bluuebunny/crossref_metadata_2025_split huggingface dataset:
Compartmentalization of calcium entry pathways in mouse rods
Authors: Krizaj David 
Published: December 2005

AbstractPhotoreceptor metabolism, gene expression and synaptic transmission take place in a highly polarized structure consisting of the ellipsoid, subellipsoid, cell body and synaptic terminal regions. Although calcium, a key second messenger, regulates cellular functions throughout the photoreceptor, the molecular mechanisms underlying local region‐specific action of Ca2+ in photoreceptors are poorly understood. I have investigated the compartmentalization of voltage‐dependent and independent Ca2+ channels in mouse photoreceptors. Transient receptor potential channels isoform 6 (TRPC6), a putative store‐operated Ca2+ channel, was selectively localized to the cell body of rods. By contrast, voltage‐operated Ca2+ channels were expressed in the synaptic terminal and in the ellipsoid/subellipsoid regions. Likewise, Ca2+ store transporters and channels were strongly associated with the subellipsoid region. A moderate TRPC6 signal was observed in cell bodies of bipolar, amacrine and ganglion cells, but was absent from both plexiform layers. These results suggest that Ca2+ entry mechanisms in mammalian photoreceptors and bipolar cells are highly compartmentalized, consistent with local, region‐specific activation of Ca2+‐dependent processes.
Effects of extracellular δ‐aminolaevulinic acid on sodium currents in acutely isolated rat hippocampal CA1 neurons
Authors: Wang Lang , Yan Dan , Gu Yan , Sun Li‐Guang , Ruan Di‐Yun 
Published: December 2005

AbstractThe effects of δ‐aminolaevulinic acid (ALA) on voltage‐gated sodium channel (VGSC) currents (INa) in acutely isolated hippocampal CA1 neurons from 10‐ to 12‐day‐old Wistar rats were examined by using the whole‐cell patch‐clamp technique under voltage‐clamp conditions. ALA from 0.01 µm to 20 µm was applied to the recorded neurons. Low concentrations of ALA (0.01–1.0 µm) increased INa amplitude, whereas high concentrations of ALA (5.0–20.0 µm) decreased it. The average INa amplitude reached a maximum of 117.4 ± 3.9% (n = 9, P < 0.05) with 0.1 µm ALA, and decreased to 78.1 ± 3.8% (n = 13, P < 0.05) with 10 µm ALA. ALA shifted the steady‐state activation and inactivation curves of INa in the hyperpolarizing direction with different V0.5, suggesting that ALA could depress the opening threshold of the voltage‐gated sodium channel (VGSC) and thus increase the excitability of neurons through facilitating the opening of VGSC. The time course of recovery from inactivation was significantly prolonged at both low and high concentrations of ALA, whereas either low or high concentrations of ALA had no significant effect on the attenuation of INa during stimulation at 5 Hz, indicating that the effect of ALA on VGSC is state‐independent. Furthermore, we found that application of ascorbic acid, which blocks pro‐oxidative effects in neurons, could prevent the increase of INa amplitude at low concentrations of ALA. Baclofen, an agonist of GABAb receptors, induced some similar effects to ALA on VGSC, whereas bicuculline, an antagonist of GABAa receptors, could not prevent ALA‐induced effects on VGSC. These results suggested that ALA regulated VGSC mainly through its pro‐oxidative effects and GABAb receptor‐mediated effects.
Nestin‐expressing cells and their relationship to mitotically active cells in the subventricular zones of the adult rat
Authors: Ernst Carl , Christie Brian R. 
Published: December 2005

AbstractNestin is a protein that is thought to be expressed in neural stem cells; however, there is a paucity of data on nestin expression in vivo, and little is known of the relationship between nestin and mitotically active cell populations in the subventricular zones (SVZ). In this study, the subventricular zone of the third ventricle contained a high proportion of cells that expressed nestin, while there were significantly fewer cells that expressed nestin in the SVZ of the lateral ventricles. In contrast, bromodeoxyuridine (BrdU) immunoreactivity was the diametric opposite, being higher in the SVZ of the lateral ventricle than in the SVZ of the third ventricle. Morphological and anatomical evidence suggests that nestin‐expressing cells in these two areas may be different cell types. In a separate set of experiments, an acute localized lesion was induced adjacent to one of the ventricles. While the number of BrdU cells and Ki‐67 cells in the SVZs increased with this manipulation, the number of nestin‐expressing cells did not change significantly. These data indicate that the expression of nestin does not correlate with mitotic activity in cells of the SVZs under either normal or inflammatory conditions. It is hypothesized that nestin‐expressing cells in the SVZs may give way to transit amplifying cells that in turn give way to immature neurons or glia. These transit‐amplifying cells may have a much higher rate of mitosis than nestin‐positive cells and may react to neural damage by increasing their rate of proliferation.
Calcium concentration changes during sensory transduction in spider mechanoreceptor neurons
Authors: Höger Ulli , Torkkeli Päivi H. , French Andrew S. 
Published: December 2005

AbstractMost mechanoreceptor neurons encode mechanical signals into action potential trains within the same cell. Evidence suggests that intracellular calcium ion concentration, [Ca2+], increases during mechanotransduction, either by direct entry through mechanically activated channels or indirectly through voltage‐activated calcium channels. However, little is known about the amounts of calcium involved or its roles in mechanotransduction. We estimated [Ca2+] in mechanoreceptor neurons of the spider, Cupiennius salei, during mechanical stimulation using Oregon Green BAPTA‐1, and a single‐compartment model of [Ca2+] as a function of action potential firing rate. Resting [Ca2+] was approximately 400 nm and increased to up to 2 µm at 30 action potentials/s. Similar levels of resting and stimulated [Ca2+] were obtained in the cell soma, axon and two parts of the sensory dendrite, including the region immediately adjacent to the site of sensory transduction. The time constant of rise and fall of [Ca2+] was 1–5 s in the dendrite and axon, but up to 15 s in the soma. Calcium elevation was dependent on action potentials and could not be induced by the receptor potential alone. Blockade of voltage‐activated calcium channels by nickel ions prevented calcium increase, but thapsigargin, which empties intracellular calcium stores, had no effect. Estimates of calcium entry per action potential from fluorescence changes agreed approximately with estimates based on action potential voltage–time profile and previous reports of calcium channel properties. This first report of calcium levels during transduction in spiking mechanoreceptors suggests that calcium signaling plays important roles in primary somatosensory neurons.
Direct pyrogenic input from prostaglandin EP3 receptor‐expressing preoptic neurons to the dorsomedial hypothalamus
Authors: Nakamura Yoshiko , Nakamura Kazuhiro , Matsumura Kiyoshi , Kobayashi Shigeo , Kaneko Takeshi , Morrison Shaun F. 
Published: December 2005

AbstractFever is induced by a neuronal mechanism in the brain. Prostaglandin (PG) E2 acts as a pyrogenic mediator in the preoptic area (POA) probably through the EP3 subtype of PGE receptor expressed on GABAergic neurons, and this PGE2 action triggers neuronal pathways for sympathetic thermogenesis in peripheral effector organs including brown adipose tissue (BAT). To explore pyrogenic efferent pathways from the POA, we determined projection targets of EP3 receptor‐expressing POA neurons with a special focus on rat hypothalamic regions including the dorsomedial hypothalamic nucleus (DMH), which is known as a center for autonomic responses to stress. Among injections of cholera toxin b‐subunit (CTb), a retrograde tracer, into hypothalamic regions at the rostrocaudal level of the DMH, injections into the DMH, lateral hypothalamic area (LH) and dorsal hypothalamic area (DH) resulted in EP3 receptor immunolabelling in substantial populations of CTb‐labeled neurons in the POA. Bilateral microinjections of muscimol, a GABAA receptor agonist, into the DMH and a ventral region of the DH, but not those into the LH, inhibited thermogenic (BAT sympathetic nerve activity, BAT temperature, core body temperature and expired CO2) and cardiovascular (arterial pressure and heart rate) responses to an intra‐POA PGE2 microinjection. Further immunohistochemical observations revealed a close association of POA‐derived GABAergic axon swellings with DMH neurons projecting to the medullary raphe regions where sympathetic premotor neurons for febrile and thermoregulatory responses are localized. These results suggest that a direct projection of EP3 receptor‐expressing POA neurons to the DMH/DH region mediates febrile responses via a GABAergic mechanism.
Effector‐independent voluntary timing: behavioural and neuroimaging evidence
Authors: Bengtsson Sara L. , Ehrsson H. Henrik , Forssberg Hans , Ullén Fredrik 
Published: December 2005

AbstractWe investigated effector‐independent aspects of voluntary motor timing, using behavioural measurements and functional magnetic resonance imaging. Two types of temporal pattern were investigated; one isochronous, the other a metric, rhythmic sequence of six temporal intervals. Each pattern was performed using tapping movements with the left or right index fingers, or rhythmic speech on one syllable. Deviations from the ideal temporal pattern in the rhythmic sequence tasks were consistent between the three different effectors, within subjects. This suggests that the same representation of the rhythm was used to time the movements with all effectors. To reveal brain regions involved in such effector‐independent timing, we localized the overlap in brain activity when the rhythmic sequence was performed with the different effectors. Activity was found in the mesial and lateral premotor cortices, posterior and anterior regions of the superior temporal gyrus and the inferior frontal cortex. Subcortical activations were in the left globus pallidus, the vermis and bilaterally in the cerebellar hemispheres (lobule VI) and the thalamus. The overlap in activity between the isochronous tasks included the same set of brain regions, except for the basal ganglia and the thalamus. Rhythmic sequences had significantly higher activity in mesial premotor cortex, the left superior temporal gyrus and the cerebellum, than had isochronous movements. These findings reveal a set of brain regions likely to be involved in effector‐independent representations of temporal patterns in voluntary motor timing. A subset of these regions plays important roles for the organization of rhythmic sequences of several intervals.
Insulin status differentially affects energy transduction in cardiac mitochondria from male and female rats
Authors: Billimoria Framroze R. , Katyare Surendra S. , Patel Samir P. 
Published: December 2005

Aim:  The incidence of coronary heart diseases (CHD), congestive heart failure (CHF) and myocardial infarction is higher in diabetic patients than in non‐diabetic groups, with these incidences being more in women than in the men. Hence, we examined involvement of mitochondrial energy transduction functions.Methods:  Mitochondrial energy metabolism in cardiomyopathy was studied using streptozotocin (STZ)‐diabetic male and female rats as the model system. Effects of insulin treatment were also evaluated.Results:  The body and heart weights decreased in both male and female diabetic rats. Insulin treatments resulted in significant increase in the body and heart weights in the female rats. Mitochondrial respiration rates with all the substrates tested decreased in diabetic condition in both males and females. Treatment with two dose‐regimens of insulin had differential restorative effect on mitochondrial substrate oxidation in the males but caused hyper‐stimulation in the females. Diabetic state brought about 19% decrease in the cytochrome aa3 content in the female rats. Treatment with 0.6 units of insulin significantly increased the cytochrome contents in general in both the sexes whereas higher dose (1.0 unit) caused decrease in the cytochromes content in the females. Diabetic state resulted in decreased dehydrogenases activities; insulin treatments had differential effect on the dehydrogenase activity in the males and the females. The results suggest that insulin treatment‐induced hyper‐stimulation of respiration in female rats may lead to increased production of reactive oxygen species. Besides, increased formation of advanced glycosylated end products may further lead to increased risk of CHF and CHD.Conclusions:  The results suggest that differential effects of STZ‐diabetes and insulin treatments in the female rats than in males may be the underlying cause for increased incidence of diabetic cardiomypathies in the females.
Pioglitazone and reductions in post‐challenge glucose levels in patients with type 2 diabetes
Authors: Khan M. , Murray F. T. , Karunaratne M. , Perez A. 
Published: December 2005

Aim:  Pioglitazone (PIO) has been shown to decrease insulin resistance in patients with type 2 diabetes, resulting in lowered blood glucose concentrations, lowered plasma insulin levels and lowered haemoglobin A1C (A1C) values. Postprandial glucose control has been recently recognized as an important target for reducing overall glycemic burden in patients with type 2 diabetes. Some authors assert that reductions in postprandial glucose levels may lead to a decrease in cardiovascular risk, one of the major complications associated with diabetes.Methods:  Data were analysed from a 26‐week PIO monotherapy study of 88 patients who underwent a 3‐h oral glucose tolerance test (75 g dose) at baseline and last measurement. Change from baseline in area under the curve (AUC) values and hourly glucose concentrations were calculated and analysed at both time points for four medication groups: placebo group and PIO 15, 30 and 45 mg groups. Changes from baseline in fasting plasma glucose (FPG) and A1C also were reported.Results:  Glucose AUC was significantly (p < 0.05) different from baseline at 15, 30 and 45 mg doses of PIO. In addition, when compared to placebo, PIO (15, 30 and 45 mg) significantly decreased post‐challenge blood glucose AUC (p < 0.05). The mean hourly blood glucose levels at last measurement for PIO 15, 30 and 45 mg all were significantly lower (p < 0.05) than placebo at all four time points. In addition, PIO significantly (p < 0.05) reduced FPG and A1C from baseline to last measurement in a dose‐related fashion.Conclusions:  PIO significantly reduced post‐challenge glucose levels following an oral glucose challenge, leading to improvements in overall glycemic control. Postprandial glucose lowering is one of several metabolic effects of PIO in addition to decreasing insulin resistance and improving some lipids components. Whether these combined metabolic effects can lead to cardiovascular risk reductions may be confirmed by the pending results of cardiovascular outcomes studies with PIO.
Biphasic insulin aspart 30 plus metformin: an effective combination in type 2 diabetes
Authors: Kvapil M. , Swatko A. , Hilberg C. , Shestakova M. 
Published: December 2005

Aim:  This study compared glycaemic control achieved with biphasic insulin aspart 30 (BIAsp 30) monotherapy, BIAsp 30 plus metformin and glibenclamide plus metformin in patients with type 2 diabetes not adequately controlled with metformin.Methods:  In this multinational, open‐labelled, parallel group, 16‐week trial, 341 patients (patients not adequately controlled with metformin for at least 1 month) with type 2 diabetes were studied. Patients were randomized to receive BIAsp 30, twice daily (n = 107 exposed to treatment), or BIAsp 30, twice daily, plus metformin (n = 108) or glibenclamide plus metformin (n = 114). The primary endpoint was HbA1c at end of trial; adverse events, hypoglycaemia episodes, blood lipids and weight were also monitored.Results:  In the total population (HbA1c 7.5–13.0% at screening), end‐of‐trial HbA1c levels were lower in patients receiving BIAsp 30 plus metformin compared with those receiving BIAsp 30 only [mean treatment difference (±s.e.m), 0.39 ± 0.15%, p = 0.007]. In a subpopulation (HbA1c ≥ 9.0% at baseline, n = 193), patients receiving BIAsp 30 plus metformin had significantly lower HbA1c levels at the end of the trial compared with those receiving glibenclamide plus metformin (treatment difference, 0.46 ± 0.21%, p = 0.027). Mean body weight (±s.d) at the end of the trial was significantly lower in patients receiving glibenclamide plus metformin compared with those receiving BIAsp 30 only (84.3 ± 13.3 kg vs. 88.9 ± 16.9 kg, p < 0.001). No major hypoglycaemic episodes were recorded during the trial, and incidence rates for minor and symptoms‐only hypoglycaemia were low and similar between treatment groups (0.03–0.04 events/patient/week).Conclusion:  BIAsp 30 added to metformin could be an appropriate therapeutic option for achieving good glycaemic control, compared with the addition of a second oral agent, particularly where HbA1c ≥ 9%.
Urogynaecology: Urethral retro‐resistance pressure and urodynamic diagnoses in women with lower urinary tract symptoms
Authors: Alessandro Digesu G , Athanasiou Stavros , Chaliha Charlotte , Michalas Stylianos , Salvatore Stefano , Selvaggi Luigi , Khullar Vik 
Published: December 2005

Objective  This study determines whether the retrograde urethral retro‐resistance pressure (URP) measurement discriminates between urodynamic diagnoses in a group of women.Design  A prospective observational study.Setting  Urogynaecology units of three tertiary referral teaching hospitals.Population  Women with lower urinary tract symptoms.Methods  Consecutive women attending the urodynamic clinics of three tertiary referral teaching hospitals were studied using a validated urinary symptom questionnaire, URP measurement and urodynamic evaluation between February and July 2004. The URP mean values were compared with urinary symptoms and urodynamic diagnoses, using the independent t test correction for multiple measurements.Main outcome measures  Retrograde URP, urodynamic diagnoses and urinary symptoms.Results  One hundred and eighty‐five women were recruited. Women with urodynamic stress incontinence (USI) have significantly lower URP than women with competent urethral sphincters (P < 0.05, independent t test). Women with mixed urodynamic incontinence had values of URP intermediate between women with detrusor overactivity (DOA) and those with USI. In the mixed group, URP mean values were not significantly different from those with DOA and competent sphincters or USI (P > 0.05, independent t test). There was no significant difference between mean URP values and different urinary symptoms (P > 0.05, independent t test).Conclusions  There are significantly different URP measurements between women with DOA and those with USI. However, the URP is not a diagnostic tool.
General obstetrics: Vaginal birth after caesarean section versus elective repeat caesarean section: assessment of maternal downstream health outcomes
Authors: Paré Emmanuelle , Quiñones Joanne N , Macones George A 
Published: December 2005

Objective  To compare the maternal implications of strategies of vaginal birth after caesarean section (VBAC) attempt versus elective repeat caesarean section in women with one previous lower segment caesarean section.Design  Decision model.Population  Women with one prior low transverse caesarean section who are eligible for trial of labour.Methods  Two decision models were built: the first one applying to women planning only one more pregnancy, the second one applying to women planning two more pregnancies. Probability estimates for VBAC success rate and risks of uterine rupture, placenta praevia, placenta accreta and hysterectomy were extracted from the available literature.Main outcome measures  Hysterectomy for uterine rupture, placenta accreta or other indications.Results  In the first model VBAC attempt led to a higher hysterectomy rate (267/100,000) compared with repeat caesarean section (187/100,000). However, in the second model a policy of elective repeat caesarean section led to higher cumulative hysterectomy rate: 1465/100,000 versus 907/100,000 for VBAC. The first model was robust to all but one variable in sensitivity analyses. The second model was robust to all variables in sensitivity analyses.Conclusions  These results indicate that long term reproductive consequences of multiple caesarean sections should be considered when making policy decisions regarding the risk–benefit ratio of VBAC.
General obstetrics: Does size matter? A population‐based study of birth in lower volume maternity hospitals for low risk women
Authors: Tracy Sally K , Sullivan Elizabeth , Dahlen Hannah , Black Deborah , Wang Yueping Alex , Tracy Mark B 
Published: December 2005

Objective  To study the association between volume of hospital births per annum and birth outcome for low risk women.Design  Population‐based study using the National Perinatal Data Collection (NPDC).Setting  Australia.Participants  Of 750,491 women who gave birth during 1999–2001, there were 331,147 (47.14%) medically ‘low risk’ including 132,696 (40.07%) primiparae and 198,451 (59.93%) multiparae.Methods  The frequency of each birth and infant outcome was described according to the size of the hospital where birth took place. We investigated whether unit size (defined by volume) was an independent risk factor for each outcome factor using public hospitals with greater than 2000 births per annum as a reference point.Main outcome measures  Rates of intervention at birth and neonatal mortality for low risk women in relation to hospitals with <100, 100–500, 501–1000, 1001–2000 and >2001 births per annum.Results  Neonatal death was less likely in hospitals with less than 2000 births per annum regardless of parity. For multiparous low risk women in hospitals of 100 and 500 births per annum compared with hospitals of >2000 births per annum the adjusted odds of neonatal mortality [adjusted odds ratio (AOR) 0.36; 99% confidence interval (CI) 0.14–0.93]. For low risk primiparous women in hospitals with less than 100 births per annum, there were lower rates of induction of labour (AOR 0.62; 99% CI 0.54–0.73); intrathecal analgesia/anaesthesia (AOR 0.34; 99% CI 0.28–0.42); instrumental birth (AOR 0.80; 99% CI 0.69–0.93); caesarean section after labour (AOR 0.59; 99% CI 0.49–0.72) and admission to a neonatal unit (AOR 0.15; 99% CI 0.10–0.22) and for low risk multiparous women in hospitals with less than 100 births per annum: induction (AOR 0.69; 99% CI 0.62–0.76); intrathecal analgesia/anaesthesia (AOR 0.32; 99% CI 0.29–0.36); instrumental birth (AOR 0.52; 99% CI 0.41–0.67); caesarean section after labour (AOR 0.41; 99% CI 0.33–0.52); and admission to a neonatal unit (AOR 0.09; 99% CI 0.07–0.12).Conclusions  In Australia, lower hospital volume is not associated with adverse outcomes for low risk women.