bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of sildenafil on human sperm function in healthy volunteers
Authors: Purvis Ken , Muirhead Gary J. , Harness Jane A. 
Published: March 2003

Aims  This double‐blind, randomized, four‐period, two‐way crossover study was conducted to evaluate the acute effects of oral sildenafil (100‐mg single dose) on sperm motility, count, density, morphology and vitality as well as ejaculate volume and viscosity in healthy male subjects. The concentrations of sildenafil and its primary circulating metabolite UK‐103,320 were measured in ejaculate and compared with those in plasma. The study also included assessments of safety and tolerability.Methods  A total of 17 healthy male volunteers aged 19–34 years were randomized to receive a single 100‐mg dose of sildenafil for two periods and a single dose of placebo for two periods, with each period separated by a minimum of 5–7 days. Sperm and ejaculate properties were evaluated from semen samples taken at screening and 1.5 h after dose. An additional semen sample was collected 4 h after dose, and drug and metabolite concentrations were measured in this sample and the sample taken 1.5 h after dose for comparison with plasma concentrations. Blood samples were collected before each dose and 0.25, 0.5, 1, 2, 3, 4 and 6 h after dose for measurement of sildenafil and metabolite concentrations.Results  Sildenafil had no statistically significant effect on sperm motility, count or density; the percentage of abnormal sperm forms; or the percentage of living sperm. It also did not affect ejaculate volume or viscosity. All measures were within normal ranges. Sildenafil distributed into the semen rapidly, resulting in significant correlations between concentrations of sildenafil in the semen and total (R2=0.588) or free (R2=0.454) plasma concentrations (P<0.0001). Total semen concentrations of sildenafil were 18% of total plasma concentrations. UK‐103,320 appeared to distribute more slowly from the plasma into the semen, resulting in a lack of correlation between semen and plasma concentrations. The amount of sildenafil and UK‐103,320 in the ejaculate was small (<2×10−4% of the administered dose at 1.5 h). Sildenafil was well tolerated; no patient withdrew from the study due to adverse events attributed to sildenafil.Conclusions  These results indicate that a single 100‐mg oral dose of sildenafil does not have an adverse effect on sperm function or ejaculate quality.
Influence of β‐adrenoceptor antagonists on the pharmacokinetics of rizatriptan, a 5‐HT1B/1D agonist: differential effects of propranolol, nadolol and metoprolol
Authors: Goldberg Michael R. , Sciberras David , De Smet Marina , Lowry Richard , Tomasko Lisa , Lee Yih , Olah Timothy V. , Zhao Jamie , Vyas Kamlesh P. , Halpin Rita , Kari Prasad H. , James Ian 
Published: March 2003

Aims  Patients with migraine may receive the 5‐HT1B/1D agonist, rizatriptan (5 or 10 mg), to control acute attacks. Patients with frequent attacks may also receive propranolol or other β‐adrenoceptor antagonists for migraine prophylaxis. The present studies investigated the potential for pharmacokinetic or pharmacodynamic interaction between β‐adrenoceptor blockers and rizatriptan.Methods  Four double‐blind, placebo‐controlled, randomized crossover investigations were performed in a total of 51 healthy subjects. A single 10 mg dose of rizatriptan was administered after 7 days' administration of propranolol (60 and 120 mg twice daily), nadolol (80 mg twice daily), metoprolol (100 mg twice daily) or placebo. Rizatriptan pharmacokinetics were assessed. In vitro incubations of rizatriptan and sumatriptan with various β‐adrenoceptor blockers were performed in human S9 fraction. Production of the indole‐acetic acid‐MAO‐A metabolite of each triptan was measured.Results  Administration of rizatriptan during propranolol treatment (120 mg twice daily for 7.5 days) increased the AUC(0,∞) for rizatriptan by approximately 67% and the Cmax by approximately 75%. A reduction in the dose of propranolol (60 mg twice daily) and/or the incorporation of a delay (1 or 2 h) between propranolol and rizatriptan administration did not produce a statistically significant change in the effect of propranolol on rizatriptan pharmacokinetics. Administration of rizatriptan together with nadolol (80 mg twice daily) or metoprolol (100 mg twice daily) for 7 days did not significantly alter the pharmacokinetics of rizatriptan. No untoward adverse experiences attributable to the pharmacokinetic interaction between propranolol and rizatriptan were observed, and no subjects developed serious clinical, laboratory, or other significant adverse experiences during coadministration of rizatriptan with any of the β‐adrenoceptor blockers. In vitro incubations showed that propranolol, but not other β‐adrenoceptor blockers significantly inhibited the production of the indole‐acetic acid metabolite of rizatriptan and sumatriptan.Conclusions  These results suggest that propranolol increases plasma concentrations of rizatriptan by inhibiting monoamine oxidase‐A. When prescribing rizatriptan to migraine patients receiving propranolol for prophylaxis, the 5 mg dose of rizatriptan is recommended. Administration with other β‐adrenoceptor blockers does not require consideration of a dose adjustment.
Use of selective serotonin reuptake inhibitors and risk of developing first‐time acute myocardial infarction
Authors: Meier Christoph R. , Schlienger Raymond G. , Jick Hershel 
Published: March 2003

Aims  Selective serotonin reuptake inhibitors (SSRIs) have been associated with serotonin depletion in platelets, potentially leading to abnormal aggregation and prolonged bleeding time. In view of the importance of serotonin in coronary thrombosis, and decreased platelet serotonin concentrations associated with SSRIs, the present study was performed to test the hypothesis of a decreased risk of acute myocardial infarction (AMI) associated with SSRIs.Methods  We conducted a population‐based case‐control analysis using the UK General Practice Research Database (GPRD). A total of 3319 patients aged 75 years or younger free of clinical conditions predisposing to ischaemic heart disease, with a first‐time diagnosis of AMI between 1992 and 1997, and 13 139 controls without AMI matched to cases for age, sex, general practice attended, and calendar time were included. Conditional logistic regression was used to estimate relative risks.Results  Adjusted odds ratios (with 95% CI) for current use of SSRIs, non‐SSRIs, or other antidepressants, compared to the group of nonusers of antidepressants were 0.9 (95% CI 0.5,1.8), 0.9 (95% CI 0.7,1.2), and 1.3 (95% CI 0.6,2.8), respectively. As compared with nonuse of SSRIs, current use (regardless of any other antidepressants used) resulted in an adjusted OR of 1.1 (95% CI 0.7,1.6).Conclusions  The current analysis provides evidence that SSRI exposure does not substantially decrease the risk of developing first‐time AMI in patients free of factors predisposing to ischaemic heart disease. However, due to relatively small numbers of exposed subjects and the resulting wide confidence intervals, further studies may be needed to document a lack of effect of SSRIs in subjects without pre‐existing diseases predisposing to AMI.
Effects of adrenomedullin on angiotensin II stimulated atrial natriuretic peptide and arginine vasopressin secretion in healthy humans
Authors: Petrie Mark C. , McDonald John E. , Hillier Chris , Morton James J. , McMurray John J. V. 
Published: March 2003

Aims  Adrenomedullin is a newly described peptide that has widespread tissue distribution. Its presence in cardiovascular (including vascular endothelial cells, smooth muscle cells, and cardiac atria and ventricles) and renal tissues, together with its vasodilatory and natriuretic properties, suggest a role in blood pressure regulation and fluid and electrolyte balance.
Methods
Nine normal volunteers were studied to determine whether or not adrenomedullin influenced plasma atrial natriuretic peptide and arginine vasopressin concentrations during systemic angiotensin II infusion.
Results
A significant (P = 0.02) augmentation of atrial natriuretic peptide concentrations, but no suppression of arginine vasopressin concentrations, was found with coinfusion of adrenomedullin and angiotensin II when compared with vehicle and angiotensin II.
Conclusions
Despite its vasodilator and natriuretic action, adrenomedullin significantly augmented angiotensin II‐stimulated plasma atrial natriuretic peptide concentrations in healthy humans. This provides further evidence of a synergistic interaction between adrenomedullin and atrial natriuretic peptide and suggests that adrenomedullin may have a role in fluid and electrolyte balance and blood pressure regulation.
Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers
Authors: Weber Artur‐Aron , Braun Marina , Hohlfeld Thomas , Schwippert Barbara , Tschöpe Diethelm , Schrör Karsten 
Published: March 2003

Aims  To study the recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers.Methods  Ten healthy volunteers were treated with clopidogrel (75 mg day−1) for 7 days. CD62P expression and PAC‐1 binding were measured by flow cytometry.Results  Adenosine diphosphate (ADP, 30 µM)‐induced platelet responses were almost completely inhibited by clopidogrel. After discontinuation of the drug, platelet function gradually increased and complete recovery was seen 7 days after the last clopidogrel dose. The mean difference (95% CI) for ADP‐induced PAC‐1 binding (fluorescence intensity) between baseline and 7 days after the last dose was 0.01 (0.61, −0.59). Single cell analysis provides direct evidence for an irreversible mode of action of clopidogrel.Conclusions  This is the first report to directly demonstrate irreversibility of clopidogrel action in humans.
Genetic polymorphism of cytochrome P450 2C9 in a Caucasian and a black African population
Authors: Scordo Maria Gabriella , Aklillu Eleni , Yasar, Umit , Dahl Marja‐Liisa , Spina Edoardo , Ingelman‐Sundberg Magnus 
Published: March 2003

Aims  CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect the therapeutic outcome during treatment with several drugs. The distribution of variant CYP2C9 alleles was therefore investigated in an Italian and an Ethiopian population.Methods  Allele‐specific PCR analysis was carried out in order to determine the frequencies of the two most common variant alleles, CYP2C9*2 and CYP2C9*3 in genomic DNA isolated from 157 Italians and 150 Ethiopians.Results  The frequencies of CYP2C9*1 (80%), CYP2C9*2 (11%) and CYP2C9*3 (9%) found in the Italian population were similar to other Caucasian groups. However in the Ethiopian population CYP2C9*1, CYP2C9*2 and CYP2C9*3 were present at a frequency of 94, 4 and 2% respectively. The 95% confidence intervals in CYP2C9*1, CYP2C9*2 and CYP2C9*3 between Italians and Ethiopians were 0.098, 0.176, 0.040, 0.098 and 0.040, 0.098, respectively.Conclusions  Our results indicate that the Ethiopian population has a unique relative distribution of the CYP2C9 alleles, which is not similar to any other ethnic group hitherto described.
The effects of rifampicin on the pharmacokinetics and pharmacodynamics of orally administered nilvadipine to healthy subjects
Authors: Saima S. , Furuie K. , Yoshimoto H. , Fukuda J. , Hayashi T. , Echizen H. 
Published: March 2003

Aims  To study the effects of rifampicin on the pharmacokinetics and pharmacodynamics of nilvadipine.Methods  Five healthy adult volunteers received nilvadipine (4 mg) orally before and after a 6 day treatment with rifampicin. Blood and urine were collected and assayed for plasma nilvadipine and urinary 6β‐hydroxycortisol and cortisol.Results  The treatment with rifampicin reduced the mean (± s.d.) AUC of nilvadipine from 17.4 ± 8.4 to 0.6 ± 0.4 µg l−1 h (mean difference −16.8 µg l−1 h, 95% CI −9.4, 24.2 µg l−1 h). While the administration of nilvadipine alone elicited a significant (P < 0.05) hypotensive (mean difference for diastolic blood pressure –8 mmHg, 95% CI −4, −12 mmHg) and reflex tachycardia (mean difference 5 beats min−1, 95% CI 1, 9 beats min−1), the treatment with rifampicin abolished these responses. The urinary 6β‐hydroxycortisol/cortisol ratio showed a significant (P < 0.05) increase from 10.3 ± 4.0 to 50.3 ± 24.6 by rifampicin: mean difference 40.1, 95% CI 20.4, 59.8.Conclusions  Because rifampicin may greatly decrease the oral bioavailability of nilvadipine, caution is needed when these two drugs are to be coadministered.
Cascading effects of variation in plant vigour on the relative performance of insect herbivores and their parasitoids
Authors: Teder Tiit , Tammaru Toomas 
Published: March 2003

Abstract1. Consequences of variation in food plant quality were estimated for a system consisting of two monophagous noctuid herbivores and three ichneumonid parasitoids.2. In a natural population, pupal weights of the herbivores in this system,Nonagria typhaeandArchanara sparganii, were found to be highly variable. Pupal weights increased strongly and consistently with the increase in the vigour of the host plant,Typha latifolia, providing support for the plant vigour hypothesis. Correspondingly, as the moths do not feed as adults, a strong, positive correlation between host vigour and fecundity of the herbivores would be expected.3. There were strong and positive relationships between adult body sizes of the parasitoids and the sizes of their lepidopteran hosts. Moreover, a direct, positive link between plant quality and parasitoid size was documented.4. For all three parasitoids, cascading effects of plant quality on body size were weaker than for the herbivores. Differences in the importance of adult feeding and oviposition behaviour suggest that dependence of fitness on body size is also weaker in the parasitoids than in the moths. It is therefore concluded that the numerical response of the herbivore population to a change in plant quality should exceed the corresponding response in the parasitoids.5. The results of this work imply that variation in plant variables may affect performance of different trophic levels to a different extent. It is suggested that the importance of adult feeding for the reproductive success (capital vs. income breeding strategies) in both herbivores and parasitoids is an essential aspect to consider when predicting responses of such a system to changes in plant quality.
A randomized, controlled trial to study the effect of exercise consultation on the promotion of physical activity in people with Type 2 diabetes: a pilot study
Authors: Kirk A. F. , Higgins L. A. , Hughes A. R. , Fisher B. M. , Mutrie N. , Hillis S. , MacIntyre P. D. 
Published: March 2003

AbstractAim  To evaluate the effect of exercise consultation on promotion of physical activity in people with Type 2 diabetes.Methods  Twenty‐six sedentary people with Type 2 diabetes were randomly assigned to receive an exercise consultation and standard exercise information (experimental) or standard exercise information alone (control). Exercise consultation is a one‐to‐one discussion, based on the transtheoretical model, designed to educate, strengthen motivation and develop realistic strategies to promote physical activity. Changes from baseline at five weeks were assessed in (a) stage of exercise behaviour (b) physical activity levels (7‐day recall questionnaire and an accelerometer) (c) quality of life (SF‐36 Health Survey and 22‐Item Well‐Being Questionnaire).Results  82% (9/11) of participants receiving a consultation increased their stage of exercise behaviour compared to 33% (4/12) of controls (χ2 = 5.4, P= 0.02). Physical activity counts/week increased by 4% (1636 067/1696 191) in the experimental group and decreased by 9% (1560 960/1725 510) in controls. A significant difference was recorded for the change in activity counts per week from baseline to follow‐up between the experimental and control group (98% CI = 60 673–710 827). The number of participants taking part in sport or leisure activity increased by 55% (6/11) in the experimental group and decreased by 6% (1/12) in controls. Positive changes were evident in the experimental group, compared to controls, in both quality of life questionnaires.Conclusion  Exercise consultation is more effective in stimulating exercise behaviour change in the short term than a standard exercise leaflet.Diabet. Med. 18, 877–882 (2001)
What is the prevalence of visual impairment in the general and diabetic populations: are there ethnic and gender differences?
Authors: Hayward L. M. , Burden M. L. , Burden A. C. , Blackledge H. , Raymond N. T. , Botha J. L. , Karwatowski W. S. S. , Duke T. , Chang Y. F. 
Published: March 2003

AbstractAims To estimate the prevalence of blindness and partial sight in the general and diabetic populations and to measure the impact of ethnicity and gender on these rates.Methods Data on visual impairment in the population to be studied was obtained from the Royal Leicestershire Rutland and Wycliffe Society for the Blind (RLRWSB). Using the validated technique of capture‐mark‐recapture (CMR), a census day was set and data from four sources collected: hospital admissions data, GP returns, wards, and mass media. Computer cross‐linkage to Leicestershire Health Authority data ensured patients were alive and resident in Leicestershire at the census date. Estimates of diabetes, ethnicity and gender prevalence were calculated using the 1991 census.Results CMR calculations revealed that there was under ascertainment of visual impairment in the RLRWSB data. The CMR calculations with direct age standardization estimate the prevalence of blindness and partial sight in the general and diabetic populations to be 51.8/10 000 (CI 50.6–53.0) and 148.8/10 000 (CI 122.1–175.5), respectively. In the diabetic population there was a higher proportion of visually impaired females than males (P < 0.05), with no overall ethnic differences; however, rates were lower than expected in female Indo‐Asians. In the general population there was a higher proportion of visually impaired Indo‐Asian people (P < 0.01).Conclusions Our study has shown the prevalence of visual impairment in both the general and diabetic populations and has demonstrated both ethnic and gender differences. CMR allows the calculation of prevalence of blindness and partial sight from existing data. When comparing the prevalence of visual impairment, whether from diabetes or other causes, it is important to know the gender and ethnicity of the ‘at risk’ population, as well as the rates in the background population.
Protein kinase C and the development of diabetic vascular complications
Authors: Way K. J. , Katai N. , King G. L. 
Published: March 2003

AbstractHyperglycemic control in diabetes is key to preventing the development and progression of vascular complications such as retinopathy, nephropathy and neuropathy. Increased activation of the diacylglycerol (DAG)‐protein kinase C (PKC) signal transduction pathway has been identified in vascular tissues from diabetic animals, and in vascular cells exposed to elevated glucose. Vascular abnormalities associated with glucose‐induced PKC activation leading to increased synthesis of DAG include altered vascular blood flow, extracellular matrix deposition, basement membrane thickening, increased permeability and neovascularization. Preferential activation of the PKCβ isoform by elevated glucose is reported to occur in a variety of vascular tissues. This has lead to the development of LY333531, a PKCβ isoform specific inhibitor, which has shown potential in animal models to be an orally effective and nontoxic therapy able to produce significant improvements in diabetic retinopathy, nephropathy, neuropathy and cardiac dysfunction. Additionally, the antioxidant vitamin E has been identified as an inhibitor of the DAG‐PKC pathway, and shows promise in reducing vascular complications in animal models of diabetes. Given the overwhelming evidence indicating a role for PKC activation in contributing to the development of diabetic vascular complications, pharmacological therapies that can modulate this pathway, particularly with PKC isoform selectivity, show great promise for treatment of vascular complications, even in the presence of hyperglycemia.Diabet. Med. 18, 945–959 (2001)
Short‐form HLA‐DP typing with 48 primer mixes using the polymerase chain reaction and sequence‐specific primers
Authors: Davidson J. A. , Poulton K. V. 
Published: March 2003

SummaryWe have developed a short‐form SSP‐based HLA‐DP typing system for routine use adapted from a comprehensive HLA‐DP typing method described by Gilchrist et al. (1998). Our short‐form system detects 93 alleles, including the 18 most common HLA‐DPB1 alleles and eight HLA‐DPA1 alleles. The primer mixes described were tested using the PCR‐SSP Manager (Bunce et al., 1998) database to confirm the specificity of selected primers, and to detect potentially ambiguous amplifications. This short‐form HLA‐DP typing system was validated using 50 fully typed samples obtained through the UCLA International DNA Exchange. All samples gave 100% concordance with the consensus type. Our laboratory routinely uses a PCR‐SSP based system of 48 primer mixes for HLA‐DRB and HLA‐DQB typing. The advantage of the short‐form HLA‐DP typing system described here is that the additional 48 HLA‐DP primer mixes required can be included on the second half of a 96‐well format tray. This method now enables a full HLA class II typing at the level of allele group resolution in 21/2 h.
Effects of the flavonoid baicalin and its metabolite baicalein on androgen receptor expression, cell cycle progression and apoptosis of prostate cancer cell lines
Authors: Chen S. , Ruan Q. , Bedner E. , Deptala A. , Wang X. , Hsieh T.C. , Traganos F. , Darzynkiewicz Z. 
Published: March 2003

Abstract.Recent studies on the Chinese herbal medicine PC SPES showed biological activities against prostate cancer in vitro, in vivo and in patients with advanced stages of the disease. In investigating its mode of action, we have isolated a few of the active compounds. Among them, baicalin was the most abundant (about 6%) in the ethanol extract of PC SPES, as determined by HPLC. Baicalin is known to be converted in vivo to baicalein by the cleavage of the glycoside moiety. Therefore, it is useful to compare their activities in vitro. The effects of baicalin and baicalein were studied in androgen‐positive and ‐negative human prostate cancer lines LNCaP and JCA‐1, respectively. Inhibition of cell growth by 50% (ED50) in LNCaP cells was seen at concentrations of 60.8 ± 3.2 and 29.8 ± 2.2 µm baicalin and baicalein, respectively. More potent growth inhibitory effects were observed in androgen‐negative JCA‐1 cells, for which the ED50 values for baicalin and baicalein were 46.8 ± 0.7 and 17.7 ± 3.4, respectively. Thus, it appears that cell growth inhibition by these flavonoids is independent of androgen receptor status. Both agents (1) caused an apparent accumulation of cells in G1 at the ED50 concentration, (2) induced apoptosis at higher concentrations, and (3) decreased expression of the androgen receptor in LNCaP cells.