bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of calcineurin inhibition and protein kinase A activation on nucleus accumbens amphetamine‐produced conditioned place preference in rats
Authors: Gerdjikov Todor V. , Beninger Richard J. 
Published: August 2005

AbstractThe nucleus accumbens (NAc) plays a critical role in amphetamine‐produced conditioned place preference (CPP). In previous studies inhibition or activation of cyclic adenosine monophosphate‐dependent protein kinase (PKA) blocked NAc amphetamine‐produced CPP. PKA activation unrelated to ongoing DA transmission may disrupt reward‐related learning. Calcineurin (CN) down‐regulates downstream PKA targets. Unlike PKA activation, CN inhibition may preserve and enhance reward‐related learning. The PKA signalling cascade is negatively regulated by calcineurin (CN). We tested the hypothesis that post‐training CN inhibition in NAc will enhance NAc amphetamine‐produced CPP and that PKA activation will block CPP. Eight but not four or two 30‐min conditioning sessions were sufficient to establish significant CPP. Immediate post‐training, NAc injection of the calcineurin inhibitor FK506 (5.0 but not 1.0 µg in 0.5 µL per side) led to a significant amphetamine CPP in rats receiving four but not two training sessions; the 5.0‐µg dose had no effect on rats trained with eight sessions. Injections of the PKA activator Sp‐cAMPS (2.5 or 10.0 µg in 0.5 µL per side) failed to affect CPP following two or four training sessions and blocked CPP produced by a standard 8‐day conditioning schedule. Results suggest that CN acts as a negative regulator in the establishment of NAc amphetamine‐produced CPP, a form of reward‐related learning.
Requirement of NMDA receptor reactivation for consolidation and storage of nondeclarative taste memory revealed by inducible NR1 knockout
Authors: Cui Zhenzhong , Lindl Kathryn A. , Mei Bing , Zhang Shuqing , Tsien Joe Z. 
Published: August 2005

AbstractWe employed an inducible, reversible and region‐specific gene knockout technique to investigate the requirements for cortical NMDA receptors (NMDAR) during the various stages (acquisition, consolidation and storage, and retrieval) of nondeclarative, hippocampal‐independent memory in mice using a conditioned taste aversion memory paradigm. Here we show that temporary knockout of the cortical NMDAR during either the learning or postlearning consolidation stage, but not during the retrieval stage, causes severe performance deficits in the 1‐month taste memory retention tests. More importantly, we found that the consolidation and storage of the long‐term nondeclarative taste memories requires cortical NMDAR reactivation. Thus, the dynamic engagement of the NMDAR during the postlearning stage leads us to postulate that NMDAR reactivation‐mediated synaptic re‐entry reinforcement is crucial for overcoming the destabilizing effects intrinsic to synaptic protein turnover and for achieving consolidation and storage of nondeclarative memories in the brain.
Inhibitory glutamate receptors in spider peripheral mechanosensory neurons
Authors: Panek Izabela , Torkkeli Päivi H. 
Published: August 2005

AbstractMost mechanosensory neurons are inhibited by GABAergic efferent neurons. This inhibition is often presynaptic and mediated by ionotropic GABA receptors at the axon terminals. GABA receptor activation opens Cl– channels, leading to membrane depolarization and an increase in membrane conductance. In many invertebrate preparations, efferent neurons that innervate mechanosensory afferents contain glutamate in addition to GABA, suggesting that the sensory neurons are also modulated by glutamate. However, the effects of glutamate on these neurons are not well understood. Peripheral parts of the spider (Cupiennius salei) mechanosensory neurons are surrounded by efferent fibers immunoreactive to antibodies against GABA and glutamate. GABA and its analogue muscimol were shown to effectively inhibit spider mechanosensory neurons innervating lyriform slit sensilla VS‐3 that detects cuticular strains in the leg. Here, we show that glutamate also inhibits the VS‐3 neurons, but its effects are different from those of GABA or muscimol, suggesting that it acts on a different group of receptors. GABA and muscimol always depolarized these neurons and the inhibitory effect was strongly correlated with the amount of depolarization. In contrast, glutamate inhibited the VS‐3 neurons even when it did not depolarize them. In addition, while glutamate inhibited both the axonal action potentials elicited with electrical stimulation and dendritic action potentials produced by mechanical stimulation, muscimol only inhibited the axonal action potentials. Therefore, the inhibitory glutamate receptors in the VS‐3 neurons are distinct from and differently distributed than the GABA receptors, providing a subtle control of the neurons' sensitivity in varying behavioural situations.
Methylazoxymethanol acetate does not fully block cell genesis in the young and aged dentate gyrus
Authors: Dupret David , Montaron Marie‐Françoise , Drapeau Elodie , Aurousseau Catherine , Le Moal Michel , Piazza Pier‐Vincenzo , Abrous Djoher Nora 
Published: August 2005

AbstractDuring adulthood, new neurons are continuously added to the mammalian dentate gyrus (DG). An increasing number of studies have correlated changes in rates of dentate neurogenesis with memory abilities. One study based on subchronic treatment with the toxin methylazoxymethanol acetate (MAM) has provided causal evidence that neurogenesis is involved in hippocampal‐dependent trace conditioning. In contrast, spatial learning is not impaired following MAM treatment. We hypothesized that this was due to the small residual number of new cells produced following MAM treatment. In the present experiment, we attempted to achieve a higher level of reduction of adult‐generated cells following MAM treatment in young and aged rats. We found only a partial reduction of adult‐generated cells in the DG. More importantly, independently of the age of the animals, MAM treatment at a dose necessary to reduce neurogenesis altered the overall health of the animals. In conclusion, the behavioural results obtained following subchronic treatment with high doses of MAM in adulthood must be interpreted with extreme caution.
Viewing the body prepares the brain for touch: effects of TMS over somatosensory cortex
Authors: Fiorio Mirta , Haggard Patrick 
Published: August 2005

AbstractViewing the body can improve tactile perception. We investigated whether this could be due to a remodeling of somatosensory cortical areas during vision of the body. Single‐pulse transcranial magnetic stimulation (TMS) was delivered over the primary and secondary somatosensory areas of subjects who showed clear visual‐tactile enhancement while they performed a tactile grating discrimination task. Before the tactile stimulus, subjects viewed either their right index finger through a semisilvered mirror or an object reflected by the mirror and positioned to appear in the same location as the finger. In a first experiment we observed that TMS over primary somatosensory cortex significantly reduced subjects' accuracy whilst viewing the hand. No such reduction was found when subjects viewed a neutral object. In a second experiment, we disrupted the activity of primary and secondary somatosensory areas in different sessions. When stimulating the primary somatosensory cortex, a reduction in accuracy was again found while viewing the hand, but not a neutral object. TMS over secondary somatosensory cortex had no effect in any condition. Our results show that vision of the body may act at an early stage in stimulus elaboration and perception, allowing an anticipatory tuning of the neural circuits in primary somatosensory cortex that underlie tactile acuity.
Clinical outcomes of androgen deprivation as the sole therapy for localized and locally advanced prostate cancer
Authors: Janoff Daniel M. , Peterson Chad , Mongoue‐Tchokote Solange , Peters Laura , Beer Tomasz M. , Wersinger Emily M. , Mori Motomi , Garzotto Mark 
Published: August 2005

Most papers in this section are written about various aspects of prostate cancer, and cover a wide cross‐section of subjects relating to this important topic. Interestingly there has been increasing interest by clinical oncologists in this area, and I am delighted to publish their views in this Journal. We as urologists now routinely have multidisciplinary team meetings, and find the insightful comments of the non‐urologists very helpful in the management not only of patients with prostate cancer, but also of all types of urological malignancy.OBJECTIVETo characterize the clinical outcomes of androgen deprivation therapy (ADT) as the sole therapy for localized prostate cancer, and to determine independent predictors of disease progression, as recent studies indicate an increasing use of ADT.PATIENTS AND METHODSThe records of all patients with cT1–4NXM0 adenocarcinoma of the prostate treated with ADT as the primary initial therapy at the Portland Veterans Affairs Medical Center between 1993 and 2000 were reviewed. Age, race, Charlson Health Index, family history, prostate‐specific antigen (PSA) level, PSA density, digital rectal examination (DRE) findings, Gleason score, and percentage of positive biopsy cores at diagnosis were recorded for 81 patients. Patients had a median (sd, range) age of 73 (5.6, 58–84) years, a PSA level of 14.3 (34.6, 1.4–252) ng/mL and tumours were classified as Gleason score ≤ 5 in 9% of patients, 6 in 31%, 7 in 31% and 8–10 in 30%. Outcomes extracted were PSA progression, PSA nadir, bone fractures, local progression, distant progression and overall survival.RESULTSWith a median (range) follow‐up of 54 (6–115) months, the incidence of local progression, distant progression, bone fractures, PSA progression, and death were 10%, 7%, 25%, 21% and 41% respectively. The percentage of positive biopsy cores ≥ 83%, age < 70 years, Gleason score ≥ 7, abnormal DRE, and PSA nadir ≥ 0.2 ng/mL were significantly associated with PSA progression by univariate analysis. The multivariate analysis identified age < 70 years (hazard ratio 6.52, 95% confidence interval 2.29–18.55) and Gleason score ≥ 6 (4.0, 2.0–12.0) as independent risk factors for PSA progression.CONCLUSIONSADT resulted in modest control of localized prostate cancer, but younger patients and those with Gleason ≥ 6 cancers were at higher risk of treatment failure. Toxicity, principally in the form of bone fractures, was high.
Long‐term sustained improvement in symptoms of benign prostatic hyperplasia with the dual 5α‐reductase inhibitor dutasteride: results of 4‐year studies
Authors: Roehrborn Claus G. , Lukkarinen Olavi , Mark Stephen , Siami Paul , Ramsdell Joe , Zinner Norman 
Published: August 2005

OBJECTIVETo report additional analyses of efficacy over the initial 2 years and during a 2‐year open‐label extension of the three pivotal phase 3 studies in which dutasteride, a dual inhibitor of type 1 and 2 5α‐reductase, was shown to be effective and well tolerated.PATIENTS AND METHODSAll patients in the placebo and active groups were eligible for entry into the 2‐year open‐label extension, with all receiving dutasteride 0.5 mg daily. Mean changes from baseline were calculated for the American Urologic Association Symptom Index (AUA‐SI) score at each scheduled time in the double‐blind and open‐label phase. The additional analyses included a breakdown of the AUA‐SI score, including stratifying patients by symptom severity, assessment by baseline age and prostate volume, and the evaluation of symptoms responders.RESULTSThere was a clinically meaningful improvement in AUA‐SI in patients on dutasteride in the double‐blind phase, but not in those on placebo. At 48 months, patients on dutasteride in both study phases had greater improvements in AUA‐SI score and individual question scores than those on dutasteride in the open‐label phase only. The proportion of patients with severe symptoms declined in both study groups, although these changes were more profound in those receiving dutasteride for the 4‐year duration of the study.CONCLUSIONIn men with symptomatic benign prostatic hyperplasia, long‐term (4‐year) treatment with the dual isozyme 5α‐reductase inhibitor dutasteride resulted in sustained and continued improvements in symptoms and flow rate. For 4 vs 2 years, longer dutasteride therapy resulted in greater symptom improvement.
Ease of removal of thermo‐expandable prostate stents
Authors: Barber Neil J. , Roodhouse Alison J. , Rathenborg Per , Nordling Jørgen , Ellis Brian W. 
Published: August 2005

OBJECTIVETo report the ease of removal of the Memokath 028 prostatic stent (Engineers & Doctors A/S, Hornbaek, Denmark), an important attribute of the ‘ideal’ prostatic stent.PATIENTS AND METHODSData on patients who had had a Memokath 028 stent removed in three different centres in Europe over an 8‐year period were collected retrospectively. Standardized forms were used to record relevant information from each physician's patient files.RESULTSNinety‐three patients had their stents removed at the three reporting centres; the mean indwelling time of their stent was 12.9 months, and most stents were inserted for symptomatic benign prostate disease. Reasons for removal included recurrent outlet or storage‐type urinary symptoms, migration of the stent, stent‐related pain, recurrent urosepsis and detrusor failure. The stents were removed on a day‐case basis in 32% of patients. Topical anaesthesia or no anaesthesia was used in 48%. Of these patients, only 9% described moderate discomfort or worse. The procedure took a mean of 11 min and was felt to be easy or fairly easy in 90% of patients.CONCLUSIONSThese data show the ease of removal of the Memokath 028 stent, reinforce its overall success in achieving the requirements of the ideal intraprostatic stent, and further emphasize the advantages of this implant over the epithelializing, permanent intraprostatic stent.
Donor‐site morbidity in buccal mucosa urethroplasty: lower lip or inner cheek?
Authors: Kamp Stefan , Knoll Thomas , Osman Mahmoud , Häcker Axel , Michel Maurice S. , Alken Peter 
Published: August 2005

Authors from Germany debate the issue as to whether the donor site for oral mucosa used in urethroplasty should be taken from the inner cheek or the lower lip, using morbidity as a deciding factor. As a result of their study they have changed their technique, now using the inner cheek as the donor site whenever possible.OBJECTIVETo evaluate donor‐site complications of buccal mucosa urethroplasty and whether there is a difference in morbidity between harvesting the mucosa graft from the inner cheek or the lower lip.PATIENTS AND METHODSTwenty‐four consecutive patients with recurrent urethral strictures were treated with buccal mucosa urethroplasty in our department between September 2002 and April 2004. In 12 patients the graft was harvested from the lower lip or cheek and lower lip (group 1), and in 12 patients from the cheek (group 2). The mean (range) age of patients was 51 (26–66) years in group 1 and 53 (32–75) years in group 2. The mean (range) graft length was 6.2 (2–16) cm in group 1 and 5.7 (2–13) cm in group 2. All patients were followed up using a mailed questionnaire that asked about pain, numbness, difficulties in mouth opening or ingestion, and satisfaction, monthly for the first 3 months and then every 6 months. The mean (range) follow‐up was 12.5 (6–23) months.RESULTSThere were no bleeding complications or disturbances in wound healing. All of the patients reported numbness in the area of the mental and buccal nerves, and graft‐site tenderness after surgery. In group 1, the pain lasted for a mean (range) of 5.9 (0.5–22) months, compared to 1 (0.1–7) months in group 2 (P = 0.022). Perioral numbness lasted for a mean (range) of 10.3 (0.5–23) months in group 1 and 0.85 (0.1–3) months (P = 0.0027) in group 2. There were no statistically significant differences in problems with mouth opening or food intake between the two groups, but the patients in group 1 seemed to be less satisfied (6/12 patients satisfied) than those in group 2 (11/12 patients satisfied).CONCLUSIONSBuccal mucosa graft harvesting from the lower lip and the inner cheek are both feasible, but harvesting from the lower lip resulted in a significantly greater long‐term morbidity, which resulted in a lower proportion of satisfied patients. This seems to be due to a long‐lasting neuropathy of the mental nerve. We therefore have changed our technique entirely from lower lip to inner cheek graft harvesting, whenever possible.
Colour Doppler ultrasonographic location of the bulbourethral artery, and its impact on surgical outcome
Authors: Kishore Thekke Adiyat , Bhat Suresh , John Roy P. 
Published: August 2005

OBJECTIVETo assess the location of bulbourethral arteries in men with a ‘normal’ urethra and to study anatomical alterations in men with urethral stricture.PATIENTS AND METHODSA linear‐array transducer was used on the ventral surface of the penis to study the urethra. Fifteen men with a normal urethra and 15 with a stricture of the bulbar urethra were assessed. After conventional grey‐scale imaging to evaluate the extent of disease, the urethral artery in the bulbar urethra was located by colour Doppler ultrasonography.RESULTSThe site of the urethral arteries in ‘normal’ men varied among individuals; they were at the 10–2 o’clock position in six men, 8–10 o’clock and 2–4 o’clock in six, and at the 4–8 o’clock position in three. In normal men the symmetry of arteries was maintained and the mean distance from the lumen was 2.67 mm. In men with urethral stricture, there was a loss of symmetry in all cases. In a dense stricture the urethral arteries could not be detected on either side in three of cases, while only a single artery was seen in three. In two men, both the arteries were on one side. The mean distance of the urethral artery from the lumen of urethra was 1.88 mm.CONCLUSIONSContrary to the popular belief that the urethral arteries are located at the 3 and 9 o’clock position, we found that there was no predictable pattern for their anatomy. These observations might have implications for treating urethral stricture disease with visual internal urethrotomy, as they could help to avoid injury to the bulbourethral artery.
Refractory monosymptomatic nocturnal enuresis: a combined stepwise approach in childhood and follow‐up into adolescence, with attention to the clinical value of normalizing bladder capacity
Authors: Vermandel Alexandra , De Wachter Stefan , Wyndaele Jean‐Jacques 
Published: August 2005

There are two papers in the paediatric urology section this month. The first, from Belgium, assessed the importance of normalising bladder capacity to the age‐expected capacity in children with refractory nocturnal enuresis, and evaluated the long‐term results when the children reached adolescence. The second paper from the USA assessed the role of apoptosis and proliferation in children with undescended testes.OBJECTIVETo assess the importance of normalizing bladder capacity to the age‐expected capacity in children with refractory monosymptomatic nocturnal enuresis (MNE), and to evaluate the long‐term results when these children grow into adolescence.PATIENTS AND METHODSThe study included 34 children with refractory MNE; all were treated > 5 years earlier for their MNE using a combined stepwise approach, consisting of retention control training, oxybutynin and an enuresis alarm. Data were obtained on their enuretic state, night‐time voiding behaviour and bladder capacity, from a questionnaire and a voiding chart.RESULTSBefore starting treatment, all patients had a bladder capacity that was too small for their age. After the combined stepwise approach, MNE improved in all patients and 24 (71%) were cured. Although the bladder capacity was increased to the age‐expected capacity in 26 (76%), most woke at night to void. Currently, at a mean of 7.7 years after the primary treatment, 28 (82%) of the patients are completely dry at night, of whom 15 (54%) arouse to void for 35% of the nights. Six patients (18%) still have some enuretic episodes. Only those who were dry after primary treatment and remained dry had a normal age‐expected increase in bladder capacity. For all others there was a decrease in age‐related bladder capacity.CONCLUSIONSIn patients with refractory MNE, a combined stepwise approach improves and may even eliminate enuresis, but normal night‐time bladder behaviour in adolescence and adulthood is only achieved in some. Furthermore, about a fifth still have some enuretic episodes.
A simple procedure for isolating microgram quantities of biologically active bikunin from human urine
Authors: Yang Lizhu , Resnick Martin I. , Marengo Susan Ruth 
Published: August 2005

OBJECTIVETo report a simple, relatively rapid protocol to isolate biologically active bikunin from human urine using ion‐exchange‐trypsin affinity chromatography. Bikunin is a protease inhibitor which has been shown to play a role in various processes, including inhibition of calcium oxalate crystallization, the regulation of proliferation and modulation of carcinogenesis. The unavailability of the purified protein has hampered studies on bikunin's expanding role in these processes.MATERIALS AND METHODSFemale human urine was dialysed (15 kDa threshold) and crudely fractionated with a double‐saturated ammonium sulphate precipitation. The first precipitation was with 35% saturated ammonium sulphate, and the supernatant was harvested, and the second with 90% saturated ammonium sulphate, and the precipitate collected. The protein mixture was then passed over Sepharose SP‐fast‐flow cation exchange and Sepharose Q‐fast‐flow anion exchange columns connected in series. The final purification was with a trypsin‐affinity column which selectively bound bikunin.RESULTSThis procedure could recover 1 µg of bikunin per 2 mL of urine, and the final product was essentially free of contaminating inter‐α‐trypsin inhibitor heavy chains or bikunin‐heavy chain conjugates. Product purity was confirmed by two‐dimensional polyacrylamide gel electrophoresis combined with silver staining or Western blot. All isolations contained the 17 kDa minimally glycoslyated/sulphated form of bikunin and the 28 kDa form of bikunin. Some preparations also contained 33–48 kDa forms of bikunin. The protein cores of all three proteins were confirmed to be bikunin by mass spectrometry and Western blot. Harvested bikunin retained its trypsin inhibitory activity ( l‐benzoylarginine‐p‐nitroanilide assay). Preparations containing the 33–45 kDa form had two to three times more trypsin inhibitory activity than preparations without this band.CONCLUSIONSThis novel ion exchange‐trypsin affinity chromatography protocol uses only two chromatographic steps. The product consists of three isomers of biologically active bikunin, free of contaminating heavy chains or bikunin‐heavy chain conjugates. The ready availability of purified bikunin should facilitate future studies of bikunin's emerging role in urolithiasis, proliferation and carcinogenesis.