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Biomedical subjects

C L Cheng

Publications and source records attributed to C L Cheng.

At least 19 recordsLinked to original sources

The role of capsaicin-sensitive afferent fibers in the lower urinary tract dysfunction induced by chronic spinal cord injury in rats.

The role of capsaicin-sensitive afferents in neurogenic voiding dysfunction was studied in chronic spinal cord injured rats (SCI). Cystometry and external urethral sphincter (EUS) electromyography were performed on 2 consecutive days after induction of urethane anesthesia in SCI rats 6-8 weeks after spinal cord injury. SCI rats exhibited voiding abnormalities including: non-voiding contractions (NVCs) before micturition, increased volume threshold (VT) for initiating voiding, increased amplitude and duration of voiding contractions, decreased voiding efficiency, increased residual urine, and changes in the pattern of the EUS-EMG. In SCI rats, the EUS electromyogram (EUS-EMG) consisted of more prominent tonic activity, shorter periods of bursting activity, and a reduction in the ratio of silent to active periods during bursting. These changes were more prominent during deeper levels of anesthesia on day 1. Capsaicin (125 mg/kg, s.c., 4 days before urodynamic examination) reduced VT and the number of NVCs, decreased the amplitude and duration of voiding contractions, partially normalized the pattern of EUS-EMG activity, and improved the voiding efficiency on day 1 after induction of anesthesia but not on day 2. Capsaicin treatment increased the percentage of animals (from 55% to 80%) that voided on day 1. The results indicate that capsaicin-sensitive C-fiber bladder afferents are not essential for reflex micturition in SCI rats. However, these afferents do contribute to overactivity of the bladder and detrusor sphincter dyssynergia in deeply anesthetized SCI rats.

Afferent Pathways↗

Determination of metformin in human plasma by high-performance liquid chromatography with spectrophotometric detection.

A simple, selective, sensitive and precise high-performance liquid chromatographic plasma assay for the hypoglycemic agent metformin is described. Acidified samples of plasma were deproteinated with acetonitrile, washed with dichloromethane and the resulting supernatant injected. Chromatography was performed at 40 degrees C by pumping a mobile phase of acetonitrile (250 ml) in pH 7, 0.03 M diammonium hydrogen phosphate buffer (750 ml) at a flow-rate of 1 ml/min through a silica column. Metformin and the internal standard (atenolol) were detected at 240 nm and were eluted 7.8 and 6.8 min, respectively, after injection. No endogenous substances were found to interfere. Calibration curves were linear (r>0.999) from 10 to 2000 ng/ml. The absolute recovery of both metformin and atenolol was greater than 76%. The detection limit and limit of quantitation were 2.5 and 10 ng/ml, respectively. The intra- and inter-day precision (C.V.) was 12%, or less, and the accuracy was within 6.2% of the nominal concentration. This method is suitable for clinical investigation and monitoring metformin concentration.

Animals↗

Effect of barrier disruption by acetone treatment on the permeability of compounds with various lipophilicities: implications for the permeability of compromised skin.

The permeability of compromised skin barrier was investigated in vitro using acetone-disrupted hairless mouse skin as a model membrane. The effect of compound lipophilicity was studied using sucrose, caffeine, hydrocortisone, estradiol, and progesterone as model compounds. The results demonstrated that permeability barrier disruption by acetone treatment significantly enhanced the permeability of the skin to both hydrophilic and amphipathic compounds, including sucrose, caffeine and hydrocortisone. This effect was more prominent with caffeine and hydrocortisone at different transepidermal water loss (TEWL) levels. Acetone treatment, however, didn't appear to alter the percutaneous penetration of highly lipophilic compounds, such as estradiol and progesterone. The characteristics of skin permeability were described by parabolic relationships between log P(WS) (permeability coefficient of whole skin) and log K(O/W) (octanol/water partition coefficient) at different degrees of permeability barrier disruption. The optimal log K(O/W) of compounds for skin penetration appeared to decrease with an increase in TEWL levels. The maximal permeability achieved was similar through skin displaying different TEWL levels. In an attempt to explore the underlying mechanisms for the changes in skin permeability, the stratum corneum/normal saline partition coefficients of water, caffeine, and hydrocortisone either decreased or remained unaffected with an increase in TEWL. Electron microscopic examinations have revealed reductions in stratum corneum lipid content and alterations in intercellular membrane structures as a result of acetone treatment, whereas negligible changes in the number of horny layers were observed by safranin staining of the stratum corneum. We have concluded that the enhancement in skin permeability to both hydrophilic and amphipathic compounds by acetone treatment arose mainly because of the increase in stratum corneum diffusivity at higher TEWL levels. The results imply the possibility of using both TEWL and drug lipophilicity to predict alterations in skin permeability and hence the dose adjustment of topically applied medication for patients with impaired skin barrier function.

Acetone↗

Simultaneous monitoring of extracellular glucose, pyruvate, and lactate in rat testies during ischemia: a microdialysis study.

A dual-probe microdialysis technique was developed for the simultaneous monitoring of glucose and related metabolite levels during testicular ischemia in rats. The determinations of lactate and pyruvate were achieved by liquid chromatography within 5 min. Glucose was determined by a microdialysis analyzer. A unilateral ligation was produced by occlusion of the right artery for 2 or 4 h in anesthetized rats. Microdialysis probes were inserted in both sides of the testis to simultaneously monitor glucose, lactate and pyruvate during basal, ischemia and reperfusion periods. Dynamic and comparative changes in these analytes in ipsilateral and contralateral testes were demonstrated. The present technique can be used as a tool for exploring energy related metabolites and their relationships in testicular ischemia.

Animals↗

Novel mutations of CYP3A4 in Chinese.

Human cytochrome P450 3A4 is a major P450 enzyme in the liver and gastrointestinal tract. It plays important roles in the metabolism of a wide variety of drugs, some endogenous steroids, and harmful environmental contaminants. CYP3A4 exhibits a remarkable interindividual activity variation as high as 20-fold. To investigate whether the interindividual variation in CYP3A4 levels can be partly explained by genetic polymorphism, we analyzed DNA samples from 102 Chinese subjects by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis for novel point mutation in the CYP3A4 coding sequence and promoter region. Using PCR and directed sequencing method to establish the complete intron sequence of CYP3A4 from leukocytes, the complete genomic sequence from exon 1 through 13 of CYP3A4 was determined and published in the GenBank database (accession no. AF209389). CYP3A4-specific primers were designed accordingly. After PCR-single-strand conformation polymorphism and restriction fragment length polymorphism screening, we found three novel mutations; two are point mutations and one is insertion. The first variant allele (CYP3A4*4), an Ile118Val change, was found in 3 of 102 Chinese subjects. The next allele (CYP3A4*5), which causes a Pro218Arg amino acid change, was found in 2 of 102 subjects. We found an insertion in A(17776), designated as CYP3A4*6, which causes frame shift and an early stop codon in exon 9, in one heterozygous subject. We also investigated the CYP3A4 activity in these mutant subjects by measuring the morning spot urinary 6beta-hydroxycortisol to free cortisol ratio with the enzyme-linked immunosorbent assay method. When compared with healthy Chinese population data, the 6beta-hydroxycortisol to free cortisol ratio data suggested that these alleles (CYP3A4*4, CYP3A4*5, and CYP3A4*6) may decrease the CYP3A4 activity. Incidences of these mutations in Chinese subjects are rare. The prevalence of these point mutations in other ethnic groups and its effect on the metabolic activity of CYP3A4 remain to be further evaluated.

Alleles↗

Renal cell carcinoma metastasized to the ureteral stump.

A rare case of ureteral stump metastasis 3 months after nephrectomy for a renal cell carcinoma is presented. A 62-year-old female had undergone right radical nephrectomy 3 months earlier because of renal cell carcinoma in our hospital, and she came back due to gross hematuria. Cystoscopy revealed a papillary mass with a vascular pedicle protruding from the right ureteral orifice. Transurethral resection of the bladder tumor over right ureteral orifice was performed and the pathologic result showed clear cell adenocarcinoma, which argued in favor of a metastatic lesion from the previous renal cell carcinoma. Ureterectomy and a bladder cuff excision were then adopted for this patient, but no residual tumor was found over the remaining ureter. Nevertheless, the patient died of cancer 36 months after the event of ureteral stump metastasis.

Carcinoma, Renal Cell↗

The role of lymphadenectomy in the radical nephrectomy for renal cell carcinoma.

BACKGROUND: The value of lymphadenectomy in the management of renal cell carcinoma (RCC) remains controversial. Most would agree that lymphadenectomy (LD) provides accurate pathologic staging for prognostic data. The question remains whether there is any significant therapeutic benefit from extensive lymph node dissection with radical nephrectomy. The aim of this study was to compare outcomes in sampled lymphadenectomy (SLD) and extensive lymphadenectomy (ELD) with radical nephrectomy for RCC. METHODS: One hundred and thirty-seven patients with RCC were enrolled in this study from Oct. 1982 to Dec. 1996. Eighty-one patients received radical nephrectomy with SLD (stage I: 43, II: 16, III: 22). Fifty-six patients received radical nephrectomy with ELD (stage I: 30, II: 11, III: 15). RESULTS: The mean number of lymph nodes removed by SLD was 4 (ranged from 1 to 8). The mean number of lymph nodes removed by ELD was 16.1 (ranged from 9 to 32). Overall 5-year survivals for SLD in stages I, II and III were 98%, 80% and 38%, respectively. Overall 5-year survivals for ELD in stages I, II and III were 92%, 84% and 40%, respectively. CONCLUSIONS: There is no significant therapeutic benefit from ELD in patients with RCC receiving radical nephrectomy.

Adult↗

Patient reliability in the administration of topical ocular medication.

PURPOSE: To evaluate patient's reliability in the administration of eyedrops. METHOD: The study is based on a randomised, controlled clinical trial in which a steroid-containing drug delivery system (DDS) was directly compared to conventional steroid eyedrops after cataract surgery. 32 eyes undergoing extracapsular cataract extraction with intra-ocular lens insertion received a DDS, while 31 eyes received 0.1% dexamethasone eyedrops q.d.s for 30 days. Patients with DDS were given a placebo eyedrop in the form of 0.9% sodium chloride, while all 63 eyes received topical chloramphenicol eyedrops q.d.s for 30 days. At the conclusion of the 30 day visit, the eyedrop containers were collected and the residual volume of medication remaining in each bottle was then measured to the nearest 10 microlitre using a pipette. RESULTS: 31 patients returned the complete set of eyedrop containers. There was no statistical significant difference in the volume used between the types of eyedrops, sex and diabetic status. All the patients used more than the prescribed amount. Older patients tended to use less medication. CONCLUSION: The amount of medication that patients actually administered in this trial varied widely according to the individual, and patient age may be a factor affecting compliance in using eyedrops.

Age Factors↗

Effects of Centella asiatica on ethanol induced gastric mucosal lesions in rats.

Centella asiatica is a herbal medicine widely used in China and India for wound healing. The aim of this study was to examine its effects on the prevention of ethanol induced gastric lesions in rats. Gastric transmucosal potential difference (PD) was reduced by the application of 50% ethanol in the gastric ex-vivo chamber model and Centella extract (CE) accelerated its recovery. Oral administration of CE (0.05 g/kg, 0.25 g/kg and 0.50 g/kg) before ethanol administration significantly inhibited gastric lesions formation (58% to 82% reduction) and decreased mucosal myeloperoxidase (MPO) activity in a dose dependent manner. These results suggested that CE prevented ethanol induced gastric mucosal lesions by strengthening the mucosal barrier and reducing the damaging effects of free radicals.

Animals↗

Neuroendoscopic biopsy of tectal glioma: a case report.

OBJECTIVE AND IMPORTANCE: A type of intrinsic dorsal midbrain glioma known as benign tectal glioma can cause obstructive hydrocephalus. Because of its slow progress and relatively good prognosis, initial treatment should be cerebrospinal fluid diversion and biopsy. CLINICAL PRESENTATION: We report a 24-year-old man with obstructive hydrocephalus from a tectal glioma, who was admitted to the hospital for malfunction of a shunt placed 16 years previously. INTERVENTION: Magnetic resonance imaging demonstrated enlargement of the dorsal midbrain associated with increased signal intensity on T2-weighted images and fluid attenuation inversion recovery (FLAIR) images. No enhancement occurred with contrast administration. We performed a neuroendoscopic third ventriculostomy and biopsy of the tumor. Histologic examination of the specimen obtained disclosed a low-grade astrocytoma. No postoperative neurologic complications occurred. CONCLUSION: FLAIR images were superior to T2-weighted images in demonstrating abnormal intensity in the dorsal midbrain. Neuroendoscopy confirmed a yellowish tumor inferior to the posterior commissure occluding the entrance of the aqueduct, an observation useful in planning biopsy of the lesion. As the tumor apparently had existed for a number of years, the case supports the notion that the prognosis associated with these tumors is good.

Adult↗

Genetic interactions between the chlorate-resistant mutant cr 8 8 and the photomorphogenic mutants cop1 and hy5.

The chlorate-resistant mutant cr88 is defective in photomorphogenesis, as shown by the phenotypes of long hypocotyls in red light and yellow cotyledons under all light conditions. A subset of light-regulated genes is expressed at subnormal levels in cr88. To analyze further the role that CR88 plays in photomorphogenesis, we investigated the genetic interactions between cr88 and mutants of two other loci affecting photomorphogenesis, CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) and LONG HYPOCOTYL5 (HY5). COP1 represses the expression of light-regulated genes in the dark, and HY5 inhibits hypocotyl elongation in the light. Using morphological, cellular, and gene expression criteria for epistasis analyses to position CR88 in the genetic hierarchy of the photomorphogenesis pathway, we determined that CR88 acts downstream of COP1 but in a branch separate from HY5. In the course of our analysis, we discovered that light causes extensive destruction of plastids in dark-grown cop1 seedlings and that cr88 prevents this destruction.

Arabidopsis Proteins↗

Studies of detrusor-sphincter synergia and dyssynergia during micturition in rats via fractional Brownian motion.

In normal humans, the bladder is supposed to empty by a synergistic contraction of the detrusor and relaxation of the sphincter during micturition. By contrast, suprasacral spinal cord injury (SCI) patients usually will have both of them contract simultaneously and result in the so-called detrusor-sphincter dyssynergia. In this study, the cystometrograms of the detrusor and the electromyograms of external urethral sphincter of intact and SCI female Wistar rats are used to investigate the detrusor-sphincter synergia and dyssynergia during micturition. Due to the statistical self-similarity of the waveforms, the cystometrogram is modeled as discrete-time fractional Brownian motion and the electromyogram as discrete-time fractional Gaussian noise. Fractal dimensions of both of them are calculated and used as indices in the investigation of synergia. Results indicate that, for intact rats, the sphincter muscle is not only active but also recruited in a synchronous fashion with the detrusor. Furthermore, clear-cut measure using the fractal dimensions can be used to diagnose detrusor-sphincter synergia and dyssynergia.

Algorithms↗

Pseudomelanosis duodeni: case report.

Pseudomelanosis duodeni is a rare benign condition. It manifests endoscopically as discrete, flat, small brown-black spots in the duodenal mucosa. It produces no symptoms and may be reversible. The cause and natural history of the pigmentation have not been clarified, although it is associated with a variety of systemic illnesses and medications. With electron microscopy and electron-probe energy dispersive X-ray analysis, the pigment corresponds principally to an accumulation of ferrous sulfide (FeS) in macrophages within the lamina propria. We report the case of a 56-year-old female patient with a past history of diabetes mellitus and hypertension. She was admitted because of nausea, vomiting, and diarrhea and underwent esophagogastroduodenoscopy because of stool occult blood test results of 3+. Endoscopy revealed diffusely scattered black spots in the bulb and second portion of the duodenum. Histological examination showed numerous pigment-laden macrophages in the lamina propria of mucosal villi. The diagnosis requires further confirmation by electron microscopy and electron-probe energy dispersive X-ray microanalysis. No special therapy is indicated for this rare lesion.

Duodenal Diseases↗

A case series of acanthamoeba keratitis in Singapore.

Acanthamoeba keratitis has become an important cause of severe ocular inflammation and visual loss in the past two decades. Its prevalence has been linked to the increasing use of contact lens. Early diagnosis, effective treatment regimes and education on proper contact lens wear are important in the management and prevention of visual loss from this debilitating disease. We described a series of two cases of culture positive acanthamoeba keratitis and their subsequent management.

Acanthamoeba Keratitis↗

Fractal geometry in urodynamics of lower urinary tract.

The physiological signals are usually extremely complicated and difficult to analyze. Recently, investigators have tried the fractal dimension that can characterize roughness and self-similarity of them. It turns out that it is also suitable for obtaining the modalities of lower urinary tract during normal micturition. In this investigation, the external urethral sphincter electromyogram (EUS EMG) and the cystometrogram (CMG) of the Wistar rats under both room temperature and cold water stimulation of the bladder are studied. The modified relative differential box-counting (RDBC) method is used to calculate the fractal dimensions of EMG and CMG time series. According to the experimental results, the modalities of micturition for the Wistar rats can be characterized as normal if both the fractal dimensions of EMG and CMG are of low values during voiding. Furthermore, the technique is validated in identifying the dyssynergia of the bladder and EUS under cold water stimulation.

Animals↗

Pharmacokinetics of metoprolol enantiomers in Chinese subjects of major CYP2D6 genotypes.

OBJECTIVE: CYP2D6 mediates both alpha-hydroxylation and O-demethylation of metoprolol. In Chinese subjects, CYP2D6*1 (the wild-type) alleles are relatively uncommon. Subjects with P34S (C188-->T188) and S486T (G4268-->C4268) mutations (CYP2D6J or CYP2D6*10A) are more frequently seen. Recently, the CYP2D6*2 (CYP2D6L) genotype that results in R296C (C2938-->T2938) and S486T mutations was also found important. In this study, metoprolol pharmacokinetics was investigated in subjects of these 3 major genotypes. METHODS: Allele-specific polymerase chain reaction was used to differentiate CYP2D6*1 and CYP2D6*2 alleles from the common CYP2D6*10A allele in Chinese. Subjects with both CYP2D6*1 and CYP2D6*2 have homozygous C188 in the exon 1, whereas subjects with CYP2D6*10A have T188. Metoprolol pharmacokinetics was compared in 16 C188 subjects (6 homozygous CYP2D6*1 subjects and 10 heterozygous CYP2D6*1/CYP2D6*2 subjects), 12 heterozygous C/T188 subjects, and 12 homozygous T188 subjects. RESULTS: No significant difference in plasma concentration profile or urinary alpha-hydroxymetoprolol excretion could be found among subjects with R296C polymorphism (CYP2D6*1/CYP2D6*2). Therefore data from subjects with CYP2D6*1 and CYP2D6*2 were pooled to compare with data from subjects with CTP2D6*10A. The area under plasma concentration curves (AUC) of S-metoprolol was 1411+/-116 (mean +/- SEM, n = 16), 1899+/-120 (n = 12), and 3588+/-435 (n = 12) nmol x hr/L for homozygous C188, heterozygous C/T188, and homozygous T188 subjects, respectively. The urinary recovery of all 4 alpha-hydroxymetoprolol diastereomers was significantly lower in T188 subjects than in C188 subjects. CONCLUSION: The P34S polymorphism but not the R296C polymorphism resulted in higher metoprolol plasma concentrations and lower urinary metoprolol metabolite levels in Chinese subjects. This finding suggests that a lower dose of metoprolol may be used in subjects with T188 mutation (CYP2D6*10A allele).

Administration, Oral↗