Biomedical subjects

C Y Cheng

Publications and source records attributed to C Y Cheng.

At least 19 recordsLinked to original sources

PubMed2006

Effect of introduced phthalate-degrading bacteria on the diversity of indigenous bacterial communities during di-(2-ethylhexyl) phthalate (DEHP) degradation in a soil microcosm.

Four previously isolated di-butyl-phthalate (DBP) degraders were tested for their abilities to degrade di-(2-ethylhexyl) phthalate (DEHP). In aqueous medium supplemented with 100mg/l of DEHP, both isolate G1 and Rhodococcus rhodochrous G2 showed excellent degradative activity; in three days they were able to degrade more than 97% of the added DEHP. Rhodococcus rhodochrous G7 degraded 32.5% of the added DEHP and Corynebacterium nitrilophilus G11 showed the least amount of DEHP degradation. The addition of surfactant Brij 30 at 0.1x critical micelle concentration (2mg/l) significantly improved DEHP degradation by Rhodococcus rhodochrous G2 (more than 90% of the added DEHP was degraded within 24 hours), but slightly inhibited the degradation of DEHP by the isolate G1 and Rhodococcus rhodochrous G7. Based on the 16S rDNA sequence data, isolate G1 was identified as Gordonia polyisoprenivorans. Soil inhibited DEHP degradation by G. polyisoprenivorans G1; fourteen days after a second addition of DEHP, 11.5% of the total added DEHP (i.e., 243.4 microg/g soil) remained detectable. Changes in the bacterial community were monitored using denaturing gradient gel electrophoresis (DGGE) and respective dendrogram analysis. It is clear that DEHP and DEHP plus G. polyisoprenivorans G1 substantially affected the bacterial community structure in the soils. However, as the population of indigenous DEHP degraders increased in the DEPH-treated soil, its bacterial communities resembled those in the DEHP plus G. polyisoprenivorans G1-inoculated soil by Day 17.

Biodegradation, Environmental↗

PubMed2006

Phytotoxicity data safeguard the performance of the recipient plants in leachate irrigation.

Leachates from an operating and a closed landfill were examined for their phytotoxicity by seed germination/root elongation tests using seeds of Brassica chinensis and Lolium perenne. Their EC50s ranged from 3% to 46% v/v, which varied remarkably with the operating status of the landfills. Seedlings of twelve tree species were grown in pots, which were irrigated with landfill leachate at the EC50 levels, with tap water as control. No tree mortality or growth inhibition was observed after 90 days of leachate application. Chlorophyll fluorescence measurement also showed that plants receiving leachate did not suffer from a decline in photosynthetic efficiency. Litsea glutinosa and Hibiscus tiliaceus had remarkable growth, and other non-N-fixers were not inferior to the N-fixing Acacia auriculiformis. Leachate irrigation improved soil N content, though P deficiency is still a problem. The seed bioassay provided a conservative estimate of the phytotoxicity of landfill leachate. Plants irrigated can be protected from growth inhibition when the leachate irrigation plan is designed with reference to phytotoxicity data.

Acacia↗

PubMed2006

Photorealistic virtual anatomy based on Chinese Visible Human data.

Virtual reality based learning of human anatomy is feasible when a database of 3D organ models is available for the learner to explore, visualize, and dissect in virtual space interactively. In this article, we present our latest work on photorealistic virtual anatomy applications based on the Chinese Visible Human (CVH) data. We have focused on the development of state-of-the-art virtual environments that feature interactive photo-realistic visualization and dissection of virtual anatomical models constructed from ultra-high resolution CVH datasets. We also outline our latest progress in applying these highly accurate virtual and functional organ models to generate realistic look and feel to advanced surgical simulators.

Adult↗

PubMed2006

A comparison of the clinical effectiveness of spinal orthoses manufactured using the conventional manual method and CAD/CAM method in the management of AIS.

Spinal orthoses are commonly prescribed to patients with moderate AIS for prevention of further deterioration. In a conventional manufacturing method, plaster bandages are used to get patient's body contour and plaster cast is rectified manually. With the introduction of CAD/CAM system, a series of automated processes from body scanning to digital rectification and milling of positive model can be performed in a fast and accurate fashion. This project is to study the impact of CAD/CAM method as compared with the conventional method. In assessing the 147 recruited subjects fitted with spinal orthoses (43 subjects using conventional method and 104 subjects using CAD/CAM method), significant decreases (p<0.05) were found in the Cobb angles when comparing the pre-intervention data with that of the first year of intervention. Regarding the learning curve, Orthotists are getting more competent with the CAD/CAM technique in four years time. The mean productivity of the CAD/CAM method is 2.75 times higher than that of the conventional method. The CAD/CAM method could achieve similar clinical outcomes and with its high efficiency, could be considered as substitute for conventional methods in fabricating spinal orthoses for patients with AIS.

Adolescent↗

PubMed2005

A buccal cell model comet assay: development and evaluation for human biomonitoring and nutritional studies.

The comet assay is a widely used biomonitoring tool for DNA damage. The most commonly used cells in human studies are lymphocytes. There is an urgent need to find an alternative target human cell that can be collected from normal subjects with minimal invasion. There are some reports of buccal cells, collected easily from the inside of the mouth, being used in studies of DNA damage and repair, and these were of interest. However, our preliminary studies following the published protocol showed that buccal cells sustained massive damage and disintegrated at the high pH [O. Ostling, K.J. Johanson. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem. Biophys. Res. Commun. 123 (1984) 291-298] used, but that at lower pH were extremely resistant to lysis, an essential step in the comet assay. Therefore, the aims of this study were to develop a protocol than enabled buccal cell lysis and DNA damage testing in the comet assay, and to use the model to evaluate the potential use of the buccal cell model in human biomonitoring and nutritional study. Specifically, we aimed to investigate intra- and inter-individual differences in buccal cell DNA damage (as strand breaks), the effect of in vitro exposure to both a standard oxidant challenge and antioxidant treatment, as well as in situ exposure to an antioxidant-rich beverage and supplementation-related effects using a carotenoid-rich food. Successful lysis was achieved using 0.25% trypsin for 30 min followed by proteinase K (1mg/ml) treatment for 60 min. When this procedure was performed on cells pre-embedded in agarose on a microscope slide, followed by electrophoresis (in 0.01 M NaOH, 1mM EDTA, pH 9.1, 18 min at 12 V), a satisfactory comet image was obtained, though inter-individual variation was quite wide. Pre-lysis exposure of cells to a standard oxidant challenge (induced by H2O2) increased DNA strand breaks in a dose related manner, and incubation of cells in Trolox (a water soluble Vitamin E analogue) conferred significant protection (P<0.05) against subsequent oxidant challenge. Exposure of buccal cell in situ (i.e. in the mouth) to antioxidant-rich green tea led to an acute decrease in basal DNA strand breaks. In a controlled human intervention trial, buccal cells from 14 subjects after 28 days' supplementation with a carotenoid-rich berry (Fructus barbarum L.) showed a small but statistically significant (P<0.05) decrease in DNA strand breaks. These data indicate that this buccal cell comet assay is a feasible and potentially useful alternative tool to the usual lymphocyte model in human biomonitoring and nutritional work.

Antioxidants↗

PubMed2004

The impact of visual impairment and use of eye services on health-related quality of life among the elderly in Taiwan: the Shihpai Eye Study.

To evaluate the effect of impaired vision on health-related quality of life (HRQoL), the authors administered the Medical Outcomes Survey Short-Form 36 (SF-36) to the elderly in a metropolitan Taiwanese community and assessed their visual impairment status. A structured questionnaire was used for door-to-door data collection. Interviewers also collected information on demographics, medical history, and HRQoL. Those who were interviewed were invited to the study hospital for a detailed eye examination. An eye examination, including presenting visual acuity and best-corrected visual acuity, was conducted by ophthalmologists. Presenting visual acuity and best-corrected visual acuity were measured in the better eye. Impaired vision was defined as presenting visual acuity in the better-seeing eye worse than 6/12 (or 20/40) and was used to evaluate the correlation to HRQoL. A total of 1361 subjects at least 65 years of age participated in both the interview and eye examination. Internal-consistency and test-retest reliability of the eight scales were high. Based on the separate multiple regression model, after controlling for all other covariates, subjects in contact with vision services offered by an ophthalmologist had more positive scores on general health perceptions (beta = 4.29; p < 0.001), vitality/energy (beta = 2.73; p < 0.001), and mental health (beta = 2.06; p = 0.01). Impaired vision was associated with significantly lower scores in physical functioning (beta = -3.62; p < 0.001) and social functioning scales (beta = -3.25; p = 0.015). The findings suggest that visual impairment is associated with lower quality of life and use of eye care services is associated with higher quality of life.

Aged↗

PubMed2003

Association study of the dopamine and serotonin transporter genetic polymorphisms and methamphetamine abuse in Chinese males.

The dopamine transporter (DAT) and the serotonin transporter (5-HTT) play important roles in methamphetamine (METH) dependence because they are the target of METH action. For this study, the association between the DAT and 5-HTT polymorphisms and METH dependence were investigated for a Chinese-male sample population. The investigated polymorphisms included those of the DAT 3'-variable number tandem repeat, the 5-HTT gene promoter and a 5-HTT variable number tandem repeat polymorphisms. No significant difference was demonstrated for genotype or allele frequency, when comparing METH dependent and control cases for the DAT and the 5-HTT polymorphisms. The findings of this study suggest that these polymorphisms do not play major roles in METH dependence in the Chinese-male population.

Adult↗

PubMed2002

Abnormal 201Tl myocardial single photon emission computed tomography in energetic male patients with myocardial bridge.

Myocardial bridge is a relatively benign condition where a major coronary artery is bridged by a band of muscle and narrows during systole, particularly during rapid heart rates. Its clinical presentation and electrocardiogram (ECG) changes overlap with that of coronary artery disease. 201Tl myocardial perfusion imaging is thus frequently prescribed for further evaluation. This retrospective study was carried out to determine the 201Tl image patterns in patients with myocardial bridge. A total of 17 male patients (aged from 30 to 63 years) who had a positive exercise ECG and angiographic evidence of myocardial bridge in the mid-third of the left anterior descending coronary artery were recruited. Most of them were robust and received routine physical check-ups. They had no known heart disease or medication that affected cardiac function. The patients' clinical presentations, echocardiograph and exercise ECG findings were analysed. 201Tl single photon emission computed tomography (SPECT) was performed by intravenous injection of 201Tl (111 MBq) immediately following stress (treadmill or dipyridamole induced) and 4 h after stress, using a fixed, right angle camera equipped with a low energy, general purpose collimator. The images were interpreted independently by two experienced nuclear medicine physicians. Nine of the 17 patients had anterior chest pain during exercise. All patients had an abnormal ECG during exercise, including ST-T wave depression in leads II, III and aVF, and v4-6. Except for eight patients revealing reversible perfusion defect (R), 16 of the 17 patients also exhibited a partial reversible perfusion defect (PR) or a significant reverse redistribution (RR) scan pattern in the anterior or inferior walls of the left ventricle. Myocardial bridge should be taken into consideration in energetic male patients who had abnormal exercise ECGs and the corresponding patterns of Tl SPECT abnormalities including R, PR and RR.

Adult↗

PubMed2001

Cloning and characterization of zfBLP1, a Bcl-XL homologue from the zebrafish, Danio rerio.

The importance of the Bcl-2 family proteins in normal vertebrate embryogenesis is being recognized; however, their regulatory mechanism is poorly understood. We report here the cloning and characterization of a novel zebrafish Bcl-2 family protein, zfBLP1. The zfBLP1 cDNA is 1942 nucleotides long, encoding a polypeptide of 238 amino acids. The primary sequence of zfBLP1 shares 50% identity to human Bcl-XL, and contains all four conserved BH domains of the Bcl-2 family proteins. Primary sequence analysis identified a consensus ER retention signal at the C-terminal end of zfBLP1. Northern blot analysis indicated that there were two major and two minor zfBLP1 mRNA species expressed during embryonic development. Among the two major mRNA species, the short one, approx. 3 kb in size, was expressed throughout embryonic development, while the long one, approx. 7 kb long, was not detectable until the gastrula stage. These results suggest that zfBLP1 is a novel Bcl-2 family protein under complicated regulations, and is likely to play an important role in zebrafish oogenesis and embryogenesis.

Amino Acid Sequence↗

PubMed2001

Bilateral neurotrophic keratopathy complicating Vidian neurectomy.

PURPOSE: To present a case of bilateral neurotrophic keratopathy with miosis after bilateral Vidian neurectomy for vasomotor rhinitis. METHODS: Observational case report. RESULTS: A 68 year-old man presented with irritation and blurred vision in both eyes 2 weeks after bilateral Vidian neurectomy. Slit-lamp examination revealed a large epithelial defect, typical of neurotrophic keratopathy, in the inferior two-thirds of cornea in both eyes. Corneal sensitivity test with a Cochet-Bonnet anesthesiometer and electrical study of the blink reflex indicated bilateral trigeminal dysfunction. Both pupils were miotic, and tests with hydroxyamphetamine 1% and epinephrine 0.1% showed postganglionic sympathetic nerve damage. The corneal epithelial defects healed after 2 months of treatment with systemic prednisolone, vitamin B(12) and tarsorrhaphy. CONCLUSION: Neurotrophic keratopathy associated with dry eye syndrome may be a serious complication of Vidian neurectomy.

Aged↗

PubMed2001

Color Doppler imaging study of retrobulbar hemodynamics in chronic angle-closure glaucoma.

PURPOSE: To evaluate the retrobulbar hemodynamics in patients with chronic angle-closure glaucoma (CACG) by using color Doppler imaging (CDI) and to correlate the degree of glaucomatous visual field loss with the hemodynamic parameters. DESIGN: Prospective case series. PARTICIPANTS AND CONTROLS: Twenty-six Chinese patients with CACG and 26 age-matched and gender-matched normal subjects were recruited. All CACG patients had history of chronic intraocular pressure (IOP) elevation and asymmetric visual field defects between their fellow eyes. After receiving laser peripheral iridotomy and/or filtration surgery, all of them had bilateral medication-free controlled IOP before enrolling into the study. METHODS: Each subject underwent CDI measurement in the central retinal artery (CRA) and the nasal and temporal short posterior ciliary arteries (PCA). Visual fields of the CACG patients were obtained with Humphrey 24-2 program. The visual field defects were scored with the Advanced Glaucoma Intervention Study (AGIS) system. For each CACG patient, the eye with lower AGIS score was defined as the better eye and the eye with higher score as the worse eye. MAIN OUTCOME MEASURES: Peak-systolic velocity (PSV), end-diastolic velocity (EDV) and resistance index (RI) were determined. RESULTS: The EDV in the CRA and the temporal PCA was decreased significantly (P = 0.041 and 0.023, respectively) in the worse eyes of CACG patients compared with those in the control eyes. The better eyes of CACG patients showed no significant change in hemodynamic parameters compared with the control eyes. While comparing the fellow eyes of CACG patients, the worse eyes had significantly lower EDV in the temporal PCA (P = 0.012) than the contralateral better eyes. In 11 CACG patients with a difference of at least 8 in AGIS visual field scores between their fellow eyes, the worse eyes had significantly lower EDV (P = 0.041) in the CRA and lower PSV (P = 0.018) and EDV (P = 0.018) in the temporal PCA compared with those in the contralateral eyes. In multivariate regression analysis, the AGIS scores were significantly correlated with the PSV in the CRA (P = 0.015) and with the EDV (P < 0.001) and RI (P = 0.027) in the temporal PCA in patients with CACG. CONCLUSIONS: Patients with well-controlled CACG may have decreased retrobulbar blood flow velocities and increased vascular resistance in the CRA and temporal PCA. The degree of retrobulbar hemodynamic impairment was well correlated with the degree of glaucomatous visual field loss.

Aged↗

PubMed2001

Visual acuity and contrast sensitivity in different types of posterior capsule opacification.

PURPOSE: To compare the visual acuity (VA) and contrast sensitivity in 2 types of posterior capsule opacification (PCO) in pseudophakic eyes before and after neodymium:YAG (Nd:YAG) capsulotomy and to evaluate vision test results after Nd:YAG capsulotomy. SETTING: Department of Ophthalmology, Taipei Veterans General Hospital, National Yang-Ming University, Taipei, Taiwan. METHODS: Fourteen eyes with fibrosis-type PCO and 15 eyes with Elschnig-pearl-type PCO were enrolled prospectively. Before and 1 week after Nd:YAG capsulotomy, VA and contrast sensitivity were assessed using the illiterate E version of the Bailey-Lovie chart and the Vistech VCTS 6000 chart, respectively. RESULTS: Before capsulotomy, the mean logMAR acuity in the group with Elschnig-pearl-type PCO was 0.47 +/- 0.32 (SD) and in the group with fibrosis-type PCO, 0.17 +/- 0.07. The difference between the 2 groups was significant (P =.002). After capsulotomy, there was no significant between-group difference (P >.05). Before capsulotomy, the contrast sensitivity was significantly worse (P <.01) at all spatial frequencies in the group with pearl-type PCO, especially at 6 cycles per degree. After capsulotomy, there was no significant between-group difference (P >.05) at any spatial frequency. CONCLUSIONS: After cataract surgery, patients with pearl-type PCO had lower VA and contrast sensitivity than those with fibrosis-type PCO. An Nd:YAG capsulotomy improved the VA and contrast sensitivity in patients with both types of PCO.

Aged↗

PubMed2001

N-Acyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano-[3,4-b][1,4]oxazine-9-carbonitriles as bladder-selective potassium channel openers.

Optically active N-acyl-5,5-dimethyl-1,2,3,4a,5,10b-hexahydro-[1]benzopyrano[3,4-b][1,4]oxazine-9-carbonitriles 2-22 were synthesized as rigid analogues of cromakalim. The (4aR, 10bR)-N-benzoyl derivative (-)-11 was identified as a bladder-selective KCO (IC50, bladder = 8.2 microM, C50, portal vein = 34.5 microM). Among the analogues of 11 with substitution on the benzoyl moiety, the 3-methyl analogue (-)-14 showed highly potent and selective activity at portal vein (IC50, bladder = 279 microM, IC50, portal vein = 0.54 microM). The 4-bromo analogue (-)-19 (IC50, bladder = 2.0 microM, IC50, portal vein = 8.1 microM) and the 4-hydroxy analogue (-)-21 (IC50, bladder = 3.8 microM, IC50, portal vein = 75 microM) showed enhanced activity at the bladder, while maintaining unprecedented bladder selectivity in vitro. The N-benzenesulfonyl analogue (-)-22, a bioisoster of (-)-11, showed similar activity at the bladder with enhanced selectivity (IC50, bladder = 11.6 microM, IC50, portal vein = 120 microM).

Animals↗

PubMed2001

Quantitative assessment of retinal thickness in diabetic patients with and without clinically significant macular edema using optical coherence tomography.

PURPOSE: To assess patients with diabetic macular edema quantitatively using optical coherence tomography (OCT). METHODS: OCT was performed in 14 eyes with diabetic retinopathy and ophthalmoscopic evidence of clinically significant macular edema (CSME) and in 19 diabetic eyes without CSME. Retinal thickness was computed from the tomograms at fovea and other 36 locations throughout the macula. RESULTS: The mean +/- standard deviation foveal thickness was 255.6 +/- 138.9 microm in eyes with CSME, and 174.6 +/- 38.2 microm in eyes without CSME (p = 0.051). Within 2000 microm of the center of the macula, eyes with CSME had significantly thicker retina in the inferior quadrant than those without CSME (p < 0.01). The foveal thickness was correlated with logMAR visual acuity (gamma = 0.68, p < 0.01). OCT identified sponge-like retinal swelling and/or cystoid macular edema in 11 (58%) eyes without CSME, and in 12 (86%) eyes with CSME. CONCLUSIONS: Criteria of CSME seem to be insufficient in really identifying macular edema. OCT may be more sensitive than a clinical examination in assessing diabetic macular edema and is a quantitative tool for documenting changes in macular thickening.

Diabetic Retinopathy↗

PubMed2001

Visual impairment in a Taiwanese population: prevalence, causes, and socioeconomic factors.

PURPOSE: We sought to estimate the prevalence of visual impairment among an elderly population in urban Taiwan, determine the causes of visual impairment, and gain information about certain socioeconomic factors associated with visual impairment. METHODS: A population-based survey of ocular diseases in residents aged 50 years or older was conducted in Peitou Precinct, Taipei, Taiwan. All participants underwent a comprehensive ophthalmic examination, including visual acuity measurement, using standardized protocols. Demographic data, marital status, employment status, and educational level were gathered through an interview. RESULTS: A total of 2034 participants completed the visual acuity measurements. The prevalence of visual impairment (defined as best-corrected visual acuity in the better eye <6/18) among this population was 2.75% (95% confidence intervals: 2.04%-3.46%). Three major causes of visual impairment were cataract (30.4%), high myopic macular degeneration (25.0%), and age-related macular degeneration (14.3%). In multivariate analysis, age was positively correlated with visual impairment (P < 0.001), and higher education level was associated with a significant decrease in the odds of being visually impaired (P < 0.001). No relation was found between visual impairment and sex, or marital and employment status. CONCLUSIONS This study provides the first information about the prevalence and causes of visual impairment in Taiwan, and identifies age and educational level as the most important factors related to visual impairment. Additional educational programs should be developed to improve individual awareness of age-related ocular diseases and the availability of current ophthalmic intervention.

Age Distribution↗

PubMed2001

Reversible inhibition of spermatogenesis in rats using a new male contraceptive, 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide.

The oral male contraceptive agent 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF2364) is a new analogue of indazole-carboxylic acid. AF2364 was orally administered to rats at 50 mg/kg body weight once weekly for five consecutive weeks. The effects on fertility efficacy, hormonal profile, organ weights, tissue morphology, and serum microchemistry were examined. Complete infertility was noted in rats 29 days after the initial dose of AF2364 and continued until 90 days. Fertility resumed in 25% of the group after 104 days and had resumed in 75% of the rats by the last mating at 197 days. Morphological examination of the testis showed rapid exfoliation of elongated spermatids and the generation of large multinucleated cells 6 days after the first treatment, with depletion of most germ cells after 40 days. Normal spermatogenesis was noted in 95% of the tubules in the animals that were fertile at 210 days. Morphological analysis of the epididymal compartments revealed reduced lumen size, whereas the prostate exhibited an increase in the glandular lumen with a reduction in epithelium height. No morphological changes were detected in the kidney, liver, and cerebrum by light microscopy. Kidney and liver function, as evaluated by serum chemistry, were not affected by the drug treatment. AF2364 did not alter the levels of FSH, and only minimal changes were noted for LH and testosterone, suggesting that the hypothalamic-pituitary-testicular axis was not affected. These results illustrate the potential of AF2364 as a male contraceptive.

Animals↗

PubMed2001

Two new male contraceptives exert their effects by depleting germ cells prematurely from the testis.

The three currently available male contraceptive approaches are 1) the barrier method such as the condom, 2) hormonal methods by disrupting the pituitary-testicular axis so as to impair spermatogenesis, and 3) immunological methods by preparing vaccines against male-specific antigens. We hereby describe an alternative approach in which attachments of developing germ cells onto the seminiferous epithelium are disrupted, thereby inducing their premature release into the tubular lumen. This in turn leads to infertility. A panel of analogues based on the core structure of 1-(2,4-dichlorobenzyl)-indazole-3-carboxylic acid was synthesized. These compounds were subjected to an in vivo screening assay assessing their effects in inducing the expression of testin, a testicular marker whose expression correlates with the integrity of Sertoli-germ cell junctions. An induction of testin expression in the testis signifies a disruption of Sertoli-germ cell junctions that is followed by depletion of germ cells from the seminiferous epithelium. Two compounds, namely 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364) and 1-(2,4-dichlorobenzyl)-indazole-3-acrylic acid (AF-2785), were identified that caused detachment of germ cells, in particular round and elongated spermatids, from the epithelium inducing their premature release into the tubular lumen as confirmed by histological analysis. Adult rats receiving several oral doses of either one of these compounds became infertile within 3-7 wk after the epididymal sperm reserve was exhausted. Depending on the dosing of the administered compound, rats became infertile for 4-14 wk before their fertility gradually bounced back, illustrating the reversibility and efficacy of these new compounds. Also, these compounds did not appear to impair the hypothalamus-pituitary-testicular axis because the serum levels of LH, FSH, and testosterone of the treated animals did not change significantly when compared to control rats. In addition, results of serum microchemistry illustrate that liver and kidney function was not affected in animals treated with both compounds.

Animals↗

PubMed2001

A 22-amino acid synthetic peptide corresponding to the second extracellular loop of rat occludin perturbs the blood-testis barrier and disrupts spermatogenesis reversibly in vivo.

When Sertoli cells were cultured in vitro on Matrigel-coated bicameral units, the assembly of the inter-Sertoli tight junction (TJ) permeability barrier correlated with an induction of occludin expression. Inclusion of a 22-amino acid peptide, NH(2)-GSQIYTICSQFYTPGGTGLYVD-COOH, corresponding to residues 209-230 in the second extracellular loop of rat occludin, at 0.2-4 microM into Sertoli cell cultures could perturb the assembly of Sertoli TJs dose-dependently and reversibly. This peptide apparently exerts its effects by interfering with the homotypic interactions of two occludin molecules between adjacent Sertoli cells at the sites of TJs, thereby disrupting TJs, which, in turn, causes a decline in transepithelial electrical resistance across the Sertoli cell epithelium. When similar experiments were performed using a 22-amino acid myotubularin peptide, NH(2)-TKVNERYELCDTYPALLAVPAN-COOH (residues 156-177), no effects on the assembly of inter-Sertoli TJs in vitro were noted. When a single dose of this synthetic occludin peptide was administered to adult rats intratesticularly at 1.5-10 mg/testis, germ cells began to deplete from the seminiferous epithelium within 8-16 days. By 27 days, virtually all tubules were devoid of germ cells. This antispermatogenic effect was reversible, because germ cells progressively repopulated the epithelium thereafter. Treated testes were indistinguishable from normal or control testes by 68 days post-occludin peptide treatment when assessed using histological analysis. In contrast, control rats receiving either no treatment, vehicle alone, or a 22-amino acid synthetic peptide of myotubularin displayed no changes in the testicular morphology at all time points. The occludin peptide-induced germ cell depletion was also accompanied by a disruption of the blood-testis barrier (BTB) when assessed by micropuncture techniques quantifying [(125)I]-BSA in rete testis fluid and seminiferous tubular fluid following i.v. administration of [(125)I]-BSA through the jugular vein. These results illustrate that the occludin peptide-induced disruption of the BTB may possibly affect the underlying adherens junctions, which causes premature release of germ cells from the epithelium and reversible infertility.

Amino Acid Sequence↗