bluuebunny/crossref_metadata_2025 huggingface dataset:
Young Adolescents' Experiences with Parents and Friends: Exploring the Connections*
Authors: Updegraff Kimberly A. , Madden‐Derdich Debra A. , Estrada Ana Ulloa , Sales Lara J. , Leonard Stacie A.
Published: August 2005

Drawing on social learning and structural family theories, we examined the connections between young adolescents' experiences with their mothers and fathers and their best friends. Young adolescents (N= 143) from Latino and European American families were recruited from a local school district in a rural southwestern community. Adolescents described the emotional qualities of their relationship with each parent, the nature of the parent‐adolescent hierarchy, and their experiences with their best friend. Findings revealed links between European American boys' experiences with their fathers and their best friends and between the nature of the parent‐adolescent hierarchy and both boys' and girls' intimacy with their best friends. The discussion highlights implications for intervention in early adolescence.
Clomiphene Citrate Effects on Testosterone/Estrogen Ratio in Male Hypogonadism
Authors: Shabsigh Ahmad , Kang Young , Shabsign Ridwan , Gonzalez Mark , Liberson Gary , Fisch Harry , Goluboff Erik
Published: August 2005

Aim

Symptomatic late–onset hypogonadism is associated not only with a decline in serum testosterone, but also with a rise in serum estradiol. These endocrine changes negatively affect libido, sexual function, mood, behavior, lean body mass, and bone density. Currently, the most common treatment is exogenous testostosterone therapy. This treatment can be associated with skin irritation, gynecomastia, nipple tenderness, testicular atrophy, and decline in sperm counts. In this study we investigated the efficacy of clomiphene citrate in the treatment of hypogonadism with the objectives of raising endogenous serum testosterone (T) and improving the testosterone/estrogen (T/E) ratio.

Methods

Our cohort consisted of 36 Caucasian men with hypogonadism defined as serum testosterone level less than 300 ng/dL. Each patient was treated with a daily dose of 25 mg clomiphene citrate and followed prospectively. Analysis of baseline and follow–up serum levels of testosterone and estradiol levels were performed.

Results

The mean age was 39 years, and the mean pretreatment testosterone and estrogen levels were 247.6 ± 39.8 ng/dL and 32.3 ± 10.9, respectively. By the first follow–up visit (4–6 weeks), the mean testosterone level rose to 610.0 ± 178.6 ng/dL (P < 0.00001). Moreover, the T/E ratio improved from 8.7 to 14.2 (P < 0.001). There were no side effects reported by the patients.

Conclusions

Low dose clomiphene citrate is effective in elevating serum testosterone levels and improving the testosterone/estadiol ratio in men with hypogonadism. This therapy represents an alternative to testosterone therapy by stimulating the endogenous androgen production pathway.
Development of a New Geometric Bicycle Saddle for the Maintenance of Genital–Perineal Vascular Perfusion
Authors: Breda G. , Piazza N. , Bernardi V. , Lunardon E. , Caruso Adara
Published: August 2005

Objective

To identify a bicycle saddle model for cyclists who cover long distances, to minimally reduce the compression on the structures of the pelvic floor, thereby protecting blood perfusion of the penis and avoiding possible consequences on penile erection.

Materials and Methods

A comparison between a new geometric development of a bicycle saddle model (SMP) and one of the more frequently used models by professional cyclists was made. The measurement of the partial pressure of penile transcutaneous oxygen (PtcO2) in 29 healthy voluntary cyclists was recorded to investigate the differences of compression from two different saddles on the vascular structures of the perineum. The PtcO2 was recorded at 3 and 10 minutes in conditions of static sitting. Then, the values of PtcO2 were recorded for 15 minutes while the cyclists were in a 60–degree position and in stable hemodynamic conditions.

Results

A t–test was performed to measure the level of confidence. The clear superiority of the SMP saddle in preventing vascular compression of the perineal structures was demonstrated to be statistically significant.

Conclusion

The experiment validated the effectiveness of the SMP saddle in limiting the compression on the pelvic floor. In addition, the SMP saddle introduces compatible seat dimensions that cyclists prefer to cover long distances.
Only the Nose Knows: Penile Hemodynamic Study of the Perineum–Saddle Interface in Men with Erectile Dysfunction Utilizing Bicycle Saddles and Seats with and Without Nose Extensions
Authors: Munarriz Ricardo , Huang Vincent , Uberoi Jayant , Maitland Scott , Payton Terry , Goldstein Irwin
Published: August 2005

Purpose

To investigate the differential impact of straddles (Ans and Bns) and noseless two–cheek seats (Antcs and Bntcs) on penile hemodynamics and perineal compressive forces in subjects who cycle in a stationary bicycle.

Materials and Methods

Subjects underwent cavernosal artery peak systolic velocity (CAPSV) measurements after intracavernosal injection of vasoactive agents while supine, sitting upright on an examination table, straddling a saddle, sitting on a seat, and again supine. Mean perineal compression pressures recorded while straddling the saddles were compared with those while sitting upright.

Results

No differences were found in right and left CAPSV values while supine, sitting upright on an examination table, sitting on a seat, and supine again. Right/left CAPSV (cm/second) values straddling Ans and saddle Bns (0.7 ± 2.9/1.5 ± 6.2 and 0/0, respectively) were significantly lower than values obtained while sitting on Antcs and Bntcs (25.6 ± 13.4/23.8 ± 12.0 and 17.3 ± 6.4/18.3 ± 6.5, respectively) (P < 0.001). Mean perineal compression pressures (mm Hg) on Ans and saddle Bns (315.2 ± 39 and 387.9 ± 64.3, respectively) were significantly higher than values obtained while sitting upright on an examination table (47.6 ± 5.2 and 46.0 ± 8.1, respectively) (P < 0.001).

Conclusions

We have identified an objective test to assess if an individual bicycle rider, sitting on a certain shape of bicycle saddle or seat generates sufficient compressive forces at the perineal–saddle interface to obstruct cavernosal arterial inflow. This study also demonstrated that straddling bicycle saddles with nose extensions is associated with perineum–saddle interface compressive pressures that exceed systolic perfusion pressures, significantly diminishing penile hemodynamics.
Efficacy and Safety of Oral Tadalafil in the Treatment of Men in Canada with Erectile Dysfunction: A Randomized, Double–Blind, Parallel, Placebo–Controlled Clinical Trial
Authors: Carrier Serge , Brock Gerald B. , Pommerville Peter J. , Shin Janey , Anglin Greg , Whitaker Steven , Beasley Charles M.
Published: August 2005

Introduction

Erectile dysfunction (ED) is a highly prevalent, often undertreated condition.

Aim

This 12–week, double–blind, parallel, placebo–controlled study was conducted at 25 sites in Canada to evaluate the efficacy and safety of oral tadalafil, a phosphodiesterase type 5 inhibitor, for the treatment of ED.

Methods

Men with ED of organic, psychogenic, or mixed etiology were stratified by baseline ED severity then randomly assigned to placebo (N = 50), tadalafil 10 mg (N = 103), or tadalafil 20 mg (N = 100), taken as needed (maximum, once daily).

Main Outcome Measures

Efficacy was assessed by the International Index of Erectile Function (IIEF), a Sexual Encounter Profile diary, and a global assessment question (GAQ).

Results

Tadalafil 10 mg and tadalafil 20 mg significantly improved erectile function compared with placebo (P < 0.001, all measures). At end point, the mean IIEF erectile function (EF) domain scores were 14.5, 21.2, and 23.3 of a possible score of 30 for placebo, tadalafil 10 mg, and tadalafil 20 mg, respectively. Patients treated with tadalafil reported greater change from baseline on the IIEF EF domain score compared with placebo, regardless of baseline ED severity. During treatment, the mean per–patient proportion of successful intercourse attempts was higher for tadalafil 10 mg and 20 mg than for placebo (placebo, 31.9%; tadalafil 10 mg, 56.7%; and tadalafil 20 mg, 61.5%), and a greater proportion of patients reported improved erections with tadalafil (GAQ; placebo, 22.0%; tadalafil 10 mg, 67.0%; tadalafil 20 mg, 79.0%). Fifty percent and 62% of patients treated with tadalafil 10 mg and 20 mg, respectively, achieved successful sexual intercourse after their first dose, compared with 31% with placebo. Treatment–emergent adverse events were generally mild or moderate.

Conclusion

Tadalafil was an effective, well–tolerated therapy for ED of broad–spectrum etiology and severity.
Bicycle Riding and Erectile Dysfunction: An Increase in Interest (and Concern)
Authors: Huang Vincent , Munarriz Ricardo , Goldstein Irwin
Published: August 2005

Introduction

From 1999 to 2004, there had been 21 publications from multiple medical specialties (sexual medicine, urology, neurology, cardiology, biomedical engineering, sports medicine, emergency medicine, and officials from the National Institute for Safety and Occupational Health) investigating the relationship between bicycle riding and erectile dysfunction (ED). In the previous 18 years, there have been 14 such studies.

Aim

The primary aim was to summarize accumulating data on the safety of bicycle riding based on medical evidence categorized by levels of evidence, including case reports, observational studies, case control studies, mechanistic studies, and population–based epidemiologic investigations. The secondary aim was to address the concerns of bicyclists and propose measures to minimize the risk of ED associated with bicycle riding.

Methods

An English–language medical literature review was made of publications in peer review journals from 1981 to 2004, including published abstract presentations at major medical meetings.

Main Outcome Measure

Ranked published epidemiologic data on bicycle riding and ED.

Results

Bicycle riding more than 3 hours per week was an independent relative risk (RR = 1.72) for moderate to severe ED. In case control studies, the prevalence of moderate to severe ED in bicyclists was 4.2% and 4% vs. age–matched runners 1.1% (P ≥ 0.018) and swimmers 2% (P = 0.05), respectively. Therefore, bicycle riders should take precautionary measures to minimize the risk of ED associated with bicycle riding: change the bicycle saddle with a protruding nose to a noseless seat, change the posture to a more upright/reclining position, change the material of the saddle (GEL), and tilt the saddle/seat downwards.

Conclusions

The mechanism is hypothetically related to the rider interaction with the bicycle saddle at the perineum–saddle interface. Straddling bicycle saddles with a nose extension is associated with suprasystolic perineal compression pressures, temporarily occluding penile perfusion and potentially inducing endothelial injury and vasculogenic ED.
Idiopathic Stuttering Priapism Treated Successfully with Low–Dose Ethinyl Estradiol: A Single Case Report
Authors: Shamloul Rany , Nashaar el Abdelrahman
Published: August 2005

Introduction

Chronic priapism represents a challenging therapeutic dilemma. Inadequate or deferred treatment can result in impaired quality of life and permanent erectile dysfunction. The etiology of stuttering priapism is speculated to be initially an ischemic injury that damages the neurologic and/or endothelial–mediated mechanisms that normally regulate detumescence and maintain penile flaccidity.

Aim

We report a case of stuttering priapism successfully treated with low–dose ethinyl estradiol.

Methods

A 51–year–old man presented with idiopathic stuttering priapism. Treatment was given in the form of low–dose ethinyl estradiol for six consecutive weeks.

Results

Moderate lowering of testosterone level and effective prevention of priapism for at least 6 months with retaining of erectile function.

Conclusion

The use of low–dose estrogen shows a potential to be an effective and relatively rapid treatment option for some cases of idiopathic stuttering priapism.
The Impact of Intralesional Interferon α–2b Injection Therapy on Penile Hemodynamics in Men with Peyronie’s Disease
Authors: Kendirci Muammer , Usta Mustafa F. , Matern Richard V. , Nowfar Sepehr , Sikka Suresh C. , Hellstrom Wayne J.G.
Published: August 2005

Introduction

Penile duplex Doppler ultrasound (PDDU) is currently the preferred method for the functional evaluation of penile hemodynamics. PDDU may be used to monitor objectively changes in penile vascular parameters in men who undergo treatment for Peyronie’s disease (PD), including intralesional interferon alpha–2b (IFN α–2b).

Aim

To investigate the impact of intralesional IFN α–2b therapy for PD on penile hemodynamics by using PDDU and to assess the objective role of PDDU in monitoring treatment outcomes.

Materials and Methods

Thirty–nine patients (20 in the placebo and 19 in the IFN α–2b treatment arm) were enrolled in this prospective, placebo–controlled, parallel study. Patients received either 10 mL saline or 5 × 106 units of IFN α–2b intralesional injections every other week for a total of six injections. Patients in each group were evaluated at baseline and after completion of treatment regarding changes in penile hemodynamic parameters, penile curvature, plaque size and density, pain on erection, and erectile function. Specific published criteria were used for PDDU measurements. Outcomes were statistically compared between each group by using Mann–Whitney U and chi–square tests.

Results

The mean age of the patients and the duration of PD were similar in both groups. The improvement in penile blood flow was significantly greater in IFN α–2b–treated patients than those in the placebo group. The number with the nonvascular classification increased significantly in the IFN α–2b arm from 31.5% to 57.8%. Additionally, improvements in penile curvature, plaque size and density, and pain on erection were better in the IFN α–2b group compared with the control. No significant improvement was observed in the erectile function domain in either group.

Conclusion

This study reveals that intralesional IFN α–2b injections have a significant benefit on penile hemodynamic parameters. Moreover, intralesional IFN α–2b is an effective, minimally invasive treatment for PD, and PDDU is a useful adjunct to monitor objectively changes in penile vascular parameters.
T–Type (α1G) Low Voltage–Activated Calcium Channel Interactions with Nitric Oxide–Cyclic Guanosine Monophosphate Pathway and Regulation of Calcium Homeostasis in Human Cavernosal Cells
Authors: Zeng Xiangbin , Keyser Brian , Li Ming , Sikka Suresh C.
Published: August 2005

Introduction

Nitric oxide–cyclic guanosine monophosphate (NO–cGMP)–mediated relaxation of cavernosal smooth muscle during erection is accompanied by a decrease in intracellular calcium concentrations ([Ca2+]i). However, it is not known whether and how an increase in [Ca2+]i is responsible for (i) initiating smooth muscle contraction/detumescence following relaxation; and (ii) maintaining the penis in a flaccid state under nonstimulating conditions.

Aim

To elucidate (i) the mechanism(s) of [Ca2+]i homeostasis regulation in human cavernosal smooth muscle cells (HCSMC); and (ii) how NO–cGMP interacts with such [Ca2+]i homeostasis.

Methods

We evaluated the expression and function of both T–type and L–type Ca2+ channels in HCSMC by employing selective probes/inhibitors using various cellular and molecular techniques (e.g., reverse transcriptase and real–time polymerase chain reaction, cell proliferation assay, fura–2 Ca2+ fluorescence spectroscopy, enzyme–linked immuno–absorbent assay (ELISA)).

Main Outcome Measure

We have demonstrated for the first time significant interactions of NO–cGMP with the T–type (α1G) Ca2+ channel in HCSMC.

Results

Our results suggest that in addition to NO–induced rapid and transient decrease in [Ca2+]i that results in smooth muscle relaxation, NO–cGMP also enhanced mRNA expression of the T–type (α1G) Ca2+ channel resulting in delayed elevation of [Ca2+]i. This could be abolished by a selective T–channel blocker, NNC 55–0396. Another unique finding of this study is that dose–dependent HCSMC proliferation in vitro by NO is associated with the activation of the T–type (α1G) Ca2+ channel that regulates [Ca2+]i homeostasis in these cells.

Conclusions

Human cavernosal cells express T–type (α1G) Ca2+ channels that are involved in maintaining [Ca2+]i homeostasis and regulation of NO–cGMP–induced smooth muscle relaxation–contraction responsible for penile erection, flaccidity, and tonicity. Targeting these Ca2+ channels may (i) associate various comorbidities with the onset of erectile dysfunction; (ii) provide a biochemical basis for differences between therapeutic profiles of various phosphodiesterase type 5 inhibitors, especially in nonresponders to current therapy; and (iii) provide biochemical basis in understanding mechanism(s) of drug tolerance.
Improving the Sexual Quality of Life of Couples Affected by Erectile Dysfunction: A Double–Blind, Randomized, Placebo–Controlled Trial of Vardenafil
Authors: Fisher William A. , Rosen Raymond C. , Mollen Martin , Brock Gerald , Karlin Gary , Pommerville Peter , Goldstein Irwin , Bangerter Keith , Bandel Tiemo-Joerg , Derogatis Leonard R. , Sand Michael
Published: August 2005

Introduction

Erectile dysfunction (ED) has a dual negative impact on men and their female partners; both are likely to face a drop in sexual quality of life and challenges to their intimate relationship as couples’ sexual activities are curtailed by the loss of erectile function.

Aim

The primary objective of this study was to compare the efficacy of vardenafil vs. placebo in terms of success of maintenance of erection in men with ED and improvement of their female partner’s sexual quality of life.

Methods

This was a randomized, double–blind, multicenter, flexible–dose, parallel–group comparison of vardenafil vs. placebo for 12 weeks in men (≥18 years) with ED of ≥ 6 months duration, and their female partners.

Main Outcome Measures

Changes in patient’s overall response rate to Sexual Encounter Profile question 3 (SEP3) “Did your erection last long enough for you to have sexual intercourse?” and female partner’s response to the quality of life domain of the modified Sexual Life Quality Questionnaire (mSLQQ–QOL) at last observation carried forward (LOCF) were considered the primary efficacy measures. In addition, patient’s response to SEP2 “Were you able to insert your penis into your partner’s vagina?,” the erectile function domain of the International Index of Erectile Function (IIEF–EF) and patient’s mSLQQ–QOL score were also assessed.

Results

Compared with placebo, vardenafil significantly improved overall least square (LS) mean per–patient SEP3 success rate (28% vs. 68%; P < 0.0001) and partner’s LS mean (standard error [SE]) mSLQQ–QOL score at LOCF (32.14 [3.24] vs. 65.80 [3.10]; P < 0.0001). In addition, compared with placebo, vardenafil also improved overall LS mean per–patient SEP2 success rate (47% vs. 80%; P < 0.0001), LS mean (SE) IIEF–EF scores at LOCF (12.7 [0.8] vs. 22.8 [0.8]; P < 0.0001) and patient’s LS mean (SE) mSLQQ–QOL (28.37 [3.46] vs. 63.85 [3.28]; P < 0.0001) at LOCF.

Conclusions

Vardenafil improved erectile function in men with ED and improved the sexual quality of life of the couple.
Assessment of Cerebrocortical Regions Associated with Sexual Arousal in Premenopausal and Menopausal Women by Using BOLD–Based Functional MRI
Authors: Jeong Gwang-Woo , Park Kwangsung , Youn Gahyun , Kang Heoung-Keun , Kim Hyung Joong , Seo Jeong-Jin , Ryu Soo-Bang
Published: August 2005

Purpose

The aim of this study was to compare the cerebral regions associated with sexual arousal between premenopausal and menopausal women by using functional magnetic resonance imaging (f MRI).

Materials and Methods

Ten premenopausal and 10 menopausal women underwent fMRI on a 1.5T MR scanner using the blood oxygen level dependent technique. To identify the activated brain regions associated with sexual response, brain activation was assessed during 1 minute of a nonerotic film, followed by 4 minutes of an erotic film.

Results

The overall activation ratios of the premenopausal women were greater than those of the menopausal women by approximately 8% on average. The limbic, temporal association areas, and parietal lobe showed greater enhancement of signal intensities in premenopausal women. However, signal enhancement in the genu of the corpus callosum and superior frontal gyrus was dominant in menopausal women.

Conclusions

The activated brain center associated with visually evoked sexual arousal showed qualitative and quantitative differences between premenopausal and menopausal women.
Linearization in Analysis of Nonlinear Stochastic Systems, Recent Results—Part II: Applications
Authors: Socha L.
Published: August 2005

The purpose of this part of the paper is to provide a review of recent results (1991–2003) in the applications of statistical and equivalent linearization in the analysis of structure and mechanical nonlinear stochastic dynamic systems. Both the applications in “traditional fields” of engineering and a few examples from new fields are reported. Traditional fields include vibration of construction elements, such as beams, frames, shells, and plates, and also vibration of complex structures under earthquake or wind or wave stochastic excitations, or a combination of earthquake and wind or wind and wave excitations. Typical constructions are multistory structures, offshore platforms, and vehicle models. In the paper several examples from new fields, such as vibration of wood structures, block rocking, rainfall-runoff modeling, a squeeze film model, and an astronomy model are reviewed. A discussion of typical advantages and faults of linearization techniques and some general conclusions close the paper. There are 121 references cited in this review article.
DIRECT DETECTION OF SUPERSYMMETRIC DARK MATTER: THEORETICAL RATES FOR TRANSITIONS TO EXCITED STATES
Authors: VERGADOS J. D. , QUENTIN P. , STROTTMAN D.
Published: August 2005

The recent WMAP data have confirmed that exotic dark matter together with the vacuum energy (cosmological constant) dominate in the flat universe. Supersymmetry provides a natural dark matter candidate, the lightest supersymmetric particle (LSP). Thus direct dark matter detection is central to particle physics and cosmology. Most of the research on this issue has hitherto focused on the detection of the recoiling nucleus. In this paper, we study transitions to the excited states, focusing on the first excited state at 50 keV of Iodine A=127. We find that the transition rate to this excited state is ≼10 percent of the transition to the ground state. So, in principle, the extra signature of the gamma ray following its de-excitation can be exploited experimentally.
EQUATION OF STATE FOR NUCLEAR MATTER BASED ON DENSITY DEPENDENT EFFECTIVE INTERACTION
Authors: BASU D. N.
Published: August 2005

An interesting method of obtaining the equation of state for nuclear matter, from a density dependent M3Y interaction, by minimizing the energy per nucleon is described. The density dependence parameters of the interaction are obtained by reproducing the saturation energy per nucleon and the saturation density of spin and isospin symmetric cold infinite nuclear matter. The nuclear matter equation of state thus obtained is then used to calculate the pressure, energy density, nuclear incompressibility and velocity of sound in nuclear medium. The results obtained are in good agreement with experimental data and provide a unified description of radioactivity, scattering and nuclear matter.
PROTON–4He ELASTIC SCATTERING AT ~ 1 GeV
Authors: KHAN Z. A. , SINGH MINITA
Published: August 2005

Based on the (spin-independent) Sugar–Blanckenbecler eikonal expansion for the T-matrix, we parametrize the (spin-dependent) NN amplitude (SNN) which successfully describes the pp and pn elastic scattering observables at ~ 1 GeV up to the available momentum transfers. Using SNN, we calculate the differential cross-section, polarization, and spin-rotation function of ~ 1 GeV protons on 4 He within the framework of the Glauber model. The analysis also includes the phase variation in the NN amplitude. It is found that the use of SNN, in comparision with the usually parametrized one-term amplitude, improves the agreement with the experimental data. The introduction of a global phase variation provides only a slight improvement over the results with a constant phase. However, if we allow different phases in the central- and spin-dependent parts of the NN amplitude, the agreement with the polarization data improves further without affecting the differential cross-section results.
BOUNDARY PROBLEMS FOR FRACTIONAL LAPLACIANS
Authors: GUAN QING-YANG , MA ZHI-MING
Published: August 2005

By making use of the reflected α-stable process on a closed domain of ℝn and its killed subprocess on part of the domain, in this paper we study the boundary value problem for the Schrödinger type equation of a fractional Laplacian. The boundary condition is imposed partly follow Dirichlet condition and partly follow Neuman condition. We obtain the existence and the uniqueness resutls. The solution is expressed as a functional of the reflected α-stable process.
Genetic manipulation of 11β-hydroxysteroid dehydrogenases in mice
Authors: Paterson Janice M. , Seckl Jonathan R. , Mullins John J.
Published: August 2005

11β-Hydroxysteroid dehydrogenases (HSDs) interconvert active 11-hydroxy glucocorticoids (cortisol, corticosterone) and their inert 11-keto derivatives (cortisone, 11-dehydrocorticosterone). 11β-HSD type 1 is a predominant reductase that regenerates active glucocorticoids in expressing cells, thus amplifying local glucocorticoid action, whereas 11β-HSD type 2 catalyzes rapid dehydrogenation, potently inactivating intracellular glucocorticoids. Both isozymes thus regulate receptor activation by substrate availability. Spatial and temporal regulation of expression are important determinants of the physiological roles of 11β-HSDs, with each isozyme exhibiting a distinct, tissue-restricted pattern together with dynamic regulation during development and in response to environmental challenges, including diet and stress. Transgenic approaches in the mouse have contributed significantly toward an understanding of the importance of these prereceptor regulatory mechanisms on corticosteroid receptor activity and have highlighted its potential relevance to human health and disease. Here we discuss current ideas of the physiological roles of 11β-HSDs, with emphasis on the key contributions made by studies of 11β-HSD gene manipulation in vivo.
Possible neural mediation of the central effects of oxytocin on uterine motility
Authors: Benoussaidh Anissa , Maurin Yves , Rampin Olivier
Published: August 2005

The central nervous system contains the nuclei at the origin of autonomic and neuroendocrine pathways to the uterus. Although the anatomical basis of these pathways is known, the conditions of their recruitment and their interactions in the context of copulation remain to be explored. We tested the hypothesis that some central mechanisms could simultaneously recruit both pathways to the uterus. In this aim, we recorded intrauterine pressure changes in anesthetized female rats at the estrus stage after intracerebroventricular (ICV) administration of oxytocin (OT). Doses of 0.3–300 ng elicited increases of frequency and amplitude of uterine contractions. These effects were partly mimicked by the OT agonist [Thr4,Gly7]OT but not by arginine vasopressin. They were blocked by the OT receptor antagonist atosiban delivered either ICV or intravenously. The latter suggests that ICV OT activated the systemic release of OT. The effects of OT were also blocked by hexamethonium, a ganglionic blocking agent, by atropine, a muscarinic receptor antagonist, and by Nω-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthesis. The results reveal that ICV OT recruits autonomic efferent pathways to the uterus. These results support our hypothesis that the activation of central nuclei can promote uterine contractility, and that OT may be a central coordinator of autonomic and neuroendocrine pathways. The hypothalamus, the source of direct OT-ergic projections to the pituitary, the brain stem, and the spinal cord, may be a target of central OT.
Comparison of Anterior Cingulate and Primary Somatosensory Neuronal Responses to Noxious Laser-Heat Stimuli in Conscious, Behaving Rats
Authors: Kuo Chung-Chih , Yen Chen-Tung
Published: August 2005

In this study, we investigated single-unit responses of the primary sensorimotor cortex (SmI) and anterior cingulate cortex (ACC) to noxious stimulation of the tail of the rat. The influences of morphine on these nociceptive responses were also compared. Multiple single-unit activities were recorded from two eight-channel microwire arrays chronically implanted in the tail region of the SmI and ACC, respectively. CO2laser-heat irradiation of the middle part of the tail at an intensity slightly higher than that causing a maximal tail flick response was used as a specific noxious stimulus. Examined individually, ACC neurons were less responsive than SmI neurons to laser-heat stimulus, in that only 51% of the ACC units ( n = 125) responded compared with 88% of the SmI units ( n = 74). Among these responsive ACC units, many had a very long latency and long-lasting excitatory type of response that was seldom found in the SmI. When ensemble activities were examined, laser heat evoked both short- (60 ∼ 150 ms) and long-latency (151 ∼ 600 ms) responses in the SmI and ACC. Latencies of both responses were longer in the ACC. Furthermore, a single dose of 2.5–10 mg/kg morphine intraperitoneally suppressed only the long latency response in the SmI, but significantly attenuated both responses in the ACC. These effects of morphine were completely blocked by prior treatment with the opiate receptor blocker, naloxone. These results provide further evidence suggesting that the SmI and ACC may play different roles in processing noxious information.
Commissural Excitation and Inhibition by the Superior Colliculus in Tectoreticular Neurons Projecting to Omnipause Neuron and Inhibitory Burst Neuron Regions
Authors: Takahashi M. , Sugiuchi Y. , Izawa Y. , Shinoda Y.
Published: August 2005

Previous electrophysiological studies have shown that the commissural connections between the two superior colliculi are mainly inhibitory with fewer excitatory connections. However, the functional roles of the commissural connections are not well understood, so we sought to clarify the physiology of tectal commissural excitation and inhibition of tectoreticular neurons (TRNs) in the “fixation ” and “saccade ” zones of the superior colliculus (SC). By recording intracellular potentials, we identified TRNs by their antidromic responses to stimulation of the omnipause neuron (OPN) and inhibitory burst neuron (IBN) regions and analyzed the effects of stimulation of the contralateral SC on these TRNs in anesthetized cats. TRNs in the caudal SC (saccade neurons) projected to the IBN region, and received mono- or disynaptic inhibition from the entire rostrocaudal extent of the contralateral SC. In contrast, TRNs in the rostral SC projected to the OPN or IBN region and received monosynaptic excitation from the most rostral level of the contralateral SC, and mono- or disynaptic inhibition from its entire rostrocaudal extent. Among the rostral TRNs with commissural excitation, IBN-projecting TRNs also projected to Forel's field H (vertical gaze center), suggesting that they were most likely saccade neurons related to vertical saccades. In contrast, TRNs projecting only to the OPN region were most likely fixation neurons. Most putative inhibitory neurons in the rostral SC had multiple axon branches throughout the rostrocaudal extent of the contralateral SC, whereas excitatory commissural neurons, most of which were rostral TRNs, distributed terminals to a discrete region in the rostral SC.
Repetitive Light Stimulation Inducing Glycine Receptor Plasticity in the Retinal Neurons
Authors: Shen Wen
Published: August 2005

Neurotransmitter receptor plasticity is a mechanism that can regulate the temporal and intensity encoding of a synapse. While this has been extensively studied as a mechanism of learning, less is known about such processes in sensory systems. This study examines modulation of glycine receptor function at the first synapse in the retina. It was found that horizontal cells, which are postsynaptic to photoreceptors, have glycine receptor currents that are enhanced when internal calcium is elevated. This can be achieved by glutamatergic synaptic input or by activation of voltage-gated calcium channels. When the retina was maintained in a dark-adapted state, the calcium levels in horizontal cells were relatively low. After a series of brief light stimuli, the internal calcium concentration in horizontal cells was elevated, and the glycine currents were faster and greater in amplitude. The increase of internal calcium levels was caused by increased transmitter release from photoreceptors. Thus glycine receptor function is state dependent and can be rapidly altered by synaptic input from photoreceptors. Light stimulation drives glycine receptor plasticity in the retinal neural network.
Novel Mass Spectrometric Methods for Evaluation of Plasma Angiotensin Converting Enzyme 1 and Renin Activity
Authors: Elased Khalid M. , Cool David R. , Morris Mariana
Published: August 2005

This article demonstrates the applicability of quantitative proteomics to assays of proteolytic enzyme activity. A novel assay was developed for measurement of renin and angiotensin-converting enzyme (ACE) activity in plasma. The method was validated in animal models associated with alterations of the renin angiotensin system (RAS). Using surface-enhanced laser desorption/ionization time of flight mass spectrometry (SELDI-TOF-MS) with a ProteinChip Array technology, plasma renin and ACE1 could be measured in <0.5 μL of plasma. Plasma is incubated with peptide substrates for renin and ACE, tetradecapeptide (TDP), and angiotensin I (Ang I), respectively. The reactions mixtures are spotted onto the ProteinChip WCX2 and detected using SELDI-TOF-MS. Peak height or area under curve for TDP, Ang I, and angiotensin II (Ang II) peaks are measured. There was a linear relationship between disappearance of substrate and appearance of products for both renin and ACE (
R
2
=0.95 to 0.98). ACE1 activity was blocked with chelating agents (EDTA and 1,10 phenanthrolene), indicating action of a metalloprotease. The ACE1 inhibitor, captopril, selectively blocked ACE1. Renin activity was specifically blocked with renin inhibitor and was not affected by phenanthrolene or captopril. Animal models tested were Ang AT1a receptor-deficient and streptozotocin (STZ) diabetic mice. Plasma renin activity was increased >2-fold in AT1a
−/−
as compared with AT1a
+/+
. In STZ diabetic mice, ACE1 was increased 2-fold as compared with controls. The advantage of the method is that it is tagless, does not require additional purification steps, and is extremely sensitive. The approach can be multiplexed and used for identification of novel substrates/inhibitors of the RAS.
Coffee Blunts Mental Stress–Induced Blood Pressure Increase in Habitual but Not in Nonhabitual Coffee Drinkers
Authors: Sudano Isabella , Spieker Lukas , Binggeli Christian , Ruschitzka Frank , Lüscher Thomas F. , Noll Georg , Corti Roberto
Published: August 2005

Coffee is widely consumed, especially during mental stress conditions. Cardiovascular impact of coffee remains debated because the underlying mechanisms of action are complex. We reported previously differential cardiovascular stimulation of coffee at rest depending on habitual consumption. The present study was designed to evaluate the effects of coffee on cardiovascular response to mental stress. In 15 healthy volunteers (6 habitual, 9 nonhabitual coffee drinkers), we assessed the effect of mental stress on blood pressure (BP), heart rate (HR), and muscle sympathetic activity (MSA) before and after a triple espresso, intravenous caffeine, and placebo in the same subjects. Under baseline conditions, mental stress significantly increases MSA (+2.5±0.7 volts per minute; +14.1±10.3%), systolic (+11.6±4.1 mm Hg) and diastolic BP (+6.4±2.0 mm Hg), and HR (+9.6±1.8 minutes
−1
). In nonhabitual coffee drinkers, a triple espresso but not caffeine induced an additional increase in systolic BP (+9±6.3 mm Hg;
P
=0.003) during mental stress, whereas in habitual drinkers, the stress-induced BP increase was blunted (+4±3.9 mm Hg;
P
=NS). As a result, nonhabitual coffee drinkers experienced significantly higher BP during mental stress than habitual drinkers (151±17.9/83±5.6 mm Hg versus 130±7.8/74±6.7 mm Hg;
P
<0.05). Caffeine induced similar effects in habitual and nonhabitual coffee drinkers at rest and during mental stress. The response to the cold pressor test was not influenced by coffee drinking in both groups. In conclusion, in nonhabitual coffee drinkers, coffee enhances the cardiovascular response to mental stress with an additional increase in systolic BP, whereas in habitual drinkers, the response is blunted. Caffeine alone does not exert any potentiating effect, confirming that ingredients other than caffeine are partially responsible for the stimulating effect of coffee on the cardiovascular system.
Arterial Aging
Authors: Najjar Samer S. , Scuteri Angelo , Lakatta Edward G.
Published: August 2005

Age is the dominant risk factor for cardiovascular diseases. However, until recently, convincing mechanistic or molecular explanations for the increased cardiovascular risks conferred by aging have been elusive. Aging is associated with alterations in a number of structural and functional properties of large arteries, including diameter, wall thickness, wall stiffness, and endothelial function. Emerging evidence indicates that these age-associated changes are also accelerated in the presence of cardiovascular diseases, and that these changes are themselves risk factors for the appearance or progression of these diseases. In this review, the evidence demonstrating that arterial aging is accelerated in cardiovascular diseases and that accelerated arterial aging is a risk factor for adverse cardiovascular outcomes is briefly reviewed, and selected advances in vascular biology that provide insights into the mechanisms that may underlie the increased risks conferred by arterial aging are summarized. Remarkably, a host of biochemical, enzymatic, and cellular alterations that are operative in accelerated arterial aging have also been implicated in the pathogenesis and progression of arterial diseases. These vascular alterations are thus putative candidates that could be targeted by interventions aimed at attenuating arterial aging, similar to the lifestyle and pharmacological interventions that have already been proven effective. Therefore, the notion that aging is a chronological process and that its risky components cannot be modulated is no longer tenable. It is our hope that a greater appreciation of the links between arterial aging and cardiovascular diseases will stimulate further investigation into strategies aimed at preventing or retarding arterial aging.
Correlates of Systolic Hypertension in Patients With Chronic Kidney Disease
Authors: Agarwal Rajiv , Andersen Martin J.
Published: August 2005

Hypertension in patients with chronic kidney disease (CKD) is predominantly systolic. The contribution of risk factors for hypertension to the overall systolic blood pressure (BP) is unknown. To study the relationship between risk factors for hypertension and systolic BP in patients with CKD, 232 veterans (mean age 67 years; 96% men; 20% black; 39% with diabetes mellitus; estimated glomerular filtration rate [GFR] 48 mL/min per 1.73 m
2
) had clinic (routine and standardized measurements) and out-of-clinic (home and 24-hour ambulatory) BPs recorded. In multivariate analysis, using 17 risk factors, the log of the urine protein/creatinine ratio was the strongest predictor of systolic BP regardless of the BP measurement technique. The strength of the relationship between proteinuria and systolic BP was in the order ambulatory > home > standardized clinic > routine clinic BP measurement. Other independent predictors were age, race, and number of antihypertensive drugs used, and the model fit was better for out-of-clinic than clinic BP recordings. Estimated GFR was not an independent predictor of systolic BP by any technique. Nocturnal dipping was associated with higher estimated GFR, higher serum albumin, younger age, and less proteinuria. Proteinuria is the most important correlate of systolic BP in older men, the strongest relationship of which was with ambulatory and home systolic BP. Out-of-clinic BP recordings correlate better with target organ damage, as measured by proteinuria, and may be of greater clinical value than clinic BP recordings in predicting hypertension-related outcomes such as end-stage renal disease and death.
Adenosine Inhibits PDGF-Induced Growth of Human Glomerular Mesangial Cells Via A2BReceptors
Authors: Dubey Raghvendra K. , Gillespie Delbert G. , Mi Zaichuan , Jackson Edwin K.
Published: August 2005

The objectives of the present study were to determine whether adenosine attenuates proliferation of glomerular mesangial cells (GMCs), which adenosine receptor (AR) mediates the antimitogeneic actions of adenosine, and the cellular mechanisms by which adenosine inhibits growth of GMCs. Studies were conducted in both human and rat GMCs. Platelet-derived growth factor (PDGF)-BB (25 ng/mL) increased DNA synthesis ([3H]thymidine incorporation), cellular proliferation (cell number), collagen synthesis ([3H]proline incorporation), and mitogen-activated protein kinase (MAPK) activity, and these effects were attenuated by 2-chloroadenosine (nonselective AR agonist) and 5′-N-methylcarboxamidoadenosine (MECA; nonselective AR agonist), but not byN6-cyclopentyladenosine (selective A1AR agonist), AB-N-MECA (selective A3AR agonist), or CGS21680 (selective A2AAR agonist). KF17837 (selective A2A/BAR antagonist) and 1,3-dipropyl-8-p-sulfophenylxanthine (nonselective AR antagonist), but not 8-cyclopentyl-1,3-dipropylxanthine (selective A1AR antagonist), blocked the growth-inhibitory effects of 2-chloroadenosine and 5′-N-MECA. Antisense, but not sense or scrambled, oligonucleotides to the A2Breceptor increased both basal and PDGF-induced DNA synthesis, cell proliferation, and collagen synthesis, and the growth-inhibitory effects of 2-chloroadenosine, 5′-N-MECA, anderythro-9-(2-hydroxy-3-nonyl)adenine (inhibitor of adenosine deaminase) plus iodotubercidin (inhibitor of adenosine kinase) were abolished by antisense, but not scrambled or sense, oligonucleotides to the A2Breceptor. We conclude that adenosine causes inhibition of GMC growth by activating A2Breceptors coupled to inhibition of MAPK activity. A2Breceptors may play an important role in regulating glomerular remodeling associated with GMC proliferation. Pharmacological or molecular biologic activation of A2Breceptors may prevent glomerular remodeling associated with glomerulosclerosis, renal disease, and abnormal growth associated with hypertension and diabetes.
Sex Difference in Vascular Injury and the Vasoprotective Effect of Valsartan Are Related to Differential AT
2
Receptor Expression
Authors: Okumura Midori , Iwai Masaru , Ide Ayumi , Mogi Masaki , Ito Masaharu , Horiuchi Masatsugu
Published: August 2005

The angiotensin II type 2 (AT
2
) receptor is upregulated in pathological conditions such as vascular injury and exerts antagonistic effects against AT
1
receptor–mediated actions. We examined the possibility that the sex difference in vascular remodeling is associated with altered AT
2
receptor expression, which is located on the X chromosome. In this study, we examined this possibility by using AT
2
receptor–null (
Agtr2−
) mice. Vascular injury was induced by polyethylene cuff placement around the femoral artery of wild-type (
Agtr2+
) and
Agtr2−
mice. In
Agtr2+
mice, AT
2
receptor expression in the injured artery was enhanced, and this increase was greater in female than in male mice, with no significant difference in AT
1
receptor expression between male and female mice. Increases in neointimal formation, DNA synthesis, expression of monocyte chemoattractant protein-1, production of superoxide anion, and NADPH oxidase activity in the injured artery were attenuated in female compared with male mice. These parameters were augmented in
Agtr2−
mice, whereas the sex differences in these parameters were smaller in
Agtr2−
than in
Agtr2+
mice. Treatment with a nonhypotensive dose of the AT
1
receptor blocker valsartan decreased these parameters significantly in
Agtr2+
mice, and these inhibitory effects of valsartan were greater in female mice. This sex difference in valsartan’s inhibitory effect was less marked in
Agtr2−
mice. Our results suggest that the sex difference in response to vascular injury could be at least partially attributed to the exaggerated AT
2
receptor expression in the injured vessel in female mice.
Potassium Supplementation Reduces Cardiac and Renal Hypertrophy Independent of Blood Pressure in DOCA/Salt Mice
Authors: Wang Qing , Domenighetti Andrea A. , Pedrazzini Thierry , Burnier Michel
Published: August 2005

We have demonstrated previously that deoxycorticosterone acetate (DOCA)/salt induces cardiac hypertrophy and left ventricular dysfunction independent of blood pressure (BP) in 1–renin gene mice. Because these mice also develop hypokalemia and metabolic alkalosis caused by mineralocorticoid excess, we investigated whether correcting hypokalemia by dietary potassium supplementation would prevent the DOCA/salt-induced cardiac hypertrophy, cardiac dysfunction, and electrocardiographic changes in normotensive, 1–renin gene and hypertensive, 2–renin gene mice. All mice were studied after 5 weeks of DOCA and salt administration. Potassium was given by adding 0.4 or 0.6% KCl to the drinking water. Our results show that correction of hypokalemia and metabolic alkalosis prevents cardiac hypertrophy and normalizes cardiac function without affecting BP in normotensive, 1–renin gene mice. In hypertensive, 2–renin gene mice, potassium supplementation induces a significant decrease in BP. The decrease in BP and correction of kalemia are associated with a significant but partial correction of cardiac hypertrophy. In both group of mice, electrocardiographic alterations were measured after administration of DOCA/salt, which could be corrected by potassium supplementation. Thus, these results show that correction of hypokalemia and metabolic alkalosis does prevent the development of cardiac hypertrophy and normalizes cardiac function independent of BP in normotensive, 1–renin gene mice that receive excess mineralocorticoid and salt. In 2–renin gene, hypertensive mice, potassium supplementation also prevents the development of cardiac hypertrophy, but the effect cannot be separated from the decrease in BP.