bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneous CPA sensitivity of spontaneous excitation in smooth muscle of the rabbit urethra
Authors: Hashitani Hikaru , Yanai Yoshimasa , Kohri Kenjiro , Suzuki Hikaru 
Published: April 2006

To investigate the role of intracellular Ca stores in generating spontaneous excitation of the urethra, the effects of cyclopiazonic acid (CPA) on spontaneous contractions, transient increases in intracellular calcium concentration ([Ca2+]i; Ca transients) and depolarizations were examined in smooth muscles of the rabbit urethra.
In about 90% of circular smooth muscle (CSM) preparations, CPA (10 μM) increased the amplitude of spontaneous contractions by about 180% and reduced their frequency to some 25% of control values (CPA‐resistant), while it readily abolished the contractions in the remaining preparations.
In about 70% of CSM preparations, CPA prevented the generation of spontaneous depolarizations termed slow waves, but increased their amplitude and duration in the remainder. CPA also prevented the generation of spontaneous Ca transients in about 40% of CSM preparations, while increasing their amplitude and duration in the remaining preparations. In CPA‐resistant preparations that had been exposed to nicardipine (1 μM), subsequent CPA invariably abolished residual spontaneous depolarizations or Ca transients. CPA abolished caffeine‐induced Ca transients in Ca‐free solutions, suggesting that it effectively depleted intracellular Ca stores.
Longitudinal smooth muscles generated spontaneous action potentials, which had a shape distinct from that of slow waves in CSM. Spontaneous action potentials were abolished by nicardipine but not CPA.
Transmural nerve stimulation increased the frequency of Ca transients to give a sustained rise in [Ca2+]i, but inhibited their generation after blocking α‐adrenoceptors with phentolamine (1 μM). These nerve‐evoked responses were preserved in preparations that had been exposed to CPA. Similarly, both in control and CPA‐treated CSM preparations, spontaneous Ca transients were accelerated by noradrenaline (NAd, 1 μM) and were suppressed by 3‐morpholino‐sydnonimine (SIN‐1, 10 μM), a nitric oxide (NO) donor.
In conclusion, CSM of the urethra generates spontaneous activity, which depends on Ca release from intracellular Ca stores. However, after blocking this primary pacemaking mechanism, L‐type Ca channel‐dependent action potentials may drive CSM. Irrespective of the origin of pacemaking, neurally‐released NAd and NO are capable of modulating spontaneous excitation.

British Journal of Pharmacology (2006) 148, 340–349. doi:10.1038/sj.bjp.0706729
Spinalα2‐adrenergic and muscarinic receptors and the NO release cascade mediate supraspinally produced effectiveness of gabapentin at decreasing mechanical hypersensitivity in mice after partial nerve injury
Authors: Takasu Keiko , Honda Motoko , Ono Hideki , Tanabe Mitsuo 
Published: April 2006

After partial nerve injury, the central analgesic effect of systemically administered gabapentin is mediated by both supraspinal and spinal actions. We further evaluate the mechanisms related to the supraspinally mediated analgesic actions of gabapentin involving the descending noradrenergic system.Intracerebroventricularly (i.c.v.) administered gabapentin (100 μg) decreased thermal and mechanical hypersensitivity in a murine chronic pain model that was prepared by partial ligation of the sciatic nerve. These effects were abolished by intrathecal (i.t.) injection of either yohimbine (3 μg) or idazoxan (3 μg),α2‐adrenergic receptor antagonists.Pretreatment with atropine (0.3 mg kg−1, i.p. or 0.1 μg, i.t.), a muscarinic receptor antagonist, completely suppressed the effect of i.c.v.‐injected gabapentin on mechanical hypersensitivity, whereas its effect on thermal hypersensitivity remained unchanged. Similar effects were obtained with pirenzepine (0.1 μg, i.t.), a selective M1‐muscarinic receptor antagonist, but not with methoctramine (0.1 and 0.3 μg, i.t.), a selective M2‐muscarinic receptor antagonist.The cholinesterase inhibitor neostigmine (0.3 ng, i.t.) potentiated only the analgesic effect of i.c.v. gabapentin on mechanical hypersensitivity, confirming spinal acetylcholine release downstream of the supraspinal action of gabapentin.Moreover, the effect of i.c.v. gabapentin on mechanical but not thermal hypersensitivity was reduced by i.t. injection ofL‐NAME (3 μg) orL‐NMMA (10 μg), both of which are nitric oxide (NO) synthase inhibitors.Systemically administered naloxone (10 mg kg−1, i.p.), an opioid receptor antagonist, failed to suppress the analgesic actions of i.c.v. gabapentin, indicating that opioid receptors are not involved in activation of the descending noradrenergic system by gabapentin.Thus, the supraspinally mediated effect of gabapentin on mechanical hypersensitivity involves activation of spinalα2‐adrenergic receptors followed by muscarinic receptors (most likely M1) and the NO cascade. In contrast, the effect of supraspinal gabapentin on thermal hypersensitivity is independent of the spinal cholinergic–NO system.British Journal of Pharmacology(2006)148, 233–244. doi:10.1038/sj.bjp.0706731
Paeoniflorin attenuates neuroinflammation and dopaminergic neurodegeneration in the MPTP model of Parkinson's disease by activation of adenosine A1receptor
Authors: Liu Hua‐Qing , Zhang Wei‐Yu , Luo Xue‐Ting , Ye Yang , Zhu Xing‐Zu 
Published: April 2006

This study examined whether Paeoniflorin (PF), the major active components of Chinese herbPaeoniae albaRadix, has neuroprotective effect in the 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD).Subcutaneous administration of PF (2.5 and 5 mg kg−1) for 11 days could protect tyrosine hydroxylase (TH)‐positive substantia nigra neurons and striatal nerve fibers from death and bradykinesia induced by four‐dose injection of MPTP (20 mg kg−1) on day 8.When given at 1 h after the last dose of MPTP, and then administered once a day for the following 3 days, PF (2.5 and 5 mg kg−1) also significantly attenuated the dopaminergic neurodegeneration in a dose‐dependent manner. Post‐treatment with PF (5 mg kg−1) significantly attenuated MPTP‐induced proinflammatory gene upregulation and microglial and astrocytic activation.Pretreatment with 0.3 mg kg−18‐cyclopentyl‐1,3‐dipropylxanthine, an adenosine A1receptor (A1AR) antagonist, 15 min before each dose of PF, reversed the neuroprotective and antineuroinflammatory effects of PF.In conclusion, this study demonstrated that PF could reduce the MPTP‐induced toxicity by inhibition of neuroinflammation by activation of the A1AR, and suggested that PF might be a valuable neuroprotective agent for the treatment of PD.British Journal of Pharmacology(2006)148, 314–325. doi:10.1038/sj.bjp.0706732
The metabotropic glutamate receptor 4 is internalized and desensitized upon protein kinase C activation
Authors: Mathiesen Jesper Mosolff , Ramirez M Teresa 
Published: April 2006

The metabotropic glutamate receptor 4 (mGluR4) is a Gαi‐coupled receptor that modulates glutamatergic neurotransmission. As mGluR4 expression and activation have been implicated in a number of pathological conditions and because the internalization and desensitization properties of this receptor are poorly understood, studies were designed to investigate these aspects of mGluR4 biology.Neither agonist activation byL‐(+)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4) norL‐glutamate caused mGluR4 internalization when cmyc‐tagged mGluR4 was expressed in a human embryonic kidney 293 cell line as assessed by cell surface enzyme‐linked immunosorbent and immunostaining assays. Instead, a modest increase in mGluR4 surface expression was observed and found to be receptor specific as the competitive antagonistα‐cyclopropyl‐4‐phosphonophenylglycine (CPPG) blocked this effect.In contrast, mGluR4 internalized when the protein kinase C (PKC) pathway was activated either by phorbol‐12‐myristate‐13‐acetate (PMA) or by the activation of the Gαq‐coupled, neurokinin 3 receptor (NK3R) when co‐expressed. This process was PKC‐dependent as the specific PKC inhibitor GF 109203X inhibited PMA and NK3R‐mediated internalization.PKC activation by PMA caused desensitization of mGluR4 as measured by forskolin‐stimulated cAMP inhibition, whereas agonist activation had no effect on desensitization.When mGluR4's coupling was redirected from adenylyl cyclase to phospholipase C by coexpression of a chimeric Gαqo5protein, mGluR4 both internalized and desensitized in response to its agonists.These findings demonstrate that mGluR4 internalization and desensitization are agonist‐independent unless pathways leading to the activation of PKC are induced.British Journal of Pharmacology(2006)148, 279–290. doi:10.1038/sj.bjp.0706733
Using mRNAs lengths to accurately predict the alternatively spliced gene products in Caenorhabditis elegans
Authors: Agrawal Ritesh , Stormo Gary D. 
Published: April 2006

Abstract
Motivation: Computational gene prediction methods are an important component of whole genome analyses. While ab initio gene finders have demonstrated major improvements in accuracy, the most reliable methods are evidence-based gene predictors. These algorithms can rely on several different sources of evidence including predictions from multiple ab initio gene finders, matches to known proteins, sequence conservation and partial cDNAs to predict the final product. Despite the success of these algorithms, prediction of complete gene structures, especially for alternatively spliced products, remains a difficult task.
Results: LOCUS (Length Optimized Characterization of Unknown Spliceforms) is a new evidence-based gene finding algorithm which integrates a length-constraint into a dynamic programming-based framework for prediction of gene products. On a Caenorhabditis elegans test set of alternatively spliced internal exons, its performance exceeds that of current ab initio gene finders and in most cases can accurately predict the correct form of all the alternative products. As the length information used by the algorithm can be obtained in a high-throughput fashion, we propose that integration of such information into a gene-prediction pipeline is feasible and doing so may improve our ability to fully characterize the complete set of mRNAs for a genome.
Availability: LOCUS is available from
Contact: stormo@genetics.wustl.edu
Pvclust: an R package for assessing the uncertainty in hierarchical clustering
Authors: Suzuki Ryota , Shimodaira Hidetoshi 
Published: April 2006

Abstract
Summary: Pvclust is an add-on package for a statistical software R to assess the uncertainty in hierarchical cluster analysis. Pvclust can be used easily for general statistical problems, such as DNA microarray analysis, to perform the bootstrap analysis of clustering, which has been popular in phylogenetic analysis. Pvclust calculates probability values (p-values) for each cluster using bootstrap resampling techniques. Two types of p-values are available: approximately unbiased (AU) p-value and bootstrap probability (BP) value. Multiscale bootstrap resampling is used for the calculation of AU p-value, which has superiority in bias over BP value calculated by the ordinary bootstrap resampling. In addition the computation time can be enormously decreased with parallel computing option.
Availability: The program is freely distributed under GNU General Public License (GPL) and can directly be installed from CRAN (), the official R package archive. The instruction and program source code are available at
Contact: ryota.suzuki@is.titech.ac.jp
Comparison of biophysical properties of skin measured by using non‐invasive techniques in the KM mice following 595 nm pulsed dye, 1064 nm Q‐Switched Nd:YAG and 1320 nm Nd:YAG laser non‐ablative rejuvenation
Authors: Dang Yongyan , Ren Qiushi , Li Wanrong , Yang Qing , Zhang Jinsheng 
Published: April 2006

Backgrounds/aims: The aim of the study was to compare the changes of the biophysical properties and to objectify the effects of 595 nm pulsed dye, 1064 nm Q‐switched Nd:YAG and 1320 nm Nd:YAG lasers non‐ablative rejuvenation by non‐invasive techniques.Methods: KM mice were used for the study. The 595 nm pulsed dye, 1064 nm Q‐switched Nd:YAG and 1320 nm Nd:YAG laser treatments were evaluated with biophysical parameter measurements including skin elasticity, skin color, skin trans‐epidermal water loss (TEWL) and skin hydration.Results: All three lasers improved the biophysical properties in the skin of KM mice. In skin elasticity measurements, the 1064 nm laser treatment showed the lowest ratio (0.61±0.09) while the 1320 nm laser showed the highest one (0.76±0.07) on day 60. For erythema values, a significant increase was observed immediately after the 1064 nm laser treatment (196.67±19.17), but the lowest values occurred with the 1320 nm laser treatment (189.83±16.54). None of the three lasers resulted in obvious changes of skin melanin. TEWL increased immediately after laser irradiation, then began to recover and decreased 60 days after the 595 and 1064 nm laser treatments. With the 1320 nm laser treatment the TEWL began to decrease from day 7 and obtained the lowest mean values (5.23±1.13). The water‐holding capacity increased initially for the 595 and 1320 nm laser irradiation, while decreased for the 1064 nm laser. At day 60 of the experiment, skin hydration values in all animals were superior to those of the controls. The 1320 nm laser treatment caused the highest ratio (1.29±0.26). Both the values of TEWL and skin hydration for the 1320 nm laser treated areas differed significantly from the other two lasers.Conclusions: Our data showed the 1064 nm Q‐switched Nd:YAG laser treatment was most effective in improving the skins' mechanical properties, while the 1320 nm Nd:YAG laser can enhance greatly the skin barrier function and the water‐holding capacity. Moreover, we demonstrated the biophysical properties differed considerably between different areas.
Simulation and analysis of optical skin lesion images
Authors: She Zhishun , Duller A. W. G. , Liu Y. , Fish P. J. 
Published: April 2006

Background/purpose: In order to properly analyse the effectiveness of methods for optically differentiating malignant from benign skin lesions, it is necessary to have a set of images for which the ground truth is known. However, aspects of the ground truth of clinical images such as true lesion boundary position are unknown or not known precisely. Therefore, a skin/lesion image simulation with known features including boundary location, skin pattern and lesion colour is needed to enable accurate assessment of feature estimation algorithms for lesion classification.Methods: In this paper, monochrome and colour skin/lesion images are synthesised with known characteristics including boundary, colour and skin pattern. Skin pattern is simulated with segmented lines with variations in length, orientation and intensity. Skin and lesion textures are modelled by an auto‐regressive (AR) process. Monochrome skin lesion images are obtained by combining monochrome skin and lesion textures under the control of a known lesion shape with the addition of skin pattern. Colour skin lesion images are generated by mixing coloured skin and lesion textures. Finally, an inflammation area and image artefacts such as hair and specular reflection are added.Results: The synthesised images provide the image set for evaluating image pre‐processing, segmentation and skin pattern analysis. The pre‐processing includes hair removal and specular reflection reduction. An AR model interpolation is suggested for hair removal, and multiple illumination processing is developed to decrease specular reflection. A fast snake algorithm is extended to detect the boundaries of skin lesion and inflammation areas. Skin line direction is detected as a feature to measure the disruption of skin pattern caused by lesion.Conclusions: Simulation of monochrome and colour skin/lesion image has been investigated, which is an alternative way to provide image set with known characteristics to validate image processing algorithms for image pre‐processing, lesion/inflammation boundary detection and skin pattern analysis.
In vivo measurement of water content of the fingernail and its seasonal change
Authors: Egawa Mariko , Ozaki Yukihiro , Takahashi Motoji 
Published: April 2006

Background/aims: Recently, there has been increasing awareness regardless keeping nails in good condition. Maintenance of an optimum water level in the nail plate is very important since water content affects the nail condition. However, a simple method for in vivo measurement of water in the nail plate quantitatively has not been reported. In this study, we applied Near infrared spectroscopy (NIR)‐based prediction of water content of the cut nail plate to in vivo measurement to obtain information about the seasonal change of water in the fingernail.Methods: Diffused reflectance spectra of the nail plate of the fingernail were collected in the NIR region with an NIR spectrometer in vivo both in summer and winter from the same 15 Japanese female subjects. The water content of the nail plate in vivo was calculated from the NIR spectrum using partial least square regression analysis.Results: It was possible to apply NIR‐based prediction of water content of the cut nail plate to in vivo measurement. We also found that the water content of the nail plate varied from person to person but not with the finger of the individual. The average water content of the nail plate was significantly lower in winter than in summer (P<0.05). In summer, the water content in the double‐layered nail tended to be higher than a nail in good condition (P<0.1) and significantly lower in the split nail (P<0.05). There was no significant difference between the groups in winter. On the contrary, the amount of water absorption tended to vary depending on the nail condition. A large amount of water was absorbed in the double‐layered nail and a small amount in the split nail both in summer and winter.Conclusion: The water content of the nail plate of fingernail was predicted by in vivo measurement using NIR spectrometry. Physiological information of the nail in vivo, such as aging and other disorders could be obtained by this method.
The Behind‐the‐Knee test: an efficient model for evaluating mechanical and chemical irritation
Authors: Farage Miranda A. 
Published: April 2006

Background/purpose: The ‘Behind‐the‐Knee’ method (BTK test), using the popliteal fossa as a test site, evaluates both the inherent chemical irritation, and the potential for mechanical irritation of substrates and products. This approach eliminates some of the difficulties of in‐use clinical test systems while still providing reliable results. In this publication, examples of the results of BTK tests on several materials are presented with direct comparisons, where possible, with results of in‐use clinical testing conducted on the same materials.Methods: In in‐use clinical tests, volunteer panelists were provided with catamenial products to use in place of their normal product. In the BTK test, samples were applied daily to the popliteal fossa using an elastic athletic band. In both studies, irritation reactions were scored visually.Results: Levels of irritation in the BTK test are consistently higher than those of standard patch tests, illustrating the contribution of mechanical irritation to the overall irritant potential of materials and products. Repeated tests on identical test materials demonstrated that the BTK test results are reproducible. Side‐by‐side comparisons of the BTK test and in‐use clinical tests demonstrated that the BTK test produces results of similar quality to the in‐use clinical. By using several concurrent panels with a common test material, it is possible to compare the irritant properties of several materials at once.Conclusions: We have tested over 25 different materials in over 35 BTK studies. The test method has proven reliable and versatile in testing a wide variety of materials, including menstrual pads, topsheets, interlabial pads, pantiliners, tampons and lotion coatings on products. Unlike in‐use clinicals, the BTK test allows the direct comparison of two products at one time on the same individual, and is easily adapted to investigative programs. It is subject to fewer confounding factors, is much easier to implement, has a shorter turnaround time, and is less expensive than in‐use clinical testing. Importantly, unlike standard patch tests, the BTK test evaluates both the inherent chemical irritation associated with materials and the mechanical irritaion owing to friction. Although the BTK test was developed using catamenial products, the test system provides a valuable alternative for evaluating any material where mechanical irritation may play a role, including textiles, facial tissues, baby and adult diapers, and laundry products that may leave residues on fabrics.
Ultrasound enhanced skin‐lightening effect of vitamin C and niacinamide
Authors: Hakozaki Tomohiro , Takiwaki Hirotsugu , Miyamoto Kukizo , Sato Yasuhiro , Arase Seiji 
Published: April 2006

Background/purpose: Cutaneous hyperpigmentation occurs in multiple conditions. There is a strong need for the improvement of hyperpigmentation especially among Asian women. However, the effect of existing skin‐lightening agents is not sufficient. One reason attributes to the limited capability of active agents to be delivered transepidermally. Ultrasound is one promising approach to enhance transepidermal transport. In this work, we investigate the effect of the use of high‐frequency ultrasound together with coupling gel containing skin‐lightening agents (ascorbyl glucoside and niacinamide) on facial hyperpigmentation in vivo in Japanese women.Methods: The effect of ultrasound on the absorption of skin‐lightening agents into the stratum corneum was evaluated in a tape‐stripping method on human forearms in vivo. The skin efficacy was assessed in a facial clinical trial involving 60 subjects with hyperpigmentation in a paired design. Subjects were assigned to two groups, each group using two treatments (one on each facial cheek): (1) skin‐lightening gel with ultrasound vs. no treatment or (2) skin‐lightening gel with ultrasound vs. skin‐lightening gel treatment. Changes in facial hyperpigmentation were objectively quantified by computer analysis and visual grading of high‐resolution digital images of the face in addition to the subjective assessment via questionnaire.Results: Ultrasound radiation enhanced the absorption of skin‐lightening agents in the stratum corneum in a radiation‐time‐dependent manner. In the facial clinical trial, use of ultrasound radiation together with the skin‐lightening gel significantly reduced facial hyperpigmented spots compared with both no treatment and skin‐lightening gel alone after 4 weeks.Conclusions: The data suggest that use of high‐frequency ultrasound radiation together with skin‐lightening gel is effective to reduce hyperpigmentation via enhancing transepidermal transport of skin‐lightening agents.
In vivo imaging of intradermal tattoos by confocal scanning laser microscopy
Authors: O'goshi Ken‐ichiro , Suihko Christian , Serup Jørgen 
Published: April 2006

Background/aims: In vivo confocal laser scanning microscopy (CLSM) is a new method for high‐resolution imaging of intact skin in situ. Horizontal mapping of the outer skin is provided (magnification × 1000).Objectives: Tattooing is popular all over the world; however, tattooed skin has not been studied in using CLSM.Results: Tattoos in two volunteers were studied using the Vivascope1500reg of Lucid Inc. Subepidermal massive deposits of dense, clustered pigment granules up to about 3 μm in size corresponding to black tattoos, and more scarce and diffuse deposits, corresponding to red, blue and green tattoos, were observed. Diffuse pigment granules tended to accumulate in the outer dermis underneath the level of the basement membrane zone.Conclusions: Dermal pigments from tattoos can be imaged in vivo using CLSM. This application of CLSM has an important future potential for pre‐evaluation of tattoos before laser removal, predicting good or poor outcome of laser removal.