Bladder acellular matrix graft: in vivo functional properties of the regenerated rat bladder

The purpose of this study was to determine whether the rat urinary bladder augmented by an acellular matrix graft can restore the bladder's low-pressure reservoir function and preserve normal micturition. After partial cystectomy (>50%) and grafting with the bladder acellular matrix graft (BAMG), storage and voiding functions were monitored in 20 rats by means of a specially designed “micturition cage,” leak-point cystography, and cystometry. After 4 months, sections (n = 6) were examined histologically to evaluate regeneration of bladder wall components within the BAMG. Bladder capacity and compliance increased progressively and were significantly higher in the grafted animals than in controls (partial cystectomy only), and volumes per void were significantly higher than in either control or normal animals. At 4 months, the regenerated urothelium, smooth muscle, blood vessels and nerves within the BAMG were qualitatively identical to normal bladder wall. Augmentation cystoplasty with the homologous BAMG leads to morphologic and functional rat bladder regeneration, thus enhancing low-pressure reservoir function and preserving normal micturition. Received: 27 May 1998 / Accepted: 20 October 1998     

Urethral pressure response patterns induced by squeeze in continent and incontinent women

Our aim was to compare the urethral pressure response pattern to pelvic floor muscle contractions in 20–27 years old, nulliparous continent women (n = 31) to that of continent (n = 28) and formerly untreated incontinent (n = 59) (53–63 years old) women. These women underwent urethral pressure measurements during rest and repeated pelvic muscle contractions. The response to the contractions was graded 0–4. The young continent women showed a mean urethral pressure response of 2.8, the middle-aged continent women 2.2 (NS vs young continent), and the incontinent women 1.5 (p < 0.05 vs middle-aged continent, p < 0.001 vs young continent). Urethral pressures during rest were significantly higher in the younger women than in both groups of middle-aged women. The decreased ability to increase urethral pressure on demand seen in middle-aged incontinent women compared to continent women of the same age as well as young women seems to be a consequence of a neuromuscular disorder rather than of age.     

The effect of capsaicin pretreatment on the cystometrograms of urethane anesthetized rats

Administration of capsaicin to newborn rats produced a slight but significant increase in bladder weight and markedly altered the cystometrograms of urethane anesthetized rats. In particular capsaicin pretreatment significantly increase micturition threshold. In many of these preparations the bladders exhibited a hypertonic response to saline filling; the flat phase of the cystometrogram was not observed. Capsaicin pretreatment of adult animals increased micturition threshold up to 1 month from capsaicin administration. In these preparations a flat volume-pressure relationship preceded micturition contractions. Administration of capsaicin to both newborn and adult animals did not alter the amplitude of micturition contractions. Intravesical installation of capsaicin had an acute excitatory effect on the responsiveness of the urinary bladder to reflex activation. These findings indicate that capsaicin pretreatment produces a functional impairment of the sensory branch of micturition reflexes and suggest that a capsaicin-sensitive mechanism(s) is involved in the regulation of micturition threshold.     

Rapid effects of estrogen and progesterone on tone and spontaneous rhythmic contractions of the rabbit bladder

Previous studies indicate that bladder instability in man may be associated with increased spontaneous rhythmic contractile activity. Ca²⁺ influx plays a central role in smooth muscle contractions, and recent evidence suggests that steroid hormones rapidly affect Ca²⁺ influx. Therefore we tested the hypothesis that estrogen and progesterone modulates spontaneous rhythmic detrusor contractions. Tissues were secured to isometric force (F) transducers in tissue baths and length-adjusted until K⁺-depolarization produced maximum contractions (F_o). Spontaneous rhythmic contractions (SRC) were sampled before and immediately after addition of estradiol or progesterone (10⁻⁵ M) to tissue baths. The average frequency and amplitude of SRC were, respectively, 0.156 Hz and 0.053 F/F_o (n = 24). Estradiol caused an immediate reduction in SRC, such that by 10 min, tone, frequency and amplitude were each reduced by, respectively, 36%, 46% and 47% (n = 7, P < 0.05). However, progesterone caused an immediate weak contraction, and at steady state (10 min), progesterone increased frequency of SRC by 152% but decreased SRC amplitude by 50% (n = 10, P < 0.05). Novel therapies using unique steroids that do not interact with genomic receptors may potentially reduce bladder smooth muscle activity, thereby reducing detrusor instability. Received: 3 December 1998 / Accepted: 4 March 1999     

Effect of Intra-Abdominal Position of the Bladder Neck and Stability of its Supporting Structures on Pressure Transmission Ratio After Colposuspension

The aim of this prospective study was to evaluate the influence of the higher intra-abdominal position of the bladder neck and the stability of its supporting structures after colposuspension, on pressure transmission to the urethra at the level of the bladder neck. Twenty-eight patients were included in the study. The pressure transmission ratio (PTR) was calculated at the level of the bladder neck, whereas the position and mobility of the bladder neck during coughing were evaluated with perineal ultrasound examination. The measurements were performed before and 3 months after colposuspension. After colposuspension we found a significant elevation of the PTR (P = 0.001), a significantly higher intra-abdominal position (P = 0.001) and decreased mobility (P = 0.001) of the bladder neck during coughing. Also, a negative correlation between the elevation of PTR and decreased mobility of the bladder neck during coughing (r=−0.5049; P = 0.006) and a weak correlation between the elevation of PTR and a higher intra-abdominal position of the bladder neck during coughing were found (r= 0.3828; P = 0.044). Reinforced tension resistance of the bladder neck supporting structures seems to be more important than intra-abdominal position of the bladder neck in achieving effective pressure transmission after colposuspension.     

Effect of aging on bladder function and the response to outlet obstruction in female rats

Bladder dysfunction in the aging population is a significant problem. However the concomitant presence of other diseases in many patients can make it difficult to distinguish between changes in bladder function and other influences. The present study was designed to study, in aging rats, bladder function and the effect of partial bladder outlet obstruction (BOO) on bladder function. Cystometrics were performed in awake, female Fischer 344 rats of four age groups (6, 12, 18 and 24 months) following subcutaneous implantation of a mediport catheter. Cystometric evaluations were carried out in control rats or those subject to three weeks of BOO. Bladder compliance significantly decreased with aging, which reflected an increase in threshold pressure without changes in bladder capacity. Partial BOO caused development of severe bladder instability. Following BOO, bladder capacity and compliance were significantly increased in all age groups. Threshold pressure was lower in obstructed animals, except for 6-month rats. Younger animals were able to generate a higher contraction pressure to compensate for the BOO, whereas older animals did not. Using an awake model of cystometric measurement, we have demonstrated that aging, by itself can affect bladder function. Furthermore, aged animals respond differently to BOO than younger animals. These results demonstrate that both aging and disease can contribute to bladder dysfunction, and suggest that treatment of bladder dysfunction may require a combination of therapies targeted to multiple etiologies. Received: 18 August 1998 / Accepted: 6 July 1999     

Morphometric and histological analysis of low-power laser influence on bone morphogenetic protein in bone defects repair

Bone morphogenetic proteins (BMPs) are secreted signaling molecules belonging to the transforming growth factor-β (TGF-β) superfamily. The objective of this study was to determine how gallium–aluminum–arsenium (GaAlAs) 650 nm laser influenced the action of BMPs on bone defects created in rat femurs. The sample consisted of 24 male albino Wistar rats. Group 1 was composed of rats with bone defects filled with bone-inducing substance, with the application of low-power laser. Group 2 contained rats with bone defects filled with a bone-inducing substance, without the application of low-power laser. Group 3 rats had bone defects not filled with a bone-inducing substance, with the application of low-power laser. Group 4 rats had bone defects and no treatment (control group). A bone defect was produced with drills. In groups 1 and 2 the defects were filled with a bone-inducing substance. The animals were treated with GaAlAs (50 mW) laser, energy density 4J/cm², for 80 ss on a 1 cm² area. Groups 2 and 4 were used as control. Bone samples were removed for histological procedures and morphometric analysis on the 7th, 14th and 21st days after surgery. Results obtained were subjected to statistical analysis. Rejection level for the null hypothesis was 0.05. Statistical differences were found in the comparison between group 1 (G1), G2, G3 and G4 [analysis of variance (ANOVA); P < 0.0134]. There was a statistically significant correlation between groups 1 and 4 (P < 0.01). The results of other correlations by Tukey’s post-hoc test were: group 1 vs group 3 (P = 0.341), group 1 vs group 2 (P = 0.862), group 2 vs group 4 (P = 0.061), group 2 vs group 3 (P = 0.744), and group 3 vs group 4 (P = 0.249). We concluded that the association of low-power laser with a bone-inducing substance produced better results than when low-power laser or BMPs were used alone.     

Comparison of transperineal and transabdominal ultrasound in the assessment of voluntary pelvic floor muscle contractions and functional manoeuvres in continent and incontinent women

Transperineal (TP) and transabdominal (TA) ultrasounds were used to assess bladder neck (TP) and bladder base (TA) movement during voluntary pelvic floor muscle (PFM) contraction and functional tasks. A sonographer assessed 60 asymptomatic (30 nulliparous, 30 parous) and 60 incontinent (30 stress, 30 urge) women with a mean age of 43 (SD = 7) years, BMI of 24 (SD = 4) kg m² and a median parity of 2 (range, 0–5), using both ultrasound methods. The mean of three measurements for bladder neck and bladder base (sagittal view) movement for each task was assessed for differences between the groups. There were no differences in bladder neck (p = 0.096) or bladder base (p = 0.112) movement between the four groups during voluntary PFM contraction but significant differences in bladder neck (p < 0.004) and a trend towards differences in bladder base (p = 0.068) movement during Valsalva and abdominal curl manoeuvre. During PFM contraction, there was a strong trend for the continent women to have greater bladder neck elevation (p = 0.051), but no difference in bladder base movement (p = 0.300), when compared to the incontinent women. The incontinent women demonstrated increased bladder neck descent during Valsalva and abdominal curl (p < 0.001) and bladder base descent during Valsalva (p = 0.021). The differences between the groups were more marked during functional activities, suggesting that comprehensive assessment of the PFM should include functional activities as well as voluntary PFM contractions. TP ultrasound was more reliable and takes measures from a bony landmark when compared to TA ultrasound, which lacks a reference point for measurements. TA ultrasound is less suitable for PFM measures during functional manoeuvres and comparisons between subjects. Few subjects were overweight so the results may not be valid in an obese population.     

Randomized controlled trial of foot reflexology for patients with symptomatic idiopathic detrusor overactivity

The aim of this study was to examine whether foot reflexology has beneficial effects on patients with idiopathic detrusor overactivity. One hundred and nine women with symptomatic idiopathic detrusor overactivity were randomized into either foot reflexology treatment group or nonspecific foot massage control group. The primary outcome measure was the change in the diurnal micturition frequency. There was significant change in the number of daytime frequency in the reflexology group when compared with the massage group (−1.90 vs −0.55, p = 0.029). There was also a decrease in the 24-h micturition frequency in both groups, but the change was not statistically significant (−2.80 vs −1.04 p = 0.055). In the reflexology group, more patients believed to have received “true” reflexology (88.9 vs 67.4%, p = 0.012). This reflects the difficulty of blinding in trials of reflexology. Larger scale studies with a better-designed control group and an improved blinding are required to examine if reflexology is effective in improving patients’ overall outcome.     

Does bladder neck descent increase with age?

It is assumed that pelvic organ descent and prolapse increase with age. Epidemiological studies support this assumption. We aimed to define the relationship between age and bladder neck descent (BND) in a retrospective observational study on 790 women referred for evaluation of pelvic floor disorders. Bladder neck descent, cystocele descent and urethral rotation were evaluated on maximal Valsalva manoeuvre, using trans-labial ultrasound. There was a weak negative correlation between bladder neck descent on Valsalva and age (r = −0.154, p < 0.001), which was absent in nulliparous women (n = 107) and stronger (r = −0.213, p < 0.001) in parous women (n = 683). This relationship was evident from the age of 50 years onwards and may be explained by increased tissue stiffness after menopause. The difference observed between parous and nulliparous women is intriguing and raises the issue of obstetric confounders such as historical changes in the likelihood of significant pelvic floor trauma.     

Efficacy of tolterodine on overactive bladder symptoms and sexual and emotional quality of life in sexually active women

We evaluated overactive bladder (OAB) symptoms and sexual and emotional health in sexually active women with OAB/urgency urinary incontinence (UUI) treated with tolterodine extended release (ER). Sexually active women with OAB symptoms were randomized to placebo or tolterodine ER. Five-day bladder diaries, Sexual Quality of Life Questionnaire—Female (SQOL-F), Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ), and Hospital Anxiety and Depression Scale (HAD) were completed at baseline and week 12. Tolterodine ER (n = 201; mean ± SD age, 49 ± 12 years) reduced UUI episodes (P = 0.0029), total (P = 0.0006) and OAB (P < 0.0001) micturitions, and pad use per 24 h (P = 0.0024), and was associated with improvements in SQOL-F (P = 0.004), PISQ total (P = 0.009), and HAD Anxiety (P = 0.03) scores versus placebo (n = 210; mean ± SD age, 47 ± 12 years). OAB symptoms improved with tolterodine ER as did the scores of sexual health and anxiety measures in sexually active women with OAB.     

Partial outlet obstruction induces chronic distension and increased stiffness of rat urinary bladder

In order to identify the passive properties of the bladder during filling, we measured cystometrograms (CMGs) of rat urinary bladders that had been outlet obstructed for 6 weeks and age-matched controls in conscious, unrestrained animals and in fully relaxed whole bladders in an organ bath. In the organ bath, each bladder was allowed to empty passively at zero transmural pressure. The volume remaining was labelled zero pressure volume (ZPV) and was used as the reference volume to normalize contained volume, deriving wall stretch. Increased ZPV implies that the bladder contains more urine at low stresses and therefore is more distended. In awake animals, the obstructed bladder CMGs showed spontaneous contractions. The pressures between contractions were similar to those in CMGs performed in the organ bath, suggesting that passive properties determine the minimum pressures during filling in vivo. The ZPV of the obstructed and control bladders was 1.07 ± 0.12 ml and 0.07 ± 0.01 ml, respectively. The differences were significant (P < 0.01). The ZPV correlated with bladder weight and thus with degree of hypertrophy. Under conditions when weight cannot be determined, e.g., clinically, ZPV may provide a useful measure of the degree of chronic distension and bladder hypertrophy. The pressure-volume curves of the obstructed bladder CMGs in vitro varied between preparations. However, when pressure-volume was converted to stress-stretch using the law of Laplace, the obstructed bladders were all significantly stiffer than the controls. We confirmed this result by step-stretching relaxed bladder strips. The obstructed bladder strips again demonstrated stiffer stress-stretch curves than the controls. © Wiley-Liss, Inc.     

Traditional Versus Single-site Placement of Adjustable Gastric Banding: A Comparative Study and Cost Analysis

In bariatric surgery, laparoscopic adjustable gastric banding (LAGB) has proven effective in reducing weight and improving obesity-associated comorbidities. Recently, however, laparoendoscopic single-site (LESS) surgery has been proposed to minimize the invasiveness of laparoscopic surgery. The aim of this study is to compare the operative cost and peri-operative outcomes of these two approaches. We undertook a retrospective review of a prospectively maintained database of patients undergoing either LAGB or LESS between March 2006 and October 2009. The outcomes and cost of 25 LESS gastric bandings were compared to 121 standard LAGB. Costs included operative time, consumables, and laparoscopic tower depreciation. Both groups had similar patient demographics, body mass index, and comorbidities; with the exception of age (37 year for single site vs. 44 years for standard; P = 0.002). There were no statistical differences for operative time (78 vs. 76 min, P = 0.69), blood loss (8.4 vs. 9 ml, P = 0.76), pain score (0.81 vs. 0.84 at 1 week, P = 0.95) or complication rates (12% vs. 14%, P = 1). Length of stay was shorter for the LESS group (0.5 day vs. 1.5 days, P = 0.02). The mean operative cost for the LESS banding was 20,502/case vs.20,502/case vs. 20,346/case for the standard LAGB, with no statistically significant difference between the approaches (P = 0.73). Operative costs and peri-operative outcomes of LESS gastric banding are comparable with those of the standard LAGB procedure. As a result, single-site surgery can be proposed as a valid alternative to the standard procedure with cosmetic advantage and comparable complication rate.     

Focal and segmental glomerulosclerosis in children: a longitudinal assessment

Recent data suggest that the histologic finding of focal and segmental glomerulosclerosis (FSGS) is increasing among children. There are, however, limited longitudinal pediatric data on prevalence, demographics, and steroid responsiveness in FSGS. We identified 201 consecutive nephrotic children diagnosed between 1977 and 2002 with 2 years follow-up; 51% had undergone renal biopsy due to steroid sequelae or resistance; 48 children with FSGS were diagnosed. Compared with non-FSGS children, FSGS children were older at diagnosis (6.9 years vs 4.4 years, P < 0.02), more likely girls (54% vs 28%, P < 0.02), Black or Hispanic (42% vs 16%, P < 0.001), and the FSGS was more likely to be steroid resistant (73% vs 10%, P < 0.001). To assess for longitudinal differences, we grouped children by presentation: pre-1985, between 1985 and 1995, and post-1995. There was no difference in proportion of children biopsied or diagnosed with FSGS during each interval. Among FSGS children, there was no difference in racial or gender composition in each period, but there was a difference in age at diagnosis (2.6 vs 5.7 vs 8.5 years; P = 0.01), also observed in the non-FSGS children (2.2 vs 3.9 vs 4.9 years; P = 0.02). In contradistinction to non-FSGS children, there was a marked increase in steroid resistance with FSGS (43% vs 62% vs 86%; P = 0.03).     

Pre-pubertal induction of experimental diabetes protects against early renal macrophage infiltration

The present study was undertaken to identify whether the age at induction of experimental diabetes modifies macrophage infiltration in the kidney. Renal macrophage infiltration was studied 10 days after the induction of experimental diabetes in 4-week-old pre-pubertal and 12-week-old adult male rats of normotensive [Wistar-Kyoto (WKY) rats] and hypertensive (spontaneously hypertensive rats, SHRs) background. Renal macrophage infiltration was evaluated by immunohistochemistry for ED1. Plasma glucose levels were similar in all diabetic groups. Adult SHRs were hypertensive, and induction of diabetes did not alter blood pressure (BP) in any group. Induction of diabetes in pre-pubertal rats did not induce macrophage infiltration in the kidney. However, in adult rats, tubulointerstitial macrophage infiltration was increased in both WKY (22.86 ± 3.93 vs 7.86 ± 2.16 per high-power field, P < 0.001) and SHR (26.41 ± 5.91 vs 11.48 ± 1.23, P < 0.001) groups after induction of diabetes. Glomerular macrophage infiltration was also increased after induction of diabetes in the adult WKY group (1.83 ± 0.50 vs 1.16 ± 0.26 per glomerular cross section, P = 0.029), which was not significant in the adult SHRs (2.52 ± 0.34 vs 1.95 ± 0.35). We conclude that the pre-pubertal induction of diabetes apparently protects against early renal macrophage infiltration, while the induction of diabetes in adults induces exaggerated macrophage infiltration in the kidney.     

Basal Serum Prolactin Levels in Obesity—Unrelated to Parameters of the Metabolic Syndrome and Unchanged After Massive Weight Loss

Background  Prolactin (PRL) has been proposed to play an important role in the pathophysiology of obesity. To further elucidate the relationship between PRL and obesity-related metabolic disturbances, we performed a large cross-sectional study and also reassessed serum PRL levels in a subsample ~1 year after gastric bypass surgery. Methods  In the cross-sectional part of the study, we assessed basal serum PRL levels in 344 obese subjects (68% women; BMI mean ± SD, 44.3 ± 6.6 kg/m²; range 27.0–67.0 kg/m²) along with measurements of glucose, insulin, C-peptide, triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol, high sensitive (hs) C-reactive protein, and fat mass assessed by bioelectrical impedance analysis. In 38 patients, we reassessed PRL levels ~1 year after they have undergone a gastric bypass operation. Results  Women displayed higher basal PRL levels than men (9.0 ± 4.8 vs. 7.9 ± 3.6 μg/l, P = 0.03). Basal PRL levels were neither significantly correlated with the BMI of the subjects (r = −0.05, P = 0.77) nor with any other of the assessed variables (all r < 0.16, P > 0.06) even after adjusting for the influence of sex. After massive surgically induced weight loss that on average almost approached 50 kg, basal serum PRL levels remained completely unchanged (before vs. after, 9.1 ± 6.0 vs. 9.2 ± 4.6 μg/l, P = 0.86). However, preoperative PRL levels significantly correlated with that assessed after the operation (r = 0.47; P = 0.005). Conclusions  In contrast to our expectation, we could detect neither any significant association between basal PRL levels and the degree of obesity or related metabolic disturbances nor any systematic changes in basal concentrations of the hormone after massive weight loss. In sum, our data do not support the notion of a major role of PRL in the pathophysiology of obesity. The authors have no commercial interest to disclose. The study was financially supported by a grant from Johnson & Johnson. The funder had no role in the study design, analysis, and publication of the data.     

Resection of Hepatic Colorectal Metastases Involving the Caudate Lobe: Perioperative Outcome and Survival

Purpose: To examine clinical features and outcome of patients who underwent hepatic resection for colorectal liver metastases (LM) involving the caudate lobe. Patients and Methods: Consecutive patients who underwent hepatic resection for LM from May 1990 to September 2004 were analyzed from a multicenter database. Demographics, operative data, pathologic margin status, recurrence, and survival were analyzed. Results: Of 580 patients, 40 (7%) had LM involving the caudate. Six had isolated caudate LM and 34 had LM involving the caudate plus one or more other hepatic segments. Patients with caudate LM were more likely to have synchronous primary colorectal cancer (63% vs. 36%; P = 0.01), multiple LM (70% vs. 51%; P = 0.02) and required extended hepatic resection more often than patients with non-caudate LM (60% vs. 18%; P < 0.001). Only four patients with caudate LM underwent a vascular resection; three at first operation, one after recurrence of a resected caudate tumor. All had primary repair (vena cava, n = 3; portal vein, n = 1). Perioperative complications (43% vs. 28%) and 60-day operative mortality (0% vs. 1%) were similar (caudate vs. non-caudate LM, both P > 0.05). Pathological margins were positive in 15 (38%) patients with caudate LM and in 43 (8%) with non-caudate LM (P < 0.001). At a median follow-up of 40 months, 25 (64%) patients with caudate LM recurred compared with 219 (40%) patients with non-caudate LM (P = 0.01). Patients with caudate LM were more likely to have intrahepatic disease as a component of recurrence (caudate: 51% vs. non-caudate: 25%; P = 0.001). No patient recurred on the vena cava or portal vein. Patients with caudate LM had shorter 5-year disease-free and overall survival than patients with non-caudate LM (disease-free: 24% vs. 44%; P = 0.02; overall: 41% vs. 58%; P = 0.02). Conclusions: Patients who undergo hepatic resection for caudate LM often present with multiple hepatic tumors and tumors in proximity to the major hepatic veins. Extended hepatectomy is required in the majority, although vascular resection is not frequently necessary; when performed, primary repair is usually possible. Despite resection in this population of patients with multiple and bilateral tumors, and despite close-margin and positive-margin resection in a significant proportion, recurrence on the portal vein or vena cava was not observed, and long-term survival is accomplished (41% 5-year overall survival). These data were presented at the American Hepato-Pancreato-Biliary Association 2006 Annual Meeting, Miami, Florida, March 12, 2006.     

Baroreceptor-heart rate reflex sensitivity enhancement after urinary bladder distention in essential hypertensives

Our objective was to determine if urinary bladder distention modifies the sensitivity of the baroreceptor-heart rate reflex in hypertensive and control subjects. The baroreceptor-heart rate reflex sensitivity was measured in 15 male patients (mean age 37 ± 8 years) with mild untreated hypertension (mean 163 ± 8/95 ± 12 mmHg) and 17 age- and sex-matched control subjects before and after urinary bladder distention. Bladder filling was performed infusing saline heated to 37°C via a urinary catheter; the volume infused in each patient corresponded to that which caused the urge to void without reaching the pain threshold. The baroreceptor-heart rate reflex sensitivity was determined correlating the variations of the systolic pressure and of the peak blood flow velocity in the common carotid artery with the variations of the ECG RR′ interval of the following heart beat, both during spontaneous and phenylephrine-induced fluctuations of the haemodynamic variables. After bladder distention the diastolic pressure of the hypertensive subjects increased significantly (95 ± 12 vs. 100 ± 12 mmHg; P < 0.02), whereas the heart rate decreased (RR=873 ± 70 vs. 926 ± 80 ms; P < 0.005). These parameters were unchanged in the normotensive subjects (84 ± 9 vs. 83 ± 8 mmHg and 914 ± 158 vs. 913±140 ms, respectively). The baroreceptor-heart rate reflex sensitivity, measured on the basis of spontaneous pressure and carotid blood flow velocity fluctuations in relationship to RR changes, decreased in the normotensive subjects after bladder distention (10.7 ± 4.6 vs. 9.4 ± 2.7 ms/mmHg; P < 0.05 and 423 ± 99 vs. 356 ± 102 ms/kHz; P < 0.01, respectively), whereas it increased in the hypertensive patients (6.9 ± 3.6 vs. 8.3 ± 2.8 ms/mmHg; P < 0.03, and 332 ± 86 vs. 381 ± 97 ms/kHz; P < 0.03 respectively). After bladder distention and phenylephrine administration the baroreceptor-heart rate reflex sensitivity, measured by the correlation between systolic pressure and RR interval, increased only in the hypertensive group (10.2 ± 5.4 vs. 15.2 ± 7.7 ms/mmHg; P < 0.005). In conclusion urinary bladder distention provokes in hypertensives but not normotensive controls a brisk parasympathetic response of the component of the baroreceptor-heart rate reflex which controls heart rate. Received: 17 June 1998 / Accepted: 20 October 1998     

Inhibition of diabetic bladder smooth muscle cell proliferation by endothelin receptor antagonists

Urinary bladder hypertrophy and hyperplasia are well recognised in diabetic cystopathy. The urinary bladder is known to synthesise endothelin-1 (ET-1), a potent vasoconstrictor peptide with mitogenic properties. Using diabetic New Zealand White (NZW) rabbits, we investigated the potential role of ET receptor subtypes (ET_A and ET_B) on the proliferation of bladder smooth muscle cells (SMC). Diabetes mellitus was induced in adult male NZW rabbits. After 6 months, control (n=6) and diabetic (n=6) bladders were removed and SMC from the dome and bladder neck were grown using standard explant methodology. At passage two, the cells were made quiescent and then further incubated in foetal calf serum (FCS), control age-matched rabbit serum (CRS) or diabetic rabbit serum (DRS) in the presence or absence of ET_A-antagonist (BQ123) or ET_B-antagonist (BQ788). SMC proliferation was then measured with 5-bromo-2′deoxy-uracil 24 h later and by cell counting (using a haemocytometer) at 48 h. Neither BQ123 nor BQ788 influenced detrusor or bladder neck SMC proliferation in FCS or CRS. However, in the presence of DRS, BQ123 and BQ788 significantly inhibited diabetic detrusor and bladder neck SMC proliferation at 30 and 100 nmol/l (P < 0.03 and P < 0.01, respectively). Cell counts were also significantly reduced from the diabetic detrusor and bladder neck (P < 0.01 and P < 0.03 with BQ123 and BQ788, respectively). These results suggest that ET may play a pathophysiological role in the bladder SMC hyperplasia associated with diabetes mellitus. Received: 24 November 1999 / Accepted: 21 March 2000     

Central Expressions of Ghrelin and Cholecystokinin in Rats with Gastric Electrical Stimulation

Background Gastric electrical stimulation (GES) has recently been proposed for the treatment of obesity. The aim of this study was to explore the possible central mechanisms involved in GES by investigating the expression of orexigenic and anorexigenic peptides in the rodent hypothalamus and hippocampus. Methods The experiment was designed in two parts: an acute experiment with 2 h GES and a chronic experiment with 14-day continuous GES. After stimulation, the expressions of an orexigenic hormone, ghrelin, in the hypothalamus and an anorexigenic hormone, cholecystokinin (CCK), in the hippocampus were detected by the immunohistochemical method. GES was performed using parameters similar to those used in clinical studies for treating obesity. Results Compared with the control group, 2 h GES resulted in a decrease in the number of ghrelin-immunoreactive (ghrelin-IR) neurons in the hypothalamic paraventricular nucleus (PVN, 34.8 ± 1.86 vs 57.2 ± 2.95, P = 0.02) and the supraoptic nucleus (SON, 51.2 ± 3.21 vs 82.8 ± 3.08, P = 0.01); the CCK-immunoreactive (CCK-IR) neurons in the hippocampus were of no changes (7.4 ± 0.87 vs 6.2 ± 0.58, P = 0.29). After the 14-day GES, the number of CCK-IR neurons in the hippocampus was increased compared with that of the control group (4.0 ± 0.32 vs 2.4 ± 0.51, P = 0.03). However, there were no changes in the number of ghrelin-IR neurons either in the PVN or in the SON. Conclusions These results indicate that the expression of ghrelin and CCK can be altered by GES. GES may be able to alter energy homeostasis by modulating the expressions of food intake-related hormones in the central nervous system: reducing the level of orexigenic ghrelin acutely and increasing the level of anorexigenic CCK chronically.