The bioconversion of beta-carotene into retinoids.
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Animals↗
Biomedical subjects
X D Wang
Publications and source records attributed to X D Wang.
Changes in the fracture toughness of bone may not be reflected in its mineral density, porosity, and tensile properties.
Age-related changes in the skeleton often lead to an increase in the susceptibility of bone to fracture. Such changes most likely occur in the constituents of bone, namely, the mineral and organic phases, and in their spatial arrangement manifested as orientation and microstructure. In the past, however, bone loss or decline in bone mineral density has been considered to be the major contributing factor for the increased risk of bone fractures, and elastic modulus and ultimate strength have been commonly used to assess bone quality and strength. However, whether these properties provide sufficient information regarding the likelihood of bone to fracture remains debatable. Using a novel fracture toughness test, which measures the energy or stress intensity required to propagate a crack within a material, the objective of this study was to investigate if the mineral density and mechanical properties of bone can accurately predict bone fragility as measured by fracture toughness. Changes in fracture toughness (K(IC)), bone mineral density (BMD), elastic modulus (E), yield and ultimate strength (sigma y and sigma s), porosity (P0), and microhardness (Hv) of bone were examined as a function of age in a baboon model. With increasing age, the fracture toughness of bone decreased, and its microhardness increased. However, no significant changes were found in BMD, E, P0, sigma y, and sigma s as a function of age. In addition, simple regression analyses revealed no significant correlation between bone fracture toughness and the other parameters, except for microhardness of bone. The results of this study indicate that changes in bone fracture toughness may not be necessarily reflected in its mineral density, porosity, elastic modulus, yield strength, and ultimate strength.
Aging↗
The association of type II pneumocytes and endothelial permeability with the pulmonary custocyte system in experimental acute pancreatitis.
BACKGROUND: Pancreatitis-associated pulmonary injury is still associated with substantial mortality, especially when seen as a part of the multiple organ dysfunction syndrome. METHODS: The present study aimed at evaluating alterations in type II pneumocytes and the potential relationship with the development of pulmonary injury after acute haemorrhagic pancreatitis induced by an intraductal infusion of 5% sodium taurodeoxycholate in the rat. RESULTS: The results demonstrated that definite alterations in type II pneumocytes were noted 12 and 24 h after induction of pancreatitis, characterized by an increase in the number of vocalized lamellae, the exposed area of type II pneumocytes to alveolar airspace, cellular separation and apoptosis without alterations in cellular membrane integrity. Dysfunction of the pulmonary endothelial barrier was evidenced by an increase in pulmonary albumin flux and the leakage index as well as the migration of lanthanum probes from capillaries to interstitial tissues. The levels of tumour necrosis factor (TNF) in bronchoalveolar lavage fluid significantly increased during the initial phase (3 and 6 h) after pancreatitis. The phagocytic activity of the pulmonary custocyte system increased 3 and 12 h after induction of pancreatitis. CONCLUSION: Thus, pulmonary endothelial barrier dysfunction, an activated custocyte system, and initial release of TNF seems to be involved in the pathogenesis of pancreatitis-associated type II pneumocyte compromise.
Acute Disease↗
Inhibition of sodium current by chloride channel blocker 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) in guinea pig cardiac ventricular cells.
The effects of 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), a potent anion transport blocker, on transmembrane action potentials (APs) and the sodium current (I[Na]) of guinea pig ventricular myocytes were examined by using conventional microelectrode and whole-cell patch-clamp recording techniques. In papillary muscle preparations, DIDS (> or =0.1 mM) suppressed the maximal upstroke velocity (.v[max]) of the AP without significant changes in other AP parameters. Extracellular application of DIDS on single cardiomyocytes isolated from the guinea pig ventricle markedly reduced the peak amplitude of the tetrodotoxin (TTX)-sensitive and voltage-activated sodium current. The concentration-dependent block of DIDS could be expressed by the Hill equation with a Hill coefficient of 0.97 and a dissociation constant of 0.15 mM at a holding potential of (VH) -120 mV. DIDS (0.1 mM) shifted the steady-state inactivation curve for I(Na) toward more negative potentials by 6.0 +/- 0.5 mV and the activation curve to more positive potentials by 5.0 +/- 1.0 mV, although the slope factors were unaffected. With repetitive depolarizing pulses from -120 mV, DIDS produced a use-dependent block on the I(Na). Recovery of I(Na) from inactivation was slowed (time constant = 245 ms, compared with 10 ms of control) in the presence of 0.1 mM DIDS. In the two-pulse experiments, DIDS produced two distinct phases of development of I(Na) block, the rapid phase (tau = 5 ms) caused by an open channel block, and the slower phase (tau = 382 ms) induced by an inactivated channel block. These results suggest that the Cl- transport blocker DIDS has a direct inhibitory effect on the cardiac sodium channel. DIDS-induced use dependence of I(Na) block may result from the interaction of the drug with sodium channels in both the open and inactivated channel states.
4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
Sonographically guided microwave coagulation treatment of liver cancer: an experimental and clinical study.
OBJECTIVE: Percutaneous microwave coagulation was performed with a modified system in animal experiments and in a clinical study to evaluate this technique as a treatment option for liver cancer. SUBJECTS AND METHODS: As an in vitro study, a microwave electrode was inserted 5-6 cm into separated egg white, homogenate of pig liver, and pig liver, with different power outputs and different lengths of inner conductors. In the animal experiment, the sonographically guided coagulation was performed percutaneously nine times and at laparotomy 43 times on 17 adult dogs. The thermal needles were placed parallel to and 5 mm, 8-12 mm, and 15 mm from the electrode. Clinically, 41 patients with hepatocellular carcinoma and 10 patients with hepatic metastases were treated with a 60-W microwave emission for 240-300 sec. RESULTS: Microwave coagulation using the modified system at 60 W for 300 sec produced a necrosis volume of 3.7 x 2.6 x 2.6 cm. The coagulated volume was elliptic when the exposed inner conductor of the electrode was 27 mm. The temperature at the periphery was 62.0 +/- 5.8 degrees C. During a mean follow-up period of 23 months, in 41 patients with hepatocellular carcinoma, 79% (46/58) of lesions became smaller, and the intratumoral blood flow disappeared in 89% (47/53). All tumors showed decreased density on unenhanced CT, and 84% (32/38) of tumors showed no enhancement on contrast-enhanced CT. In 21 patients with an elevated alpha-fetoprotein level, the level decreased in all 21 and was normalized in 17. A second biopsy on 19 patients showed complete destruction of tumor in 18. In 10 patients with hepatic metastases, the mean follow-up period was 13 months. Shrinkage of lesions occurred in 84% (21/25), and the blood flow inside the tumor disappeared in 75% (12/16) of lesions. Seventy-three percent (8/11) of the nodules showed no enhancement. A second biopsy on six patients showed complete necrosis in five. CONCLUSION: Sonographically guided microwave coagulation performed with this modified system was an effective and safe treatment for liver cancer.
Adult↗
Perturbation of the antigen-binding site and staphylococcal protein A-binding site of IgG before significant changes in global conformation during denaturation: an equilibrium study.
Although conformational perturbation of the active sites of many enzymes has been reported to precede global molecular conformational changes [Tsou (1993) Science 262, 380-381], little effort has been made to compare the susceptibility of the ligand-binding site of proteins and the protein molecules as a whole to perturbation by denaturants. Immunoglobulin is chosen in this study to address this problem. It is found that the variable and constant regions (Fv and Fc) of a monoclonal antibody of an IgG subclass against adenylate kinase lose their abilities to bind antigen and staphylococcal Protein A after treatment with guanidinium chloride concentrations considerably lower than those required to change the global conformation of the antibody as a whole, as detected by fluorescence and second-derivative UV absorption spectroscopy. These results indicate that both ligand-binding sites of the antibody concerned are more fragile than the molecule as a whole and that the Fv and Fc regions of the antibody molecule unfold sequentially during denaturation.
Antigens↗
Identification and quantification of retinoic acid and other metabolites from beta-carotene excentric cleavage in human intestine in vitro and ferret intestine in vivo.
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Animals↗
The influence of circulatory and gut luminal challenges on bidirectional intestinal barrier permeability in rats.
BACKGROUND: The endothelial and epithelial barriers are important for maintenance of intestinal barrier function. The present study evaluated the response of these barriers after various challenges. METHODS: Mucosal endothelial and epithelial barrier integrity was evaluated by the leakage of human serum albumin, labeled with different isotopes, from the circulation to the interstitium and the intestinal lumen, or from the intestinal lumen to the interstitium and the circulation, in rats with endothelial or epithelial challenge. RESULTS: Epithelial barrier dysfunction and alterations in epithelial microvillous ultrastructure showed a pattern dependent on the dose of the intraluminal detergents, whereas only higher doses induced an increase in endothelial barrier permeability. Intravenous challenge with CHAPS or Triton caused a dose-dependent increase in both endothelial and epithelial barrier permeability. The development of endothelial barrier dysfunction was related to a decrease in blood pH values. CONCLUSIONS: The results indicate that capillary endothelial barrier integrity may play an important role in maintaining intestinal barrier function and that endothelial injury may initiate or at least be involved in the development of intestinal barrier failure.
Acetic Acid↗
[Orthognathic surgery for patient with deformity of the jaw and OSAS: Report of one case]
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Journal Article↗
Role of macrophage overactivation in the development of acute pancreatic injury in rats.
BACKGROUND: An increase in systemic inflammatory mediators from stimulated leucocytes and macrophages has been noted during acute pancreatitis. The role of cytolytic inflammatory macrophages and potential mechanisms in the development of acute pancreatic injury and endothelial barrier dysfunction are less well defined. METHODS: Rats were challenged by an intraperitoneal injection of cytolytic or non-cytolytic inflammatory macrophage stimulators at various concentrations. The effects of oxygen free radicals, prostaglandin and extracellular calcium influx on macrophage-associated pancreatic endothelial compromise, measured by pancreatic intravascular plasma volume, pancreatic interstitial fluid volume, and the pancreatic extravascular human serum albumin distribution volume, were explored. RESULTS: Zymosan-induced overactivation of cytolytic inflammatory macrophages resulted in the development of acute pancreatic endothelial dysfunction in a dose- and time-dependent pattern. An increase in pancreatic water content and interstitial fluid volume was observed following a higher dose (0.5 mg/g) of concanavalin A without alteration in plasma lipase level, while thioglycollate medium did not compromise pancreatic endothelial barrier function. Oxygen free radicals, but also prostaglandins and extracellular calcium influx, seemed to be involved in macrophage overactivation-induced pancreatic injury. CONCLUSION: Overactivation of cytolytic macrophages plays a role in the pathogenesis of pancreatic injury by initiating the development of endothelial barrier dysfunction. Multiple inflammatory mediators from overactivated macrophages act as intercellular signals between macrophages and the endothelium during acute pancreatic injury.
Animals↗
[Cell transformation by Src kinase: role of cell adhesion system as a signal transducer].
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Cadherins↗
Four types of late Na channel current in isolated ventricular myocytes with reference to their contribution to the lastingness of action potential plateau.
Patch clamp technique was employed to record single Na channel current in isolated guinea-pig ventricular myocytes. Four types of late Na channel currents were observed with whole cell and inside-out recording, which are (1) isolated brief openings, (2) scattered openings, (3) long openings and (4) bursts. The occurrence frequencies of the four types were different. Bursts appeared about 1 in every 2,000 depolarizations, with an open time constant longer than others. However, all the four types of late current openings, as well as the early openings occurring immediately upon depolarization, could be blocked by tetrodotoxin. It was also found that at a certain stimulation frequency, normal action potential duration (APD) was not invariable as supposed before, but varied from stimulation to stimulation. Special Na channel blocker, TTX, shortened the APD and refractory period and abolished the dispersion. The above results suggest that the activities of the various types of late Na channel play an important role in the formation of action potential plateau.
Action Potentials↗
Beta-oxidation in rabbit liver in vitro and in the perfused ferret liver contributes to retinoic acid biosynthesis from beta-apocarotenoic acids.
The biosynthesis of retinoic acid from beta-apocarotenoic acids was examined for a beta-oxidation-like process using both rabbit liver mitochondrial fractions with various beta-apocarotenoic acids (beta-apo-14'-, beta-apo-12'-, and beta-apo-8'-carotenoic acid) and perfusion in ferret liver through the portal vein with beta-apo-8'-carotenoic acid. The in vitro incubation of beta-apo-8', beta-apo-12'-, and beta-apo-14'-carotenoic acids gave rise to shorter chain beta-apocarotenoic acids as well as retinoic acid. The rate of retinoic acid synthesis from 10 microM beta-apo-8', beta-apo-12'-, and beta-apo-14'-carotenoic acids was 11 +/- 2, 18 +/- 3, and 30 +/- 7 pmol/h/mg of protein, respectively. The stepwise oxidation of beta-apocarotenoic acid in mitochondria was dose-related to both protein concentration and substrate concentration. beta-Apocarotenoic acid oxidation was inhibited in a dose-dependent manner when it was co-incubated with oleoyl-CoA. The in vivo perfusion of ferret liver with beta-apo-8'-carotenoic acid resulted in a linear increase in the retinoic acid concentration of bile, which was completely abolished by co-perfusion of 3-mercaptopropionic acid, an inhibitor of long chain acyl-CoA dehydrogenase, and partially inhibited by 2-tetradecylglycidic acid, an inhibitor of carnitine-palmitoyl-CoA transferase I. However, the formation of retinoic acid from the beta-apocarotenoic acids was not inhibited, either in vitro or in vivo, by citral, an inhibitor of retinal oxidase. Thus, the formation of retinoic acid was not occurring by the central cleavage pathway. These data suggest that the oxidation of intermediate compounds between beta-carotene and retinoic acid may undergo a type of beta-oxidative process to form retinoic acid, which is reminiscent of mitochondrial fatty acid beta-oxidation. This pathway may play an important role in the biosynthesis of retinoic acid from beta-carotene.
Animals↗
Alterations in intestinal function in acute pancreatitis in an experimental model.
Gastrointestinal tract failure may be involved in the development of systemic septic complications in acute pancreatitis. Systemic and intestinal circulation, intestinal permeability and absorptive function were evaluated in the early course of acute pancreatitis induced in rats by retrograde intraductal injection of 0.2 ml of 5 per cent sodium taurodeoxycholate and 0.4 nmol trypsin. A decrease in systemic arterial pressure and intestinal blood flow and an increase in intestinal permeability as measured by the leakage of 125I-labelled human serum albumin from blood to lumen were noted in the distal ileum and colon, reaching statistically significant differences 6 h after induction of pancreatitis. The transport of small molecular markers (sodium fluorescein and 51Cr-labelled ethylenediamine tetra-acetic acid) through the distal ileum and colon in vitro from the mucosal to the serosal site in Ussing chambers significantly increased in the early periodic (20-60 min) of incubation, while the passage of a macromolecular marker (ovalbumin) demonstrated a definite increase at 60-120 min of incubation. D-Xylose absorption from the gut lumen to the portal vein was significantly less in acute pancreatitis than after sham operation. Intravenous administration of the hydroxyl radical scavenger dimethylsulphoxide prevented the compromised intestinal permeability and gut absorptive capacity induced by acute pancreatitis, but did not affect the reduced arterial pressure and intestinal microcirculation. Cytotoxic oxygen-derived free radicals may contribute to the development of alterations in intestinal permeability and absorptive function found in the early stage of acute pancreatitis in the rat.
Acute Disease↗
Bacterial translocation in acute liver injury induced by D-galactosamine.
Acute liver injury is associated with a high rate of infectious and septic complications. Most of these infections are produced by gram negative enteric bacteria. We evaluated bacterial translocation, intestinal permeability, blood flow, portal pressure, and intestinal microflora after induction of liver injury and 70% liver resection in the rat. The rate of translocation to both portal and arterial blood was 100% at 24 hours and 50% at 48 hours after liver resection compared with 83% to portal vein and 50% to aortic blood at both time points after acute liver injury. Translocation to intraabdominal organs (liver, spleen, and mesenteric lymph nodes) was 100% in both groups at both 24 and 48 hours. The rate of translocation increased after liver injury at 48 hours with progression of the liver injury but was decreased in the 70% liver resection group with improvement of liver function. "Total aerobic" and "total anaerobic" bacterial counts in small intestine and cecum were not affected. Pulmonary, distal small intestine, and cecal blood flow were decreased in both groups, whereas blood flow in the proximal small intestine was unaffected. Portal pressure and flow were increased after 70% liver resection, but they were decreased in acute liver injury. After acute liver injury, permeability of both distal small intestine and cecum increased, but after liver resection only cecal permeability increased. The results of this experiment show that bacterial translocation occurs in experimental acute liver injury and that its dynamic, pattern and fate are different from that observed after liver resection, which is a reversible surgical model of liver insufficiency.
Analysis of Variance↗
Influence of colostomy on in vivo and in vitro permeability of the rat colon.
PURPOSE: Barrier properties of an isolated colon loop and the remnant colon in continuity with the gastrointestinal tract after colostomy were studied in the rat. METHODS: The in vivo absorption after colonic loop administration of the marker fluorescein sodium was measured as the urinary recovery. The in vitro permeability was measured in Ussing diffusion chambers as the transmucosal passage of [14C]mannitol and of human serum albumin in the isolated and the nonexcluded colonic segments and was compared with the corresponding colonic regions from sham-operated rats at 1 to 14 days after operation. RESULTS: Body weight gain of the rats decreased and diarrhea appeared from day 2 after colostomy. Histologic examination showed mucosal atrophy with decreased villus height in the isolated colonic loop and an increased villus height in the nonexcluded colon segment. Absorption of fluorescein sodium in the isolated loop was increased at 8 and 14 days. Moreover, permeability in the isolated loop was increased for both mannitol and human serum albumin from four days after colostomy compared with the corresponding colonic segments after the sham operation, whereas a decrease in the passage of mannitol was noted in the nonexcluded colon. CONCLUSIONS: Experimentally performed colostomy diversion in the rat induced alterations of the barrier function in both the isolated colonic loop and the nonexcluded colon in continuity with the fecal stream.
Animals↗
Heat shock inhibits the hypoxia-induced effects on iodide uptake and signal transduction and enhances cell survival in rat thyroid FRTL-5 cells.
Chronic hypoxia inhibits rat thyroid function in vivo. To determine possible mechanisms, we studied the effect of hypoxia on iodide uptake, the involvement of second messengers, and cell membrane permeability in rat thyroid FRTL-5 cells. Since sublethal heat stress protects tissues from ischemia, we also determined effects of heat stress. The initial rate of iodide uptake in untreated cells was between 12.98 and 15.28 pmol/micrograms DNA/min. Hypoxia (5% O2) increased the rate of uptake in a time-dependent manner. Heating cells at 45 degrees C for 15 min (heat shock) prior to exposure to hypoxia for 3 days inhibited the increase in the initial rate of I-uptake. Using fura-2, we found that the resting [Ca2+]i in suspended FRTL-5 cells was 65 +/- 7 nM (n = 16). [Ca2+]i was not increased in cells exposed to hypoxia for 1 day, while a 3-day exposure increased [Ca2+]i by 43 +/- 4% (p < 0.05); no additional increase occurred after 7 days of exposure. When cells were heated prior to hypoxia exposure for 3 days, the hypoxia-induced increase in [Ca2+]i did not occur. Similar observations were found with inositol trisphosphates (InsP3). Exposure of cells to hypoxia for 3 days increased InsP3 from 0.08 +/- 0.02 (n = 5) to 0.32 +/- 0.04% total cpm (n = 5, p < 0.05), but sublethal heating of cells prior to hypoxia exposure prevented the increase. Three-day hypoxia increased PKC activity in the membrane fraction (from 67 +/- 7 to 86 +/- 4% of total activity, p < 0.05), and heat shock inhibited these changes also. Immunoblots showed that hypoxia treatment alone and heat shock plus hypoxia resulted in the translocation of PKC-alpha, -delta, -epsilon, and -zeta isoforms, whereas heat shock alone translocated only PKC-beta I, -beta II, and -zeta. Cell membrane integrity was assayed by trypan blue exclusion. Hypoxia alone for 3 days did not affect membrane permeability, but only 49 +/- 3% of cells excluded trypan blue when a 3-day hypoxia exposure was followed by a 6 h reoxygenation. Heat shock prior to hypoxia and reoxygenation protected cell membrane function. Heat shock also induced heat shock protein 70 kDa (HSP-70) synthesis at the transcriptional level. Results suggest that heat shock protects FRTL-5 cells from hypoxic injury, perhaps by inhibiting the initial rate of iodide uptake and second messengers. It is likely that HSP-70 plays an essential role in the process of protection.
Animals↗
Reverse cholesterol transport in the rat following a short-term intravenous infusion of fat emulsion.
The effect on cholesterol transport of an intravenous infusion of a fat emulsion (10%) Intralipid or 10% Lipovenös) in vivo was investigated in the rat. Intralipid (1.85 ml/hr/kg body weight in rts for 3 hr) caused a reduction (P < 0.05) in free cholesterol in the aorta (by 25%), in plasma high-density lipoproteins (64%) and in erythrocytes (11%) with a concomitant enrichment of liver free cholesterol (16%), suggesting an enhanced reverse cholesterol transport in this species. Lipovenös under the same conditions gave similar results. Our data support our previous in vivo study in man indicating that infusion of a fat emulsion is able even to remove cholesterol from the arterial wall and thereby possibly be considered as an antiatherosclerotic agent.
Animals↗