bluuebunny/crossref_metadata_2025 huggingface dataset:
EVIDENCE FOR THE REGULATION OF L‐TYPE Ca2+ CHANNELS IN THE HEART BY REACTIVE OXYGEN SPECIES: MECHANISM FOR MEDIATING PATHOLOGY
Authors: Hool Livia C
Published: August 2007

It is well recognized that reactive oxygen species (ROS) can activate transduction pathways to mediate pathophysiology. An increase in ROS has been implicated in a number of cardiovascular disorders. Reactive oxygen species regulate cell function through redox modification of target proteins. One of these target proteins is the L‐type Ca2+ channel.

There is good evidence that thiol reducing and oxidizing compounds, including hydrogen peroxide, can influence calcium channel function. The evidence for regulation of the channel protein and regulatory proteins by thiol‐specific modifying agents and relevance to hypoxia and oxidative stress is presented.

Clinical studies suggest that calcium channel antagonists may be beneficial in reducing myocardial injury associated with oxidative stress. The identification of cysteines as possible targets for intervention during hypoxic trigger of arrhythmia or chronic pathological remodelling is discussed.
EFFECT OF GENDER AND SEX HORMONES ON VASCULAR OXIDATIVE STRESS
Authors: Miller Alyson A , De Silva T Michael , Jackman Katherine A , Sobey Christopher G
Published: August 2007

It is well documented that the incidence and severity of several vascular diseases, such as hypertension, atherosclerosis and stroke, are lower in premenopausal women than men of similar age and post‐menopausal women. The mechanisms responsible for gender differences in the incidence and severity of vascular disease are not well understood. However, emerging evidence suggests that sex hormone‐dependent differences in vascular oxidative stress may play an important role. The aim of the present brief review is to provide an insight into the effect of gender and sex hormones on vascular oxidative stress.

When production of reactive oxygen species (ROS) is enhanced and/or their metabolism by anti‐oxidant enzymes is impaired, a condition known as ‘oxidative stress’ can develop. Oxidative stress is believed to play an important role in both the initiation and progression of a variety of vascular diseases, including hypertension and atherosclerosis. NADPH oxidases are believed to be the major source of vascular ROS. Moreover, excessive production of ROS by NADPH oxidases has been linked to the development of vascular oxidative stress.

Increasing evidence suggests that levels of vascular ROS may be lower in women than men during health and disease. Indeed, the activity and expression of vascular NADPH oxidase is lower in female versus male animals under healthy, hypertensive and atherosclerotic conditions.

Gonadal sex hormones may play an important role in the regulation of vascular oxidative stress. For example, oestrogens, which are present in highest levels in premenopausal women, have been reported to lower vascular oxidative stress by modulating the expression and function of NADPH oxidases, as well as anti‐oxidant enzymes.

Further studies are needed to clarify whether lower vascular oxidative stress in women in fact protects against the initiation and development of vascular disease and to further define the roles of gonadal sex hormones in such an effect. Knowledge gained from these studies may potentially lead to advances in the clinical diagnosis and treatment of vascular disease in both genders.
COMBINED SPINAL AND EPIDURAL ANAESTHESIA WITH CHLOROPROCAINE FOR HYSTERECTOMY
Authors: Fu Run‐Qiao , Tian Yu‐Ke , Fang Wei‐Ran
Published: August 2007

The aim of the present study was to determine the clinical efficacy and safety of chloroprocaine (CP) for gynaecological surgery.

One hundred and twenty gynaecological patients scheduled for hysterectomy were divided randomly into four groups: Group A (n = 30), 2.5% CP 1.0 mL; Group B (n = 30), 2.5% CP 1.2 mL; Group C (n = 30), 2.5% CP 1.4 mL; and Group D (n = 30), 2.5% CP 1.6 mL. The dose of CP used in each group was mixed with 1 mL vehicle containing 5% glucose and 1.5% ephedrine. Spinal anaesthesia was achieved by lumbar puncture in the L2–3 interspace and injection of the mixture. Wherever necessary, CP (2.5%) was used for epidural anaesthesia.

Although the times to onset and peak effect, as well as the grade of motor block of the lower limbs (Bromage scale), were similar among the four groups, the level of the highest sensory nerve block increased gradually, from T7 (± 1), T6 (± 1), T4 (± 1) to T3 (± 1) in Groups A, B, C and D, respectively. The rate of unsatisfactory spinal anaesthesia was 80 and 16.7% in Groups A and B, respectively, and consequently epidural anaesthesia was superimposed in those patients for surgery to start. Spinal anaesthesia was very satisfactory for surgery in Groups C and D. In contrast, the incidence of hypotension in Groups B, C and D was 6.7, 16.7 and 67.7%, respectively; however, respiratory depression only occurred in Group D in nine cases (30%). No other adverse events or neurologic deficits were found.

The present results suggest that 30–35 mg CP in a total volume of 2.2–2.4 mL used for spinal anaesthesia in hysterectomy is safe and efficient. The combination of spinal and epidural anaesthesia with 2.5% CP can achieve 100% satisfactory anaesthesia for this type of surgery.
IMMUNOCHEMICAL CHARACTERIZATION OF THE FUNCTIONAL CONSTITUENTS OF TRIPTERYGIUM WILFORDII CONTRIBUTING TO ITS ANTI‐INFLAMMATORY PROPERTY
Authors: Wong Kwong‐Fai , Chan Jacqueline K , Chan Kwong‐Leung , Tam Paul , Yang Dan , Fan Sheung‐Tat , Luk John M
Published: August 2007

Tripterygium wilfordii (TW) contains bioactive compounds that possess immunosuppressive properties. These compounds are considered to be potential drugs in the treatment of acute graft rejections. However, their structure–activity relationships remain unknown.

The aim of the present study was to delineate the molecular moieties of triptolide that could account for its ability to inhibit inflammatory responses. In this context, purified TW active compounds (triptolide and triptonide) and synthetic triptolide derivatives were prepared to investigate the structure–activity relationships of triptolide. To this end, rat splenocytes were treated with increasing concentrations of the compounds and then allogenically stimulated using a mixed lymphocyte reaction to determine their antiproliferative activities. From the results, the IC50 value of each compound was calculated.

Modification of the β‐hydroxyl group at the C‐14 position of the triptolide molecule significantly affected the immunosuppressive activity of T59, as demonstrated by a sevenfold increase of the IC50. Conversely, reduction of the γ‐butyrolactone group in T60 and T61 completely abrogated the antiproliferative effect. Alterations in the C‐14 β‐hydroxyl and γ‐butyrolactone groups also resulted in reduced cytotoxicity.

The present findings demonstrate that the C‐14 β‐hydroxyl and γ‐butyrolactone moieties of the triptolide molecule are crucial for its anti‐inflammatory properties and cytotoxicity and are responsible for the compound's antiproliferative activity.
EFFECT OF POLYPHENOL‐CONTAINING AZUKI BEAN (VIGNA ANGULARIS) EXTRACT ON BLOOD PRESSURE ELEVATION AND MACROPHAGE INFILTRATION IN THE HEART AND KIDNEY OF SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Sato Shin , Mukai Yuuka , Yamate Jyoji , Kato Jun , Kurasaki Masaaki , Hatai Asako , Sagai Masaru
Published: August 2007

Hypertension is a major risk factor for myocardial infarction and renal damage, and it has also been shown to have pro‐inflammatory actions that increase the formation of reactive oxygen species. Macrophage infiltration has been suggested to play a role in the pathogenesis of hypertension. Azuki beans are known to contain pro‐anthocyanidins, a group of polyphenolic bioflavonoids with remarkable radical‐scavenging activities in vitro. Therefore, the aim of the present study was to investigate the effect of polyphenol‐containing azuki bean extract (ABE) on systolic blood pressure (SBP) and macrophage infiltration in the heart and kidney of spontaneously hypertensive rats (SHR).

Spontaneously hypertensive rats and control normotensive Wistar‐Kyoto (WKY) rats were divided into two groups fed either 0 or 0.8% ABE in their diets. Tail SBP and macrophage kinetics in the heart and kidney were examined.

The SBP of the SHR group was higher than that of age‐matched WKY rats throughout the treatment period. After 8 weeks of treatment, the increased SBP in ABE‐treated SHR was significantly less than that in untreated SHR.

Nicotinamide adenine dinucleotide (NADH) or nicotinamide adenine dinucleotide phosphate (NADPH)‐stimulated superoxide () production was enhanced in the kidney and heart in SHR and WKY rats compared with levels in the absence of NADH or NADPH. The NADPH‐stimulated levels in the kidney in untreated SHR was significantly higher than that in untreated WKY rats. The levels in ABE‐treated SHR were significantly decreased compared with the untreated SHR group.

In immunohistochemical analyses, the number of macrophages in the heart and in the glomeruli and tubulointerstitium of the kidney was significantly higher in ABE‐untreated SHR than in ABE‐untreated WKY rats. Conversely, there was a significant decrease in the number of macrophages in ABE‐treated SHR compared with the untreated SHR. There were significant positive correlations between SBP and the number of ED1‐positve macrophages in the heart and tubulointerstitial and glomerular areas of the kidney in WKY rats and SHR.

In conclusion, the results of the present study suggest that ABE attenuates the elevation of SBP and macrophage infiltration in the heart, as well as in the glomeruli and tubulointerstitium of the kidney, in our SHR model.
Outcomes after medical and surgical treatment of diverticulitis: A systematic review of the available evidence
Authors: Peppas George , Bliziotis Ioannis A , Oikonomaki Dora , Falagas Matthew E
Published: August 2007

There is still controversy regarding the appropriate management of diverticulitis of the colon in cases when both surgical and conservative treatment may be an option.

We performed a systematic review of the available evidence regarding the outcomes after medical and surgical treatment of diverticulitis from studies published after 1980 and indexed in the PubMed database. We included original studies that reported comparative data for at least one outcome in medically‐ and surgically‐treated patients with transverse or left colon diverticulitis. The main outcomes of interest were mortality, morbidity, and recurrence of diverticulitis after medical or surgical treatment.

There were 21 studies fulfilling our inclusion criteria out of 1360 initially identified as possibly relevant. More patients were treated conservatively in the included studies compared to emergency surgery (24 862 vs 6504). Emergency surgery was the main option for patients with severe complications of diverticular disease, including peritonitis. In most studies, in‐hospital mortality for patients treated surgically was generally higher than that of patients treated medically, whereas there were insufficient comparative data regarding mortality during follow up. However, readmission to the hospital due to diverticular disease during follow up was more common in the group of patients treated conservatively compared to those treated surgically (4358/23 446 [18.6%]vs 22/359 [6.1%]). Conservatively‐treated patients, with a first or second episode of diverticulitis, required surgery for recurrent disease during follow up in a maximum of 45% of cases, with larger studies reporting percentages lower than 11%.

It should be emphasized that medical and surgical treatments have not ever been compared in a randomized controlled trial in patients with diverticulitis (without generalized peritonitis that is a surgical emergency). Although medical treatment results in more readmissions due to recurrence, it may be reasonable to avoid surgical therapy in the vast majority of patients with acute diverticulitis. It is unclear what the best treatment option is for younger patients (<50 years), namely whether elective surgery should be considered with the first episode of diverticulitis.
Quantitative Crack Surface Morphology of Bone Cements in Relation to Propagation Rate
Authors: ERANI PAOLO , CRISTOFOLINI LUCA , BALEANI MASSIMILIANO , BIGNOZZI MARIA CHIARA , COTIFAVA MARCO , IHADDADENE NABILA , TOMEI FEDERICO , VICECONTI MARCO
Published: August 2007

Morphology of the crack surface of surgical bone cements has seldom been studied in the past despite the clinical relevance of cement failure. Previous studies on a specific cement type suggest that crack morphology depends on crack propagation rate. The objectives of this work were: (i) to develop a quantitative indicator for describing crack morphology; and (ii) to assess if dependency on crack‐propagation rate is affected by cement formulation. Known crack surfaces were obtained from specimens under controlled loading conditions. Crack surface roughness was measured for different crack‐propagation rates, and compared against the amount of cleaved pre‐cured beads (measured with a semi‐automated procedure based on micrographs). Such indicators were extremely robust, operator‐independent, highly correlated, and sensitive to the type of fracture. Moreover, it was found that crack surface morphology heavily depends upon cement composition. Thus, crack surface roughness is proposed as a method for quantitatively identifying crack morphology, and finally classifying fracture type.
Strain‐life approach in thermo‐mechanical fatigue evaluation of complex structures
Authors: ROSA UROŠ , NAGODE MARKO , FAJDIGA MATIJA
Published: August 2007

This paper is a contribution to strain‐life approach evaluation of thermo‐mechanically loaded structures. It takes into consideration the uncoupling of stress and damage evaluation and has the option of importing non‐linear or linear stress results from finite element analysis (FEA). The multiaxiality is considered with the signed von Mises method. In the developed Damage Calculation Program (DCP) local temperature‐stress‐strain behaviour is modelled with an operator of the Prandtl type and damage is estimated by use of the strain‐life approach and Skelton's energy criterion. Material data were obtained from standard isothermal strain‐controlled low cycle fatigue (LCF) tests, with linear parameter interpolation or piecewise cubic Hermite interpolation being used to estimate values at unmeasured temperature points. The model is shown with examples of constant temperature loading and random force‐temperature history. Additional research was done regarding the temperature dependency of the Kp used in the Neuber approximate formula for stress‐strain estimation from linear FEA results. The proposed model enables computationally fast thermo‐mechanical fatigue (TMF) damage estimations for random load and temperature histories.
Comparative assessment of fatigue and fracture behaviour of cast and forged railway wheels
Authors: TARAFDER S. , SIVAPRASAD S. , RANGANATH V. R.
Published: August 2007

A comparative evaluation of fatigue and fracture behaviour of commercially produced cast and forged rail wheels has been made using specimens extracted from various locations of the wheel quadrant. A systematic investigation in the web and rim regions of the wheel quadrant with various notch orientations showed that the forged material exhibited a better intrinsic resistance to fatigue crack growth than the cast material. Since linear elastic fracture mechanics (LEFM) based fracture toughness could not be validated for both the cast and forged wheel material, elastic plastic fracture mechanics (EPFM) based characteristic fracture toughness was used. Results showed that fracture resistance of the forged material is superior to that of the cast material. Cast wheel specimens exhibited unstable crack extension in comparison to substantial stable tearing in forged specimens. Microstructural and fractographic analyses showed that the cast wheel material contained large amounts of inclusions. The poor fracture resistance of cast wheel material is therefore attributed to the inferior material quality.
3D meso‐mechanical analysis of concrete specimens under biaxial loading
Authors: CABALLERO A. , CAROL I. , LÓPEZ C. M.
Published: August 2007

In recent years, the mechanics of materials group at ETSECCPB‐UPC has developed an approach for meso‐mechanical analysis of concrete using zero‐thickness interface elements in 2D and more recently in 3D. In this methodology, the meso‐structure is generated with in‐house developed computer programs based on Voronoï/Delaunay theory. In the analysis, continuum elements are assumed linear elastic. Non‐linearity and fracture phenomena are made possible by the systematic use of zero‐thickness interface elements inserted on a priori determined potential fracture planes. In this paper, the results obtained for a 3D specimen under biaxial loading are presented. The results turn out to be very satisfactory and, in particular, it is observed that even the specimens which contain a reduced number of aggregates (14 in the present calculations) lead to a realistic failure envelope under biaxial loading, and they also capture the tendencies of cracking and fracture orientations observed in experiments for different rates of biaxial loading. The special limit case of biaxial loading under restrained out‐of‐plane deformations is also analysed, leading to practically elastic behaviour as shown by available experimental evidence.
Spatial receptive field properties of lateral geniculate cells in the owl monkey (Aotus azarae) at different contrasts: a comparative study
Authors: Kilavik B. E. , Silveira L. C. L. , Kremers J.
Published: August 2007

Several physiological properties of owl monkey lateral geniculate nucleus (LGN) cells were studied to verify whether its nocturnal habit has an influence on the organization of its subcortical visual system. Receptive field (RF) dimensions were measured using drifting gratings and bipartite field stimuli. We found that owl monkey cells LGN have larger RFs and were on average more non‐linear than those of diurnal monkeys. But, as in other anthropoids, there is an increase in RF centre size with increasing eccentricity, and there is a limited correlation between these centre sizes and retinal ganglion cell dendritic tree sizes. The influence of contrast on sizes and peak sensitivities of RF centres and surrounds and on the response phases was studied. Both the sizes and peak sensitivities of the RF centres and surrounds decrease as contrast increases. As a result, the responses to low spatial frequency stimuli saturate with increasing contrast. Estimates of contrasts at half‐maximal responses confirm the presence of saturation. It was found that the magnocellular cells saturate more strongly than parvocellular cells. The response phase increases with increasing contrast. These data resemble those obtained in the common marmoset, indicating that these are basic features of the primate visual system. We conclude that during evolution and as an adaptation to a nocturnal lifestyle, cells in the owl monkey LGN display an increased spatial integration in comparison with diurnal primate species, without a change in the basic organization common to the primate subcortical visual system.
Spatio‐temporal prediction and inference by V1 neurons
Authors: Guo Kun , Robertson Robert G. , Pulgarin Maribel , Nevado Angel , Panzeri Stefano , Thiele Alexander , Young Malcolm P.
Published: August 2007

In normal vision, visual scenes are predictable, as they are both spatially and temporally redundant. Evidence suggests that the visual system may use the spatio‐temporal regularities of the external world, available in the retinal signal, to extract information from the visual environment and better reconstruct current and future stimuli. We studied this by recording neuronal responses of primary visual cortex (area V1) in anaesthetized and paralysed macaques during the presentation of dynamic sequences of bars, in which spatio‐temporal regularities and local information were independently manipulated. Most V1 neurons were significantly modulated by events prior to and distant from stimulation of their classical receptive fields (CRFs); many were more strongly tuned to prior and distant events than they were to CRFs bars; and several showed tuning to prior information without any CRF stimulation. Hence, V1 neurons do not simply analyse local contours, but impute local features to the visual world, on the basis of prior knowledge of a visual world in which useful information can be distributed widely in space and time.
PI3K/akt, JAK/STAT and MEK/ERK pathway inhibition protects retinal ganglion cells via different mechanisms after optic nerve injury
Authors: Luo Jian‐Min , Cen Ling‐Ping , Zhang Xin‐Mei , Chiang Sylvia Wai‐yee , Huang Yao , Lin Dusheng , Fan You‐Ming , Van Rooijen Nico , Lam Dennis Shun Chiu , Pang Chi Pui , Cui Qi
Published: August 2007

Recently we unexpectedly found that PI3K/akt, JAK/STAT and MEK/ERK pathway inhibitors enhanced retinal ganglion cell (RGC) survival after optic nerve (ON) axotomy in adult rat, a phenomenon contradictory to conventional belief that these pathways are pro‐survival. In this study we showed that: (i) the RGC protection was pathway inhibition‐dependent; (ii) inhibition of PI3K/akt and JAK/STAT, but not MEK/ERK, activated macrophages in the eye, (iii) macrophage removal from the eye using clodronate liposomes significantly impeded PI3K/akt and JAK/STAT inhibition‐induced RGC survival and axon regeneration whereas it only slightly affected MEK/ERK inhibition‐dependent protection; (iv) in the absence of recruited macrophages in the eye, inhibition of PI3K/akt or JAK/STAT did not influence RGC survival; and (v) strong PI3K/akt, JAK/STAT and MEK/ERK pathway activities were located in RGCs but not macrophages after ON injury. In retinal explants, in which supply of blood‐derived macrophages is absent, MEK/ERK inhibition promoted RGC survival whereas PI3K/akt or JAK/STAT inhibition had no effect on RGC viability. However, MEK/ERK inhibition exerted opposite effects on the viability of purified adult RGCs at different concentrations in vitro, suggesting that this pathway may be bifunctional depending on the level of pathway activity. Our data thus demonstrate that inhibition of the PI3K/akt or JAK/STAT pathway activated macrophages to facilitate RGC protection after ON injury whereas the two pathways per se did not modulate RGC viability under the injury conditions (in the absence of the pathway activators). In contrast, the MEK/ERK pathway inhibition protected RGCs via macrophage‐independent mechanism(s).
Requirement of the tumour suppressor APC for the clustering of PSD‐95 and AMPA receptors in hippocampal neurons
Authors: Shimomura Atsushi , Ohkuma Mahito , Iizuka‐Kogo Akiko , Kohu Kazuyoshi , Nomura Ryuji , Miyachi Ei‐ichi , Akiyama Tetsu , Senda Takao
Published: August 2007

Mutations in the adenomatous polyposis coli (APC) gene are associated with familial adenomatous polyposis and sporadic colorectal tumours. The APC gene is expressed ubiquitously in various tissues, especially throughout the large intestine and central nervous system (CNS). In the CNS, the expression of the APC protein is highest during embryonic and early postnatal development. APC associates through its C‐terminal region with postsynaptic density (PSD)‐95, a neuronal protein that participates in synapse development. Here, we examined the involvement of APC in synaptogenesis. In cultured hippocampal neurons, both overexpression of a dominant‐negative construct that disrupts the APC–PSD‐95 interaction and knockdown of APC expression using small interfering RNA (siRNA) inhibited the clustering of PSD‐95 and a glutamate receptor subunit, and reduced alpha‐amino‐3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate (AMPA)‐induced activity of AMPA receptors; however, the clustering of an N‐methyl‐d‐aspartate (NMDA) receptor subunit was unaffected. These results are suggestive of APC involvement in the development of glutamatergic synapses.
The mental retardation gene CC2D1A/Freud‐1 encodes a long isoform that binds conserved DNA elements to repress gene transcription
Authors: Rogaeva Anastasia , Albert Paul R.
Published: August 2007

The CC2D1A/Freud‐1 gene has recently been linked to non‐syndromic mental retardation and a short isoform of mouse Five prime REpressor Under Dual repression binding protein 1 (Freud‐1) can repress the serotonin‐1A (5‐HT1A) receptor gene in rodent cells. In this study, we addressed the expression, localization and regulation of the human 5‐HT1A receptor gene by a long isoform of human Freud‐1 protein (Freud‐1L). We show that human CC2D1A/Freud‐1 RNA is expressed in brain and peripheral tissues and encodes short and long isoforms, which differ by an upstream in‐frame translational start site. Whereas previous studies identified the short isoform of Freud‐1 as the predominant isoform in rodent cells, we demonstrate that the long isoform is more abundant in human cells, especially in the nuclear fraction. The nuclear localization of Freud‐1L was enriched upon inhibition of chromosome region maintenance 1/exportin 1‐dependent nuclear export, indicating a dynamic regulation of Freud‐1 nuclear localization. Consistent with a functional role in the nucleus, human Freud‐1L bound specifically to its dual repressor element in the 5‐HT1A receptor gene in vitro and repressed transcription from these sites. Importantly, chromatin immunoprecipitation using antibodies specific for human Freud‐1L demonstrated that it is bound to the dual repressor element in chromatin, indicating a functional role in regulating the basal expression of the 5‐HT1A receptor gene. Taken together, these results indicate that both the short and long isoforms of Freud‐1 are expressed, although Freud‐1L is the major isoform that regulates the human 5‐HT1A receptor gene. Disruption of transcriptional regulation by mutation of Freud‐1 may play a role in abnormal brain function leading to mental retardation.
Suppression of vibrotactile discrimination by transcranial magnetic stimulation of primary somatosensory cortex
Authors: Morley J. W. , Vickery R. M. , Stuart M. , Turman A. B.
Published: August 2007

A number of human and animal studies have reported a differential representation of the frequency of vibrotactile stimuli in the somatosensory cortices: neurons in the primary somatosensory cortex (SI) are predominantly responsive to lower frequencies of tactile vibration, and those in the secondary somatosensory cortex (SII) are predominantly responsive to higher frequencies. We employed transcranial magnetic stimulation (TMS) over SI in human subjects to investigate the extent to which the inactivation of SI disrupted the discrimination of vibrotactile stimulation at frequencies that give rise to the tactile sensations of flutter (30 Hz) and vibration (200 Hz). Frequency discrimination around the 30‐Hz standard following application of TMS to SI was reduced in seven of the eight subjects, and around the 200‐Hz standard was reduced in all eight subjects. The average change in discrimination following TMS was about 20% for both low and high frequencies of vibrotactile stimulation. These data suggest that disruption of SI: (1) has a direct effect on the discrimination of both low and high frequencies of vibrotactile stimuli, consistent with a serial model of processing, or (2) has a direct effect on low‐frequency vibrotactile stimuli and an indirect effect on the processing of high‐frequency vibrotactile stimuli by SII via cortico‐cortical connections between the two regions.
Activation of afferents to the ventral tegmental area in response to acute amphetamine: a double‐labelling study
Authors: Colussi‐Mas Joyce , Geisler Stefanie , Zimmer Luc , Zahm Daniel S. , Bérod Anne
Published: August 2007

The ventral tegmental area (VTA), primary source of the mesocorticolimbic dopaminergic system, is regarded as a critical site for initiation of behavioural sensitization to psychostimulants. The present study was undertaken to identify the neural pathways converging on the VTA that are potentially implicated in this process. Rats were sensitized by a single exposure to amphetamine (5 mg/kg, s.c.). The distribution of VTA‐projecting neurons activated by amphetamine was examined by combining retrograde transport of the cholera toxin β subunit (CTb), injected into the VTA, with immunodetection of Fos. The quantitative analysis of CTb–Fos double labelling demonstrates that amphetamine induced a rapid activation of Fos in a large number of brain areas projecting to the VTA. More than half of the CTb–Fos double‐labelled neurons were located in the prefrontal cortex, lateral preoptic area–lateral hypothalamus, pontomesencephalic tegmentum, dorsal raphe nucleus, ventral pallidum and nucleus accumbens. In addition, scattered CTb–Fos double‐labelled cells were observed in many other VTA afferent structures, such as claustrum, lateral septum, diagonal band–magnocellular preoptic nucleus, deep mesencephalic nucleus, oral part of pontine reticular nucleus and dorsomedial tegmental area. This suggests that systemic amphetamine activates a wide population of neurons projecting to the VTA that may be important for the modulation of neurobehavioural plasticity produced by this psychostimulant.
Conservative management resulting in complete resolution of a double intussusception in an adult haemophiliac
Authors: Howard J. M. , Hanly A. M. , Stephens R. B.
Published: August 2007

Acute abdominal pain in haemophiliacs should be approached as haemorrhage until proven otherwise. With advancements in factor repletion and coagulopathic management a conservative approach should be considered. We describe a case of double colo‐colonic intussusception lead by an intramural haematoma occurring spontaneously and resolving with conservative management in a young haemophiliac. This demonstrates that intussusception in these cases may be transient, and does not require surgical intervention.
Investigation to predict faecal continence in patients undergoing reversal of a defunctioning stoma (Porridge enema test)
Authors: Parés D. , Duncan J. , Dudding T. , Phillips R. K. S. , Norton C.
Published: August 2007

Objective  A defunctioning stoma is often performed in cases of major anorectal surgery or sphincter injury. This study aimed to assess the Porridge enema (PE) test as a tool to evaluate function prior to stoma closure.

Method  Thirty‐eight patients underwent PE test at a median of 12.5 months after stoma formation prior to consideration of stoma closure. Outcome was assessed by immediate leakage after PE test on lying, standing, walking and the ability to hold the enema for 30 min. Patients available for follow‐up were divided into two groups: group 1 (n = 20) patients with stoma closure performed and group 2 (n = 10) patients where the stoma remains. Eight patients were excluded from analysis as the stoma had not been reversed for reasons unrelated to continence. The results of other investigations performed in these patients were analysed. Finally, we studied the agreement in the interpretation of the test by two investigators blinded to the patient's group and each other's interpretation and to functional results after the stoma was reversed.

Results  Anorectal physiology testing and imaging assessment of the anal sphincters was not statistically different between the two groups. There was a significant difference in the percentage of patients in each group that had enema leakage in: lying position (P = 0.002), standing position (P = 0.013), walking (P = 0.002) and ability to defer for 30 min (P = 0.005). There was a good correlation in the interpretation of PE test results by two investigators. Among patients whose stoma was closed and who were evaluated functionally, 55% were fully continent.

Conclusion  This report suggests that the PE test is a promising tool as part of evaluation of anorectal function prior to stoma reversal.
The treatment of adolescents presenting with a varicocele
Authors: Çayan Settin , Woodhouse Christopher R.J.
Published: August 2007

In the last 10 years there have been many reports of children and adolescents with varicocele, but virtually none from the UK. There is an increasing incidence with age, to 19% by the age of 19 years. There is some evidence that a varicocele impairs the development of the affected testis; 9.3% of boys of 19 years old have a small testis as a result. Some aspects of testicular function are compromised. Treatment of the varicocele allows compensatory growth and testicular function. The surgical technique must be meticulous to avoid complications, particularly the formation of a hydrocele. Despite much research, the effect on fertility is unknown. The incidence of varicocele is much higher than that of male factor infertility. It is not known whether varicocele in adolescence impairs fertility or whether surgery restores fertility. At present the main indications for surgery are persistent delay in growth of >20%, bilateral varicocele and impaired spermatogenesis persisting beyond 18 years old.
Oral ciprofloxacin or trimethoprim reduces bacteriuria after flexible cystoscopy
Authors: Johnson Mark I. , Merrilees David , Robson Wendy A. , Lennon Teresea , Masters John , Orr Kathy E. , Matthews John N.S. , Neal David E.
Published: August 2007

OBJECTIVE

To report a large prospective, pragmatic, double‐blind randomized controlled trial to determine whether oral prophylactic antibiotics reduce the risk of bacteriuria after flexible cystoscopy (FC), as up to 10% of patients develop urinary infection afterwards, with significant morbidity and costs for health services.

PATIENTS AND METHODS

In all, 2481 patients were recruited into a three‐arm placebo controlled trial and 2083 completed it. Patients were randomly assigned to one of three treatments; (i) placebo; (ii) one oral dose of trimethoprim (200 mg); or (iii) one oral dose of ciprofloxacin (500 mg), each administered 1 h before a FC under local anaesthetic. A mid‐stream urine specimen was taken before and 5 days after FC; significant bacteriuria was defined as a pure growth of >105 colony‐forming units/mL.

RESULTS

The rate of bacteriuria after FC was reduced from 9% in the placebo group to 5% and 3% in patients receiving trimethoprim and ciprofloxacin prophylaxis, respectively. When rates of bacteriuria before FC were considered the odds of developing bacteriuria after FC relative to baseline were 5, 2 and 0.5 for placebo, trimethoprim and ciprofloxacin, respectively.

CONCLUSION

This large trial shows clearly that one dose of oral ciprofloxacin significantly reduces bacteriuria after FC.
Treating patients with overactive bladder syndrome with antimuscarinics: heart rate considerations
Authors: Andersson Karl‐Erik , Olshansky Brian
Published: August 2007

In this excellent mini‐review, the authors present an extensive and relevant paper on the effect of antimuscarinic agents on the heart. This is without doubt the most detailed and the most reader‐friendly paper on this subject, and I am sure that it will help urologists to assist in further educating their patients when prescribing these compounds.
Outcome after cytoreductive nephrectomy for metastatic renal cell carcinoma is predicted by fractional percentage of tumour volume removed
Authors: Pierorazio Phillip M. , McKiernan James M. , McCann Tara R. , Mohile Supriya , Petrylak Daniel , Benson Mitchell C.
Published: August 2007

OBJECTIVE

To determine if the fractional percentage of tumour volume (FPTV) removed at cytoreductive nephrectomy predicts disease‐specific survival (DSS), as metastatic renal cell carcinoma ((M+)RCC) is associated with poor overall survival with only a 10–20% patient survival at 2 years.

PATIENTS AND METHODS

The Columbia Urologic Oncology Database was reviewed; 1016 patients had renal surgery from 1988 to 2005, 78 patients with (M+)RCC underwent nephrectomy. The FPTV removed was determined using pathological and imaging reports. The patients were stratified as having a > or <90% FPTV. Kaplan–Meier analysis with log‐rank test was used to determine survival advantage between groups. A Cox proportional hazard model was used for FPTV in both univariate and multivariate analyses. Secondary analyses were conducted to determine if the size of the primary tumour or volume of metastases affected outcome and if the FPTV affected hospitalization time.

RESULTS

In all, 55 patients had their FPTV calculated exactly; 45 had a >90% FPTV. The median DSS times were 11.6 and 2.9 months for patients with >90% and <90% FPTV removed (P = 0.002). The hazard ratio for death was 0.24 for patients with a >90% FPTV in a univariate model (P = 0.016) and 0.29 in multivariate analysis (P = 0.02). Patients with a <90% FPTV spent a greater percentage of time hospitalized before death, 21.2% vs 6.5% (P = 0.03).

CONCLUSION

For patients with (M+)RCC, overall survival is limited, but can be extended by cytoreductive nephrectomy. The FPTV expected to be removed is a simple and available method to counsel patients regarding the benefits of surgical intervention.
Improving the prognosis of patients after radical cystectomy. Part I: the role of lymph node dissection
Authors: Suttmann Henrik , Kamradt Jörn , Lehmann Jan , Stöckle Michael
Published: August 2007

The first two reviews are from the same unit in Germany and describe the well‐known but still much discussed ways of improving the prognosis of patients undergoing cystectomy for bladder cancer. The authors review the roles of lymph node dissection and perioperative chemotherapy, and draw conclusions which will be of help for patients having this form of therapy.

In a further review, authors from Egypt debate the requirement for a refluxing or non‐refluxing uretero‐ileal anastomosis in low‐pressure reservoirs, drawing on their extensive experience in this field.

The optimum treatment for patients with muscle‐invasive bladder cancer remains a matter of intense debate; some authors still question the role of radical cystectomy (RC) per se, as it can be a potentially mutilating procedure with subsequent impairment in quality of life. However, the impairment has not been investigated using validated quality‐of‐life studies. By contrast, it is commonly accepted that no alternative treatment yields similar long‐term survival data to RC. However, survival rates after RC are far from satisfying, particularly for patients with ≥ pT3 and/or pN+ disease. Therefore, various strategies were introduced to improve survival in these patients, i.e. extension of lymph node dissection during radical surgery and perioperative chemotherapy. Both strategies are analysed and discussed in two mini‐reviews, based on data from current publications and from theoretical considerations.
Partitioning phylogenetic and adaptive components of the geographical body‐size pattern of New World birds
Authors: Ramirez Lizabeth , Diniz‐Filho José Alexandre Felizola , Hawkins Bradford A.
Published: August 2007

Aim To evaluate seasonal body‐size patterns for New World birds in geographical space, to develop environmental models to explain the gradients, and to estimate phylogenetic and adaptive contributions.

Location The Western Hemisphere.

Methods We used range maps to generate gridded geometric mean body masses. Summer and winter patterns were distinguished based on breeding and non‐breeding ranges. We first generated the geographical gradients, followed by phylogenetic eigenvector regression to generate body sizes predicted by the birds’ positions in a phylogenetic tree, which were used to generate the expected phylogenetic gradient. Subtracting the expected pattern from the observed pattern isolated the adaptive component. Ordinary least squares multiple‐regression models examined factors influencing the phylogenetic, adaptive and combined components of the seasonal body‐size patterns, and non‐spatial and spatial models were compared.

Results Birds are larger in the temperate zones than in the tropics. The gradient is quantitatively stronger in winter than in summer. Regression models explained 66.6% of the variance in summer mass and 45.9% of the variance in winter mass. In summer, phylogenetic and adaptive responses of birds contribute equally to the gradient. In winter, the gradient in North America is much stronger than that expected by taxonomic turnover, and responses of species independent of their family membership drive the overall pattern.

Main conclusions We confirm Bergmann's rule in New World birds and conclude that winter temperatures ultimately drive the pattern, exerting selection pressures on birds that overwhelm patterns expected by phylogenetic inertia at the family level. However, in summer, the movement of migratory species into the temperate zone weakens the gradient and generates a pattern more congruent with that expected from the taxonomic composition of the fauna. The analytical method we develop here represents a useful tool for partitioning the phylogenetic and non‐phylogenetic components of spatially explicit macroecological data.
Leaf area index for northern and eastern North America at the Last Glacial Maximum: a data–model comparison
Authors: Williams John W. , Gonzales Leila M. , Kaplan Jed O.
Published: August 2007

Aim  To estimate the effects of full‐glacial atmospheric CO2 concentrations and climate upon leaf area index (LAI), using both global vegetation models and palaeoecological data. Prior simulations indicate lowered LAIs at the Last Glacial Maximum (LGM), but this is the first attempt to corroborate predictions against observations.

Location  Eastern North America and eastern Beringia.

Methods  Using a dense surface pollen data set and remotely sensed LAIs from the Moderate Resolution Imaging Spectroradiometer (MODIS) instrument, we evaluate the ability of analogue‐based techniques to reconstruct modern LAIs from pollen data. We then apply analogue techniques to LGM pollen records, calculate the ratio of LGM to modern LAIs (RLAI) and compare reconstructed RLAIs to RLAIs simulated by BIOME4. Sensitivity experiments with BIOME4 distinguish the effects of CO2 and climate on glacial LAIs.

Results  Modern LAIs are skilfully predicted (r2= 0.83). Data and BIOME4 indicate that LAIs at the LGM were up to 12% lower than modern values in eastern North America and 60–94% lower in Beringia. In eastern North America, LGM climates partially counteracted CO2‐driven decreases in LAI, while in Beringia both contributed to lowered LAIs.

Main conclusions  In both regions climate is the primary driver of LGM LAIs. The decline in eastern North America LAIs is smaller than previously reported, so regional vegetation feedbacks to LGM climate may have been less significant than previously supposed. CO2 exerts both physiological and community effects upon LAI, by regulating resource availability for leaf production and by influencing the competitive balance among species and hence the composition and structure of plant communities. Pollen‐based reconstructions using analogue methods do not incorporate the physiological effect and so are upper estimates of full‐glacial LAIs. BIOME4 sensitivity experiments indicate that the community and physiological effects together caused 10% to 20% decrease in LAIs at the LGM, so simulated RLAIs that are 80–100% of reconstructed RLAIs are regarded as consistent with data.
Maize streak virus‐resistant transgenic maize: a first for Africa
Authors: Shepherd Dionne N. , Mangwende Tichaona , Martin Darren P. , Bezuidenhout Marion , Kloppers Frederik J. , Carolissen Charlene H. , Monjane Adérito L. , Rybicki Edward P. , Thomson Jennifer A.
Published: August 2007

In this article, we report transgene‐derived resistance in maize to the severe pathogen maize streak virus (MSV). The mutated MSV replication‐associated protein gene that was used to transform maize showed stable expression to the fourth generation. Transgenic T2 and T3 plants displayed a significant delay in symptom development, a decrease in symptom severity and higher survival rates than non‐transgenic plants after MSV challenge, as did a transgenic hybrid made by crossing T2 Hi‐II with the widely grown, commercial, highly MSV‐susceptible, white maize genotype WM3. To the best of our knowledge, this is the first maize to be developed with transgenic MSV resistance and the first all‐African‐produced genetically modified crop plant.
Coordinated regulation of maize genes during increasing exposure to ultraviolet radiation: identification of ultraviolet‐responsive genes, functional processes and associated potential promoter motifs
Authors: Blanding Carletha R. , Simmons Susan J. , Casati Paula , Walbot Virginia , Stapleton Ann E.
Published: August 2007

Genetic gain in the yield of modern maize reflects increased stress tolerance. The manipulation of genes for deliberate alterations in tolerance relies on an understanding of the regulation and components of stress responses. Transcriptome analysis of an ultraviolet (UV) radiation time course with paired treatment and control measurements yielded groups of coordinately regulated genes and gene ontology processes. A comparison of the patterns of gene expression with patterns of morphological changes allowed the identification of physiologically relevant gene expression regulons. A set of genes significantly affected by UV radiation in maize leaves was selected by linear modelling plus order‐restricted inference profile matches. This gene list was used to find upstream sequence motifs that predict the UV regulation of maize gene expression.
Developmental States in the New Millennium: Concepts and Challenges for a New Aid Agenda
Authors: Fritz Verena , Menocal Alina Rocha
Published: August 2007

The developmental state is back at the centre of the international policy debate. But policy‐makers still have much to learn from the large research‐based literature on the subject. In introducing a theme issue of DPR on this subject, this article provides an overview of three central topics: the relationship between the project of building or rebuilding effective states and the ‘good governance’ agenda; the role of the international aid community in stimulating or hindering state‐building; and the search for a way forward which incorporates awareness of the variety of successful development models and of the role that aid inevitably plays in the incentive structure of state elites in poor developing countries.
The Logic of African Neopatrimonialism: What Role for Donors?
Authors: Cammack Diana
Published: August 2007

Today a number of sub‐Saharan African countries display the outward signs of modern, democratic states. International aid agencies often treat them as though power and decision‐making reside within government institutions and that they function as designed. When they do not they are labelled dysfunctional though their action is actually quite logical when viewed through a ‘neopatrimonial lens’. This article outlines a number of neopatrimonial practices observed in Africa in the past two decades and attempts to explain the ‘logic’ that underpins them. It provides several recommendations about the way donors should assist states where deeply rooted anti‐democratic and non‐developmental behaviour dominates.
Financing the Developmental State: Tax and Revenue Issues
Authors: Sindzingre Alice
Published: August 2007

Asian developmental states do not rely on high levels of taxation. Their key features are the capacity to commit and intervene credibly in the form of policies directed towards growth rather than taxation. These features are often lacking in sub‐Saharan Africa where the problem is compounded by three main constraints that prevent taxation from financing African states in a developmental way: their dependence on commodities, the effects of trade liberalisation, and the impact of aid, which provides incentives that may undermine the tax structures and key institutions of recipient countries.