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Biomedical subjects

Naoki Yoshimura

Publications and source records attributed to Naoki Yoshimura.

At least 37 records · Page 2Linked to original sources
PubMed2006

15-deoxy-Delta12,14-prostaglandin J2 attenuates development of cyclophosphamide-induced cystitis in rats.

OBJECTIVES: To investigate whether an endogenous prostaglandin (PG) D2 metabolite, 15-deoxy-Delta12,14-PGJ2 (15d-PGJ2), can attenuate cyclophosphamide (CYP)-induced cystitis in the rat. METHODS: Male Sprague-Dawley rats received a single intraperitoneal injection of CYP (200 mg/kg). In a separate group of animals, 15d-PGJ2 (10 and 100 microg/kg intraperitoneal bolus 10 minutes before and 24 hours after CYP injection) or a selective inducible nitric oxide synthase (iNOS) inhibitor, N-(3-(aminomethyl)benzyl)acetamidine ([1400W] 10 mg/kg intraperitoneal bolus 10 minutes before and 12 and 24 hours after CYP injection), was administered. At 48 hours after CYP injection, the rats were killed, and tissues were removed for evaluation of cystitis. RESULTS: CYP injection resulted in severe cystitis. 15d-PGJ2, as well as 1400W, significantly reduced the increase in plasma protein extravasation (Evans blue dye method), iNOS enzymatic activity, urinary excretion of nitric oxide metabolites, and myeloperoxidase activity in the bladder caused by CYP. Moreover, 15d-PGJ2 significantly decreased the cytokine interleukin-1beta in the bladder. In addition, 15d-PGJ2 significantly reduced the degree of CYP-induced bladder tissue damage and increase in immunohistochemical staining for iNOS in the bladder. CONCLUSIONS: These results indicate that 15d-PGJ2 can attenuate the development of CYP-induced cystitis by suppression of cytokine production and iNOS induction. Thus, treatment with cyclopentenone prostaglandins such as 15d-PGJ2 may be effective against CYP-induced cystitis.

Animals↗
PubMed2006

Novel action of botulinum toxin on the stromal and epithelial components of the prostate gland.

PURPOSE: Intraprostatic injection of BTX-A has demonstrated clinical improvement in men with bladder outlet obstruction. We investigated the mechanisms of action of BTX-A on the prostate. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were injected with varying doses of BTX-A into the prostate and the prostates were harvested after 1 or 2 weeks. The effects of BTX-A on prostate histology, and the proliferative and apoptotic indexes were determined using hematoxylin and eosin staining, proliferative cell nuclear antigen staining and TUNEL staining, respectively. Changes in alpha(1A) adrenergic receptor and androgen receptor were evaluated by Western blotting. RESULTS: One week after BTX-A injection generalized prostate atrophy was observed. There was a significant increase in apoptotic cells (12, 16 and 22-fold), and decrease in proliferative cells (38%, 77% and 80%) and alpha(1A) adrenergic receptor (13%, 80% and 81%) for 5, 10 and 20 U, respectively. There was no significant change in androgen receptors. The effects were decreased 2 weeks after BTX-A treatment. CONCLUSIONS: BTX-A injection into the prostate alters cellular dynamics by inducing apoptosis, inhibiting proliferation and down-regulating alpha(1A) adrenergic receptors. BTX-A may potentially be the drug that has dual actions on the static and dynamic components of benign prostatic hyperplasia.

Animals↗
PubMed2006

Roles of peripheral and central nicotinic receptors in the micturition reflex in rats.

PURPOSE: We investigated the effects of nicotinic acetylcholine receptor activation in the bladder and central nervous system on the micturition reflex in urethane anesthetized rats. MATERIALS AND METHODS: The effects of nicotinic acetylcholine receptor activation on bladder activity were examined during continuous infusion cystometrogram. Nicotine with or without the nicotinic acetylcholine receptor antagonist mecamylamine (Sigma Chemical Co., St. Louis, Missouri) was administered intravesically, intrathecally or intracerebroventricularly in normal or capsaicin pretreated rats. We also examined nicotine induced responses in dissociated bladder afferent neurons from L6 to S1 dorsal root ganglia that were sensitive to capsaicin using whole cell patch clamp recordings. RESULTS: Intravesical nicotine (1 to 10 mM) significantly decreased intercontraction intervals in dose dependent fashion. This excitatory effect was abolished by co-application of mecamylamine (3 mM) as well as by capsaicin pretreatment. On patch clamp recordings 300 muM nicotine evoked rapid inward currents that were antagonized by mecamylamine in capsaicin sensitive bladder afferent neurons. Intrathecal and intracerebroventricular administration of nicotine (10 mug) decreased and increase intercontraction intervals, respectively. Each effect was antagonized by mecamylamine (50 mug) administered intrathecally and intracerebroventricularly. The spinal excitatory effect was significantly inhibited by the N-methyl-D-aspartate receptor antagonist (+)-MK-801 hydrogen maleate (20 mug) given intrathecally or by capsaicin pretreatment, although the effects of capsaicin pretreatment were significantly smaller than those of (+)-MK-801 hydrogen maleate. CONCLUSIONS: These results indicate that nicotinic acetylcholine receptor activation in capsaicin sensitive C-fiber afferents in the bladder can induce detrusor overactivity. In the central nervous system nicotinic acetylcholine receptor activation in the spinal cord and brain has an excitatory and an inhibitory effect on the micturition reflex, respectively. In addition, the nicotine induced spinal excitatory effect may be mediated by the activation of glutamatergic mechanisms.

Administration, Intravesical↗
PubMed2006

Mechanisms underlying the recovery of lower urinary tract function following spinal cord injury.

The lower urinary tract has two main functions, the storage and periodic expulsion of urine, which are regulated by a complex neural control system in the brain and lumbosacral spinal cord. This neural system coordinates the activity of two functional units in the lower urinary tract: (1) a reservoir (the urinary bladder) and (2) an outlet (consisting of bladder neck, urethra and striated muscles of the pelvic floor). During urine storage the outlet is closed and the bladder is quiescent, thereby maintaining a low intravesical pressure over a wide range of bladder volumes. During micturition the outlet relaxes and the bladder contracts to promote the release of urine. This reciprocal relationship between bladder and outlet is generated by visceral reflex circuits, some of which are under voluntary control. Experimental studies in animals indicate that the micturition reflex is mediated by a spinobulbospinal pathway passing through a coordination center (the pontine micturition center) located in the rostral brainstem. This reflex pathway is in turn modulated by higher centers in the cerebral cortex that are presumably involved in the voluntary control of micturition. Spinal cord injury at cervical or thoracic levels disrupts voluntary control of voiding as well as the normal reflex pathways that coordinate bladder and sphincter functions. Following spinal cord injury, the bladder is initially areflexic but then becomes hyperreflexic due to the emergence of a spinal micturition reflex pathway. Studies in animals indicate that the recovery of bladder function after spinal cord injury is dependent in part on plasticity of bladder afferent pathways and the unmasking of reflexes triggered by capsaicin-sensitive C-fiber bladder afferent neurons. The plasticity is associated with changes in the properties of ion channels and electrical excitability of afferent neurons, and appears to be mediated in part by neurotrophic factors released in the spinal cord and the peripheral target organs.

Adrenergic Fibers↗
PubMed2006

Intravesical instillation of human urine after oral administration of trospium, tolterodine and oxybutynin in a rat model of detrusor overactivity.

OBJECTIVE: To study the effects of antimuscarinics excreted into human urine on normal bladder in a rat model of detrusor overactivity. MATERIALS AND METHODS: Two 'normal' adult volunteers collected voided urine after taking trospium (20 mg, twice daily), tolterodine LA (4 mg, four times daily), or oxybutynin XL (10 mg, four times daily). The drugs were taken in a random order for 5 days with a 7-day washout period between the drugs. The urine collected from the two volunteers was mixed together and then blindly labelled and used for testing. Control human urine (no oral antimuscarinics) was also used. The effect of intravesical administration of human urine on carbachol-induced bladder overactivity was studied in female Sprague-Dawley rats anaesthetised with urethane. Cystometric variables during continuous infusion (0.04 mL/min) for >1 h each of saline, human urine, then a mixture of carbachol (30 microm) and human urine were compared in the four groups (control and the three different antimuscarinics tested; six rats per group). RESULTS: Human urine, with or with no intake of antimuscarinic agents, had no effect on normal bladder function. Bladder capacity and intercontraction intervals were significantly decreased after adding carbachol to urine containing vehicle, tolterodine or oxybutynin. However, urine collected from the humans who had taken trospium prevented the carbachol-induced reduction in bladder capacity and intercontraction intervals. Maximum voiding pressure and pressure threshold were not changed in any case. CONCLUSION: This is the first report that the urine excreted after oral ingestion of trospium (20 mg, twice daily) has a significant inhibitory effect in a rat model of detrusor overactivity. This suggests that antimuscarinic agents have a local bladder effect during the bladder-storage phase in addition to the smooth muscle-mediated voiding phase.

Administration, Intravesical↗
PubMed2006

Open heart operation in a child with congenital heart disease and hereditary spherocytosis.

An 18-month-old girl with hereditary spherocytosis underwent closure of the ventricular septal defect, commissurotomy of the pulmonary valve, and patch angioplasty of the pulmonary trunk without previous splenectomy. No serious complications as a result of hemolysis occurred in the perioperative period. Open heart surgery can therefore be safely performed in young children with congenital heart disease and hereditary spherocytosis who have not previously undergone splenectomy.

Female↗
PubMed2005

Comparison of leak point pressure methods in an animal model of stress urinary incontinence.

We compared three different methods of testing leak point pressure (LPP) in rats with or without the pudendal nerves and nerves to the iliococcygeus/pubococcygeus muscles transected: (1) sneeze induced with a whisker in the nostril (sneeze LPP), (2) manually increased abdominal pressure (Crede LPP), and (3) increased intravesical pressure using the vertical tilt table method (vertical tilt table LPP). In sham rats, passive intravesical pressure rises in Crede and vertical tilt table methods induced active urethral closure mechanisms that contributed to high LPPs (41.4 and 35.5 cm H2O, respectively), which were significantly reduced by nerve transection. During sneezing, leakage was observed in nerve-transected rats, but not in sham rats, indicating that sneezing can activate an additional urethral closure mechanism. Measuring LPP during sneezing or passive intravesical pressure rises in the vertical tilt table and Crede method seems to be useful for assessing the continence mechanisms under different stress conditions in rats.

Abdomen↗
PubMed2005

Adacolumn for selective leukocytapheresis as a non-pharmacological treatment for patients with disorders of the immune system: an adjunct or an alternative to drug therapy?

Inflammatory and/or autoimmune diseases like ulcerative colitis (UC) or Crohn's disease (CD) are debilitating chronic disorders that poorly respond to pharmacological interventions. Further, drug therapy has adverse effects that add to disease complications. The current thinking is that disorders like inflammatory bowel disease (IBD) reflect an over exuberant immune activation driven by cytokines including TNF-alpha. Major sources of cytokines include myeloid leukocytes (granulocytes, monocytes/macrophages), which in IBD are elevated with activation behavior and are found in vast numbers within the inflamed intestinal mucosa. Accordingly, myeloid cells should be the targets of therapy. Adacolumn is filled with cellulose acetate beads that selectively adsorb and deplete myeloid cells and a small fraction of lymphocytes (FcgammaR and complement receptors bearing cells). In one study, 20 steroid naive patients with moderate (n = 14) or severe (n = 6) UC according to Rachmilewitz despite 1.5-2.25 g/day of 5-aminosalicylic acid received 6 to 10 Adacolumn sessions at 2 sessions/week. Efficacy was assessed 1 week after the last session. The majority of patients responded to 6 sessions, 17 (85%) achieved remission. In 2 of the 3 non-responders, CAI was 8 and 12 in 1; all 3 had deep colonic ulcers at study initiation. Decreases were seen in total leukocytes (P = 0.003), % neutrophils (P = 0.003), % monocytes (P = 0.004), an increase in lymphocytes (P = 0.001), decreases in C-reactive protein (P = 0.0002), and rises in blood levels of soluble TNF-alpha receptors I (P = 0.0007), II (P = 0.0045). In a separate study, a case with very severe steroid refractory UC who received up to 11 sessions responded well and avoided colectomy. Further, myeloid cell purging with Adacolumn has been associated with the release of IL-1 receptor antagonist, suppression of TNF-alpha, IL-1beta, IL-6, IL-8, down-modulation of L-selectin and the chemokine receptor CXCR3. In conclusion, selective depletion of myeloid cells appears to induce anti-inflammatory effects and represents a non-pharmacological treatment for patients with active IBD. The treatment has a clear drug-sparing role. Changes in blood levels of inflammatory and anti-inflammatory factors are thought to contribute to the efficacy of this procedure.

Autoimmune Diseases↗
PubMed2005

Inhaled nitric oxide therapy after Fontan-type operations.

PURPOSE: Inhaled nitric oxide (NO) therapy is a newly developed strategy designed to reduce pulmonary vascular resistance after the Fontan-type operation. We reviewed our experience to evaluate its efficacy and true indications. METHODS: We retrospectively examined 47 children who received inhaled NO therapy after the Fontan-type operation between August 1996 and December 2002. The maximal dose of NO ranged from 5 to 30 ppm (median 10 ppm), and the duration of inhaled NO therapy ranged from 5 h to 52 days (median 2 days). RESULTS: Inhaled NO significantly decreased the central venous pressure (CVP), from 16.2 +/- 2.2 to 14.6 +/- 2.2 mmHg (P < 0.0001), and the transpulmonary pressure gradient between the CVP and left atrial pressure, from 9.9 +/- 2.9 to 8.4 +/- 2.7 mmHg (P < 0.0001). It also increased the systolic systemic arterial pressure from 71.9 +/- 15.2 to 76.8 +/- 14.5 mmHg (P < 0.05). In 26 patients with additional fenestration, inhaled NO led to a significant improvement in SaO(2) from 90.1% +/- 9.6% to 93.3% +/- 7.9% (P < 0.01). However, patients with a CVP <15 mmHg or a transpulmonary pressure gradient <8 mmHg, or both, after the Fontan-type operation, showed no significant changes in hemodynamics during inhaled NO therapy. CONCLUSIONS: We propose that a CVP >/=15 mmHg or a transpulmonary pressure gradient >/=8 mmHg, or both, after Fontan-type operations are appropriate indications for inhaled NO therapy.

Administration, Inhalation↗
PubMed2005

Appropriate additional pulmonary blood flow at the bidirectional Glenn procedure is useful for completion of total cavopulmonary connection.

BACKGROUND: The role and effect of additional pulmonary blood flow at the time of bidirectional Glenn procedure (BDG) is controversial. We assessed our experiences to clarify the effects of controlled additional pulmonary blood flow on outcomes after BDG. METHODS: Thirty-eight patients who underwent BDG (2.1 +/- 2.1 years of age) were enrolled in this study. In group A (n = 29) additional pulmonary blood flow was controlled by the banding of the pulmonary trunk, or the previously created Blalock-Taussig shunt, to keep the central venous pressure equal to or less than 16 mm Hg at BDG. In group B (n = 9), BDG was the only source of pulmonary blood flow. RESULTS: One operative death occurred in group B. In group A, 24 patients underwent total cavopulmonary connection (TCPC) 14 +/- 6 months after BDG, and the remaining 5 patients are waiting for TCPC in good condition. In group B, 6 patients underwent TCPC 8 +/- 7 months after BDG. One patient is awaiting TCPC and the remaining patient is considered unsuitable for TCPC. Cardiac catheterization performed in 32 patients showed significant decrease of pulmonary artery (Nakata) index from 307 +/- 73 to 215 +/- 45 mm2/m2 after BDG in group B (p < 0.05). On the other hand, the Nakata index stayed in higher range from 316 +/- 115 to 287 +/- 74 mm2/m2 in group A, and there was a significant correlation between the Nakata index and the percentage of its difference (Y = 40.823 - 0.144 X; n = 26, R = 0.740, p < 0.0001). CONCLUSIONS: Appropriate additional pulmonary blood flow is useful for the completion of TCPC by means of suppressing the decrease in the size of the pulmonary artery, especially in patients with underdeveloped pulmonary arteries.

Cardiac Output↗
PubMed2005

The dependence of myocardial damage on age and ischemic time in pediatric cardiac surgery.

OBJECTIVE: Heart fatty acid-binding protein is a rapid indicator for assessment of myocardial damage in cardiac surgery. The purpose of this study was to investigate the effects of age and ischemic time on the biochemical evidence and clinical outcomes of myocardial damage in pediatric cardiac surgery. METHODS: A prospective observational cohort study conducted over 2.5 years was performed in 98 consecutive patients (51 infants and 47 children) undergoing cardiac surgery for ventricular septal defects. Serial measurements of serum levels of heart fatty acid-binding protein and the respective areas under the curve were obtained, with particular reference to age and aortic crossclamp time. Assessment of clinical outcomes included inotropic support, ventilatory support, and intensive care unit stay. RESULTS: There was a linear dependence of the logarithm of age and the logarithm of heart fatty acid-binding protein release(r = 0.737, P < .0001). This logarithm-logarithm plot showed a power function of age for heart fatty acid-binding protein release. The exponent and amplitude parameter of the power function was the aortic crossclamp time. Compared with children, infants had significantly more myocardial damage and worse clinical outcomes, and these factors were related to the aortic crossclamp time. CONCLUSIONS: The younger the age of patients, the more vulnerable are their myocardia to injury caused by ischemia during definitive repair of congenital heart disease. Therefore, perioperative management for pediatric patients after cardiac surgery should be performed, taking into consideration the dependence of the myocardial damage on age and ischemic time.

Age Factors↗
PubMed2005

Transmembrane interaction mediates complex formation between peptidase homologues and Kv4 channels.

An asthma-related peptidase homologue (DPP10) may act as an auxiliary subunit of Kv4 channels, similar to DPPX. Here we show that DPP10 preferentially binds to Kv4 channel proteins to increase current density and alter channel gating. DPP10 also forms complexes by themselves and with DPPX in the absence of Kv4 channels. DPP10 mRNA is abundantly expressed in nodose and dorsal root ganglia, suggesting that DPP10 participates in controlling airway reactivity and mechanosensation. The region from the N-terminus to the end of the transmembrane of DPP10 mediates its association with the channel, whereas the S1-S2 portion of the channel is sufficient for complex formation. This N-terminal portion of DPP10 also confers all the gating effects produced by the peptidase homologue. Thus, interaction between transmembranes of DPP10/DPPX and Kv4 channel mediates functional complex formation. We call this protein DPPY, instead of DPP10, because of its revealed role as a Kv4 channel regulator.

Alternative Splicing↗
PubMed2005

Single-institution experience in 110 patients with botulinum toxin A injection into bladder or urethra.

OBJECTIVES: To detail, in a review, one institution's 6-year experience using botulinum toxin A (BTX-A) in the bladder and urethra in 110 patients for a variety of lower urinary tract disorders. METHODS: A total of 110 patients (35 men and 75 women, age range 19 to 82 years) received injections of BTX-A into the bladder (n = 42) or urethra (n = 68). Voiding dysfunction included neurogenic detrusor overactivity and/or detrusor sphincter dyssynergia, overactive bladder, bladder neck obstruction, and interstitial cystitis. Under light sedation in most cases, patients were treated with either 100 to 200 U of BTX-A in 4 mL divided in equal doses into the four quadrants of the external sphincter or by injection into the bladder base using 100 to 300 U of BTX-A diluted in approximately 10 to 30 mL of sterile saline. At last follow-up, 27 patients had received additional injections (up to six) at intervals of 6 months or longer. RESULTS: All patients who underwent bladder BTX-A injection had preoperative evidence of involuntary detrusor contractions during urodynamic testing. Analysis of the 110 patients indicated that 67.3% reported a decrease or absence of incontinence. Diaries indicated a decrease in both daytime and nighttime voiding symptoms. Maximal efficacy occurred between 7 and 30 days and lasted for at least 6 months. Condition-specific quality-of-life symptom scores also demonstrated improvement. No long-term complications had occurred at last follow-up. Two women with multiple sclerosis and mild baseline stress urinary incontinence reported increased leakage with stress after BTX-A external sphincter injection, and one woman with multiple sclerosis noted new onset stress urinary incontinence after external sphincter injection. However, they all reported significant improvement in their detrusor sphincter dyssynergia with decreased postvoid residual urine volume, improved uroflow, decreased urge incontinence, and decreased daytime and nighttime frequency. One woman with multiple sclerosis who underwent bladder injection had increased postvoid residual urine volume from 78 to 155 mL. She did not have to perform intermittent catheterization. CONCLUSIONS: BTX-A injection is a safe and promising treatment modality for a variety of lower urinary tract dysfunctions for both skeletal and smooth muscle dysfunction. In our series, BTX-A is equally effective in women as it is in men. When injected into the sphincter, the risk of stress incontinence is low. Bladder injections with BTX-A are effective for not only neurogenic detrusor overactivity, but also overactive bladder. BTX-A can even be considered for interstitial cystitis.

Adolescent↗
PubMed2005

Gene gun particle encoding preproenkephalin cDNA produces analgesia against capsaicin-induced bladder pain in rats.

OBJECTIVES: To evaluate the efficacy of gene therapy using a gene gun or direct injection for the transfer of human preproenkephalin (PPE) plasmid cDNA using a capsaicin-induced bladder pain model in rats. Opioid peptides play an essential role in the modulation of micturition reflex and control of inflammatory pain. PPE is one such precursor molecule. METHODS: Human PPE cDNA was cloned into a modified pCMV plasmid and delivered into the bladder wall of adult female rats by direct injection or gene gun. At 4 and 7 days after gene therapy, continuous cystometrograms were performed under urethane anesthesia by filling the bladder (0.08 mL/min) with saline, followed by 15 muM capsaicin. Immunohistochemical staining was used to detect enkephalins in the bladder after PPE cDNA transfer. RESULTS: The intercontraction interval was decreased after intravesical instillation of capsaicin (65.0% and 63.1% decrease) in the control group or direct PPE gene injection group, respectively. However, the gene gun-treated group showed a significantly reduced response to capsaicin instillation at day 4 and day 7 (intercontraction interval 16.2% and 42.8% decrease, respectively). This analgesic effect was reversed by intravenous naloxone, an opioid antagonist (5 mg/kg). Increased enkephalin immunoreactivity in the bladder was observed in the gene gun-treated group at day 4, which was reduced at day 7. CONCLUSIONS: The PPE gene can be effectively transferred and suppress the nociceptive response in the bladder using the gene gun method. These results support potential clinical application of PPE gene gun delivery system for the treatment of bladder pain and other types of visceral pain.

Analgesia↗
PubMed2005

Antimuscarinic agents exhibit local inhibitory effects on muscarinic receptors in bladder-afferent pathways.

OBJECTIVES: To investigate the potential of antimuscarinic agents for sensory mechanisms in overactive bladder using intravesical instillation. METHODS: Antimuscarinic agents were instilled intravesically in rats using two protocols. In the high-dose protocol, 5 mg atropine, oxybutynin, and dimethindene (M2-selective muscarinic receptor antagonist) were instilled into the bladder, and cystometric parameters, such as bladder capacity, intercontraction interval, pressure threshold, and maximal voiding pressure were monitored. In the low-dose protocol, 0.1 and 0.5 mug/mL oxybutynin, trospium, tolterodine, and dimethindene were continuously infused into the bladder. The doses chosen were based on the calculated urine-excreted concentrations of trospium typically achieved from human oral treatment of 40 mg/day. The effect of carbachol with and without the low-dose agents was then assessed. RESULTS: With the high-dose protocol, bladder capacity, intercontraction interval, and pressure threshold were increased when atropine and oxybutynin were instilled, but not when dimethindene was used. The maximal voiding pressure was not affected by any of the agents tested. In the low-dose protocol, none of the cystometric parameters were altered with antimuscarinic agents alone. The intercontraction interval decreased with intravesical carbachol (65% +/- 0.1% compared with baseline), but this was prevented with concomitant antimuscarinic agents. CONCLUSIONS: We have separated the local inhibitory effects of antimuscarinic agents during the storage phase from a decrease in voiding pressure. Intravesical instillation of antimuscarinic agents at clinically meaningful concentrations also suppressed carbachol-induced bladder overactivity. Antimuscarinic agents may be effective in treating overactive bladder, not only by suppression of muscarinic receptor-mediated detrusor muscle contractions, but also by blocking muscarinic receptors in bladder-afferent pathways.

Acetylcholine↗
PubMed2005

Neurologic recovery and improved detrusor contractility using muscle-derived cells in rat model of unilateral pelvic nerve transection.

OBJECTIVES: To create a model of peripheral neuropathy and explore the potential of using muscle-derived cells (MDCs) to facilitate the regeneration of autonomic nerves and improve bladder function. Damage to the peripheral nerves that innervate the bladder from radical pelvic surgery is refractory to the currently available treatments. METHODS: Rat MDCs were isolated from the gastrocnemius muscle using the preplate technique. The unilateral pelvic nerve was cut in female Sprague-Dawley rats. Three experimental groups were included: control (n = 5); unilateral pelvic nerve transected with sham injection (n = 5); and unilateral pelvic nerve transected with injection of MDC (3 x 10(5) cells/site; n = 5). Two weeks after injection, the intravesical pressures were measured during electrical stimulation of the proximal transected preganglionic nerve. The contralateral major pelvic ganglion was excised to ensure that any observed bladder activity was due exclusively to inputs on the unilateral side. The rats were killed, the experimental side major pelvic ganglion was removed, and enkephalin immunoreactivity was counted. RESULTS: After unilateral pelvic nerve transection, no change occurred in bladder weight or capacity or postvoid residual urine volume. The maximal intravesical pressures for the control, sham, and MDC groups, after the contralateral pelvis had been cut, was 31.7 +/- 10.3, 9.6 +/- 4.5, and 15.2 +/- 7.7 cm H2O, respectively (P <0.05). After transecting the preganglionic pelvic nerve, the intensity of pericellular enkephalin immunoreactivity varicosities was significantly decreased in the sham group but unchanged in the MDC group compared with the control group. CONCLUSIONS: MDCs can promote peripheral autonomic nerve regeneration. The morphologic changes correlated with the functional neurologic recovery effect of MDCs. The underlying neurologic recovery mechanisms of MDCs need to be exploited.

Animals↗
PubMed2005

Botulinum toxin type A improves benign prostatic hyperplasia symptoms in patients with small prostates.

OBJECTIVES: To expand the clinical use of botulinum toxin A (BTX-A) in treating patients with small prostates and symptomatic benign prostatic hyperplasia (BPH). BTX-A injection into the prostate in patients with voiding dysfunction and large prostates has been reported. METHODS: Sixteen men with symptomatic BPH, a prostate volume less than 30 cm3, peak flow rate less than 12 mL/s, and with refractory disease after at least 1 month of alpha-blocker treatment received BTX-A 100 U injection into the prostate transperineally under transrectal ultrasound guidance. The clinical effects were evaluated at baseline and after treatment. RESULTS: No significant local or systemic side effects were observed in any of the patients. All patients reported subjective improvement starting at approximately 1 week and achieved a maximal effect after 1 month that was maintained at 3 and 6 months. At 6 to 12 months (mean 10) of follow-up, no patient had symptom recurrence. The mean prostate volume, symptom score, and quality-of-life index were significantly reduced by 13.3% (from 19.6 +/- 1.2 to 17.0 +/- 1.1 cm3), 52.6% (from 18.8 +/- 1.6 to 8.9 +/- 1.9), and 44.7% (from 3.8 +/- 0.3 to 2.1 +/- 0.3), respectively. The maximal flow rate increased significantly by 39.8% (from 7.3 +/- 0.7 to 11.8 +/- 0.8 mL/s). In 2 patients who underwent biopsy 1 month after BTX-A injection, terminal deoxynucleotidyl-mediated deoxyuridine triphosphate nick end labeling staining demonstrated an increase in apoptotic activity, not only in the glandular component, but also in the stromal component of the prostatic tissue. CONCLUSIONS: BTX-A injected into the prostate is a promising treatment for patients with small prostates and symptomatic BPH.

Aged↗