NeuroAiD® (MLC601) and amyloid precursor protein processing.

BACKGROUND: Amyloid precursor protein (APP) undergoes cleavage under physiological conditions, predominantly by α- and γ-secretases, to form the nonpathogenic sAPPα and p3 fragments. By contrast, amyloid-beta (Aß) is produced via proteolytic cleavage by ß- and γ-secretases. In Alzheimer's disease (AD), APP is preferentially processed via the amyloidogenic pathway, producing large amounts of Aß that form the major constituent of senile plaques and tau-containing neurofibrillary tangles. Similarly, stroke patients have a higher level of Aß around the area of infarct, suggesting that Aß may mediate at least some of the secondary neurotoxicity observed in stroke patients. METHODS: To investigate the effects of MLC601 (NeuroAiD(®)) on regulation of APP processing, the human neuroblastoma cell line SH-SY5Y was used for all experiments. Stocks of MLC601 were prepared at a final concentration of 50 mg/ml. Cells were treated with different concentrations of MLC601 before assessing changes in the levels of released lactate dehydrogenase (LDH), full-length APP and secreted sAPPα. RESULTS: Concentrations of MLC601 between 1 and 1,000 µg/ml significantly lowered the levels of LDH released into the media when compared to control cells. In contrast, MLC601 concentrations at 5,000 and 10,000 µg/ml resulted in a significant increase in the LDH release. Treatment with 100, 500 and 1,000 µg/ml of MLC601 significantly increases the levels of sAPPα secreted by SH-SY5Y into the media. Treatment with 1,000 µg/ml of MLC601 significantly decreased the levels of full-length APP. CONCLUSION: MLC601 is a possible modulator of APP processing and has implications as a putative therapeutic strategy for the treatment of poststroke dementia and AD.

Anticipatory and consummatory components of the experience of pleasure in schizophrenia: cross-cultural validation and extension.

This study examined anticipatory and consummatory pleasure in schizophrenia patients with and without negative symptoms. Negative symptom patients experienced less anticipatory pleasure than non-negative symptom patients; only one facet of consummatory pleasure was unaffected in negative schizophrenia. Greater pleasure deficits were correlated with more severe positive and negative symptoms.

Loss of [3H]4-DAMP binding to muscarinic receptors in the orbitofrontal cortex of Alzheimer's disease patients with psychosis.

RATIONALE: Neuropsychiatric behaviours in Alzheimer's disease (AD) patients have been associated with neocortical alterations of presynaptic cholinergic and muscarinic M2 receptor markers. In contrast, it is unclear whether non-M2 muscarinic receptors have a role to play in AD behavioural symptoms. OBJECTIVES: To correlate the alterations of neocortical postsynaptic muscarinic receptors with clinical features of AD. MATERIALS AND METHODS: [(3)H]4-DAMP were used in binding assays with lysates of Chinese hamster ovary (CHO) cells stably transfected with M1-M5 receptors. [(3)H]4-DAMP was further used to measure muscarinic receptors in the postmortem orbitofrontal cortex of aged controls and AD patients longitudinally assessed for cognitive decline and behavioural symptoms. RESULTS: [(3)H]4-DAMP binds to human postmortem brain homogenates and M1-, M3-, M4- and M5-transfected CHO lysates with subnanomolar affinity. Compared to the controls, the [(3)H]4-DAMP binding density is reduced only in AD patients with significant psychotic symptoms. The association between reduced [(3)H]4-DAMP binding and psychosis is independent of the effects of dementia severity or neurofibrillary tangle burden. CONCLUSIONS: This study suggests that the loss of non-M2 muscarinic receptors in the orbitofrontal cortex may be a neurochemical substrate of psychosis in AD and provides a rationale for further development of muscarinic receptor ligands in AD pharmacotherapy.

Optimal C2 concentration of cyclosporin corrected with good efficacy and safety in Asian kidney transplant recipients.

INTRODUCTION: Calcineurin inhibitors (CNI) are known for their renal toxicity. Lower CNI exposure is a reasonable option to mitigate potential CNI-induced renal toxicity. Herein we have presented our long-term results after lower cyclosporine (CsA) exposure in the first year. MATERIALS AND METHODS: Between 1997 and 2004, 63 renal transplant recipients received CsA-based immunosuppression. CsA dosing was adjusted according to the 2-hour whole blood concentration (C2) level. We retrospectively reviewed acute rejection and graft survivals rates, as well as whole blood C2 levels. RESULTS: Review of serial mean C2 concentrations at 1, 2, 3, 6, and 12 months after transplantation were 1341, 1241, 1191, 1059, and 927 ng/mL, respectively. These levels were slightly lower than those suggested by the Consensus for C2 levels by Levy et al in 2002, namely, 1600 to 2000 ng/mL (mean, 1700); 1400 to 1600 ng/mL (mean, 1500); 1200 to 1400 ng/mL (mean, 1300); 1000 to 1200 ng/mL (mean, 1100), and 800 to 1000 ng/mL (mean, 900), respectively. Acute rejection rate at 3 months and 1 year are 17.5% and 23.8%. Graft survival at 1 year was 97% and at 5 years, 89%. Two patient were lost to fulminant hepatitis and acute myocardial infarction during the first year, which were not associated with underimmunosuppression. CONCLUSION: Appropriate CsA C2 levels may be lower among Taiwanese. Our C2 dosing strategy resulted in good outcomes with acceptable side effects in our single-center experience. Appropriate CsA C2 levels for Asians deserve more attention in trials of larger scale; most reference levels are presently concluded from studies of Caucasians.

Sirolimus does not absolutely abolish the occurrence/recurrence of urothelial carcinoma in renal transplant recipients.

OBJECTIVE: Sirolimus (SRL), an immunosuppressant shown to possess anti-proliferative properties, was hypothesized to mitigate the occurrence of posttransplantation malignancy. We examined its effect on posttransplantation urothelial carcinoma (UC). METHODS: This retrospective case analysis included renal allograft recipients with UC treated with SRL in a single institute. RESULTS: Among 90 renal recipients treated with SRL, 6 had previous/new-onset UC in the native kidney/ureter or bladder: at a mean period of 28 months (range, 7-49) of administering SRL for these recipients, UC occurred/recurred in 4 of the 6 patients. Individual cases are presented in detail. CONCLUSION: SRL does not absolutely abolish the occurrence/recurrence of UC among renal transplant recipients. Its potency as an anti-cancerous immunosuppressant for transplant recipients with UC deserves to be further defined in larger studies, probably by controlling SRL blood levels at lower or much higher ranges than used herein.

Latent structure of the Test of Everyday Attention in a non-clinical Chinese sample.

The validity and clinical viability of Posner and Petersen's (1999) 3-factor model of attention was tested through a confirmatory factor analysis of attentional performance (Test of Everyday Attention [Robertson, I. H., Ward, T., Ridgeway, V., & Nimmo-Smith, I. (1996). The structure of normal human attention: The Test of Everyday Attention. Journal of the International Neuropsychological Society, 2, 525-534]) in a sample of 133 Chinese participants. This study served both as a cross-cultural replication of the clinical implementation of this leading theoretical model of attention, and as a more stringent test of the validity of the hypothesized attentional processes underlying human cognitive control. The results support the validity of a 3-factor model of attention consistent with that proposed by Posner and Petersen (selective attention, sustained attention, and attentional switching/control), and demonstrate that clinical assessment of neuroanatomically-distinct attentional processes using simulated real life activities is possible.

Loss of serotonin 5-HT2A receptors in the postmortem temporal cortex correlates with rate of cognitive decline in Alzheimer's disease.

RATIONALE: Previous studies have demonstrated reductions of serotonin 5-HT 2A receptors in the neocortex of Alzheimer's disease (AD) patients. However, it is unclear whether such losses play a role in the cognitive decline of AD. OBJECTIVES: To correlate neocortical 5-HT 2A receptor alterations with cognitive decline in AD. METHODS: Postmortem frontal and temporal cortical 5-HT 2A receptors were measured by [3H]ketanserin binding in aged controls as well as in a cohort of AD patients who had been longitudinally assessed for cognitive decline and behavioral symptoms. RESULTS: 5-HT 2A receptor densities in both regions were reduced in severely demented AD patients compared to age-matched controls. In the temporal cortex, this reduction also correlated with the rate of decline of Mini-Mental State Examination (MMSE) scores. The association between 5-HT 2A receptor loss and cognitive decline was independent of the effects of choline acetyltransferase (ChAT) activity and presence of behavioral symptoms. CONCLUSIONS: Our data suggest that loss of neocortical 5-HT 2A receptors may predict for faster cognitive decline in AD, and point to serotomimetics as potentially useful adjuvants to cholinergic replacement therapies.

The early diagnosis of atypical thyroid acropachy.

The differential diagnosis of the condition of a patient with acral thickening and normal bone roentgenograms but without obvious signs of Graves' disease may be perplexing. A patient was seen with this disorder, in which the early diagnosis of thyroid acropachy could not be made roentgenographically but was accomplished by bone-scanning techniques. To our knowledge, this is the first demonstration of the evolution of thyroid acropachy, as temporally proved by serial roentgenograms and bone radiographs. The patient complained of severe swelling and decreased finger mobility. His hands were treated in a novel manner, using fluorinated topical steroids under an occlusive dressing, because of the failure of previously described localized medical therapeutic regimens. Treatment, using one hand as a control, resulted in a substantial decrease in hand circumference and volume, as well as increased finger mobility.

Psychosis of Alzheimer's disease is associated with elevated muscarinic M2 binding in the cortex.

OBJECTIVES: Results from recent drug trials suggest a role for the cholinergic system in the manifestation of neuropsychiatric symptoms in AD. To date, the status of muscarinic acetylcholine receptor subtypes in AD in relation to accompanying behavioral disturbances is unknown. This study aimed to measure alterations of muscarinic M(1) and M(2) receptor binding in the frontal and temporal cortex of AD and to correlate the neurochemical findings with clinical features. METHODS: The cognitive and behavioral features of 26 patients with AD were assessed prospectively using standardized tests. Together with 14 matched controls, the status of muscarinic M(1) and M(2) receptors in the postmortem frontal and temporal cortex of these patients were measured by radioligand binding assays and were correlated with clinical data. RESULTS: Compared with controls, M(2) receptor density was reduced only in the frontal cortex of AD, whereas M(1) was unaffected. Within the AD group, the neurochemical variables were not affected by demographic factors, disease severity, or cognition. Instead, M(2) receptor density was increased in the frontal and temporal cortex of patients with AD with psychotic symptoms compared with those without these symptoms. CONCLUSIONS: This study suggests a role for M(2) receptors in the psychosis of AD and may provide the rationale for treatment of behaviorally perturbed patients with AD with cholinomimetics and M(2) antagonists.

Hepatitis B liver disease in cyclosporine-treated renal allograft recipients.

To establish the impact of cyclosporine on the development of chronic hepatitis in hepatitis B surface antigen (HBsAg)-positive renal allograft recipients, the incidence and outcome of chronic hepatitis in 20 cyclosporine-treated patients (CsA group) were compared with 13 azathioprine-treated patients (AZA group). All 33 patients had a functioning graft for 2 years or longer. Twenty-nine of the 33 patients were HBsAg-positive prior to the initiation of hemodialysis. The difference in the incidence of chronic hepatitis between these 2 groups was not statistically significant (78.6% in the AZA group vs. 52.4% in the CsA group, P = 0.12). In the CsA group, 3 patients (15%) developed liver cirrhosis, and there was a 5% mortality. The AZA group had a 7.7% mortality, and 4 patients (30.8%) developed liver cirrhosis. Serial serum samples obtained from these 33 HBsAg-positive renal allograft recipients were analyzed for antibody to hepatitis D virus (anti-HD). Anti-HD was found in 3 patients. Two of them developed anti-HD seroconversion after renal transplantation during a mean follow-up of 4 years. All 3 patients developed chronic hepatitis and 2 of them have subsequently developed liver cirrhosis. There was a mortality of 6.1% in 33 HBsAg-positive patients compared with a 5.3% mortality in 57 HBsAg-negative renal allograft recipients. The difference was not statistically significant. We conclude from this study that (1) CsA-treated HBsAg-positive renal allograft recipients have a tendency to develop chronic hepatitis like AZA-treated patients; (2) HBsAg-positive patients have an increased risk of HDV superinfection after renal transplantation, and this may result in rapid progression to liver cirrhosis; (3) HBsAg-positive patients who acquire HBsAg prior to renal transplantation have a low overall mortality, including death due to liver disease, for a mean follow-up of 4 years.

Early indices of warm ischemic damage in autotransplanted canine kidneys preserved by simple hypothermic storage.

After measurement of normal renal function, dog kidneys (n = 52) were subjected to 3, 15, or 30 min of normothermic warm ischemia (WI). After 24 hr of preservation by simple hypothermic storage (SHS) in a modified Collins solution, autotransplant was done and renal function was again measured beginning at 1 hr. Compared with preharvest values, kidneys with minimal (3 min) WI had significantly decreased clearances of creatinine (Cr) and para-aminohippuric acid (PAH), PAH extraction, absolute and fractional Na reabsorption, Na excretion, and urinary Na concentration; no change in urine flow rate or K excretion; and significantly increased fractional excretion of Na, K, and H2O. Compared with minimal WI, 30-min WI produced further significant decreases in clearances of Cr, PAH, and PAH extraction; and further increases in fractional excretion of Na, K, and H2O. Urine flow was also decreased by about half and urine Na concentration rose significantly. Several parameters were very significantly correlated with the length of WI, but the most reliable index was the fractional reabsorption of Na. When several functional parameters were used together, kidneys with significant (30 min) WI prior to preservation could be identified with a high degree of statistical reliability.

The clinical outcome of hepatitis C virus antibody-positive renal allograft recipients.

In order to investigate the prevalence of antibody to hepatitis C virus (anti-HCV) in renal transplant patients, the evolution of anti-HCV status, and clinical outcome in anti-HCV-positive renal allograft recipients, we tested the sera from 120 renal transplant patients for anti-HCV. Thirty-eight patients were hepatitis B surface antigen (HBsAg)-positive. Two patients were anti-delta-positive. A total of 79 patients (65.8%) had at least one serum positive for anti-HCV. Anti-HCV positivity decreased after transplantation for more than 5 years (65.5% at transplantation versus 37.9%, 78.3 +/- 13.4 months later). Among those with positive anti-HCV, the HBsAg-positive group had significantly higher incidence of chronic hepatitis (50% vs. 25.5%, P = 0.026) and liver cirrhosis (21.4% vs. 0%, P = 0.001) than HBsAg-negative group. Among the 82 HBsAg-negative patients, the prevalence of anti-HCV was significantly higher in those with chronic hepatitis than in those without (86.7% vs. 56.7%, P = 0.027). We conclude from this study: (1) anti-HCV positivity is quite prevalent in renal transplant patients; (2) coinfection of hepatitis B virus (HBV) and hepatitis C virus (HCV) may lead to aggressive liver disease and cirrhosis; HCV infection alone has a more benign clinical outcome; and (3) HCV infection is an important cause of posttransplant chronic hepatitis in HBsAg-negative patients.

Ouabain-induced increases in resting tone of human hyperplastic prostate following repeated noradrenaline and electrical field stimulation.

1. The effect of ouabain on contractions to repeated noradrenaline stimulation and electrical field stimulation of human hyperplastic prostate was examined. Ouabain (1 microM) did not induce contractile response per se but progressively increased the resting tone (i.e., the tone between one noradrenaline stimulation, or electrical field stimulation, and the following) of human hyperplastic prostate. 2. The increased tone by ouabain following repeated noradrenaline stimulations or electrical field stimulation was fully relaxed by the removal of external calcium, and recovered following restoration of calcium. 3. The effect of noradrenaline on NA+ uptake was measured. Noradrenaline (10 microM) significantly increased the rate of Na+ accumulation in the presence of ouabain (1 microM); this stimulatory effect was almost completely blocked by prazosin (0.1 microM) and ethylisopropylamiloride (100 microM). In contrast, tetrodotoxin (1 microM) had no effect on noradrenaline-stimulated Na+ transport in human hyperplastic prostate. 4. Intracellular Na+ loading by noradrenaline (10 microM) in the presence of ouabain (1 microM) significantly increased the transmembrane Ca2+ uptake as compared with the absence of ouabain; however, nifedipine (1 microM) was ineffective on Ca2+ uptake under this condition. 5. Transmembrane CA2+ efflux was stimulated by noradrenaline (10 microM) in human hyperplastic prostate; this effect was significantly decreased in the presence of ouabain (1 microM). 6. It is suggested that the increased tone of human hyperplastic prostate following repeated excitation in the presence of ouabain is due to increased Ca2+ entry and reduced efflux of Ca2+ through the Na+/Ca+ exchange system as a consequence of Na+ pump inhibition by ouabain.

Differential expression of type 1 angiotensin II receptor mRNA and aldosterone responsiveness to angiotensin in aldosterone-producing adenoma.

Aldosterone secretion in most patients with aldosterone-producing adenomas (APAs) is typically unresponsive to angiotensin II stimulation (AII-unresponsive, AII-U). In some patients, however, plasma aldosterone increases in response to AII stimulation (AII-responsive, AII-R). This differential aldosterone responsiveness could be related to the levels of type 1 AII receptors (AT1R) in the APA. To test this hypothesis, plasma aldosterone levels in response to upright posture and/or sequential high- and low-salt diets were measured by radioimmunoassay in nine patients with APAs. AT1R mRNA levels in the adenomas were quantified by competitive reverse transcription-polymerase chain reaction and correlated to the cellular composition of the adenoma. Two patients were categorised as AII-R by an increase of plasma aldosterone greater than 50% over the baseline. The remaining seven patients who had blunted plasma aldosterone responses were classified as AII-U. Histologically, the AII-R APAs consisted predominantly of zona glomerulosa (ZG)-like cells (> 90%), while the AII-U APAs contained zona fasciculata (ZF)-like cells ranging from 28 to 72%. There was an inverse relationship between the levels of AT1R mRNA in the APA and the percentage of ZF-like cells in the adenoma (n = 9, r = 0.73, P < 0.05). In situ hybridisation findings demonstrated that AT1R mRNA was more uniform and intensive in ZG-like cells than in ZF-like cells. These results suggest that heterogenous aldosterone responsiveness to angiotensin in APAs is histologically dependent and related to the differential expression of AT1R mRNA in the adenoma.

Treatment of gynecomastia with tamoxifen: a double-blind crossover study.

Benign asymptomatic or painful enlargement of the male breast is a common problem, postulated to be due to an increased estrogen/testosterone ration or due to increased estrogenic or decreased androgenic stimulation via estrogen or androgen receptor interactions. Treatment at present consists of analgesic medication or surgery. However, treatment directed against the preponderance of estrogenic stimulation would seem to represent a more specific form of therapy. In the present double-blind crossover study, one-month courses of a placebo or the antiestrogen tamoxifen (10 mg given orally bid) were compared in random order. Seven of ten patients experienced a decrease in the size of their gynecomastia due to tamoxifen (P less than 0.005). Overall, the decrease for gynecomastia for the whole group was significant (P less than 0.01). There was no beneficial effect of placebo (P greater than 0.1). Additionally, all four patients with painful gynecomastia experienced symptomatic relief. There was no toxicity. The reduction of breast size was partial and may indicate the need for a longer course of therapy. A followup examination was performed in eight out of ten patients nine months to one year after discontinuing placebo and tamoxifen. There were no significant changes from the end of the initial study period except for one tamoxifen responder who developed a recurrence of breast tenderness after six months, and one nonresponder who demonstrated an increase in breast size and a new onset of tenderness after ten months. Therefore, antiestrogenic treatment with tamoxifen may represent a safe and effective mode of treatment for selected cases of cosmetically disturbing or painful gynecomastia.

The usefulness of prostate-specific antigen (PSA) density in patients with intermediate serum PSA level in a country with low incidence of prostate cancer.

OBJECTIVES: To evaluate if a calculated PSA density (PSAD) prior to biopsy could be useful to determine the need for prostate biopsies in patients with serum PSA levels of 4.1-20.0 ng/mL in a country with low incidence of prostate cancer (PCa). METHODS: A total of 185 consecutive patients aged 50-79 years who underwent prostate biopsies were evaluated by correlating the biopsy results with the results of digital rectal examination (DRE), transrectal ultrasonography (TRUS), serum PSA levels, and PSAD. Prostate volume was calculated from TRUS using prolate ellipse formula and PSAD was obtained by dividing serum PSA level by prostate volume. RESULTS: In this study population, 27 cases (14.6%) had positive biopsies. Of 158 cases with negative biopsies, 43 (23.2%) had histologically verified prostatic inflammation. The diagnostic value of DRE and TRUS was hampered by unsatisfactory sensitivity and specificity in differentiating patients with positive biopsies from those with negative biopsies. The use of PSAD alone as an indicator for biopsy was also limited by its low specificity. A PSAD cutoff value of 0.15 resulted in a sensitivity of 100% and a specificity of only 12%. Prostatic inflammation was a confounding factor for the inadequate specificity of DRE, TRUS and PSAD. Combined use of DRE and PSAD provided the best information regarding the need for biopsies. Accordingly, if the 47 patients (25.4%) who presented with both a negative DRE and a PSAD < or = 0.20 were not biopsied, the rate of positive biopsy could have increased to 19.6% (27 of 138) without missing any cancer detection. CONCLUSIONS: It is concluded from this study that for patients with serum PSA levels of 4.1-20.0 ng/mL, biopsies should only be recommended for those with abnormal DRE and/or PSAD >0.20.

Intrarenal and in situ kidney workbench surgery under hypothermia.

Two methods are described to cool the kidney. The surgact type of device can cover the entire kidney or a single pole. The second method for cooling the kidney is use of an intracellular hypothermic solution with methylprednisolone; the kidney is flushed via the renal artery to achieve cooling. Two interesting cases are presented which illustrate the methods used to achieve hypothermia.

Deoxyribonucleic acid flow cytometric study in pheochromocytomas and its correlation with clinical parameters.

OBJECTIVES: To study deoxyribonucleic acid flow cytometry (DNA-FC) in pheochromocytomas and its correlation with clinical parameters. METHODS: Fifty cases of pheochromocytomas of a total of 58 cases were studied for DNA-FC from archival paraffin-embedded tissue blocks and were correlated with clinical parameters (ie, size of tumor, benign or malignant pathologic type, vanillymandelic acid [VMA] level in 24 hour urine, age, sex, duration of symptoms, symptom scores). RESULTS: A total of 19 cases were diploid while 31 cases (62%) showed DNA aneuploidy with 21 cases tetraploid. Four cases were malignant. All of them were tetraploid. However, among the 46 benign cases, 10 were aneuploid and 17 were tetraploid. All 19 cases with DNA diploidy were benign. The DNA-FC did not correlate with other clinical parameters in our study. CONCLUSIONS: We confirmed a high incidence of DNA aneuploidy in pheochromocytomas. All malignant pheochromocytomas were tetraploid and all cases with DNA diploidy were benign. Long-term follow-up of all cases, especially those with DNA aneuploidy (including tetraploidy), is mandatory.

Inhibition by tamsulosin of tension responses of human hyperplastic prostate to electrical field stimulation.

Tamsulosin (10(-10)-10(-9) M) or prazosin (10(-9)-10(-8) M) concentration dependently blocked the tension responses to electrical field stimulation (0.3 ms duration, 80 V and 20 Hz) in human hyperplastic prostate with lC50 values of (1.93 +/- 0.26) x 10(-10) M and (2.11 +/- 0.21) x 10(-9) M, respectively. The relative potency of tamsulosin with reference to prazosin was 10.96. The pA2 values for tamsulosin and prazosin against phenylephrine-induced contractions were 10.05 +/- 0.16 and 9.25 +/- 0.07, respectively. The relative potency of tamsulosin with reference to prazosin was 6.31. In the presence of prazosin to block alpha 1-adrenoceptor-mediated responses, nifedipine (10(-5) M), but not tamsulosin (10(-9) M), significantly blocked the tension responses in human hyperplastic prostate induced by increasing [Ca2+]o concentrations (10(-4) to 3 x 10(-3) M) in a Ca(2+)-free environment pre-depolarized with 60 mM K+. Additionally, the effects of prazosin and tamsulosin on electrical field stimulation-evoked [3H]noradrenaline release were studied on the S3/S2 ratios. It appeared that both drugs had little effect on this release reaction, with S3/S2 ratios of 0.96 +/- 0.02 and 0.90 +/- 0.02, respectively. These results indicate that tamsulosin is a potent antagonist against endogenous sympathetic stimulation in human hyperplastic prostate.

An experimental model to evaluate the in vivo response of rat seminal vesicle to electrical stimulation.

This investigation demonstrated a good model to record the pressure change of rat seminal vesicle (SV) in response to electrical stimulation (ES) of lesser splanchnic nerve (LSN) in vivo. LSN was easily identified and isolated grossly. Antegrade catheterization via the SV tail to the main lumen was performed similar to the technique of i.v. catheterization, and the pressure recording was quite satisfactory. The vesicle response to ES was frequency-dependent and reproducible. Under the conditions of 10 V and 1 ms, the maximal vesicle pressure was 81.7 +/- 2.8 mmHg with 80 Hz of ES. The inhibitory response of SV to ES by clomipramine was concentration-dependent. Clomipramine (3 mg/kg) could inhibit 53% of control responses (n = 7). This experimental model is relevant to neurophysiologic and neuropharmacologic studies of SV.