Search PubMed⌕ Search

Biomedical subjects

C F Chen

Publications and source records attributed to C F Chen.

At least 73 records · Page 4Linked to original sources

Concurrent quantification and pharmacokinetic analysis of cefotaxime in rat blood and brain by microdialysis and microbore liquid chromatography.

A simple but effective coupling of microdialysis and microbore liquid chromatograph with UV detection technique was applied to the simultaneous studying of the pharmacokinetics of cefotaxime in both the peripheral compartment and central nervous system. The mobile phase consisted of methanol-100 mM monosodium phosphoric acid (25:75, v/v, pH 5.5) pumped through a C18 microbore column at a flow-rate of 0.05 ml/min. Detection of cefotaxime was set at a UV wavelength of 254 nm. Microdialysis probes were inserted into the jugular vein and striatum of the rat. Following stabilization of microdialysate levels, rats received cefotaxime (20 mg/kg, i.v., n=6) via the femoral vein, and complete concentration versus time profiles for blood and striatum were constructed. The results indicated that cefotaxime rapidly (within 10 min) entered the extracellular fluid of brain striatum following intravenous administration. Noncompartmental pharmacokinetics analysis indicated that the area under the concentration versus time ratio of cefotaxime in rat brain and blood was 6.9%, suggesting appreciable blood-brain barrier penetration. The method was relatively simple, imposed minimal physiological perturbance as it involved no body fluid consumption and sampled in particular protein-unbound drugs, generally believed to be the active fraction.

Animals↗

Enterohepatic circulation of chloramphenicol and its glucuronide in the rat by microdialysis using a hepato-duodenal shunt.

A system consisting of a hepato-duodenal shunt in which the bile of a drug-treated donor rat was diverted to the duodenum of an untreated recipient rat via a bile cannula was used to assess the role of hepatic metabolism and enterohepatic circulation in the pharmacokinetics of chloramphenicol. Blood concentrations of unbound chloramphenicol and its glucuronide were measured by on-line microdialysis coupled to a microbore liquid chromatographic system. Results indicated that chloramphenicol and its glucuronide were detected in the blood of both donor and recipient rats following an intravenous 100 mg/kg dose of chloramphenicol succinate to the donor rat. Our finding suggests that although enterohepatic circulation contributed only to a minor extent (approximately 1.8%) was involved in the disposition of unbound chloramphenicol in the rat on-line microdialysis techniques were applicable for such studies.

Animals↗

Neural mechanisms of impaired micturition reflex in rats with acute partial bladder outlet obstruction.

To determine the contribution of neural elements to micturition, we evaluated, in intact rats, the cystometrogram, pelvic afferent nervous activity, pelvic efferent nervous activity and external urethral sphincter-electromyogram activity in the normal and acute partial bladder outlet obstruction states. In the normal state, in response to saline filling, mechanoreceptor-dependent pelvic afferent nervous activity gradually activated and finally triggered a voiding reflex, including four phases of detrusor contractions. Phase 1 was characterized by an initial rising intravesical pressure, Phase 2 was characterized by a series of high-frequency oscillations in intravesical pressure, Phase 3 contraction was characterized by a rebound intravesical pressure and Phase 4 contraction was characterized by a rapid fall in intravesical pressure. In the acute partial bladder outlet obstruction state, Phase 1 contraction rose and high-frequency oscillations fell in Phase 2. This voiding dysfunction is ascribed to the bursting extraurethral sphincter activity being converted to tonic extraurethral sphincter activity. In summary, the suppressed high-frequency oscillations in Phase 2 of the detrusor muscle contraction could be detrimental to efficient voidings in the acute partial bladder outlet obstructed rat.

Acute Disease↗

Anti-diarrheal effect of water extract of Evodiae fructus in mice.

Our previous study showed that Evodiae fructus (the dried, unripe fruit of Evodia rutaecarpa) has an inhibitory effect on the intestinal transit (anti-transit effect) in mice. In the present study, a water extract of Evodiae fructus was used to examine its effect on castor oil-induced diarrhea and to compare with its anti-transit effect in mice. The results indicated that Evodiae fructus had both anti-transit and anti-diarrheal effects with comparable ID(50) (the dose for 50% inhibition) values of 54+/-7 and 76+/-17 mg/kg. The time-courses of Evodiae fructus pretreatment for both anti-transit and anti-diarrheal effects were very similar. Because no significant influences of both nitric oxide (NO) precursor L-arginine (600 mg/kg, i.p.) and NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (25 mg/kg, i.p.) pretreatment, the NO system was not involved in both the anti-transit and anti-diarrheal effects of Evodiae fructus. Like Evodiae fructus, a muscarinic acetylcholine receptor antagonist atropine inhibited castor oil-induced increase in fecal weight and loss of body weight. However, the potencies or time-courses of atropine pretreatment for both anti-transit and anti-diarrheal effects were different. Furthermore, the anti-diarrheal effect of atropine was independent of its anti-transit effect at the lower dose (0.5 mg/kg, i.p.). Therefore, the action of Evodiae fructus appeared to be something different from atropine, suggesting that an action other than the anti-muscarinic action, as previously proposed for Evodiae fructus, may be involved.

Animals↗

Anticonvulsant effect of water extract of Scutellariae radix in mice.

Since a previous study indicated that the water extract of Scutellariae radix (SR) had high affinity for the benzodiazepine (BDZ) binding site of GABA(A) receptors, the present study examined whether SR water extract has an anticonvulsant effect in vivo and an enhancing effect on gamma-amino-n-butyric acid (GABA)-stimulated uptake of 36Cl(-) in cortex preparation in vitro in mice. The results showed that SR water extract had little effect on pentylenetetrazol (PTZ, 85 mg/kg, s.c.)-induced clonic seizures but significantly inhibited maximal electroshock-induced tonic seizures with an ED(50) of 3.6 g/kg. The BDZ agonist chlordiazepoxide (10 mg/kg, i.p.) had anticonvulsant activity on both types of seizures. In 36Cl(-) uptake assay, SR water extract (1-500 microg/ml) had no significant effect on 25 microM GABA-stimulated 36Cl(-) uptake, whereas chlordiazepoxide (10 microM) increased the 36Cl(-) uptake to 125% of control. Therefore, the present results showed for the first time that SR water extract had anticonvulsant activity against maximal electroshock-induced tonic seizures, and suggested that this anticonvulsant effect might be not via the activation of the BDZ binding site of GABA(A) receptors, but probably via the prevention of seizure spread.

Animals↗

Antihyperglycemic action of isoferulic acid in streptozotocin-induced diabetic rats.

Wistar rats with streptozotocin-induced diabetes (STZ-diabetic rats), which is similar to human insulin-dependent diabetic mellitus (IDDM), were employed to investigate the antihyperglycemic action of isoferulic acid. A single intravenous injection of isoferulic acid decreased the plasma glucose in a dose-dependent manner in the STZ-diabetic rats. Repeated intravenous administration of STZ-diabetic rats with isoferulic acid (5.0 mg kg(-1)) also resulted in the lowering of plasma glucose after one day. Stimulatory effects of isoferulic acid on the glucose uptake and glycogen synthesis in soleus muscles isolated from STZ-diabetic rats were also obtained indicating an increase of glucose utilization following isoferulic acid treatment which was not dependent on insulin. The mRNA level of glucose transporter subtype 4 form (GLUT4) in soleus muscle was raised by isoferulic acid after repeated treatment for 1 day in STZ-diabetic rats. Similar repeated treatment with isoferulic acid reversed the elevated mRNA level of phosphoenolpyruvate carboxykinase (PEPCK) in liver of STZ-diabetic rats to the normal level. However, expression of GLUT4 and PEPCK genes in nondiabetic rats were not influenced by similar treatment with isoferulic acid. These results suggest that isoferulic acid can inhibit hepatic gluconeogenesis and/or increase the glucose utilization in peripheral tissue to lower plasma glucose in diabetic rats lacking insulin.

Animals↗

Mechanisms of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide.

Andrographolide, an active component found in leaves of Andrographis paniculata, has been reported to exhibit nitric oxide (NO) inhibitory property in endotoxin-stimulated macrophages, however, the detailed mechanisms remain unclear. In the present study we investigated the effect of andrographolide on the expression of inducible NO synthase (iNOS) mRNA, protein, and enzyme activity in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS) plus interferon-gamma (IFN-gamma). RAW 264.7 cells stimulated with LPS/IFN-gamma activated NO production; in this condition andrographolide (1-100 microM) inhibited NO production in a dose-dependent manner with an IC(50) value of 17.4+/-1.1 microM. Andrographolide also reduces the expression of iNOS protein level but without a significant effect on iNOS mRNA. The reduction of iNOS activity is thought to be caused by decreased expression of iNOS protein. In a protein stability assay, andrographolide moderately but significantly reduced the amount of iNOS protein as suggested by accelerating degradation. Furthermore, andrographolide also inhibited total protein de novo synthesis as demonstrated by [(35)S]-methionine incorporation. As a whole, these data suggest that andrographolide inhibits NO synthesis in RAW 264.7 cells by reducing the expression of iNOS protein and the reduction could occur through two additional mechanisms: prevention of the de novo protein synthesis and decreasing the protein stability via a post-transcriptional mechanism. It is also possible that inhibition of iNOS protein expression and NO production under immune stimulation and/or bacteria infection may explain, in part, the beneficial effects of andrographolide as an anti-inflammatory agent.

Animals↗

Possible biphasic changes of free radicals in ethylene glycol-induced nephrolithiasis in rats.

OBJECTIVE: To evaluate the possible role of free radicals in nephrolithiasis in rats induced by ethylene glycol, and to examine the correlation between the urinary enzymes N-acetyl-beta-glucosaminidase (NAG), beta-galactosidase (GAL) and neutral endopeptidase (NEP), and free radical production. MATERIALS AND METHODS: Hyperoxaluria was produced in male Wistar rats by adding ethylene glycol to their drinking water. After 7, 21 and 42 days of treatment, urinary oxalate, creatinine clearance and urinary enzymes (NAG, GAL and NEP) were measured. The nitroblue tetrazolium perfusion method was used to locate the sites of free-radical production. Ultrasensitive chemiluminescence was used to directly measure the production of reactive oxygen species (ROS) in vivo. Vitamin E and potassium citrate were fed to rats, in addition to ethylene glycol, to assess their effects on free radical production. RESULTS: Urinary oxalate increased significantly and was associated with an increase in NAG and GAL at all sample times. However, urinary NEP activity was unchanged on day 7, although there was four times as much NEP on days 21 and 42 than in the control groups. Formazan particles in the renal cortex were scored as 3+ to 4+ in rats treated for 7 days with ethylene glycol. Blood ROS levels were also higher in this group than in the controls (P < 0.01). After vitamin E and potassium citrate treatment, blood ROS levels were lower than in rats treated with ethylene glycol alone. CONCLUSION: Free radicals may be produced in the early stages of nephrolithiasis in rats fed with ethylene glycol. Free radicals occurred mainly in blood and might be associated with NEP inactivation.

Animals↗

Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats.

UNLABELLED: Renal afferent signaling diuretic response is impaired in streptozotocin-induced diabetic rats. BACKGROUND: Renal insufficiency develops in diabetes and shows structural and functional abnormalities. Renal afferents, including chemoreceptors and mechanoreceptors located in the vascular and ureteropelvic portions of the kidney, may reflect changes in the environment and trigger an afferent nerve-mediated regulatory function that is known as the renorenal reflex. In this study, the involvement of these renal sensory receptors during the early diabetic state is defined. METHODS: Diabetes was induced in rats after a tail vein injection of streptozotocin (STZ; 60 mg/kg intravenously). Four groups of rats, control (C), diabetic (DM), diabetic with acute insulin treatment (DMAI, 9 U/rat, subcutaneously, on the experimental day), and chronic insulin treatment (DMCI, 9 U/rat, subcutaneously, daily) were studied. Spontaneous firing type 2-renal chemoreceptor (CR2), arterial mechanoreceptor (MRa), ureteropelvic mechanoreceptor (MRu), and venous mechanoreceptor (MRv) were identified by single-unit analysis of renal afferent nervous activity. The receptor activities were confirmed by their response patterns to stimuli elicited by renal arterial occlusion (RAO), backflow of urine, increasing arterial pressure, increasing ureteropelvic pressure (UP), or renal venous occlusion (RVO). The response of these afferent receptors to a challenge of volume expansion and their functional activities on renorenal reflexes were also examined. Immunostaining with PGP 9.5 was applied for examination of the nerve distribution in the diabetic kidney. The tissue level of histamine in the renal pelvis was determined. We explored the effect of histamine on renal receptor activity in these animals to address the possible role of histamine in MRu receptor activity. RESULTS: In early diabetics, signaling activities in MRa and MRv were maintained; however, activity in CR2 and MRu was depressed. For CR2, the reduced basal discharge and the repressed responses to RAO, backflow of urine, and volume expansion found in DM rats were recovered by acute insulin treatment to restore glucose levels to near normal. For MRu, the depressed response to increasing UP and volume expansion was not restored by acute correction of hyperglycemia in DMAI rats. However, antihistamine treatment or chronic insulin treatment recovered the MRu response to mechanical stimuli in DM rats. Because of the desensitized CR2 and MRu activity, renorenal reflexes elicited by backflow of urine and increasing UP were depressed in DM rats. CONCLUSION: Despite a lack of structural changes, the operating system, signaling ability, and renorenal reflex regulatory function of two renal afferent nerve receptors, CR2 and MRu, are altered in the early diabetic state.

Animals↗

Suppression of rat neutrophil reactive oxygen species production and adhesion by the diterpenoid lactone andrographolide.

The present study was to examine whether andrographolide, a diterpenoid lactone isolated from the anti-inflammatory herbal medicine Andrographis paniculata (Burm. f.) Nees. (Acanthaceae), has the ability to prevent phorbol-12-myristate-13-acetate (PMA)-induced reactive oxygen species (ROS) production, as well as N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced adhesion by rat neutrophils. Results demonstrated that PMA (100 ng/ml) induced rapid accumulation of H2O2 and O2. in neutrophils within 30 minutes. Andrographolide (0.1 to 10 microM) pretreatment (10 min, 37 degrees C) significantly attenuated the accumulation of these two oxygen radical metabolites. Administration of andrographolide also significantly prevented fMLP-induced neutrophil adhesion. These data suggest that preventing ROS production and neutrophils adhesion may confer andrographolide the ability to be an anti-inflammatory drug.

Animals↗

Relaxant effects of petasins in isolated guinea pig trachea and their structure-activity relationships.

In the present study, we attempted to compare four petasins, isolated from Petasites formosanus Kitamura, and to look for structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four petasins, including petasin, isopetasin, S-petasin and S-isopetasin, concentration-dependently relaxed histamine (10 microM)-, carbachol (0.2 microM)-, KCl (30 mM)-, and leukotriene D4 (10 nM)-induced precontractions of isolated guinea pig trachealis. The IC50 values strongly showed that the relaxant effects of the sulfur-containing petasins, S-petasin and S-isopetasin, were more potent than those of non-sulfur-containing petasins, petasin and isopetasin. S-isopetasin, with IC50 values around 10 microM, selectively relaxed carbachol- and KCl-induced precontractions, and had almost no effects (IC50s > 300 microM) on histamine- and leukotriene D4-induced precontractions. However, S-petasin, with IC50 values about 6-9 microM, non-selectively relaxed the precontractions induced by all these contractile agents. The influence of isomerization of either petasin to isopetasin or S-petasin to S-isopetasin on the relaxant effects is not clear.

Animals↗

Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis.

By using an HBV-producing cell line (MS-G2) in vitro culture system, we found that wogonin isolated from Scutellaria baicalensis can suppress HBV surface antigen production (P < 0.001) without evidence of cytotoxicity. By assaying the endogenous HBV DNA polymerase activity, we found that both the relaxed circular and the linear forms of HBV DNA are significantly reduced in the wogonin-treated group. Wogonin deserves to be further evaluated for the treatment of human HBV infection.

Flavanones↗

Building the Hospital Without Walls--a CSIRO home telecare initiative.

Aging populations and rising health costs have created the need to care for more patients in their own homes. Australia's Commonwealth Scientific and Industrial Research Organization (CSIRO) is developing a project, Hospital Without Walls, which aims to provide continuous monitoring of patients in certain diagnostic categories. The key technology is a miniature, wearable, low-power radio that can transmit vital sign and activity information to a home computer, from which data may be sent by telephone line and the Internet to appropriate medical professionals. The initial clinical scenario for this work is monitoring of elderly patients who have presented to hospitals following repeated falls. Accelerometers built into the radio sets will monitor activity and detect and characterise falls. Simultaneous measurement of heart rate will provide information about abnormalities of cardiovascular physiology at the time of a fall. The system has been tested in laboratory conditions and is being adapted for initial clinical trials.

Accidental Falls↗

Simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis.

A sensitive microbore HPLC method was developed for the simultaneous determination of unbound cefoperazone in rat blood and brain using microdialysis. Two microdialysis probes were inserted into the jugular vein/right atrium and brain striatum of Sprague-Dawley rats. Cefoperazone (50 mgkg(-1), i.v.) was then administered via the femoral vein. Blood and brain dialysates were collected and eluted with a mobile phase containing methanol-100 mM monosodium phosphoric acid (30:70, v/v, pH 5.5). The wavelength of the UV detector was set at 254 nm. The detection limit of cefoperazone was 20 ng mL(-1). Isocratic separation of cefoperazone was achieved within 10 min. The intra- and inter-assay accuracy and precision of the analyses were < or =10% in the range of 0.05-10 microg mL(-1). The ratio of the area under the concentration curve of cefoperazone in rat brain and blood was estimated to be about 7-8%. It is concluded that cefoperazone is capable of penetrating the blood-brain barrier.

Animals↗

Effects of extracted Cordyceps sinensis on steroidogenesis in MA-10 mouse Leydig tumor cells.

Extracts from the mycelium of Cordyceps sinensis (CS) were tested to determine the in vitro effect on Leydig cell function. MA-10 mouse Leydig tumor cells were used to conduct the experiments. Results showed that progesterone production gradually increased as the dosage of combined water and ethanol extracted CS increased, and there was a statistically significant difference in progesterone production stimulated by 20 mg/ml of CS extracts compared to the control. The combined water and ethanol extracted CS significantly stimulated MA-10 cell steroid production at 12 and 24 h of incubation. In addition, a protein synthesis inhibitor, cycloheximide, did not block the stimulatory effects of CS extracts on MA-10 cell steroid production or total protein expression. Moreover, the expression of steroidogenic acute regulatory (StAR) protein, which is a critical protein for steroidogenesis, stimulated by CS extracts, could not be detected by Western blot analysis. These data indicate that CS extracts might not induce StAR protein and/or other protein expressions to stimulate steroidogenesis in MA-10 mouse Leydig tumor cells.

Animals↗