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Zhenhua Li

Publications and source records attributed to Zhenhua Li.

At least 19 recordsLinked to original sources
PubMed2026

Prevalence of pharmacogenomically implicated prescriptions in multi-ethnic populations in Singapore.

AIM: To assess the potential impact of implementing pre-emptive pharmacogenomic (PGx) testing in Singapore, focusing on prevalence and genetic actionability of PGx prescriptions. METHODS: Electronic Health Records from 2014 to 2021 were obtained from the National University Hospital (NUH), a tertiary medical centre serving approximately 6% of Singapore's population, which were filtered for pharmacogenomically implicated medicines (CPIC Level A or A/B), defined as PGx medications. Coupling this with published data of whole-genome sequencing of 9051 Singaporeans, we estimated the proportion of patients whose prescriptions might have been modified based on pre-emptive PGx at population level. RESULTS: From 2014 to 2021, a total of 1 157 359 unique patients were seen at NUH, with 38.1% to 43.0% of patients with prescriptions receiving at least one PGx medication annually, exhibiting minimal variance over year of prescription, sex or race/ethnicity. The most frequently prescribed PGx medications were omeprazole, statins and tramadol, while the most implicated pharmacogenes were CYP2C19, CYP2D6 and SLCO1B1. The age-dependent increase in PGx medication exposure varied significantly by sex, with males prescribed these medications earlier in life than females. Similarly, Indians and Malays were more likely to be prescribed these medicines at a younger age than Chinese. Based on frequency of PGx variants in Singaporeans, we estimate that 18.4% of patients could have their prescriptions modified from pre-emptive PGx testing. DISCUSSION: Pharmacogenomically implicated medication prescriptions are common in Singapore and are particularly prevalent in elderly populations. Strategic investments in infrastructure and policy development will be pivotal to the successful integration of pre-emptive PGx into clinical practice.

Asian genomes↗
PubMed2026

Comparison of the predictive performance of systemic immune-inflammation index and neutrophil-to-lymphocyte ratio for three-month poor functional outcome in ischemic stroke: a systematic review and meta-analysis.

INTRODUCTION: Ischemic stroke (IS) is a leading cause of global mortality and disability. Early and accurate prognosis is crucial for patient management. The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are emerging inflammatory biomarkers; however, their relative predictive value for three-month poor functional outcome (modified Rankin Scale [mRS]&#x2009;>&#x2009;2) remains uncertain. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to 20 July 2025, adhering to PRISMA guidelines. Observational studies reporting the association of SII or NLR with three-month poor outcome were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Area under the curve (AUC), odds ratios (OR), and standardized mean differences (SMD) were pooled using random-effects models in Stata 16.0. RESULTS: Twenty-one studies involving 7520 IS patients were analysed. NLR demonstrated marginally superior discriminative ability compared to SII (AUC 0.71, 95% CI: 0.67-0.76 vs. 0.68, 95% CI: 0.64-0.71), though this difference was not statistically significant. Elevated NLR was significantly associated with poor outcome (OR = 1.26, 95% CI: 1.17-1.37, p&#x2009;<&#x2009;.001), whereas SII was not (OR = 1.00, 95% CI: 1.00-1.00, p&#x2009;=&#x2009;.384). Both markers showed moderate effect sizes (SMD: NLR = 0.69, SII = 0.72; p&#x2009;<&#x2009;.001). NLR performed better in non-intervention and Chinese subgroups, while SII exhibited consistent AUC values across treatment and ethnic subgroups. CONCLUSION: NLR and SII are accessible prognostic markers in IS. NLR demonstrates superior accuracy and a significant association with poor outcome, while SII shows greater stability across patient subgroups. Both may assist in risk stratification, in resource-limited settings.

Humans↗
PubMed2006

Hexylene- and octylene-bridged polysilsesquioxane hybrid crystals self-assembled by dimeric building blocks with ring structures.

We report the synthesis of novel polysilsesquioxane hybrid crystals prepared from two precursors with hexylene- and octylene-bridged groups. Both crystals are composed of bimolecular rings (18- and 22-membered, respectively) formed by one-step condensation of two hydrolyzed monomers. The hydrogen bonds between silanol groups and the weak van der Waal's interactions between alkyl chains link the large rings as building blocks together into self-assembled, three-dimensional molecular crystalline structures. The precise control of the sol-gel process is considered to be the crucial factor in fabricating flexible long alkyl chains into an ordered stacking. These contributions extend the understanding of the sol-gel chemistry of polysilsesquioxanes.

Journal Article↗
PubMed2006

Circadian pharmacokinetics of mycophenolic Acid and implication of genetic polymorphisms for early clinical events in renal transplant recipients.

BACKGROUND: We investigated the mycophenolic acid (MPA) chronopharmacokinetics and the relation between MPA circadian exposure and the incidence of acute rejection (AR). The association between selected genetic polymorphisms and clinical events or MPA circadian exposure was also studied. METHODS: Thirty recipients were studied one month after renal transplantation. Mycophenolate mofetil (MMF) was administered twice a day at a single dose of 0.5 g in four patients, 0.75 g in eight patients, and 1 g in 18 patients. RESULTS: The daytime area under the concentration-time curve (AUC0-12) was larger than the nighttime AUC0-12 (55.09 vs. 50.54 microg.hr/ml, P=0.049). The Cmax and tmax of MPA after the morning dose were respectively higher and shorter than those after the night dose. Seven patients (23.3%) had AR episodes. The MMF single dose per body weight (12.46 mg/kg in patients with AR vs. 16.99 in patients without AR), daytime and nighttime AUC0-12 (32.41 vs. 62.00 and 24.44 vs. 57.88 microg.hr/ml) and morning trough level of MPA (1.03 vs. 3.83 microg/ml) were significantly lower in patients with AR than in those without AR. The percentage of patients requiring diminished dose of MMF due to diarrhea was higher among patients with the multidrug resistance 1 (MDR1) C3435T T allele than among those with the CC genotype (P=0.049). CONCLUSION: MPA pharmacokinetics showed circadian variations, and a lower MPA AUC in both daytime and nighttime was associated with the occurrence of AR in the early stage after renal transplantation. The MDR1 C3435T polymorphism might be associated with diarrhea due to MPA.

Adult↗
PubMed2005

Experimental measurement of the refractive index of biological tissues by total internal reflection.

We discuss the refractive-index measurement of biological tissues by total internal reflection. The methodology of the measurement is illuminated comprehensively, and an experimental setup, combined with a data processing program, is developed correspondingly. Refractive indices of typical tissue samples are measured by use of the developed methodology. The agreement of our measurements with the reported results shows the validity of our scheme, which has the potential for being a simple, quick, and low-cost practical means for determining the refractive index of a turbid medium. Moreover, an empirical formula for evaluating the refractive index of Intralipid suspensions with different concentrations is also presented according to experimental measurements.

Adipose Tissue↗
PubMed2004

Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients.

BACKGROUND: A body-weight-based dose of tacrolimus often results in marked individual diversity of blood drug concentration. Tacrolimus is a substrate for cytochrome P450 (CYP) 3A5 and p-glycoprotein encoded by CYP3A5 and MDR1 (ABCB1), respectively, having multiple single nucleotide polymorphisms. In this study, we genotyped CYP3A5 A6986G, MDR1 G2677(A/T), and C3435T polymorphisms and investigated the association between these polymorphisms and the pharmacokinetics of tacrolimus in renal transplant recipients. METHODS: Thirty consecutive recipients were enrolled in this study. The pharmacokinetics of tacrolimus was analyzed on day 28 after transplant, when the daily dose was adjusted to the target trough level of 10-15 ng/mL. The polymerase chain reaction-restriction fragment length polymorphism and direct sequence method were used for genotyping the CYP3A5 and MDR1 polymorphisms, respectively. RESULTS: The single tacrolimus dose per body weight was significantly higher in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.143+/-0.050 vs. 0.078+/-0.031 mg/kg, P<0.001). The dose-adjusted trough level and the area under the concentration-time curve (AUC0-12) were significantly lower in CYP3A5 *1 carriers than CYP3A5 *3/*3 carriers (0.040+/-0.014 vs. 0.057+/-0.024 ng/mL/mg/kg, P=0.015 and 0.583+/-0.162 vs. 0.899+/-0.319 ng.hr/mL/mg/kg, P=0.004), respectively. The MDR1 polymorphism was not associated with any pharmacokinetic parameters. CONCLUSIONS: Kidney transplant recipients with the CYP3A5 *1 allele required a higher daily tacrolimus dose compared with those with the CYP3A5 *3/*3 genotype to maintain both the target trough level and AUC0-12, suggesting that this polymorphism is useful for determining the appropriate dose of tacrolimus.

Adult↗
PubMed2004

Sustained delivery and expression of plasmid DNA based on biodegradable polyester, poly(D,L-lactide-co-4-hydroxy-L-proline).

Gene expression mediated by a non-viral vector usually lasts only a few days. The objective of this study was to synthesize and characterize a non-toxic, polymeric gene carrier, poly(D,L-lactide-co-4-hydroxy-L-proline) (PLHP) for sustained gene delivery. The copolymer was synthesized by ring-opening polymerization of D,L-lactide (DLLA) with N-cbz-4-hydroxy-L-proline (HP) in the presence of stannous octoate (Sn(Oct)(2)). The resulting copolymer was characterized by (1)H nuclear magnetic resonance (NMR) and gel permeation chromatography (GPC). Degradation of PLHP was examined by monitoring the medium pH change and molecular weight (MW) of the remaining polymer. It showed a rapid initial degradation and followed by a slower degradation for about 30 days at 37 degrees C. The cytotoxicity of copolymer was significantly lower than polyethylenimine (PEI) and poly-L-lysine hydrochloride (PLL) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The plasmid DNA (pDNA)-loaded microspheres based on the copolymer were prepared by a water-oil-water (w/o/w) solvent evaporation emulsion method. The release profile of pDNA from PLHP microspheres showed an initial burst release, and then a slower and continuous release for about 18 days at 37 degrees C. Gene transfer efficiency of PLHP/pDNA delivery system showed a sustained activity (over a week) when compared with PEI and PLL, and can be further improved by the addition of cationic liposomes. The results suggest that PLHP is a promising candidate for long-term gene delivery with good biocompatibility and biodegradability.

Cell Survival↗
PubMed2004

Sustained intravesical drug delivery using thermosensitive hydrogel.

PURPOSE: Direct instillation of drug solutions into the bladder through a urethral catheter (i.e., intravesical therapy) evades systemic adverse effects of drugs used for bladder diseases. However, conventional vehicles for these drugs fail to extend duration of drug exposure in the bladder beyond the first voiding of urine postinstillation. The current study seeks to overcome the aforementioned inherent limitation of intravesical drug administration by using thermosensitive hydrogel as a matrix for sustained intravesical drug delivery. METHODS: Under halothane anesthesia, normal adult female Sprague-Dawley rats were catheterized with PE-50 tubing to instill either 0.02% w/v solution of fluorescein isothiocyanate (FITC) or the same amount of FITC in a 30% w/v dispersion of thermosensitive [Poly(ethylene glycol)-Poly[lactic acid-co-glycolic acid]-Poly(ethylene glycol)) (PEG-PLGA-PEG) polymer in a 0.1 M phosphate buffer. After instillations, rats were kept in metabolic cages for urine collection. Fluorescence emanating from FITC was measured in the urine at various time points up to 24 h after instillation. A rat model of cyclophosphamide-induced cystitis was chosen for the efficacy study using misoprostol as a model drug entrapped in the thermosensitive hydrogel in place of FITC. Efficacy of hydrogel containing misoprostol was compared against rat groups instilled with saline, hydrogel, and misoprostol independently. RESULTS: Prolonged drug exposure to the bladder afforded by hydrogel was evident from the time course of FITC elimination in the urine and by the green fluorescence of FITC seen at the bladder surface when isolated 24 h after instillation. Rats instilled with free FITC voided almost all of the fluorescence in the urine within the first 8 h, whereas rats instilled with hydrogel encapsulated FITC showed sustained release up to 24 h after instillation. Using a cyclophosphamide-induced cystitis model, rats instilled with misoprostol, a synthetic PGE1 analog, showed significantly reduced frequency of urine voiding (p < 0.05) as compared to the rats instilled with saline. Histological examination of the urothelium showed near normal morphology in rats instilled with misoprostol in hydrogel, whereas extensive tissue damage was observed in rats instilled with saline. CONCLUSION: Our study showed that PEG-PLGA-PEG polymer could be used as a viable sustained drug delivery system for intravesical therapy of diseases of the bladder such as cystitis using misoprostol.

Animals↗
PubMed2004

Urodynamic and immunohistochemical evaluation of intravesical capsaicin delivery using thermosensitive hydrogel and liposomes.

PURPOSE: Aqueous insolubility of the vanilloids such as capsaicin is a major disincentive in their intravesical therapy of detrusor hyperreflexia. We sought to overcome the delivery of this hydrophobic neurotoxin by entrapping it in a lipid bilayer of positively charged multilamellar lipid vesicles (liposomes) or in a hydrophobic polymer matrix of thermosensitive hydrogel. MATERIALS AND METHODS: Liposomes, hydrogel and 30% ethanol/normal saline were prepared with or without 1 mM capsaicin (0.5 ml) and administered intravesically for 30 minutes to 7 groups of age matched, normal female adult Sprague-Dawley rats under halothane anesthesia. At 48 hours after intravesical instillation cystometric studies were performed using urethane anesthesia (0.04 ml per minute). The animals were subsequently sacrificed and whole bladders were harvested for histology and immunohistochemistry. RESULTS: In normal urethane anaesthetized rats capsaicin in 30% ethanol and liposomes completely blocked micturition reflexes. Capsaicin in hydrogel did not completely block the micturition reflex but it significantly decreased bladder contraction frequency compared with vehicle controls. The results of cystometry with capsaicin in liposomes and capsaicin in 30% ethanol correlated with a significant decrease in calcitonin gene-related peptide staining of afferent nerves in the bladder wall. Photographs taken after hematoxylin and eosin staining of the bladder treated with liposomes and hydrogel in the absence of capsaicin did not reveal any adverse histological changes. There were significant histological changes in bladders treated with 30% ethanol alone. CONCLUSIONS: In comparison with 30% ethanol liposomes are a superior vehicle for the intravesical administration of capsaicin, producing comparable efficacy with less tissue damage. Hydrogel can also serve as safe alternative option for capsaicin delivery.

Administration, Intravesical↗
PubMed2004

Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection.

OBJECTIVE: To prospectively compare the prevention of tumour recurrence by four intravesical adjuvant administration protocols, and thus elucidate the efficacy of early and high total dose instillations of epirubicin to prevent superficial bladder tumour recurrence after transurethral resection of bladder tumour (TURBT). PATIENTS AND METHODS: In all, 69 patients with Ta/T1 bladder cancer were randomly assigned to four intravesical administration protocols: A, delayed instillation (first instillation 7 days after TURBT) and low-dose (30 mg once every 2 weeks, six times): B, early instillation (three instillations before 7 days after TURBT) and low-dose; C, delayed and high-dose (30 mg once weekly 12 times) instillation; D, early and high-dose. The influence of the instillation protocols and tumour characteristics on the probability of recurrence-free survival was examined using Kaplan-Meier analysis and a Cox regression hazard model. RESULTS: The early-instillation and high-dose groups had relatively lower recurrence rates after 6 months (A, 30%; B, 25%; C, one of 12; and D, none) and 1 year (50%, 35%, four of nine and one of eight, respectively). Patients who received 360 mg epirubicin (C and D) had a significantly better recurrence-free survival than those receiving 180 mg (A and B; P = 0.012). Preoperative urine cytology and tumour multiplicity were significantly associated with recurrence. However, multivariate analysis of the risk of recurrence using a Cox proportional hazard model showed that urine cytology (hazard ratio 3.11, 95% confidence interval 1.08-8.94, P = 0.04) and total dose (0.32, 0.11-0.92, P = 0.03) were independent prognostic factors for recurrence. CONCLUSION: Patients who received a high-dose epirubicin instillation had a significantly lower recurrence rate but the benefit of early instillation was not confirmed, as the study group was too small.

Administration, Intravesical↗
PubMed2004

[A brief history of diagnosis and treatment of primary aldosteronism.].

Primary aldosteronism is a clinical syndrome characterized by hypokalemia, suppressed activities of plasma renin and high urinary and plasma aldosterone levels in hypertensive patients. It was first defined and reported by Jerome W. Conn in 1955. From 1960s to early 1970s, its techniques of diagnosis and treatment were greatly improved by the availability of spironolactone, realization of the renin-angiotensin-aldosterone system, and progress in laboratory tests and adrenal venous sampling. In 1970s, notwithstanding the extensive application of modern imaging modalities, such as CT scanning, adrenal venous sampling and steroid analysis have remained to be the most accurate and reliable localization method. From 1980s, more and more patients with primary aldosteronism were screened out from the hypertensive population by plasma renin activity/plasma aldosterone concentration ratio and cured by surgical interventions; laparoscopic unilateral adrenalectomy has become the generally accepted golden standard of operation.

Adrenalectomy↗
PubMed2003

Increased risk of prostate cancer and benign prostatic hyperplasia associated with transforming growth factor-beta 1 gene polymorphism at codon10.

Transforming growth factor-beta 1 (TGF-beta1) plays a significant role in regulating the proliferation and apoptosis of prostate epithelial and stromal cells. We explored the association between the T (Leu) to C (Pro) polymorphism at codon10 of the TGF-beta1 gene (TGFB1) and the risk of prostate cancer (PCa) or benign prostatic hyperplasia (BPH) in 351 PCa patients, 221 BPH patients and 303 male controls in Japan. There were significant differences in the CC versus TC + TT genotype distribution between PCa patients and male controls (P=0.008), and between BPH patients and male controls (P=0.041). Males with the TC or TT genotype had a 1.62-fold increased risk of PCa [95% confidence interval (95% CI)=1.14-2.30, P=0.007] and a 1.51-fold increased risk of BPH (95% CI=1.02-2.24, P=0.041) compared with those with the CC genotype, therefore suggesting the dominant effect of the TGFB1 T allele on development of PCa and BPH. There were no significant differences in the TGFB1 genotype distribution between different groups of tumor grades and stages in the PCa patients and no significant differences when PCa patients were stratified by the age of onset. The results suggest that the codon10 polymorphism in TGFB1 may have a significant influence on the development of PCa and BPH, therefore underscoring the importance of the TGF pathway in the development of these prostatic diseases. However, it appeared to have no impact on the disease status or age of onset of PCa.

Aged↗
PubMed2003

Increased risk of prostate cancer associated with AA genotype of cyclin D1 gene A870G polymorphism.

CCND1 mRNA is alternatively spliced to produce 2 transcripts, and the splicing pattern may be modulated by a frequent A870G single-nucleotide polymorphism within the conserved splice donor site of exon 4. Several studies have suggested a significant association between the CCND1 genotype and onset or progression of various cancers. To investigate the correlation of the polymorphism with genetic susceptibility to PCa and its disease status, we examined the polymorphism in 214 cases of PCa, 234 cases of BPH and 254 male controls. The CCND1 A allele was more frequently observed in the PCa group (p = 0.015) and the BPH group (p = 0.018) than the control group. Men with the AA genotype had an increased risk of PCa (aOR = 1.93, 95% CI 1.13-3.30, p = 0.016) and BPH (aOR = 1.84, 95% CI 1.09-3.09, p = 0.023) compared to those with the GG genotype. No significant association was observed when men with the AG genotype were compared to those with the GG genotype (PCa: aOR = 1.00, 95% CI 0.65-1.54, BPH: aOR = 0.91, 95% CI 0.60-1.39). The risk of PCa associated with the AA genotype appeared to be stronger in men aged 73 years or younger (aOR = 2.89, 95% CI 1.38-6.01, p = 0.005), whereas no association was found in men older than 73 years (aOR = 1.02, 95% CI 0.44-2.34). No significant difference in genotype frequency was found among patients with low-, intermediate- and high-grade tumors (p = 0.730) or between patients with localized and metastatic PCa (p = 0.679). However, in patients with high-grade or metastatic PCa, a significantly increased risk associated with the AA genotype compared to controls was observed, while no significant results were found in those with low/intermediate or localized PCa. The A allele of the CCND1 A870G polymorphism was recessively associated with susceptibility to PCa and BPH in a Japanese population, giving a 2-fold increased risk of PCa and BPH in men with the AA genotype compared to those with the GG genotype. Although the risk of PCa associated with the AA genotype appeared to contribute especially to men aged 73 years or younger and the A allele may be associated with disease status of PCa, these conjectures require validation in future studies on a larger number of subjects.

Adenocarcinoma↗
PubMed2003

Controlled gene delivery system based on thermosensitive biodegradable hydrogel.

PURPOSE: Currently, most pDNA delivery systems based on synthetic polymers are either nonbiodegradable or not sensitive to the release environment. The primary objective of this study was to develop and evaluate an aqueous-based, thermosensitive, biodegradable and biocompatible triblock copolymer to control pDNA delivery in vitro and in vivo. METHODS: The triblock copolymers, poly[ethylene glycol-b-(D, L-lactic acid-co-glycol acid)-b-ethylene glycol] (PEG-PLGA-PEG), were synthesized as previously described. The molecular weight and polydispersity of PEG-PLGA-PEG were monitored by gel permeation chromatography (GPC). The cytotoxicity of PEG-PLGA-PEG was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The release of 32P-labeled pDNA entrapped in aqueous dispersion of PEG-PLGA-PEG in 0.1 mol/L sodium phosphate buffer solution (pH 7.4) was studied at 37 degrees C under agitation. Gene transfection efficiency was evaluated in a skin wound model in CD-1 mice. RESULTS: The aqueous dispersion of PEG-PLGA-PEG flows freely at room temperature but form a gel at 37 degrees C body temperature. The in vitro degradation of PEG-PLGA-PEG lasted for more than 30 days. The cytotoxicity of PEG-PLGA-PEG evaluated in HEK 293 cells was significantly lower than that of poly-L-lysine hydrochloride. The release profile of supercoiled pDNA from the polymer followed the zero-order kinetics up to 12 days. Maximal gene expression of luciferase was at 24 h in the skin wound of CD-1 mice and by 72 h, the expression dropped by nearly 94%. CONCLUSION: These results suggest hydrogel formed by PEG-PLGA-PEG could be a promising platform for delivery of pDNA, which represents a novel strategy that may serve as a non-viral vector for gene therapy in wound healing.

Animals↗
PubMed2003

Thermosensitive hydrogel as a Tgf-beta1 gene delivery vehicle enhances diabetic wound healing.

PURPOSE: To accelerate diabetic wound healing with TGF-beta1 gene delivery system using a thermosensitive hydrogel made of a triblock copolymer, PEG-PLGA-PEG. METHODS: Two 7 x 7 mm full thickness excisional wounds were created in parallel at the back of each genetically diabetic mouse. The hydrogel containing plasmid TGF-beta1 was administered to the wound and formed an adhesive film in situ. Controls were either untreated or treated with the hydrogel without DNA. We used a commercial wound dressing, Humatrix, either with or without DNA, to compare the therapeutic effect with the thermosensitive hydrogel. RESULTS: We found that thermosensitive hydrogel alone is slightly beneficial for reepithealization at early stage of healing (day 1-5), but significantly accelerated repithelializaion, increased cell proliferation, and organized collagen were observed in the wound bed treated with thermosensitive hydrogel containing plasmid TGF-beta1. The accelerated reepithelialization was accompanied with enhanced collagen synthesis and more organized extracellular matrix deposition. Humatrix alone or with plasmid TGF-beta1, had little effect. CONCLUSIONS: Thermosensitive hydrogel made of PEG-PLGA-PEG triblock copolymer provides excellent wound dressing activity and delivers plasmid TGF-beta1 to promote wound healing in a diabetic mouse model.

Animals↗
PubMed2003

Association of V89L SRD5A2 polymorphism with prostate cancer development in a Japanese population.

PURPOSE: The SRD5A2 gene codes the steroid 5-reductase type II, a critical mediator of androgen action, and the V89L and A49T polymorphisms of this gene may be associated with a distinct enzyme activity. We explored the association among these polymorphisms and the risk of prostate cancer or benign prostatic hyperplasia (BPH) in a Japanese population. MATERIALS AND METHODS: This study included 302 patients with prostate cancer, 228 with BPH and 243 male controls. V89L and A49T polymorphisms were analyzed by the polymerase chain reaction restriction fragment length polymorphism method. Genotypes were evaluated by electrophoresis on agarose gel. RESULTS: For the V89L polymorphism there were no significant differences in genotype frequencies in patients with prostate cancer and controls (p = 0.071) or in patients with BPH and male controls (p = 0.219). However, males with the VV or VL genotype were at significantly increased risk for prostate cancer compared with those with the LL genotype (adjusted OR 1.69, 95% CI 1.07 to 2.65, p = 0.024). The risk of BPH in males with the VV or VL genotype was not significantly elevated in comparison with those with the LL genotype (adjusted OR 1.37, 95% CI 0.85 to 2.20, p = 0.194). The V89L variant was not associated with the grade or stage of prostate cancer, or with patient age. For the A49T polymorphism all subjects had the AA genotype. CONCLUSIONS: The V allele of the V89L polymorphism in the SRD5A2 gene may dominantly increase the risk of prostate cancer.

Aged↗
PubMed2003

Age-dependent changes in beta-adrenoceptor function in human detrusors and possible mechanisms.

OBJECTIVE: To study age-dependent changes in beta-adrenergic responsiveness and their possible mechanisms. METHODS: Responsiveness to the beta-adrenergic agonists isoprenaline, BRL37344, forskolin, and dibutyryl cyclic AMP (DBcAMP) was examined in samples from 10 older patients by using a cellular function test. A radioligand binding assay was performed using the non-selective beta-adrenergic receptor ligand [3H]-dihydroalprenolol ([3H]-DHA). Specimens from 10 young men were used as controls. RESULTS: There were no age-dependent changes in contractile response to KCl. The relaxation responses to isoprenaline, BRL37344, and forskolin decreased in the aged group by 15.0%, 17.6%, and 12.6%, respectively (P < 0.001). The pD2 values for isoprenaline and BRL37344 also declined significantly. There was no difference in the responsiveness to dibutyryl cyclic AMP (DBcAMP) between the two groups; the maximum binding site decreased significantly with increasing age, but the equilibrium-dissociation constant did not change. CONCLUSIONS: There is an age-related decline in beta-adrenergic responsiveness which might be one of the causative factors of reduced bladder compliance in the elderly. A decrease in cAMP level caused by reduced receptor density and adenylyl cyclase activity might be the underlying molecular mechanism of the changes in beta-adrenergic responsiveness.

Adrenergic beta-Agonists↗