthetic peptides corresponding to positions 118-134 of Ig lambda light chain and positions 116-133 of Ig kappa light chain. Nineteen cases of systemic Ig lambda light chain amyloidosis (Alambda amyloidosis), 10 cases of systemic Ig kappa light chain amyloidosis (Akappa amyloidosis), one case of immunohistochemically unclassified systemic amyloidosis and five cases of localized Alambda amyloidosis were tested with these antibodies. Anti-lambda (118-134) antiserum and the affinity-purified antibody both reacted with 18 of the 19 cases of systemic Alambda amyloidosis and all cases of localized Alambda amyloidosis, although the immunoexpression was somewhat variable in intensity in different areas within the same specimen in both systemic and localized amyloidosis. The signal intensities in plasma cells and serum reacted for anti-lambda (118-134) antiserum were weaker than signals obtained with commercially available anti-Ig lambda light chain antibodies. Anti-kappa (116-133) antiserum and the affinity-purified antibody reacted with nine of the 10 cases of systemic Akappa amyloidosis. We conclude that these antibodies against synthetic peptides corresponding to the Ig light chain constant region are useful for the classification of amyloidosis on formalin-fixed, paraffin-embedded tissue sections.

Amyloidosis↗

PubMed2001

Influence of recipient-bed isolation on survival rates of skin-flap transfer in rats.

The effect of recipient-bed isolation with artificial barriers on skin-flap survival, compared to flap transfer without bed isolation, was evaluated in a modified rat epigastric skin-flap model. The pattern of blood flow in the raised flap with a proximal axial portion and distal random portion was confirmed by laser Doppler flowmetry. Forty rats were divided into four groups. Three of the groups had one of three different artificial barriers-silicone, polypropylene, or gelatin sponge. In each of these three groups, one of the artificial barriers was placed between the flap and its recipient bed after flap replacement. The flaps without bed isolation (Group 4) were used as controls. The survival area was measured 7 days postoperatively. Results demonstrated that necrosis in the groups with silicone and polypropylene barriers was significantly higher than in the controls. Histologically, neovascularization was shown in the flaps without artificial barriers. Foreign-body reactions were observed in the flaps with bed isolation and among these, severe inflammation and congestion were seen in the flaps with polypropylene isolation. In this study, the authors demonstrated that the random portion of a rat skin flap could survive partially through imbibition of plasma and the ingrowth of new vessels from the recipient bed. This neovascularization can be prevented by recipient-bed isolation with an artificial barrier. Bed isolation with a silicone sheet is suggested for use in the study of rat skin-flap survival.

Animals↗

PubMed2001

Improvement of skin paddle survival by application of vascular endothelial growth factor in a rat TRAM flap model.

The effect of vascular endothelial growth factor (VEGF) on skin flap survival and its ability to induce a pharmacological delay by promoting angiogenesis in a flap was studied in a rat transverse rectus abdominis musculocutaneous flap, using a 3 x 8-cm skin paddle with the inferior epigastric vessels as its main vascular supply. Forty-three Sprague-Dawley rats were divided into four groups. In group 1, VEGF was injected into the femoral vein after the flap was elevated. In group 2, VEGF was injected intra-arterially into the flap through the superior epigastric artery after the flap was elevated. In group 3, VEGF was injected into the subcutaneous fascial layer in the area where the flap would be dissected, and the flap was then raised 7 days after injection. In group 4, the flap was dissected and replaced, using saline injection as the control. On postoperative day 5, the survival area of each skin paddle was measured and the flap was harvested for histological analysis. The results showed that the mean survival area +/- standard deviation for the skin paddle was 6.82 +/- 4.89 cm2 (28.4 +/- 20.4% of the whole skin paddle) in the control group, and 4.2 +/- 3.0 cm2 (17.5 +/- 12.5%) and 6.02 +/- 5.97 cm2 (25.1 +/- 24.9%) in the groups with VEGF systemic and intra-arterial administration respectively. The skin survival area in the group with preoperative subcutaneous administration of VEGF was 17.85 +/- 2.88 cm2 (74.4 +/- 12%), which was significantly higher than the other three groups (p < 0.01). Histological semiquantitative analysis showed increased neovascularization in the flap treated with VEGF preoperatively. The data demonstrate that preoperative treatment with VEGF can induce angiogenesis and enhance skin paddle survival in a musculocutaneous flap.

Analysis of Variance↗

PubMed2001

Phospholipase D and phosphatidic acid-mediated generation of superoxide in Arabidopsis.

Phospholipase D (PLD), which hydrolyzes phospholipids into free head groups and phosphatidic acid (PA), may regulate cellular processes through the production of lipid and lipid-derived messengers. We have genetically abrogated PLD alpha, the most prevalent isoform of PLD in plants, and the depletion of PLD alpha in Arabidopsis decreased the levels of PA and superoxide production in Arabidopsis leaf extracts. Addition of PA promoted the synthesis of superoxide in the PLD alpha-depleted plants, as measured by chemiluminescence and superoxide dismutase-inhibitable, NADPH-dependent reduction of cytochrome c and nitroblue tetrazolium. The PA-enhanced generation of superoxide was associated mainly with microsomal membranes. Among various lipids tested, PA was the most effective stimulator with the optimal concentrations between 100 and 200 microM. The PA-promoted production of superoxide was observed also in leaves directly infiltrated with PA. The added PA was more effective in stimulating superoxide generation in the PLD alpha-depleted leaves than in the PLD alpha-containing, wild-type leaves, suggesting that PA produced in the cell was more effective than added PA in promoting superoxide production. These data indicate that PLD plays a role in mediating superoxide production in plants through the generation of PA as a lipid messenger.

Antisense Elements (Genetics)↗

PubMed2001

Enzyme kinetics of cytochrome P450-mediated reactions.

The most common drug-drug interactions may be understood in terms of alterations of metabolism, associated primarily with changes in the activity of cytochrome P450 (CYP) enzymes. Kinetic parameters such as Km, Vmax, Ki and Ka, which describe metabolism-based drug interactions, are usually determined by appropriate kinetic models and may be used to predict the pharmacokinetic consequences of exposure to one or multiple drugs. According to classic Michaelis-Menten (M-M) kinetics, one binding site models can be employed to simply interpret inhibition (pure competitive, non-competitive and uncompetitive) or activation of the enzyme. However, some cytochromes P450, in particular CYP3A4, exhibit unusual kinetic characteristics. In this instance, the changes in apparent kinetic constants in the presence of inhibitor or activator or second substrate do not obey the rules of M-M kinetics, and the resulting kinetics are not straightforward and hamper mechanistic interpretation of the interaction in question. These unusual kinetics include substrate activation (autoactivation), substrate inhibition, partial inhibition, activation, differential kinetics and others. To address this problem, several kinetic models can be proposed, based upon the assumption that multiple substrate binding sites exist at the active site of a particular P450, and the resulting kinetic constants are, therefore, solved to adequately describe the observed interaction between multiple drugs. The following is an overview of some cytochrome P450-mediated classic and atypical enzyme kinetics, and the associated kinetic models. Applications of these kinetic models can provide some new insights into the mechanism of P450-mediated drug-drug interactions.

Algorithms↗

PubMed2001

[A pathologic study on the bronchioles and lung tissues in guinea pig asthma models].

OBJECTIVE: To probe further the pathologic changes in peripheral airways and lung tissues and to observe the changes of surfactant in asthma. METHODS: (1) The guinea pig asthma models were established with ovalbumin challenge method. (2) 6 groups were studied: control group, asthma group of day 1, asthma group of day 4, asthma group of day 14, intraperitoneal dexamethasone group, and budesonide inhalation group. (3) The pathologic changes were observed under optical and electron microscope. (4) The total and differential white blood cells counts of bronchoalveolar lavage fluid(BALF) were carried out. (5) The total amounts of phospholipids which represent the levels of pulmonary surfactant were measured with phosphorus detection method. RESULTS: (1) Significant hyperplasia of mucous membrane, basement membrane, and smooth muscle layer of central and peripheral airways in the asthma groups were seen. The alveolar walls were significantly thickened and alveolar spaces diminished (P < 0.001, compared with the control group). Significant infiltration of eosinophils and lymphocytes were observed in airways and lung tissues. (2) The total cell number and the number eosinophils and lymphocytes in BALF were significantly increased in the asthma groups than those in the control group(P < 0.01). Neutrophils were dominant at early stage, but eosinophils and lymphocytes at late stage. (3) The ultrastructural changes of type II alveolar cells in asthma group included cell swelling, evacuation of lamellar bodies and partial cell desquamation. (4) The total amount of phospholipids in BALF was significantly decreased in the asthma groups as compared with that in the control group (P < 0.01). The above changes were significantly improved in both corticosteroid treated groups. CONCLUSION: Widespread and significant inflammation with eosinophilic infiltration exists in the bronchioles and alveolar walls in guinea pig asthma models. Not only there is structural change, but also the function of alveolar cells is influenced. Asthma is a disease involving the whole airway and lung system.

Animals↗

PubMed2001

[A study on pathological changes and the potential role of growth factors in the airway wall remodeling of COPD rat models].

OBJECTIVE: To study the pathological features of the smooth muscles and collagen in small airways of the COPD rat models and their roles in the airway obstruction, to evaluate the relationship between TGF-beta(1), EGF and bFGF and the airway wall remodeling. METHOD: Rat COPD model (model group) was established by intratracheal instillation of lipopolysaccharide (LPS 200 microgram/200 microL) twice and exposure to cigarette smoke daily. Drug intervention groups received either daily inhalation of budesonide, ipratropine or heparin respectively, starting on the 8 th day or TGF-beta(1) monoclonal antibody (TB21) 0.5 mg twice (6 th and 19 th day) via the tail veinous injection. At the end of four weeks, the thickness of the smooth muscles and collagen in bronchi and pulmonary arteriole wall were measured by means of image analyzer (CMIAS). Expression and localization of the 3 growth factors were observed in trachea, bronchi and lung tissues by immunohistochemistry and in situ hybridization. The levels of PC III, Ln and HA in the serum and BALF were determined by the RIA method. RESULTS: Significant thickening of the smooth muscles and collagen were found in the bronchi and pulmonary arterioles of the model group in comparison with those of the control group. There was significant decrease in the thickness of the collagen and smooth muscles in the small airways in TB21 group and heparin group. Statistically negative relationships were shown between the thickness of either smooth muscles or collagen in the small airways and FEV(0.3) (all P < 0.05). The levels of PC III, Ln and HA in COPD rat models were higher than those of control groups to varying extent. Expressions of TGF-beta(1), EGF and bFGF in the epithelial cells of bronchi, endothelial cells of pulmonary arterioles and in the macrophages of the model group were significantly higher than those of control group. The above mentioned parameters were reduced in different extent in drug intervention groups, in particular, the smooth muscles thickness in heparin group and the collagen thickness in TB21 group were significantly decreased compared to the model group. CONCLUSION: Thickening of smooth muscles and collagen in the bronchi constitutes the fundamental pathology of airway remodeling in the rat COPD model. The excessive depositions of ECM are important characteristics of COPD. TGF-beta(1), EGF and bFGF may play an important role in the airway wall as well as pulmonary arteriole remodeling. The intervention against TGF-beta(1) and long term inhalation of heparin may be of use in the inhibition of airway remodeling in COPD.

Animals↗

PubMed2001

[Clinical observation of TNF-alpha content in nasopharyngeal secretion of patients with nasopharyngeal carcinoma].

OBJECTIVE: To detect the changes of tumor necrosis factor-alpha (TNF-alpha) in nasopharyngeal secretion of patients with nasopharyngeal carcinoma(NPC). METHOD: The content of TNF-alpha in nasopharyngeal secretion was determined by radioimmunoassay (RIA) in 20 controls, 52 patients with NPC. RESULT: The average concentrations of TNF-alpha were (12.95 +/- 4.62) pmol/L in control group, (33.68 +/- 15.13) pmol/L in NPC group and (64.00 +/- 11.57) pmol/L in NPC with necrosis group. The content of TNF-alpha in nasopharyngeal secretion in control group was lower significantly than that of patients with NPC (P < 0.01). CONCLUSION: The level of TNF-alpha in nasopharyngeal secretion of NPC patients was higher than that of normal subjects. To detect the content of TNF-alpha in nasopharyngeal secretion is a useful test for the study and diagnosis of NPC.

Adult↗

PubMed2000

A kinetic model for the metabolic interaction of two substrates at the active site of cytochrome P450 3A4.

In many cases, CYP3A4 exhibits unusual kinetic characteristics that result from the metabolism of multiple substrates that coexist at the active site. In the present study, we observed that alpha-naphthoflavone (alpha-NF) exhibited a differential effect on CYP3A4-mediated product formation as shown by an increase and decrease, respectively, of the carboxylic acid (P(2)) and omega-3-hydroxylated (P(1)) metabolites of losartan, while losartan was found to be an inhibitor of the formation of the 5,6-epoxide of alpha-NF. Thus, to address this problem, a kinetic model was developed on the assumption that CYP3A4 can accommodate two distinct and independent binding domains for the substrates within the active site, and the resulting velocity equations were employed to predict the kinetic parameters for all possible enzyme-substrate species. Our results indicate that the predicted values had a good fit with the experimental observations. Therefore, the kinetic constants can be used to adequately describe the nature of the metabolic interaction between the two substrates. Applications of the model provide some new insights into the mechanism of drug-drug interactions at the level of CYP3A4.

Benzoflavones↗

PubMed2000

Determination of the site of glucuronidation in an N-(3,5-dichlorophenyl)succinimide metabolite by electrospray ionization tandem mass spectrometry following derivatization to picolinyl esters.

Derivatization using 3-pyridylcarbinol coupled with liquid chromatography electrospray ionization tandem mass spectrometry (LC/MS/MS) was used to characterize a novel Phase II metabolite of the nephrotoxic agricultural fungicide, N-(3,5-dichlorophenyl)succinimide (NDPS). A glucuronide conjugate of N-(3,5-dichlorophenyl)-2-hydroxysuccinamic acid (2-NDHSA) was identified in the urine from a rat dosed with [14C]NDPS. However, 2-NDHSA contains an aliphatic hydroxyl group and a carboxylic acid group, both of which are potential sites for glucuronidation. Mass spectrometry alone was unable to distinguish between these possibilities. Since the position of glucuronidation may be important in the mechanism of NDPS-induced nephrotoxicity, chemical derivatization in conjunction with mass spectrometry was used to characterize the glucuronide. The 2-NDHSA glucuronide conjugate was isolated from rat urine, derivatized with 3-pyridylcarbinol, and the derivatized metabolite was then analyzed by LC/MS/MS. Two known NDPS metabolites, 2-NDHSA and N-(3,5-dichlorophenyl)succinamic acid (NDPSA), were also isolated from rat urine and derivatized similarly. 3-Pyridinylcarbinol reacted rapidly with the carboxylic acid groups and formation of the picolinyl esters increased the ionization potential under positive ion conditions. The urinary glucuronide of 2-NDHSA was identified as an alcohol-linked glucuronide by examination of the molecular ions and the collision-induced dissociation (CID) product ion spectra of the derivatized products. When used in combination with mass spectrometry, derivatization of carboxylic acids with 3-pyridylcarbinol provided useful mass fragmentations and is a rapid way to obtain structural information about the position of glucuronidation of NDPS metabolites.

Animals↗

PubMed2000

Identification of the major human liver cytochrome P450 isoform(s) responsible for the formation of the primary metabolites of ziprasidone and prediction of possible drug interactions.

AIMS: To identify the cytochrome P450 (CYP) isoform(s) responsible for the formation of the primary metabolite of ziprasidone (ziprasidone sulphoxide), to determine the kinetics of its formation and to predict possible drug interactions by investigating CYP isoform inhibition in an in vitro study. METHODS: In vitro metabolism of [14C]-ziprasidone was studied using human liver microsomes. The metabolites were identified using mass spectrometry. The kinetics of metabolite formation were determined using [14C]-ziprasidone (10-200 microM) over 5 min, and Km and Vmax were estimated from Lineweaver-Burk plots. IC50 values for the inhibition of specific probe substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A4, by ziprasidone, risperidone and 9-hydroxyrisperidone were also determined using human liver microsomes from three subjects. Mean Ki values were calculated. RESULTS: Three CYP-mediated metabolites - ziprasidone sulphoxide, ziprasidone sulphone and oxindole acetic acid - were identified. The apparent Km and Vmax values for the formation of the major metabolite, ziprasidone sulphoxide (measured as the sum of sulphoxide and sulphone) were 235 microM and 1.14 nmol mg(-1) protein min(-1), respectively. Isoform-selective inhibitors and recombinant enzymes indicated that CYP3A4 is responsible for the formation of ziprasidone metabolites. Ziprasidone was not a substrate for the other isoforms studied. Similar in vitro inhibition of CYP2D6 (Ki 6.9-16 microM) and CYP3A4 (Ki 64-80 microM) was obtained with ziprasidone, risperidone and 9-hydroxyrisperidone. The in vivo free drug concentrations associated with clinically effective doses of ziprasidone are at least 1500-fold lower than the mean Ki for either CYP2D6 inhibition or CYP3A4 inhibition. CONCLUSIONS: Ziprasidone is predominantly metabolized by CYP3A4 in human liver microsomes and is not expected to mediate drug interactions with coadministered CYP substrates, at clinically effective doses.

Antipsychotic Agents↗

PubMed2000

High-level dietary vitamin A enhances T-helper type 2 cytokine production and secretory immunoglobulin A response to influenza A virus infection in BALB/c mice.

Vitamin A supplementation during acute pneumonia has not improved recovery in most human clinical trials. We hypothesize that high vitamin A intake may decrease the production of T-helper type-1 (Th1) cytokines and thereby inhibit antiviral responses. Such decreases might impair recovery from viral respiratory infections. We thus examined the effect of three interventions on viral pneumonia: 1) a high level vitamin A [250,000 IU/kg diet or 75,000 retinol equivalents (RE)/kg], or 2) control diet (4000 IU/kg diet or 1200 RE/kg) given before and during infection, and 3) initiating the high level diet upon infection to simulate the adjuvant therapy used in clinical trials. No difference was seen among the interventions in severity of disease (weight loss, lung virus titers and survival). However, both the high level diet group and the group in which vitamin A was increased at the time of infection had greater salivary immunoglobulin (Ig)A responses (geometric means, 166 and 105 microg/L, respectively) than did the control group (59 microg/L) (P = 0.0019). In contrast, the serum IgG response was higher in the control group (324+/-158 mg/L) than in the high level group (225+/-95 mg/L) (P = 0.028), although it did not differ from the group in which the diet was changed upon infection (230+/-163 mg/L) (P = 0.084). The production of interferon-gamma (IFN-gamma), a Th1 cytokine, was lower in the high level diet group (median, 0.153 microg/L) compared with the control group (median, 0.839 microg/L) (P = 0.014), whereas the production of interleukin-10 (IL-10), a Th2 cytokine, was higher with the high level diet (median, 0.304 microg/L) than with the control (median, 0.126 microg/L) (P = 0.022). This change in the Th1/Th2 pattern was not sufficient to affect recovery from viral pneumonia but may account for the increased IgA and decreased IgG responses seen with high level dietary vitamin A in this study. These data reinforce the lack of utility of vitamin A in treating acute pneumonia in children and suggest that high dose vitamin A supplements may enhance Th2-mediated immune responses, which are particularly beneficial in the case of extracellular bacterial and parasitic infections and IgA-mediated responses to mucosal infections.

Animals↗