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W D Steers

Publications and source records attributed to W D Steers.

At least 19 recordsLinked to original sources
PubMed2001

Treatment of aged rat sensory neurons in short-term, serum-free culture with nerve growth factor reverses the effect of aging on neurite outgrowth, calcium currents, and neuronal survival.

Impaired NGF production and release has been documented in aged animals, suggesting that decreased NGF receptor stimulation may be one factor contributing to neuronal dysfunction with aging. Other studies have suggested that aging may be associated with impaired intracellular responses to NGF. Because aging-associated neuronal dysfunction contributes to morbidity and mortality in the geriatric population, it is important to determine whether the effects of aging on sensory neuron function and survival are reversible. In the present study, we observed significantly decreased neurite outgrowth and neuronal survival in short-term cultures (0-96 h) of dorsal root ganglion (DRG) neurons from aged (>22 months) Fisher 344 x Brown Norway F1 hybrid rats, compared to young (4-6 month) and middle-aged (14 month) animals. From 24 to 96 h in culture, diminished survival of aged neurons appeared to be due to an increased rate of apoptotic cell death. DRG neurons from aged animals also exhibited significantly decreased whole cell, high-threshold voltage-dependent calcium currents, with a larger proportion of L-type current, compared to youthful and middle-aged animals. Treatment of aged DRG neurons with NGF restored neurite outgrowth, neuronal survival and calcium current amplitude and subtype distribution to those observed in youthful DRG neurons.

Animals↗
PubMed2001

Depression and incontinence.

The urologic literature suggests that there is an association between a variety of psychiatric disorders and incontinence. Most notably, depression is found in a significant percentage of patients with urinary incontinence. Depression also occurs in other conditions associated with urinary urge incontinence, such as aging and dementia, and in neurologic disorders such as normal pressure hydrocephalus. Correction of some neurologic disorders eliminates both depression and urge incontinence. Although chronic medical disorders such as urge incontinence may lead to depression, an alternative hypothesis is that these two conditions share a common neurochemical pathogenesis. Lowering monoamines such as serotonin and noradrenaline in the central nervous system (CNS) leads to depression and urinary frequency and a hyperactive bladder in experimental animals. Thus, depression may not only be the result of persistent urinary incontinence, but individuals with altered CNS monoamines could manifest both depression and an overactive bladder. The latter condition may lead to urge incontinence, urinary frequency, urgency, or enuresis. Uncovering further evidence for such a linkage could serve as the basis for the development of genetic markers and novel therapeutic interventions for these two conditions.

Depressive Disorder↗
PubMed2001

5alpha-reductase activity in the prostate.

The prostate gland depends on androgen stimulation for its development and growth. However, testosterone is not the major androgen responsible for growth of the prostate. Testosterone is converted to dihydrotestosterone (DHT) by the enzyme Delta(4), 3 ketosteroid, 5alpha-reductase in prostatic stromal and basal cells. DHT is primarily responsible for prostate development and the pathogenesis of benign prostatic hyperplasia (BPH). Inhibitors of 5alpha-reductase reduce prostate size by 20% to 30%. This reduction in glandular tissue is achieved by the induction of apoptosis, which is histologically manifested by ductal atrophy. Inhibition also diminishes the number of blood vessels in the prostate because of a reduction in vascular-derived endothelial growth factor. 5alpha-Reductase occurs as 2 isozymes, type 1 and type 2, with the prostate expressing predominantly the type-2 isozyme, and the liver and skin expressing primarily the type-1 isozyme. Patients have been identified with deficiencies in the type-2 5alpha-reductase, but not type 1. Knockout mice with the type-2 5alpha-reductase demonstrate a phenotype similar to that seen in men with 5alpha-reductase deficiency. Type-1 5alpha-reductase knockout male mice are phenotypically normal. Enzymatic activity for 5alpha-reductase or immunohistochemical detection has been noted in other genitourinary tissues, such as the epididymis, testes, gubernaculum, and corporal cavernosal tissue. Preputial skin predominately expresses the type-1 5alpha-reductase, whereas stromal cells in the seminal vesicle also express type-2 isozyme. However, epithelial cells in the epididymis, but not surrounding stroma, express type-1 5alpha-reductase. In addition to influencing prostatic growth, 5alpha-reductase also influences the expression of neuronal nitric-oxide synthase in the corpus cavernosum. The contribution of DHT in the serum, which is partially derived from type-1 5alpha-reductase in the liver and the small amount of type-1 5alpha-reductase in the prostate, may play a role in maintaining prostatic enlargement. Thus, in an effort to increase efficacy of treatment for BPH, clinical trials are under way using new drugs, such as GI-198745 (Glaxo-Wellcome, Research Triangle Park, NC), PNU 157706 (Pharmacia & Upjohn, Peapack, NJ), FR146687 (Fujisawa, Osaka, Japan), and LY 320236 (Lilly, Indianapolis, IN), which inhibit both the type-1 and type-2 5alpha-reductase.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2001

Introduction.

Explore the source record for details and available documents.

5-alpha Reductase Inhibitors↗
PubMed2001

Activation of the transcription factors nuclear factor-kappaB and activator protein-1 in bladder smooth muscle exposed to outlet obstruction and mechanical stretching.

PURPOSE: Transcriptional control of bladder genes in response to outlet obstruction, growth factors and mechanical force is poorly understood. We analyzed the effects of bladder obstruction, mechanical stretching and platelet derived growth factor on the activation of the major growth controlling transcription factors nuclear factor-kappaB and activator protein-1. MATERIALS AND METHODS: Complete outlet obstruction was created in female rats by proximal urethral ligation and bladders were harvested 3, 6 and 24 hours later, respectively. Bladder cells were grown in culture and stimulated with 10 ng./ml. platelet derived growth factor or 10 cycles per minute of mechanical stretching for 0.5 to 4 hours. Nuclear proteins were high salt extracted and incubated with 32phosphorus double strand oligonucleotides containing a consensus binding sequence for activator protein-1 or nuclear factor-kappaB. The resulting DNA protein complexes were analyzed by electrophoretic mobility shift assay. RESULTS: Nuclear extract isolated from obstructed bladders showed intense activator protein-1 binding activity 3, 6 and 24 hours after obstruction as well as increased nuclear factor-kappaB binding activity after 6 and 24 hours. Binding activity was absent or minimal in sham operated rats. Cultured cells exposed to mechanical stretching for 2 and 4 hours showed increased activator protein-1 and nuclear factor-kappaB DNA binding compared with unstretched cells. Likewise stimulation with platelet derived growth factor caused a consistent increase in activator protein-1 and nuclear factor-kappaB binding activity. The binding of nuclear proteins was abolished by a 40-fold excess of an unlabeled specific oligonucleotide but not by excess irrelevant oligonucleotide. Thus, the assays were specific for the factors involved. CONCLUSIONS: Bladder obstruction and mechanical stretching cause the formation of activator protein-1 and nuclear factor-kappaB DNA complexes, consistent with a role of these transcription factors in the control of hypertrophy associated gene activation.

Animals↗
PubMed2001

In vivo and in vitro investigation of the effects of sildenafil on rat cavernous smooth muscle.

PURPOSE: We investigated the effect of sildenafil on rat erectile tissues in vivo and in vitro. MATERIALS AND METHODS: Intracavernous pressure was recorded in pentobarbital anesthetized, male Sprague-Dawley rats and we studied the effect of 100 or 200 microg/kg(-1) sildenafil given intravenously. In an isolated endothelin-1 contracted strip preparation of rat corpus cavernosum we also assessed the effect of sildenafil on the response to electrical field stimulation of the nerves. RESULTS: Electrical stimulation of the cavernous nerve induced a frequency dependent increase in intracavernous pressure of a mean plus or minus standard error of mean 55 +/- 3 mm Hg at 20 Hz, corresponding to a mean of 47% +/- 2% of mean arterial pressure. The 100 microg/kg(-1) dose did not increase intracavernous pressure but significantly increased mean decay time of the pressure response from 16 +/- 3 to 35 +/- 3 seconds (p <0.001). In vitro sildenafil significantly enhanced the amplitude and duration of the relaxation induced by the electrical stimulation of corpus cavernosum strips in a concentration dependent fashion. CONCLUSIONS: In anesthestized rats sildenafil significantly prolonged the decay period of the intracavernous pressure response induced by electrical stimulation of the cavernous nerve but it did not increase the amplitude. Sildenafil enhanced the amplitude and duration of the relaxant response to electrical field stimulation in isolated corpus cavernosum tissue.

Animals↗
PubMed2001

Histological and neurotrophic changes triggered by varying models of bladder inflammation.

PURPOSE: We determined whether bladder inflammation causes elevated expression of nerve growth factor by bladder parenchymal cells, leading to alterations in neurons innervating the bladder. To answer this question biochemical, histological and neuronal size data were obtained in rats following various experimental models of bladder inflammation. MATERIALS AND METHODS: Chemical (2.5% formalin), immune (lipopolysaccharide 2 x 104 cfu/ml.) and mechanical (chromic catgut) inflammation was evaluated at various times and compared to control bladders. Hematoxylin and eosin, and Giemsa staining was done to characterize inflammation and quantify mast cells in the bladder. Nerve growth factor protein and messenger RNA were assayed in the bladder and major pelvic ganglion using 2-site enzyme-linked immunosorbent assay and reverse transcriptase-polymerase chain reaction, respectively. Retrograde axonal tracing was done to size bladder neurons in the major pelvic and dorsal root ganglia. RESULTS: All forms of inflammation increased bladder weight and produced diffuse hyperplasia, intramural edema, acute and chronic inflammatory cells, infiltration and mastocytosis. Generally bladder inflammation resulted in a 50% increase in nerve growth factor and 52% to 58% enlargement of peripheral neurons. CONCLUSIONS: Inflammation results in altered nerve growth factor content of the bladder, and morphological changes in sensory and motor neurons innervating the bladder. Such neuroplasticity may be a possible explanation for the association of bladder inflammation with long-term symptoms and pain after inflammation subsides.

Animals↗
PubMed2000

Stretch-activated signaling of nerve growth factor secretion in bladder and vascular smooth muscle cells from hypertensive and hyperactive rats.

Elevated vascular (VSMC) and bladder smooth muscle (BSMC) NGF are associated with altered visceral innervation in the spontaneously hypertensive rat (SHR: hypertensive, behaviorally hyperactive) compared with control Wistar-Kyotos (WKYs). Stretch stimulates increased NGF production in BSMCs. To elucidate whether stretch induces NGF synthesis in VSMCs, and to determine if disturbances in stretch-mediated NGF production contribute to the elevated tissue levels of NGF in SHRs, we subjected VSMCs and BSMCs cultured from four established inbred rat strains (WKY, WKHA: hyperactive; SHR and WKHT: hypertensive) to several stretch paradigms. For VSMCs, acute and cyclic stretch affected cells derived from hypertensive rats (80-100% increase over control) but not from normotensive strains. For BSMCs, cyclic and static stretch increased NGF secretion in all four strains, but had a two- to threefold greater effect in cells from SHRs and WKHTs (increase up to 600%) at early time points. At later time points of a 24-h experimental period, stretch increased NGF output up to 400% in SHR and WKHA cultures. Thus, defects that influence early induction of stretch-mediated SHR NGF secretion cosegregate with the hypertensive phenotype. Stretch-gated ion channel inhibitors, voltage-gated ion channel inhibitors, and protease inhibitors failed to affect stretch-induced BSMC NGF secretion. In contrast, gene transcription, intracellular calcium, protein kinase C (PKC), and autocrine release of an unknown factor may play a role in the elevated NGF secretion observed in smooth muscle from hypertensive animals. Altered stretch-induced smooth muscle NGF secretion may contribute to the augmented vascular and bladder NGF content associated with high blood pressure and hyperactive voiding in SHRs.

Animals↗
PubMed2000

Altered neural control of micturition in the aged F344 rat.

The purpose of this study was to determine whether micturition reflexes are altered in aged rats. Voiding frequencies and awake cystometrograms (CMGs) were measured in young (3-5 months old) and aged (24 months) F344 male rats. Bladder contractions induced by subcutaneous apomorphine and intravesical capsaicin stimulation were measured using awake CMGs. Urodynamic parameters were compared. Aged rats voided less frequently (4.1 vs 6.9 times/18 h, P = 0.006), with a higher volume per void (1.1 vs 0.7 ml, P = 0.02) and had a higher micturitional threshold pressure (8.7 vs 4.6 mmHg, P = 0.0001) than the young rats. Apomorphine induced a higher frequency of bladder contractions in aged animals compared to young animals (5.5 vs 3.1 contractions/min, P = 0.03). Intravesical capsaicin caused a lower pressure bladder response in the aged rats (38.5 vs 70.6 mmHg, P = 0.01) compared to the young rats. Bladder afferents and central micturition pathways may be altered in aged rats. Impaired bladder contractility in the elderly may be exacerbated by reduced sensory input, whereas the propensity for detrusor instability could result from altered central processing. This study demonstrated the utility of the F344 animal model to study micturitional changes resulting from aging.

Aging↗
PubMed2000

Voiding dysfunction in the orthotopic neobladder.

The orthotopic neobladder has become the preferred method of handling the urinary tract after removal of the bladder in men and women. However, an improved quality of life compared to urinary diversion fails to be realized when voiding dysfunction arises. These difficulties with urination range from retention to incontinence. Voiding dysfunction following neobladder construction that persists beyond 6-12 months warrants fluoro-urodynamic evaluation to determine the cause and plan therapy. Although colonic, ileocolonic, gastric, and ileal neobladders have all been deemed acceptable, the S or W-configured, spheroidal shaped neobladders created from ileum are the most popular. Voiding pressures and micturition patterns depend on the type, length, and configuration of bowel segment harvested. These variables also determine the risk of voiding dysfunction, along with the choice of surgical technique, and the age and sex of the patient. Urinary retention is more common in women, especially after urethral nerve sparing. Obstruction is often due to inferior displacement of the bladder neck, which can angulate the urethra. Daytime stress incontinence arises from reduced urethral outlet resistance accentuated by low neobladder capacity, reduced compliance, or elevated neobladder pressures. Night-time incontinence develops as a consequence of absent sensation that permits excessive nocturnal volumes to overcome the impaired continence mechanisms of the bladder outlet. This situation is exacerbated by the loss of physiological storage reflexes. Therapy for retention rests primarily with intermittent self-catheterization. Stress urinary incontinence can be treated with periurethral bulking agents or an artificial urethral sphincter. Nocturnal enuresis is often effectively managed by the use of an alarm clock to awaken the patient several times per night. Knowledge of the pathogenesis and identification of risk factors implies that prevention through proper design of the neobladder, meticulous surgical technique, and patient selection is paramount.

Humans↗
PubMed2000

Neural pathways and central sites involved in penile erection: neuroanatomy and clinical implications.

Penile erection occurs in response to tactile, visual, and imaginative stimuli in humans. In animals olfactory and auditory cues are particularly important. The participation of multiple sites with the brain and spinal cord, and coordination of somatic and autonomic pathways make sexual behavior in general, and erection in particular, vulnerable to neurologic injury and disease. Sites within the brain and spinal cord act in concert to process, coordinate, then distribute the neural inputs necessary for sexual behavior including erection. Activation of neurons in some of these regions either pharmacologically or by electrical stimulation has been associated with penile tumescence. This review will provide a geographic framework for understanding the neuroanatomical basis of penile erection based primarily on animal data. Following discussion of the anatomical substrates, a clinical correlation is then provided to confirm and reinforce these experimental observations.

Animals↗
PubMed2000

alpha(1)-Adrenoceptor selectivity and the treatment of benign prostatic hyperplasia and lower urinary tract symptoms.

The storage (irritative) and voiding (obstructive) symptoms associated with benign prostatic hyperplasia are generally attributed to prostate enlargement and increased prostatic smooth muscle tone mediated by the prevailing alpha(1)-adrenoceptors in the bladder neck and prostate. This results in obstruction and subsequent secondary changes to the bladder. However, there is growing evidence that many of these symptoms may be due to changes in extraprostatic alpha(1)-adrenoceptors, possibly alpha(1D)-adrenoceptors. Findings from the VA cooperative trial challenge the current theory that the common side effects associated with these agents are due to vascular action of alpha(1)-adrenoceptor blockers. Prostate Cancer and Prostatic Diseases (2000) 3, 76-83

Journal Article↗
PubMed2000

Biomechanical performance of silicone and latex external condom catheters.

Standard in vivo biomechanical performance tests and a pilot clinical study of latex external condom catheters (ECCs) and silicone ECCs demonstrated the superior performance of the silicone ECC over that of the latex ECC. The silicone ECC has a self-adhesive that binds more securely to human skin than the self-adhesive of latex ECC. In addition, the moisture vapor transmission through silicone is significantly greater than through latex. The aggressive self-adhesive of the silicone ECC significantly reduced ECC catheter pop-off compared to that of latex ECC. Silicone ECC removal can be facilitated by the application of a warm, wet cloth to the exterior surface of the silicone ECC, which significantly reduces its self-adhesive force. Constant, gentle traction is then applied to the silicone catheter outlet end to achieve atraumatic silicone ECC removal. On the basis of the results of these standardized tests and pilot study, the silicone ECC is recommended for incontinent men without obstructive uropathy.

Adhesives↗
PubMed1999

Urinary incontinence and depression.

PURPOSE: Serotonergic neuronal systems have been implicated in anxiety and depression. Because descending serotonin pathways from the brain stem inhibit bladder contractions, we postulated that depression associated with altered serotonin function may predispose to urge incontinence. We demonstrate an association between depression and idiopathic urge incontinence. MATERIALS AND METHODS: A total of 115 consecutive incontinent patients presenting to an incontinence clinic were compared to 80 continent controls. Patients were queried for a history of depression and completed a Beck Depression Inventory (BDI). Cases were classified by history and video urodynamics as genuine stress (36), urge (44) or mixed (35) incontinence. RESULTS: A BDI of greater than 12 and/or a history of depression was noted in 30% of incontinent patients and 17% of controls (odds ratio 2.3, 95% confidence interval 1.0 to 5.0, p = 0.044). An abnormal BDI or history of depression was revealed in 60% of patients with idiopathic urge incontinence (p<0.001). Patients with stress or urge incontinence due to neuropathology or obstruction had no greater odds of having depression than continent controls. CONCLUSIONS: These data suggest a strong association between depression and idiopathic urinary incontinence. This link may be due to altered serotonin function and may help explain the efficacy of serotonergic based antidepressants in the treatment of urge incontinence.

Depression↗