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Biomedical subjects

A Rane

Publications and source records attributed to A Rane.

At least 19 recordsLinked to original sources
PubMed2006

A novel polymorphism in the 17beta-hydroxysteroid dehydrogenase type 5 (aldo-keto reductase 1C3) gene is associated with lower serum testosterone levels in caucasian men.

Genetic variation in the androgen metabolizing enzymes is important to identify and feature as they may influence the risk of prostate cancer and help clarify the etiology of the disease. Human 17beta-hydroxysteroid dehydrogenase type 5 (AKR1C3) is highly expressed in the prostate gland and plays a major role in the formation and metabolism of androgens. We identified five novel polymorphisms in the AKR1C3 gene. One of those an A>G substitution in exon 2 that confers a Glu77Gly change occurred in 4.8% in Caucasians but was completely absent in Orientals. Interestingly, the testosterone level in serum was significantly lower in subjects with the Gly77 allele. A promoter A>G polymorphism was associated with significantly altered promoter activity in reporter constructs, but was not associated with any change in testosterone levels. In conclusion, the Glu77Gly polymorphism is associated with lower testosterone levels in serum.

17-Hydroxysteroid Dehydrogenases↗
PubMed2006

SHBG gene promoter polymorphisms in men are associated with serum sex hormone-binding globulin, androgen and androgen metabolite levels, and hip bone mineral density.

CONTEXT: SHBG regulates free sex steroid levels, which in turn regulate skeletal homeostasis. Twin studies have demonstrated that genetic factors largely account for interindividual variation in SHBG levels. Glucuronidated androgen metabolites have been proposed as markers of androgenic activity. OBJECTIVE: Our objective was to investigate whether polymorphisms in the SHBG gene promoter [(TAAAA)(n) microsatellite and rs1799941 single-nucleotide polymorphism] are associated with serum levels of SHBG, sex steroids, or bone mineral density (BMD) in men. DESIGN AND STUDY SUBJECTS: We conducted a population-based study of two cohorts of Swedish men: elderly men (MrOS Sweden; n congruent with 3000; average age, 75.4 yr) and young adult men (GOOD study; n = 1068; average age, 18.9 yr). MAIN OUTCOME MEASURES: We measured serum levels of SHBG, testosterone, estradiol, dihydrotestosterone, 5alpha-androstane-3alpha,17beta-diol glucuronides, androsterone glucuronide, and BMD determined by dual-energy x-ray absorptiometry. RESULTS: In both cohorts, (TAAAA)(n) and rs1799941 genotypes were associated with serum levels of SHBG (P < 0.001), dihydrotestosterone (P < 0.05), and 5alpha-androstane-3alpha,17beta-diol glucuronides (P < 0.05). In the elderly men, they were also associated with testosterone and BMD at all hip bone sites. The genotype associated with high levels of SHBG was also associated with high BMD. Interestingly, male mice overexpressing human SHBG had increased cortical bone mineral content in the femur, suggesting that elevated SHBG levels may cause increased bone mass. CONCLUSIONS: Our findings demonstrate that polymorphisms in the SHBG promoter predict serum levels of SHBG, androgens, and glucuronidated androgen metabolites, and hip BMD in men.

Adolescent↗
PubMed2006

Short term urinary catheter policies following urogenital surgery in adults.

BACKGROUND: Urinary catheterisation (by the urethral or suprapubic routes) is common following urogenital surgery. There is no consensus on how to minimize complications and practice varies. OBJECTIVES: To establish the optimal way to manage urinary catheters following urogenital surgery in adults. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised trials register (searched 30 May 2005) and the reference lists of relevant articles. SELECTION CRITERIA: Randomised and quasi-randomised trials were identified. Studies were excluded if they were not randomised or quasi-randomised trials of adults being catheterised following urogenital surgery. DATA COLLECTION AND ANALYSIS: Data collection was performed independently by two of the review authors and cross-checked. Where data might have been collected but not reported, clarification was sought from the trialists. MAIN RESULTS: Thirty nine randomised trials were identified for inclusion in the review. They were generally small and of poor or moderate quality reporting data on only few outcomes. Confidence intervals were all wide. USING A URINARY CATHETER VERSUS NOT USING ONE: The data from five trials were heterogeneous but tended to indicate a higher risk of (re)catheterisation if a catheter was not used postoperatively. The data gave only an imprecise estimate of any difference in urinary tract infection. URETHRAL CATHETERISATION VERSUS SUPRAPUBIC CATHETERISATION: In six trials, a greater number of people needed to be recatheterised if a urethral catheter rather than a suprapubic one was used following surgery (RR 3.66, 95% CI 1.41 to 9.49). SHORTER POSTOPERATIVE DURATION OF CATHETER USE VERSUS LONGER DURATION: In 11 trials, the seven trials with data suggested fewer urinary tract infections when a catheter was removed earlier (for example 1 versus 3 days, RR 0.50, 95% CI 0.29 to 0.87) with no pattern in respect of catheterisation. CLAMP AND RELEASE POLICIES BEFORE CATHETER REMOVAL VERSUS IMMEDIATE CATHETER REMOVAL: In a single small trial, the clamp-and-release group showed a significantly greater incidence of urinary tract infections (RR 4.00, 95% 1.55 to 10.29) and a delay in return to normal voiding (RR 2.50, 95% CI 1.16 to 5.39). AUTHORS' CONCLUSIONS: Despite reviewing 39 eligible trials, few firm conclusions could be reached because of the multiple comparisons considered, the small size of individual trials, and their low quality. Whether or not to use a particular policy is usually a trade-off between the risks of morbidity (especially infection) and risks of recatheterisation.

Adult↗
PubMed2005

Two-dimensional and three-dimensional ultrasound imaging of suburethral slings.

OBJECTIVE: Suburethral slings have become the most commonly performed anti-incontinence procedures in many developed countries. Three types of implant account for the majority of such surgery in Australia: tensionless vaginal tape (TVT), suprapubic arc procedure (SPARC) and intravaginal slingplasty (IVS). The aim of this study was to determine differences in position and mobility of these implants, and to determine whether such differences explain variations in clinical outcome. METHODS: In a prospective randomized controlled trial, 195 women were randomized to TVT (n = 67), IVS (n = 64) or SPARC (n = 64). Thirteen women were excluded from the study due to incomplete preoperative data. Of the remaining 182 women, 146 (50 TVT, 48 IVS, 48 SPARC) were seen between 2 and 23 months after their procedure (80%). After an interview, two-dimensional (2D) and three-dimensional (3D) pelvic floor ultrasound was performed. 3D-volume analysis was carried out on a computer with the help of proprietary software (GE Kretz 4D View). Assessors of ultrasound data were blinded against group allocation. RESULTS: There were no significant differences in subjective cure/improvement of stress or urge incontinence or overall subjective cure/improvement. Symptoms, including those of voiding dysfunction, did not vary between groups. All tapes could be imaged by ultrasound. TVT and SPARC were highly echogenic, with the SPARC generally flatter and of wider weave. The IVS seemed narrower and less echogenic. Tape position and mobility were similar, with a trend towards greater distances between tape and symphysis pubis and greater horizontal tape mobility in the SPARC group. CONCLUSIONS: The three types of suburethral sling, namely TVT, SPARC and IVS, investigated using 2D and 3D ultrasound, have comparable short-term clinical and anatomical outcomes.

Female↗
PubMed2005

[Transobturator correction of cystocele].

OBJECTIVE: We present our initial experience with the Perigee system for anterior vaginal wall prolapses repair. MATERIAL AND METHOD: 15 patients with anterior vaginal wall prolapse (mean age: 62 years old) underwent implanted with Perigee system which is composed by a mesh for correcting central defect and four self-attached horns for correcting lateral defect. The implanted procedure consist of four steps: 1) lateral vaginal wall dissection as far as isquiopubic branch; 2) performance of two upper marks at genitofemoral fold and two lower marks at 2 cm laterally and 3 cm lower; 3) insertion of the upper needles parallel to the isquiopubic branch and connection with the mesh's "arms" plus insertion of the lower needles vertically and connection with mesh's "legs"; 4) to adjust the mesh free tension. The system POP-Q was used as an objective measure of correction rate. RESULTS: Preoperatively, the point Aa was 0.09. After 6 weeks and three months postoperatively was -3.00 and -2.73 respectively. Preoperatively, the point Ba was 1.73. After 6 weeks and three months postoperatively was -2.82 and -2.82 respectively. No major complications were presented. No vascular damage or significant bleeding was observed. CONCLUSION: The transobturator correction of cystocele is an attractive alternative. The initial good outcome may be expected to be long lasting.

Adult↗
PubMed2005

Cyclophosphamide induces mRNA, protein and enzyme activity of cytochrome P450 in rat.

The effects of cyclophosphamide (CPA) on CYP enzymes in vivo and its auto induction in rat were investigated in Wistar/Fu male rats at a single dose (40 or 200 mg kg(-1)) or as repeated dose of 200 mg kg(-1) CPA. After a single dose of CPA, mRNAs of CYPs 2B1, 2B2, 3A2, 2C11 were significantly induced up to 220-, 6.7-, 5.0- and 5.8-fold at the low dose CPA, and 4800-, 52-, 22- and 2.5-fold at the high dose. CYP2B1/2 and CYP3A proteins were increased by 4- and 2-fold (low dose) and by 28- and 1.7-fold (high dose). CYP2C11 protein levels were not altered. Microsomal activities of CYP2B, CYP3A and 2C11 were increased by 2-, 1.8- and 1.3-fold at low dose CPA, and 3.2-, 1.7- and 1.6-fold at high dose. A significant (p<0.05) decrease in CPA concentration and a significant (p<0.05) increase in 4-OH-CPA levels were observed with repeated administration of CPA. Acute induction effect on CYP2B1, 2B2, 2C11 and 3A2 and a substantial up regulation of CYP2B1 mRNA were observed after a single dose of CPA, auto induction was observed by repeated administration.

Animals↗
PubMed2005

Use of Ligasure bipolar diathermy system in vaginal hysterectomy.

The use of Ligasure, a computer-controlled bipolar diathermy system is proven beneficial in a wide range of surgical procedures. This study was to evaluate its application to vaginal hysterectomy. Over forty patients underwent vaginal hysterectomy with (n = 32) or without (n = 12) Ligasure using standard surgical techniques. The main diagnoses, the age of patients, time for surgery, hospital stay and estimated blood loss during operation were compared. The average operating time was shorter in the Ligasure vaginal hysterectomy group (30 mins (24-48) P < 0.05), the estimated blood loss was less in the Ligasure hysterectomy group (39 mins (25-60) P < 0.05), and the hospital stay was shorter in the Ligasure hysterectomy group (1.2 days (1-2) vs 3 days (3-5) P < 0.05). There were no postoperative complications or re-admissions in either group. Vaginal hysterectomy using Ligasure reduced operating time and blood loss, and therefore shortened hospital stay.

Adult↗
PubMed2004

Human and rodent type 1 11beta-hydroxysteroid dehydrogenases are 7beta-hydroxycholesterol dehydrogenases involved in oxysterol metabolism.

Interconversion between cortisone and the glucocorticoid receptor ligand cortisol is carried out by 11beta-hydroxysteroid dehydrogenase (11beta-HSD)isozymes and constitutes a medically important example of pre-receptor control of steroid hormones. The enzyme 11beta-HSD type 1 (11beta-HSD1) catalyzes the conversion of cortisone to its active receptor-binding derivative cortisol, whereas 11beta-HSD type 2 performs the reverse reaction. Specific inhibitors against the type 1 enzyme lower intracellular levels of glucocorticoid hormone, with an important clinical application in insulin resistance and other metabolic disorders. We report here on the in vitro oxysterol-metabolizing properties of human and rodent 11beta-HSD1. The enzyme, either as full-length, membrane-attached, or as a transmembrane domain-deleted, soluble form, mediates exclusively conversion between 7-ketocholesterol and 7beta-hydroxycholesterol with similar k(cat) values as observed with glucocorticoid hormones. Thus, human, rat, and mouse 11beta-HSD1 have dual enzyme activities like the recently described 7alpha-hydroxysteroid dehydrogenase/11beta-hydroxysteroid dehydrogenase from hamster liver, but differ fundamentally from the latter in that 7beta-OH rather than 7alpha-OH dehydrogenase constitutes the second activity. These results demonstrate an enzymatic origin of species differences in 7-oxysterol metabolism, establish the origin of endogenous 7beta-OH cholesterol in humans, and point to a possible involvement of 11beta-HSD1 in atherosclerosis.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗
PubMed2004

A functional C-G polymorphism in the CYP7B1 promoter region and its different distribution in Orientals and Caucasians.

Cytochrome P450 (CYP) 7B1 is involved in many metabolic processes including androgen metabolism. Genetic variation in the CYP7B1 gene may play a role in predisposition to prostate cancer. Here, we screened the human CYP7B1 gene for possible polymorphisms. Only one single polymorphism was detected, a C-G change in the promoter -104 base pair from the transcription start site. The allele frequency was investigated in Swedish men and compared to a Korean population, as it is known that the frequency of prostate cancer is low among Orientals. We found that the frequency of the G-allele was 4.04% in Swedes (n=150) but only 0.33% among Koreans (n=153). Computer analysis indicated that the two variants bind with different affinities to a CCAAT-box binding protein. Expression studies with reporter constructs showed significantly higher transcriptional activity of the G variant in Hek293 cells (2.7-fold, P<0.05). In conclusion, we report here for the first time the detection of a single polymorphism in the CYP7B1 gene. This polymorphism is associated with phenotypic differences in an expression system and a widely different allele frequency in two ethnic populations, with great differences in the incidence of prostate cancer.

Asian People↗
PubMed2004

Genetic polymorphisms of cytochrome P450 2C9 causing reduced phenprocoumon (S)-7-hydroxylation in vitro and in vivo.

The effect of cytochrome P450 (CYP) 2C9 polymorphisms on the stereoselective biotransformation of the oral anticoagulant phenprocoumon (PPC) to inactive, monohydroxylated metabolites was studied in vitro and in vivo. In human liver microsomes, the (S)-7-hydroxylation--being the major metabolic pathway--was significantly compromised in a gene-dose-dependent manner in samples expressing the CYP2C9*2 or CYP2C9*3 allele. The CYP2C9*3/*3 genotype corresponded to an almost fourfold lower (S)-7-hydroxylation rate than CYP2C9*1/*1 (wild-type). The intrinsic clearance of human recombinant CYP2C9*2 and CYP2C9*3 for the (S)-7-hydroxylation was 28.9 and 50.9% lower than of CYP2C9*1, respectively. The area under the plasma concentration-time curve (AUC) of PPC metabolites after oral intake of 12 mg racemic PPC was significantly lower in volunteers expressing the CYP2C9*2 or CYP2C9*3 allele. Increasing plasma AUC metabolic ratios (parent compound/metabolite) in CYP2C9*2 and CYP2C9*3 variant allele carriers were found for each hydroxylation reaction and the CYP2C9*3/*3 genotype corresponded to an about 10-fold higher metabolic ratio of PPC (S)-7-hydroxylation relative to CYP2C9*1/*1. CYP2C9 polymorphisms cause a markedly compromised PPC (S)-7-hydroxylation. However, PPC metabolism appears overall less influenced by CYP2C9 genotype compared with other oral anticoagulants and it may thus be a valuable alternative for therapeutic anticoagulation of patients expressing CYP2C9 variant alleles.

Alleles↗
PubMed2004

Maternal intravaginal prostaglandin E2 gel before elective caesarean section at term to induce catecholamine surge in cord blood: randomised, placebo controlled study.

OBJECTIVE: To test the hypothesis that the application of intravaginal prostaglandin E(2) gel before elective caesarean section (ECS) will induce a catecholamine surge in umbilical arterial blood. DESIGN: Randomised, double blind, placebo controlled trial. SETTING: A regional perinatal referral centre. PATIENTS: Mothers booked for ECS at or above 38 weeks gestation. INTERVENTIONS: Thirty six consenting mothers were randomly allocated to receive either 2 mg intravaginal prostaglandin E(2) gel (study group; n = 18) or an equal volume of K-Y jelly as a placebo (control group; n = 18) 60 minutes before the ECS. Computer generated random numbers contained in coded, sealed envelopes were used for allocation. The obstetric and neonatal teams were blinded to the randomisation status of enrolled mothers. MAIN OUTCOME MEASURES: Catecholamine concentrations in the umbilical arterial blood samples collected at delivery. RESULTS: The median (interquartile range) neonatal gestation and birth weight were 271 (269-274) days and 3605 (3072-3970) g for the study group and 271 (270-273) days and 3340 (3000-3622) g for the control group. Median (interquartile range) noradrenaline (norepinephrine) concentrations in the umbilical arterial blood were significantly higher in the study group than the control group (15.9 (9.8-28.92) v 4.6 (1.65-14.4) ng/l, p = 0.03). Adrenaline (epinephrine) concentrations did not differ significantly between the two groups (1.6 (< 0.5-3.1) v 1.4 (< 0.5-2.75) ng/l, p = 0.6). No treatment related complications occurred. CONCLUSION: A labour related catecholamine surge could be simulated by intravaginal prostaglandin E(2) gel.

Administration, Intravaginal↗
PubMed2003

Suburethral vaginal erosion and pyogenic granuloma formation: an unusual complication of intravaginal slingplasty (IVS).

We report an unusual case of suburethral vaginal erosion and pyogenic granuloma formation 14 months after intravaginal slingplasty (IVS). A 64-year-old woman underwent IVS for recurrent stress incontinence 12 years after Burch colposuspension. Following seemingly uncomplicated surgery and recovery, she developed a recurrent urinary tract infection which was treated with antibiotics. When she presented with vaginal pain and postmenopausal bleeding approximately 14 months postoperatively, she was found to have suburethral vaginal erosion of the tape and a pyogenic granuloma. The exposed tape was removed, the granuloma excised, and the overlying vaginal skin was then closed. She then made an uneventful recovery.

Female↗
PubMed2003

Alteration of pharmacokinetics of cyclophosphamide and suppression of the cytochrome p450 genes by ciprofloxacin.

Recently, it has been reported that prophylactic administration of ciprofloxacin during cyclophosphamide (CY) conditioning was a high-risk factor for relapse in patients undergoing allogeneic BMT. In the present study, we investigated the possible mechanisms of this interaction in male Sprague-Dawley rats. The kinetics of CY and its active 4-OH-CY metabolite were determined, after 3 days pretreatment with ciprofloxacin (200 mg/kg) and compared to control rats without treatment. CY was administered as a high or low single intravenous dose (150 and 90 mg/kg, respectively). The expression of the CYP2B1, CYP2B2, CYP2C11, CYP3A1 and CYP3A2 genes was evaluated by SYBR Green I Dye real-time PCR for quantification of mRNA. The administration of ciprofloxacin resulted in a significant increase in the AUC (P=0.007) and a significant decrease in clearance (P=0.007) when CY was given as a high dose. In accordance, the metabolic ratio (AUC4-OH-CY/AUCCY) was significantly lower (P=0.007) compared to that found in the control group. Ciprofloxacin significantly suppressed gene expression of CYP2C11 (P=0.01) and CYP3A1 (P=0.04); however, no effect was observed on the gene expression of CYP3A2, CYP2B1 and CYP2B2. Our study revealed that ciprofloxacin interacts with CY and suppressed relevant cytochromes p450 at the transcriptional level. This study may have a great clinical impact when ciprofloxacin is used in therapy.

Animals↗
PubMed2003

Role of polymorphic human CYP2B6 in cyclophosphamide bioactivation.

The role of polymorphic CYP2B6 in cyclophosphamide (CPA) bioactivation was investigated in human liver microsomes. A total of 67 human liver specimens were first genotyped with respect to the CYP2B6*5 and CYP2B6*6 variant alleles. CYP2B6 apoprotein levels in 55 liver microsomal preparations were assessed by immunoblotting. 4-Hydroxy-CPA and hydroxy-bupropion were quantified by using HPLC and LC-MS, respectively. 7-Ethoxy-4-trifluoromethyl coumarin O-deethylase activity was measured fluorometrically. The frequencies of CYP2B6*5 and CYP2B6*6 mutant alleles were 9.0 and 16.4%, respectively. CYP2B6 protein expression was detected in 80% of the samples, with a large variation (0.003-2.234, arbitrary units). There was a high correlation between CYP2B6 apoprotein content and CPA 4-hydroxylation (n=55, r=0.81, P<0.0001). When based on the CYP2B6 apoprotein levels, the *6 carriers had significantly higher CPA 4-hydroxylation (P<0.05). CPA 4-hydroxylation also correlated significantly with other CYP2B6-specific reactions (n=20, P<0.0001). V(max) and K(m) for CPA 4-hydroxylation in recombinant CYP2B6 enzyme were 338 nmol/min/nmol enzyme and 1.4 mM, respectively. CYP2B6 showed much higher in vitro intrinsic clearance than previously observed in recombinant CYP2C19 and CYP2C9 variants in yeast expression system. Our results demonstrate that the polymorphic CYP2B6 is a major enzyme in the bioactivation of CPA. Moreover, we identified a strong impact of CYP2B6*6 on CPA 4-hydroxylation.

Analysis of Variance↗
PubMed2002

Management of the very weak pelvic floor. Is there a point?

Conservative treatment in the form of pelvic muscle exercises is effective in the treatment of stress urinary incontinence. There are no studies specifically looking at women who have extremely weak pelvic muscles and their response to conservative treatment. This study looks at the effectiveness of pelvic muscle therapy in women with very weak pelvic muscles. Out of 965 women attending the bladder clinic at Kirwan Hospital, 219 were assessed to have weak pelvic muscles by digital palpation. All patients were subjected to a detailed urogynecological questionnaire, a frequency/volume chart, and clinical assessment. All patients were then given detailed verbal and written instructions on good bladder habits, including posture, dietetic habits and pelvic muscle exercises. Of the 219 women, 163 were able to complete their treatment and presented for review. Out of 163 women 118 (72%) reported a subjective improvement; 89 (54%) demonstrated an objective improvement in pelvic muscle strength.

Adult↗
PubMed2002

Intra-individual variation and sex differences in gene expression of cytochromes P450 in circulating leukocytes.

To clarify partly inconsistent results in gene expression of cytochromes P450 (CYP) in the circulation, we undertook a systematic study over a long time period in 19 healthy men and women. CYP specific mRNA for 1A2, 1B1, 2E1 and 3A4 was studied in the leukocytes collected repeatedly on 20 occasions over a 10-week period. Our study revealed a varying pattern of CYP expression over time. CYP3A4 specific mRNA exhibited the largest intra-individual variation with an average coefficient of variation between 40 and 250%. CYP1B1 and CYP2E1 did not vary as much (39-110%). CYP1A2 was sporadically detected in only ten individuals, but varied considerably when measurable (61-256%). The expression in CYP1B1 was significantly higher in women than in men (P = 0.02). We conclude that CYP gene expression in blood varies considerably over time. It is conceivable that the variation reflects a hitherto unknown influence of exogenous or endogenous factors such as hormones, cytokines, and other circulating factors on the hematogeneous cytochromes.

Adult↗
PubMed2002

Growth hormone replacement therapy induces codeine clearance.

BACKGROUND: The increasing clinical use of growth hormone (GH) has raised questions about other than growth-related metabolic effects of this treatment. GH regulates the expression of several hepatic drug metabolising enzymes in the rat, but it is not known whether GH treatment alters the expression of such liver enzymes in man. We have investigated the effects of GH on codeine clearance and two enzymes of the cytochrome P450 (CYP) family, CYP3A and CYP2D6, and UDP-glucuronosyl transferase (UDPGT). These enzymes have a superior importance in hepatic biotransformation of numerous drugs. In addition, CYP3A and UDPGT are catalysts of many reactions with endobiotics such as steroid hormones. METHODS: We used codeine as a probe drug for assessment of the enzyme activities. Codeine was administered as a single-dose prior to, and after 3 months of GH substitution in GH-deficient patients. Total clearance, and clearance along each of the three primary metabolic pathways of codeine, was assessed. RESULTS: Three months of GH substitution increased the total clearance of codeine (21%, P < 0.01) and clearance catalysed by UDPGT significantly (31%, P < 0.05). The treatment tended to increase the clearance via the CYP3A pathway (83%, P = 0.05). CONCLUSIONS: The effects of GH replacement therapy on drug metabolism may have clinical implications when combined with drugs that are substrates of UDPGT and CYP3A. Effects on steroid hormone metabolism with endocrine consequences can not be ruled out.

Adult↗