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Naoki Yoshimura

Publications and source records attributed to Naoki Yoshimura.

At least 19 recordsLinked to original sources
PubMed2003

Urethral closure mechanisms under sneeze-induced stress condition in rats: a new animal model for evaluation of stress urinary incontinence.

The urethral closure mechanism under a stress condition induced by sneezing was investigated in urethane-anesthetized female rats. During sneezing, while the responses measured by microtip transducer catheters in the proximal and middle parts of the urethra increased, the response in the proximal urethra was almost negligible when the bladder response was subtracted from the urethral response or when the abdomen was opened. In contrast, the response in the middle urethra during sneezing was still observed after subtracting the bladder response or after opening the abdomen. These responses in the middle urethra during sneezing were significantly reduced approximately 80% by bilateral transection of the pudendal nerves and the nerves to the iliococcygeous and pubococcygeous muscles but not by transection of the visceral branches of the pelvic nerves and hypogastric nerves. The sneeze leak point pressure was also measured to investigate the role of active urethral closure mechanisms in maintaining total urethral resistance against sneeze-induced urinary incontinence. In sham-operated rats, no urinary leakage was observed during sneeze, which produced an increase of intravesical pressure up to 37 +/- 2.2 cmH2O. However, in nerve-transected rats urinary leakage was observed when the intravesical pressure during sneezing exceeded 16.3 +/- 2.1 cmH2O. These results indicate that during sneezing, pressure increases elicited by reflex contractions of external urethral sphincter and pelvic floor muscles occur in the middle portion of the urethra. These reflexes in addition to passive transmission of increased abdominal pressure significantly contribute to urinary continence mechanisms under a sneeze-induced stress condition.

Animals↗
PubMed2003

Histological and electrical properties of rat dorsal root ganglion neurons innervating the lower urinary tract.

We investigated whether primary afferent neurons innervating different regions of the lower urinary tract have different histochemical and electrophysiological properties. Neurons in rat L6-S1 DRG were identified by axonal transport of a fluorescent dye. Neurofilament-negative C-fiber cells comprise approximately 70% of bladder and proximal urethral afferent neurons that send axons through the pelvic nerves, but comprise a smaller proportion (51%) of distal urethral neurons that send axons through the pudendal nerves. Isolectin-B4 (IB4) binding was detected in a higher percentage (49%) of C-fiber neurons innervating the distal urethra than in those innervating the bladder or proximal urethra (18-22%). Neurofilament-positive A-fiber neurons innervating the distal urethra had a larger average somal size than neurons innervating the bladder or proximal urethra. In patch-clamp recordings, the majority (70%) of bladder and proximal urethral neurons were sensitive to capsaicin and exhibited TTX-resistant, high-threshold action potentials, whereas a smaller proportion (53%) of distal urethral neurons exhibited TTX-resistant spikes. T-type Ca2+ currents were observed in 47% of distal urethral neurons with TTX-sensitive spikes, but not in TTX-sensitive bladder or proximal urethral neurons. In summary, afferent neurons innervating bladder or proximal urethra differ from those innervating distal urethra. The latter, which more closely resemble cutaneous afferent neurons, consist of a smaller number of C-fiber neurons containing a higher percentage of IB4-positive cells and a more diverse population of A-fiber neurons, some of which exhibit T-type Ca2+ channels. These differences may be related to different functions of respective target organs in the lower urinary tract.

Amidines↗
PubMed2003

Tetrodotoxin-resistant sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN in afferent neurons innervating urinary bladder in control and spinal cord injured rats.

Tetrodotoxin-resistant (TTX-R) sodium channels Na(v)1.8/SNS and Na(v)1.9/NaN are preferentially expressed in small diameter dorsal root ganglia (DRG) neurons. The urinary bladder is innervated by small afferent neurons from L6/S1 DRG, of which approximately 75% exhibit high-threshold action potentials that are mediated by TTX-R sodium channels. Following transection of the spinal cord at T8, the bladder becomes areflexic and then gradually hyper-reflexic, and there is an attenuation of the TTX-R sodium currents in bladder afferent neurons. In the present study, we demonstrate that Na(v)1.8 is expressed in both bladder and non-bladder afferent neurons, while Na(v)1.9 is expressed in non-bladder afferent neurons but is rarely observed in bladder afferent neurons. In spinal cord transected rats 28-32 days following transection, there is a decreased expression of Na(v)1.8 sodium channels in bladder afferents, but no change in the expression of Na(v)1.8 in non-bladder afferent neurons. Both bladder and non-bladder afferent neurons exhibit limited increases in Na(v)1.9 expression following spinal cord transection. These results demonstrate that the expression of TTX-R channels in bladder afferent neurons changes after spinal cord transection, and these changes may contribute to the increased excitability of these neurons following spinal cord injury.

Animals↗
PubMed2003

Vascular endothelial growth factor in children with congenital heart disease.

BACKGROUND: Children with cyanotic congenital heart disease may experience the development of abnormal vessels that become a source of significant morbidity. Abnormal vessel proliferation in these children may take several forms, including systemic-to-pulmonary collateral arteries, systemic-to-pulmonary venous collaterals, systemic venous collateral channels after bidirectional cavopulmonary anastomosis, and pulmonary arteriovenous malformations. However, no entity responsible for these abnormalities has been identified yet. This study determined whether children with cyanotic congenital heart disease have elevated serum levels of vascular endothelial growth factor (VEGF) and whether elevated VEGF correlated with these abnormal vessels. METHODS: Mean systemic room air oxygen saturation (SpO2), blood cell counts (RBC), and serum VEGF levels were measured preoperatively. Samples were obtained from 61 children with acyanotic heart disease (group N) and 102 children with cyanotic heart disease (group C) before cardiac surgery. Postoperative catheterization was performed 1-month after the operation to evaluate the abnormal vessels in group C. RESULTS: The VEGF level was significantly elevated in group C (355.0 +/- 287.1 pg/mL) compared with group N (203.0 +/- 221.6 pg/mL; p < 0.001). VEGF levels in patients with a single ventricle associated with asplenia syndrome (n = 7) in group C were significantly elevated (711.9 +/- 443.5 pg/mL) compared with other patients. There was no significant correlation between VEGF level and SpO2 or RBC. Abnormal vessels were diagnosed in 19.6% (20/102) patients in group C. There was no difference in VEGF levels between the patients with abnormal vessels (336.8 +/- 182.5 pg/mL) and the patients without abnormal vessels (359.1 +/- 306.8 pg/mL). CONCLUSIONS: Children with cyanotic heart disease have elevated systemic levels of VEGF, especially in those patients with a single ventricle associated with asplenia syndrome. There was no significant relationship in VEGF levels between the patients with abnormal vessels and without these vessels.

Adolescent↗
PubMed2003

Cardioprotective effects and the mechanisms of terminal warm blood cardioplegia in pediatric cardiac surgery.

OBJECTIVES: Terminal warm blood cardioplegia has been shown to enhance myocardial protection in adult patients. However, the cardioprotective effects and the mechanisms of terminal warm blood cardioplegia in pediatric heart surgery were still unknown. METHODS: One hundred three consecutive patients were prospectively randomized to one of two groups. In the control group (n = 52), myocardial protection was achieved with intermittent hyperkalemic cold blood cardioplegia and topical cardiac cooling. In the terminal warm blood cardioplegia group (n = 51), this was supplemented with terminal warm blood cardioplegia before the aorta was declamped. Arterial and coronary sinus blood samples were analyzed to determine myocardial energy metabolism and tissue injury. RESULTS: There were no significant differences between the two groups in age (5.5 +/- 0.6 years in the control group vs 5.6 +/- 0.5 years in the terminal warm blood cardioplegia group), body weight (17.2 +/- 1.4 kg in the control group vs 19.8 +/- 1.7 kg in the terminal warm blood cardioplegia group), percentage of cyanotic heart diseases (50% in the control group vs 51% in the terminal warm blood cardioplegia group), number of patients who required right ventriculotomy (33% in the control group vs 39% in the terminal warm blood cardioplegia group), cardiopulmonary bypass time (194 +/- 12.1 minutes in the control group vs 177 +/- 8.6 minutes in the terminal warm blood cardioplegia group), aortic crossclamp time (83.3 +/- 5.9 minutes in the control group vs 82.3 +/- 5 minutes in the terminal warm blood cardioplegia group), lowest rectal temperature (27.4 +/- 0.3 degrees C in the control group vs 28.1 +/- 0.3 degrees C in the terminal warm blood cardioplegia group), and myocardial temperature (9.6 +/- 0.6 degrees C in the control group vs 9.6 +/- 0.7 degrees C in the terminal warm blood cardioplegia group). Spontaneous defibrillation occurred after reperfusion in 80% in the terminal warm blood cardioplegia group, which was significantly (P <.05) higher than the control group (62%). The lactate extraction rate at 60 minutes of reperfusion was significantly (P <.05) higher in the terminal warm blood cardioplegia group (9.0 +/- 2.8%) than the control group (-3.3 +/- 2.4%). The postreperfusion values of cardiac troponin T (7.4 +/- 0.6 ng/mL vs 11.2 +/- 1.0 ng/mL at 6 hours; 4.6 +/- 0.6 ng/mL vs 9.3 +/- 1.6 ng/mL at 18 hours) and heart-type fatty acid binding protein (137 +/- 28 ng/mL vs 240 +/- 30 ng/mL at 2 hours; 88 +/- 19 ng/mL vs 162 +/- 26 ng/mL at 3 hours) were significantly (P <.05 vs the control group) lower in the terminal warm blood cardioplegia group. CONCLUSION: Terminal warm blood cardioplegia enhances myocardial protection in pediatric cardiac surgery by an improvement in aerobic energy metabolism and a reduction of myocardial injury or necrosis.

Adolescent↗
PubMed2003

Intravesical protamine sulfate and potassium chloride as a model for bladder hyperactivity.

OBJECTIVES: An acute animal model for hyperactive bladder in rats was developed using intravesical infusion of protamine sulfate (PS), an agent thought to break down urothelial barrier function, and physiologic concentrations of potassium chloride (KCl). METHODS: Continuous cystometrograms (CMGs) were performed in urethane-anesthetized female rats by filling the bladder (0.04 mL/min) with normal saline followed by intravesical infusion of a test solution consisting of either KCl (100 or 500 mM) or PS (10 or 30 mg/mL) for 60 minutes. Subsequently, the 10 mg/mL PS-treated animals were infused intravesically with 100, 300, or 500 mM KCl. Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. RESULTS: Unlike KCl (100 or 500 mM) or a low concentration of PS (10 mg/mL) alone, the intravesical administration of a high concentration of PS (30 mg/mL) produced irritative effects with a decreased intercontraction interval (by 80.6%). After infusion of a low concentration of PS, infusion of 300 or 500 mM KCl produced irritative effects (intercontraction interval decreased by 76.9% or 82.9%, respectively). The onset of irritation occurred more rapidly after 500 mM KCl (10 to 15 minutes) than after 300 mM KCl (20 to 30 minutes). Capsaicin pretreatment delayed the onset (approximately 60 minutes) and reduced the magnitude (intercontraction interval decreased by 35.5%) of irritative effects. CONCLUSIONS: Intravesical administration of KCl after PS treatment activates capsaicin-sensitive afferents and detrusor muscle and presumably capsaicin-resistant afferents. Modest, noncytotoxic affronts to urothelial barrier function can result in dramatic irritative responses. This model may be useful in the study of bladder irritation and hyperactivity.

Administration, Intravesical↗
PubMed2003

Intravesical liposome administration--a novel treatment for hyperactive bladder in the rat.

OBJECTIVES: To examine the effect of intravesical administration of liposomes (LPs) on chemically induced bladder hyperactivity in the rat. It has been suggested that interstitial cystitis (IC) is associated with a dysfunctional or leaky epithelium. Thus, enhancement of epithelial barrier function might be useful in the treatment of IC. LPs are vesicles that are concentric phospholipid bilayers separated by an aqueous compartment and can fuse with cells to provide a molecular film that can promote wound healing. METHODS: The intravesical pressure was recorded using a transurethral catheter in adult female Sprague-Dawley rats anesthetized with urethane (1.2 g/kg subcutaneously). Some animals were pretreated with capsaicin (125 mg/kg subcutaneously) 4 days before the experiments. Continuous cystometrograms were performed by slowly filling the bladder (0.04 mL/min) with solutions of varying compositions, including saline, acetic acid (AA, 0.1%), potassium chloride (KCl, 500 mM), protamine sulfate (PS, 10 mg/mL), LPs, PS/KCl, or LPs/KCl. The parameters measured included the intercontraction interval (ICI), amplitude of bladder contractions, compliance, and micturition pressure threshold. RESULTS: The ICI was decreased after exposure to AA (79.8% decrease) or PS/KCl (81% decrease); however, the ICI was not changed after LPs, PS, or KCl alone. The decreased ICI was partially reversed after infusion of LPs (172.8% increase) or LPs/KCl (63% increase), but was not significantly changed after switching to saline or KCl administration. Pretreatment with capsaicin delayed the onset of the irritative effects of AA by approximately 30 to 60 minutes, but had not changed the magnitude after 2 hours of infusion. CONCLUSIONS: Intravesical administration of PS/KCl or AA activates capsaicin-sensitive and capsaicin-resistant afferents in a time-dependent sequence that is partially reversed by LP infusion. We hypothesize that LPs might enhance the barrier properties of a dysfunctional uroepithelium and increase resistance to irritant penetration. Thus, intravesical LP administration could be a novel treatment of patients with IC.

Administration, Intravesical↗
PubMed2003

Implications of diabetes mellitus in urology.

The incidence of DM is rapidly growing among Americans. DM will rival cancer and heart disease in terms of cost and suffering. The National Institute of Health is tripling the research dollars that are spent on diabetic-related research in an attempt to combat this disease. Urologists are on the front line in the diagnosis and treatment of the complications of DM. The complications of DM that we reviewed in this article, diabetic cystopathy and diabetic ED, can occur in the early stage of DM and often progress in a silent fashion. More awareness and interest are needed to improve our understanding of diabetic complications in urology. Exciting new approaches in the treatment of diabetic cystopathy and ED are being investigated.

Clinical Trials as Topic↗
PubMed2003

Dopaminergic mechanisms underlying bladder hyperactivity in rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal pathway.

1. This study was undertaken to elucidate dopaminergic mechanisms underlying bladder hyperactivity in a rat model of Parkinson's disease (PD) induced by a unilateral 6-OHDA injection into the substantia nigra pars compacta. 2. In 6-OHDA-lesioned rats, voided volume per micturition (0.41+/-0.04 ml, mean+/-s.e.m.) measured during 24 h in a metabolic cage was significantly smaller than in sham-operated rats (0.67+/-0.07 ml). 3. Cystrometrograms (CMG) in conscious animals revealed significantly smaller bladder capacity (BC) (0.46+/-0.03 ml) in 6-OHDA-lesioned rats than in sham rats (0.72+/-0.06 ml). 4. SKF38393 (D1/D5 receptor agonist, i.v.) significantly increased BC in 6-OHDA rats without apparent effects in sham rats. SKF38393 applied intracerebroventricularly (i.c.v.) under urethane anesthesia also increased BC in 6-OHDA-lesioned rats and by a smaller increment in sham rats. 5. In contrast, quinpirole (D2/D3/D4 receptor agonist, i.v.) significantly reduced BC in sham and 6-OHDA-lesioned rats. Intrathecal injection of quinpirole similarly reduced BC in sham and 6-OHDA-lesioned rats. 6. PD128907 (D(3)-receptor agonist) did not have significant effects on BC in 6-OHDA-lesioned rats. 7. These results indicate that a rat model of PD exhibited bladder hyperactivity as observed in patients with PD, and that stimulation of D1/D5 dopamine receptors at a supraspinal site can suppress bladder hyperactivity in PD, whereas stimulation of D2/D4, but not D3, dopamine receptors had the opposite effect to reduce bladder capacity. Thus, D1/D5 dopamine receptor agonists might be effective in treating neurogenic bladder hyperactivity in PD.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed2003

Surgical management of trabecular ventricular septal defects: the sandwich technique.

BACKGROUND: Surgical closure of trabecular ventricular septal defects is difficult and often unsuccessful. OBJECTIVE: We performed closure of trabecular ventricular septal defects by sandwiching the septum between 2 polyester felt patches placed in the left ventricle and right ventricle without ventriculotomy. METHODS: Eleven patients (7 boys and 4 girls) underwent a sandwiching closure at a mean age of 4.7 years (range, 0.4-9.7 years) and a mean weight of 16.7 kg (range, 4.6-52 kg). Associated cardiac malformations were present in 9 of the 11 patients. Seven patients had undergone previous operations. The trabecular ventricular septal defects are exposed through the tricuspid valve and also from the left ventricular side through a coexisting large perimembranous ventricular septal defect or through the mitral valve through an interatrial septostomy. Two forceps, one each from the right and left ventricular side, lead a 3F Nelaton catheter through the trabecular defect. An oversized circular polyester felt patch mounted on a 3-0 Nespolen suture attached to the Nelaton catheter is then passed into the left ventricle. The suture ends are then passed through a slightly smaller polyester felt patch on the right ventricular side of the septum. The Nespolen suture is then tied, thereby sandwiching the septum between the 2 patches. RESULTS: Time required for the procedure was less than 20 minutes in each case. There were no hospital deaths, and the postoperative course was uneventful in all patients. There was no residual shunt in 3 patients, and a minimal residual shunt was observed in 5 patients. Mild residual shunt was observed in 3 patients. Cardiac catheterization was performed 1 month postoperatively in 8 patients in whom residual shunt was noted on echocardiography. Five of 8 patients had a minimal residual shunt (pulmonary blood flow/systemic blood flow ratio = 1.0). Three patients had a residual shunt (pulmonary blood flow/systemic blood flow ratio = 2.0, 1.6, and 1.2). The patient with a pulmonary blood flow/systemic blood flow ratio of 2.0 had a "Swiss cheese" ventricular septal defect, and a residual shunt remained around the patch. However, the residual shunt decreased to a pulmonary blood flow/systemic blood flow ratio of 1.6 at examination 16 months postoperatively. Echocardiography showed that the residual shunt had also decreased in another 2 patients. CONCLUSIONS: We conclude that the sandwich technique is safe and easy. Even in cases with a residual shunt present, the shunt is expected to decrease as time passes. Further experience and longer follow-up of these patients are necessary to conclude whether this technique is applicable to neonates and young infants.

Blood Flow Velocity↗
PubMed2003

[New insights into neural mechanisms controlling the micturition reflex].

The functions of the lower urinary tract, to store and periodically release urine, are dependent on the activity of smooth and striated muscles in the bladder, urethra, and external urethral sphincter. This activity is in turn controlled by neural circuits in the brain, spinal cord, and peripheral ganglia. During urine storage, the outlet is closed and the bladder smooth muscle is quiescent. When bladder volume reaches the micturition threshold, activation of a micturition center in the dorsolateral pons (the pontine micturition center) induces a bladder contraction and a reciprocal relaxation of the urethra, leading to bladder emptying. During voiding, sacral parasympathetic (pelvic) nerves provide an excitatory input (cholinergic and purinergic) to the bladder and inhibitory input (nitrergic) to the urethra. The brain rostral to the pons (diencephalon and cerebral cortex) is also involved in excitatory and inhibitory regulation of the micturition reflex. Various transmitters including dopamine, serotonin, norepinephrine, GABA, excitatory and inhibitory amino acids, opioids, acetylcholine, and neuropeptides are implicated in the modulation of the micturition reflex in the central nervous system. Therefore, injury or diseases of the nervous system, as well as drugs and disorders of the peripheral organs, can produce bladder and urethral dysfunctions such as urinary frequency, urgency and incontinence, or inefficient bladder emptying.

Central Nervous System↗
PubMed2002

Effect of KW-7158, a putative afferent nerve inhibitor, on bladder and vesico-vascular reflexes in rats.

The effects of KW-7158, a putative afferent nerve inhibitor, on reflex bladder activity and vesico-vascular reflexes were evaluated in urethane anesthetized SD rats with normal and xylene-irritated bladders. The bladder was filled with saline until the appearance of large amplitude spontaneous bladder contractions (LA-BC). Vesico-vascular reflexes were measured as increases in systolic arterial blood pressure during LA-BC or when the bladder was distended by a range of pressures. In normal rats, KW-7158 (10 and 100 microg/kg, i.v.) did not alter the amplitude or volume threshold for inducing LA-BC but increased the intercontraction interval. After xylene-irritation, which decreased volume threshold and intercontraction interval and induced small amplitude bladder contractions, KW-7158 increased volume threshold (65%) and intercontraction interval (150%) and decreased the number of small amplitude bladder contractions. Vesico-vascular reflexes induced during LA-BC or by bladder distension were suppressed (19.4-100%) by KW-7158. The effect of KW-7158 to depress vesico-vascular reflexes as well as xylene-induced bladder hyperactivity without altering the amplitude of contractions is consistent with the view that the drug affects reflex bladder activity at least in part by depressing afferent pathways.

Animals↗
PubMed2002

Effects of modified ultrafiltration on coagulation factors in pediatric cardiac surgery.

PURPOSE: Modified ultrafiltration (MUF) after cardiopulmonary bypass (CPB) in children has been reported to reduce the need for postoperative blood transfusion and minimize postoperative blood loss. This study was undertaken to quantify the effects of MUF on coagulation factors in pediatric patients. METHODS: Seven children scheduled to undergo open-heart surgery for congenital heart defects were studied. CPB circuits were primed with crystalloid solutions and no blood transfusions were performed. Hematocrit, platelet count, total plasma proteins, albumin, fibrinogen, prothrombin, factor VII, factor IX, and factor X were measured preoperatively, at the termination of cardiopulmonary bypass, and at the end of modified ultrafiltration. RESULTS: MUF was associated with significant (P < 0.05) increases in hematocrit (17.6% +/- 1.6% to 21.6% +/- 2.4%), platelet count 11.1 +/- 2.5 to 12.8 +/- 2.4 x 10(4)/mm3), total plasma proteins (2.7 +/- 0.3 to 3.4 +/- 0.4 g/dl), and albumin (1.6 +/- 0.2 to 2.1 +/- 0.2 g/dl). Fibrinogen, prothrombin, and factor VII also increased significantly (P < 0.05) during MUF, but factor IX and factor X did not change. CONCLUSION: We conclude that MUF attenuates the dilutional coagulopathy that occurs during CPB in children. There were slight improvements in the coagulation factors when MUF was employed.

Blood Coagulation Factors↗
PubMed2002

Current and future pharmacological treatment for overactive bladder.

PURPOSE: Urinary incontinence and overactive bladder are important and common conditions that have received little general medical attention. We reviewed the magnitude and impact of these conditions, and discuss pharmacotherapy as well as new drugs under investigation. MATERIALS AND METHODS: The main emphasis of this review is pharmacological therapy for the bladder. We discuss currently available agents, drugs under development and pharmacological targets that would be suitable targets for treating overactive bladder. Drugs such as duloxetine that target not bladder smooth muscle, but rather central nervous system control of the micturition reflex are undergoing clinical trials. We also discuss intravesical therapy and alternative drug delivery methods, such as intravesical capsaicin and botulinum toxin, with special emphasis on approaches to modulate bladder afferent nerve function for preventing overactive bladder. RESULTS: There are many advantages to advanced drug delivery systems, including long-term therapeutic efficacy, decreased side effects and improved patient compliance. Future speculation such as gene therapy holds great promise for overactive bladder because it is possible to access all genitourinary organs via endoscopy and other minimally invasive techniques that are ideally suited for gene therapy. CONCLUSIONS: Traditional anticholinergic therapies are limited in their effectiveness. There is great hope for future research regarding voiding dysfunction and urinary incontinence through a focus on afferent nerve intervention for preventing overactive bladder.

Adult↗
PubMed2002

Immunoneutralization of nerve growth factor in lumbosacral spinal cord reduces bladder hyperreflexia in spinal cord injured rats.

PURPOSE: We investigated the effects of intrathecal application of nerve growth factor (NGF) antibodies (Ab) on bladder hyperreflexia in chronic spinalized rats. MATERIALS AND METHODS: In adult female rats an intrathecal catheter was implanted at the level of the L6 to S1 spinal cord, followed by complete transection of the Th8 to 9 spinal cord. At 10 days after spinalization the intrathecal catheter was connected to an osmotic pump for continuous delivery of vehicle or NGF Ab (10 microg daily) for 2 weeks. Awake cystometry was then performed. NGF levels in the L5 to S1 dorsal root ganglia, L6 spinal cord and bladder were also measured using enzyme-linked immunosorbent assay. RESULTS: The number of uninhibited bladder contractions per voiding cycle, maximal pressure of uninhibited bladder contraction and maximal voiding pressure were significantly decreased in NGF Ab treated versus vehicle treated spinalized rats. Intercontraction interval, baseline intravesical pressure, pressure threshold for voiding and voiding efficiency were not significantly changed by NGF Ab treatment. NGF levels in the bladder, L6 spinal cord and L5 to S1 dorsal root ganglia of vehicle treated spinalized rats was 1.6 to 4.8 times higher than in spinal cord intact rats. After intrathecal NGF Ab treatment NGF levels were significantly lower in the L6 to S1 dorsal root ganglia (30% to 35%) and L6 spinal cord (53%) but not in the bladder or L5 dorsal root ganglia compared with levels in vehicle treated spinalized rats. CONCLUSIONS: Increased levels of NGF in the bladder, spinal cord and dorsal root ganglia were associated with bladder hyperreflexia after spinal cord injury. Immuno-neutralization of NGF in the spinal cord suppressed NGF levels in the L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, and also suppressed bladder hyperreflexia. Thus, suppression of NGF levels in afferent pathways could be useful for treating bladder hyperreflexia associated with spinal cord injury.

Afferent Pathways↗
PubMed2002

Diabetic cystopathy correlates with a long-term decrease in nerve growth factor levels in the bladder and lumbosacral dorsal root Ganglia.

PURPOSE It has been proposed that a deficiency in the axonal transport of nerve growth factor (NGF) may have an important role in inducing diabetic neuropathy, which contributes to diabetic cystopathy. Therefore, in streptozotocin (Sigma Chemical Co., St. Louis, Missouri) induced diabetic rats we investigated the relationship of bladder function with NGF levels in the bladder and lumbosacral dorsal root ganglia, which contain afferent neurons innervating the bladder. MATERIALS AND METHODS At 6 and 12 weeks after the induction of diabetes with streptozotocin (65 mg./kg. intraperitoneally) the effects of diabetes on Adelta afferent fiber dependent, conscious voiding were evaluated by metabolic cage measurements and awake cystometry. The effects of diabetes on C-fiber mediated bladder nociceptive responses were also investigated by cystometry with intravesical instillation of 0.25% acetic acid in the rats under urethane anesthesia. NGF levels in the bladder and L6 to S1 dorsal root ganglia were measured by enzyme-linked immunosorbent assay 3, 6, 9 and 12 weeks after streptozotocin injection. RESULTS In diabetic rats NGF levels in the bladder and L6 to S1 dorsal root ganglia were significantly decreased 12 weeks after streptozotocin injection (p <0.01). In cystometry and metabolic cage studies bladder capacity and post-void residual volume were significantly increased 12 weeks after streptozotocin injection (p <0.01). Bladder nociceptive responses revealed by a reduction in inter-contraction intervals after acetic acid infusion were significantly decreased in a time dependent manner 12 weeks after streptozotocin injection.CONCLUSIONS Rats with streptozotocin induced diabetes mellitus showed a significant time dependent decrease in NGF levels in the bladder and L6 to S1 dorsal root ganglia that was associated with voiding dysfunction attributable to defects in Adelta and C-fiber bladder afferents. Therefore, reduced production of NGF in the bladder and/or impaired transport of NGF to L6 to S1 dorsal root ganglia, which contain bladder afferent neurons, may be an important mechanism inducing diabetic cystopathy.

Animals↗