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1.
Cell Rep ; 43(7): 114422, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943642

RESUMO

Platelet-activating factor (PAF) is a potent phospholipid mediator crucial in multiple inflammatory and immune responses through binding and activating the PAF receptor (PAFR). However, drug development targeting the PAFR has been limited, partly due to an incomplete understanding of its activation mechanism. Here, we present a 2.9-Å structure of the PAF-bound PAFR-Gi complex. Structural and mutagenesis analyses unveil a specific binding mode of PAF, with the choline head forming cation-π interactions within PAFR hydrophobic pocket, while the alkyl tail penetrates deeply into an aromatic cleft between TM4 and TM5. Binding of PAF modulates conformational changes in key motifs of PAFR, triggering the outward movement of TM6, TM7, and helix 8 for G protein coupling. Molecular dynamics simulation suggests a membrane-side pathway for PAF entry into PAFR via the TM4-TM5 cavity. By providing molecular insights into PAFR signaling, this work contributes a foundation for developing therapeutic interventions targeting PAF signal axis.

2.
Proc Natl Acad Sci U S A ; 121(26): e2321710121, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38885377

RESUMO

Somatostatin receptor 5 (SSTR5) is an important G protein-coupled receptor and drug target for neuroendocrine tumors and pituitary disorders. This study presents two high-resolution cryogenicelectron microscope structures of the SSTR5-Gi complexes bound to the cyclic neuropeptide agonists, cortistatin-17 (CST17) and octreotide, with resolutions of 2.7 Å and 2.9 Å, respectively. The structures reveal that binding of these peptides causes rearrangement of a "hydrophobic lock", consisting of residues from transmembrane helices TM3 and TM6. This rearrangement triggers outward movement of TM6, enabling Gαi protein engagement and receptor activation. In addition to hydrophobic interactions, CST17 forms conserved polar contacts similar to somatostatin-14 binding to SSTR2, while further structural and functional analysis shows that extracellular loops differently recognize CST17 and octreotide. These insights elucidate agonist selectivity and activation mechanisms of SSTR5, providing valuable guidance for structure-based drug development targeting this therapeutically relevant receptor.


Assuntos
Octreotida , Receptores de Somatostatina , Receptores de Somatostatina/metabolismo , Receptores de Somatostatina/agonistas , Receptores de Somatostatina/química , Humanos , Octreotida/química , Octreotida/farmacologia , Octreotida/metabolismo , Neuropeptídeos/metabolismo , Neuropeptídeos/química , Microscopia Crioeletrônica , Ligação Proteica , Peptídeos Cíclicos/química , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/metabolismo , Somatostatina/metabolismo , Somatostatina/química , Somatostatina/análogos & derivados , Modelos Moleculares , Células HEK293
3.
Infect Drug Resist ; 16: 4857-4865, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37520453

RESUMO

Purpose: Time-consuming culture methods and wet-mount microscopy (WMM) with low sensitivity have difficulties in diagnosing Vulvovaginal candidiasis (VVC). Rapid and highly sensitive polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) for the diagnosis of VVC has not been reported to date. This study was the first to evaluate the performance of PCR-QDFA for diagnosis of Candida strains in the leukorrhea samples from patients with suspected VVC. Patients and Methods: Leukorrhea samples from all visited patients were taken from the vagina using vaginal swabs by clinicians. We evaluated patients admitted with suspected VVC who completed WMM for diagnosis and reported the diagnostic effectiveness of PCR-QDFA and Candida culture (gold standard) when testing leucorrhea samples. Results: A total of 720 leukorrhea samples from 387 VVC-positive patients and 333 VVC-negative patients were included in this study. Of the 387 leukorrhea samples from the VVC-positive patients, 391 Candida strains were identified by culture. 99.23% (388/391) Candida strains were included in the PCR-QDFA list. The 388 Candida strains belonged to four different species of Candida, including C. albicans (n = 273, 70.36%), C. glabrata (n = 85, 21.91%), C. tropicalis (n = 16, 4.12%), and C. krusei (n = 14, 3.61%). PCR-QDFA diagnosed Candida strains in 340/384 (88.54%) of the leucorrhea samples with Candida strains infection. The sensitivity of PCR-QDFA for C. albicans, C. glabrata, C. tropicalis, and C. krusei was 89.01%, 85.88%, 81.25% and 92.86%, respectively. The specificity of PCR-QDFA for C. albicans, C. glabrata, C. tropicalis and C. krusei was 93.69%, 99.37%, 99.71%, and 99.57%, respectively. Conclusion: The highly sensitive and specific PCR-QDFA technique can be exploited as a rapid (approximately 4 h) diagnostic tool for common Candida strains of leucorrhea samples from patients with suspected VVC.

4.
Nat Chem Biol ; 19(11): 1351-1360, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37169960

RESUMO

The complement receptors C3aR and C5aR1, whose signaling is selectively activated by anaphylatoxins C3a and C5a, are important regulators of both innate and adaptive immune responses. Dysregulations of C3aR and C5aR1 signaling lead to multiple inflammatory disorders, including sepsis, asthma and acute respiratory distress syndrome. The mechanism underlying endogenous anaphylatoxin recognition and activation of C3aR and C5aR1 remains elusive. Here we reported the structures of C3a-bound C3aR and C5a-bound C5aR1 as well as an apo-C3aR structure. These structures, combined with mutagenesis analysis, reveal a conserved recognition pattern of anaphylatoxins to the complement receptors that is different from chemokine receptors, unique pocket topologies of C3aR and C5aR1 that mediate ligand selectivity, and a common mechanism of receptor activation. These results provide crucial insights into the molecular understanding of C3aR and C5aR1 signaling and structural templates for rational drug design for treating inflammation disorders.


Assuntos
Anafilatoxinas , Receptores de Complemento , Transdução de Sinais
5.
Plants (Basel) ; 12(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36904058

RESUMO

YTH domain-containing proteins are one kind of RNA-binding protein involved in post-transcriptional regulation and play multiple roles in regulating the growth, development, and abiotic stress responses of plants. However, the YTH domain-containing RNA-binding protein family has not been previously studied in cotton. In this study, a total of 10, 11, 22, and 21 YTH genes were identified in Gossypium arboreum, Gossypium raimondii, Gossypium barbadense, and Gossypium hirsutum, respectively. These Gossypium YTH genes were categorized into three subgroups by phylogenetic analysis. The chromosomal distribution, synteny analysis, structures of Gossypium YTH genes, and the motifs of YTH proteins were analyzed. Furthermore, the cis-element of GhYTH genes promoter, miRNA targets of GhYTH genes, and subcellular localization of GhYTH8 and GhYTH16 were characterized. Expression patterns of GhYTH genes in different tissues, organs, and in response to different stresses were also analyzed. Moreover, functional verifications revealed that silencing GhYTH8 attenuated the drought tolerance in the upland cotton TM-1 line. These findings provide useful clues for the functional and evolutionary analysis of YTH genes in cotton.

6.
Microb Biotechnol ; 16(4): 827-837, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36722318

RESUMO

Bloodstream infections are serious and complex infectious diseases that often require a rapid diagnosis. Polymerase chain reaction coupled with quantum dot fluorescence analysis (PCR-QDFA) is a novel diagnostic technique. This study aimed to evaluate the diagnostic performance of PCR-QDFA for pathogen detection in patients with suspected bloodstream infections (BSIs). It evaluates 29 kinds of common pathogens (24 bacteria and 5 yeasts) from blood culture bottles. The results of PCR-QDFA identification and traditional microbial laboratory identification were compared, and the latter was used as the 'gold standard' to analyse the diagnostic performance of the PCR-QDFA. In total, 517 blood culture bottles were included in this study. The PCR-QDFA identified microorganisms in 368/422 (87.2%) samples with monomicrobial growth. For the pathogens on the PCR-QDFA list, the assay showed a higher sensitivity of 97.4% (368/378). When polymicrobial growth was analysed, the PCR-QDFA successfully detected 19/25 (76%) microorganisms on the PCR-QDFA list. In addition, 82/82 negative blood culture bottles also showed no pathogens by PCR-QDFA with a specificity of 100%. In conclusion, the PCR-QDFA assay could identify a majority of the common pathogens encountered in clinical practice, showing excellent diagnostic performance for pathogen detection in patients with suspected BSIs.


Assuntos
Pontos Quânticos , Sepse , Humanos , Sepse/diagnóstico , Bactérias/genética , Reação em Cadeia da Polimerase/métodos , Leveduras/genética , Sensibilidade e Especificidade
7.
Front Genet ; 12: 757109, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34659369

RESUMO

RNA editing, a vital supplement to the central dogma, yields genetic information on RNA products that are different from their DNA templates. The conversion of C-to-U in mitochondria and plastids is the main kind of RNA editing in plants. Various factors have been demonstrated to be involved in RNA editing. In this minireview, we summarized the factors and mechanisms involved in RNA editing in plant organelles. Recently, the rapid development of deep sequencing has revealed many RNA editing events in plant organelles, and we further reviewed these events identified through deep sequencing data. Numerous studies have shown that RNA editing plays essential roles in diverse processes, such as the biogenesis of chloroplasts and mitochondria, seed development, and stress and hormone responses. Finally, we discussed the functions of RNA editing in plant organelles.

9.
Front Microbiol ; 12: 698478, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34367098

RESUMO

The rapidly increasing prevalence of Klebsiella pneumoniae carbapenemase 2 (KPC-2)-producing bacteria has become a serious challenge to public health. Currently, the bla KPC- 2 gene is mainly disseminated through plasmids of different sizes and replicon types. However, the plasmids carrying the bla KPC- 2 gene have not been fully characterized. In this study, we report the complete genome sequences of two novel bla KPC- 2-harboring incompatibility group U (IncU) plasmids, pEC2341-KPC and pEC2547-KPC, from international high-risk clones of Escherichia coli isolated from Zhejiang, China. Two KPC-2-producing E. coli isolates (EC2341 and EC2547) were collected from clinical samples. Whole-genome sequencing (WGS) analysis indicated that EC2341 and EC2547 belonged to the ST410 and ST131 clones, respectively. S1-nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and conjugation experiments confirmed the presence of the bla KPC- 2 gene on the pEC2341-KPC plasmid and that this was a conjugative plasmid, while the bla KPC- 2 gene on the pEC2547-KPC plasmid was a non-conjugative plasmid. In addition, plasmid analysis further revealed that the two bla KPC- 2-harboring plasmids have a close evolutionary relationship. To the best of our knowledge, this is the first report of E. coli strains carrying the bla KPC- 2 gene on IncU plasmids. The emergence of the IncU-type bla KPC- 2-positive plasmid highlights further dissemination of bla KPC- 2 in Enterobacteriaceae. Therefore, effective measures should be taken immediately to prevent the spread of these bla KPC- 2 -positive plasmids.

10.
Anal Methods ; 13(11): 1412-1421, 2021 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-33683249

RESUMO

Core-satellite-structured magnetic nanosorbents (MNs) used for the selective extraction of macrolide antibiotics (MACs) were prepared in this study. The MNs (core-satellite polydopamine-coated Fe3O4 nanoparticles-hollow porous molecularly imprinted polymer) consisted of polydopamine-coated Fe3O4 nanoparticles (Fe3O4@PDA) "core" linked to numerous hollow porous molecularly imprinted polymer (HPMIP) "satellites" with bridging amine functional groups. It is worth mentioning that HPMIPs act as "anchors" for selectively capturing target molecules. Polymers were characterized using TEM, SEM, FT-IR, VSM, and TGA and applied as magnetic dispersive solid-phase extraction (MDSPE) sorbents for the enrichment of trace MACs from a complex food matrix prior to quantification by HPLC-MS/MS. Nanocomposites revealed outstanding magnetic properties (36.1 emu g-1), a high adsorption capacity (103.6 µmol g-1), selectivity (IF = 3.2), and fast kinetic binding (20 min) for MACs. The multiple advantages of the novel core-satellite-structured magnetic molecularly imprinted nanosorbents were confirmed, which makes us believe that the preparation method of the core-satellite MNs can be applied to other fields involving molecular imprinting technology.


Assuntos
Polímeros Molecularmente Impressos , Nanopartículas , Antibacterianos , Cromatografia Líquida de Alta Pressão , Indóis , Macrolídeos , Polímeros , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Espectrometria de Massas em Tandem
11.
J Chromatogr A ; 1641: 462006, 2021 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-33640807

RESUMO

Bio-based and low-cost hybrid polyvinyl alcohol (PVA) and gelatin (Gel) hydrophilic macromolecular complex coated microspheres were prepared based on one-pot process, characterized, and applied as novel sorbent materials for the purification of trace aminoglycosides from complex matrices. PVA acts as a "rigid" component in the hybrid complex to enhance its mechanical properties, while Gel's "flexible" role is to improve the swelling properties of the hybrid complex in water. It is shown that hybrid PVA/Gel-functionalized sorbents are more efficient than the respective PVA or Gel sorbents since the presence of Gel increases the material selectivity for aminoglycosides, which is due to the specific interactions occurring between the targets and amino acid residues in the hybrid materials. Under the optimum conditions, material preparation and pretreatment processes were entirely carried out in single water system without toxic organic solvent. The detection limit (LOD) of spectinomycin, kanamycin, streptomycin and dihydrostreptomycin in honey were 0.811, 0.303, 0.168, 0.045 µg⋅kg-1 respectively. Linearity was obtained in the range of 20 to 2000 ug⋅kg-1, relative recovery yield up to 84.1-111.7% were obtained and matrix effect of all four aminoglycosides was within 100.8-107.6%. Intra-day and inter-day precision under four spiking levels (5, 200, 500 and 1000 ug⋅kg-1) were less than 10.9% (n=6) and 13.6% (n=3) respectively. In addition, the sorbents exhibited excellent reusability even after six recycles. This work demonstrates the potential of bio-based and low-cost hybrid polymer extraction platforms as promising bonded phase alternatives, in which eco-friendly and natural-based polymers can be used to improve the material selectivity and are conducive to the realization of "green chemistry".


Assuntos
Aminoglicosídeos/isolamento & purificação , Álcool de Polivinil/química , Dióxido de Silício/química , Adsorção , Calibragem , Géis , Mel/análise , Limite de Detecção , Microesferas , Padrões de Referência , Reprodutibilidade dos Testes , Extração em Fase Sólida
12.
Environ Sci Technol ; 52(18): 10839-10847, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30075626

RESUMO

Shale gas reservoir-produced brines may contain elevated levels of naturally occurring radioactive material, including Ra-226 and Ra-228, which come from the decay of U-238 and Th-232 in shale. While the total Ra activity in shale gas wastewaters can vary by over 3 orders of magnitude, the parent radionuclides tend to only vary by 1 order of magnitude. The extent of Ra mobilization from the shale into produced brines is thought to be largely controlled by adsorption/desorption from the shale, which is influenced by shale cation exchange capacity (CEC) and reservoir brine salinity, often reported as the total dissolved solids (TDS). To determine how these factors lead to such large variation in Ra activity of produced brines, the U content and CEC of shale samples from the Antrim and Utica-Collingwood shales in Michigan and the Marcellus shale in Pennsylvania were evaluated. Analysis of produced brine from 17 Antrim shale gas wells was then used to develop an empirical relationship between Ra-226 activity and produced water TDS for a given U content of the shale. This correlation will provide an a priori estimate of the expected Ra activity of a produced brine from a given shale gas play when the brine salinity and U content of the shale are known. Such information can serve as a guide for optimal wastewater treatment and disposal strategies prior to any drilling activity, thereby reducing risks associated with elevated Ra activity in shale gas wastewaters.


Assuntos
Rádio (Elemento) , Urânio , Michigan , Gás Natural , Campos de Petróleo e Gás , Pennsylvania , Sais
13.
Am J Physiol Renal Physiol ; 311(1): F166-75, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27147676

RESUMO

The role of 5-HT1A receptors in regulating voiding functions remains unclear, particularly regarding the urine flow rate (UFR) during voiding. This study examined the effects of 5-HT1A receptors on regulating urethral functions in female rats and investigated underlying modulatory mechanisms. Intravesical pressure (IVP), external urethral sphincter-electromyography (EUS-EMG), and UFR were simultaneously recorded during continuous transvesical infusion to examine the effects of a 5-HT1A receptor agonist (8-OH-DPAT) and antagonist (WAY-100635) on bladder and urethral functions. In addition, this study evaluated the independent roles of urethral striated and smooth muscles in the UFR in rats after a neuromuscular blockade (NMB) treatment and bilateral hypogastric nerve transection. Our results revealed that 8-OH-DPAT significantly increased the maximal UFR but reduced the mean UFR. This discrepancy may be because 8-OH-DPAT markedly increased the maximal UFR during the initial segment of the flow duration and subsequently induced an approximately zero level of long oscillatory waves during the remaining flow duration. Thus the mean UFR was reduced because of the prolonged approximately zero level of the UFR. However, paralyzing the EUS with an NMB agent, 8-OH-DPAT, significantly increased the maximal and mean UFRs because the prolonged zero level of the oscillatory UFR did not continue. These results support the hypothesis that the increased UFR in female rats during voiding is due to the induction of urethral smooth muscle relaxation by 8-OH-DPAT. This paper provides a detailed understanding of the role of 5-HT1A receptors in controlling the UFR in female rats.


Assuntos
Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina/uso terapêutico , Urodinâmica/efeitos dos fármacos , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Denervação , Eletromiografia , Feminino , Plexo Hipogástrico/fisiologia , Bloqueadores Neuromusculares/farmacologia , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas da Serotonina/farmacologia , Uretra/fisiopatologia , Micção/efeitos dos fármacos
14.
Chemistry ; 21(37): 12947-59, 2015 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-26214754

RESUMO

A new family of 120° carbazole-based dendritic donors D1-D3 have been successfully designed and synthesized, from which a series of novel supramolecular carbazole-based metallodendrimers with well-defined shapes and sizes were successfully prepared by [2+2] and [3+3] coordination-driven self-assembly. The structures of newly designed rhomboidal and hexagonal metallodendrimers were characterized by multinuclear NMR ((1) H and (31) P) spectroscopy, ESI-TOF mass spectrometry, FTIR spectroscopy, and the PM6 semiempirical molecular orbital method. The fluorescence emission behavior of ligands D1-D3, rhomboidal metallodendrimers R1-R3, and hexagonal metallodendrimers H1-H3 in mixtures of dichloromethane and n-hexane with different n-hexane fractions were investigated. The results indicated that D1-D3 featured typical aggregation-induced emission (AIE) properties. However, different from ligands D1-D3, metallodendrimers R1-R3 and H1-H3 presented interesting generation-dependent AIE properties. Furthermore, evidence for the aggregation of these metallodendrimers was confirmed by a detailed investigation of dynamic light-scattering, Tyndall effect, and SEM. This research not only provides a highly efficient strategy for constructing carbazole-based dendrimers with well-defined shapes and sizes, but also presents a new family of carbazole-based dendritic ligands and rhomboidal and hexagonal metallodendrimers with interesting AIE properties.

15.
Sensors (Basel) ; 15(6): 12802-15, 2015 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-26039421

RESUMO

Recent advances in microelectronics and wireless transmission technology have led to the development of various implantable sensors for real-time monitoring of bladder conditions. Although various sensing approaches for monitoring bladder conditions were reported, most such sensors have remained at the laboratory stage due to the existence of vital drawbacks. In the present study, we explored a new concept for monitoring the bladder capacity on the basis of potentiometric principles. A prototype of a potentiometer module was designed and fabricated and integrated with a commercial wireless transmission module and power unit. A series of in vitro pig bladder experiments was conducted to determine the best design parameters for implementing the prototype potentiometric device and to prove its feasibility. We successfully implemented the potentiometric module in a pig bladder model in vitro, and the error of the accuracy of bladder volume detection was <±3%. Although the proposed potentiometric device was built using a commercial wireless module, the design principles and animal experience gathered from this research can serve as a basis for developing new implantable bladder sensors in the future.


Assuntos
Potenciometria/instrumentação , Bexiga Urinária/fisiologia , Tecnologia sem Fio/instrumentação , Animais , Desenho de Equipamento , Monitorização Ambulatorial/instrumentação , Tamanho do Órgão/fisiologia , Próteses e Implantes , Suínos , Bexiga Urinária/cirurgia
16.
Am J Physiol Regul Integr Comp Physiol ; 307(10): R1239-50, 2014 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-25209414

RESUMO

This study extensively examined the role of a 5-HT(1A) receptor in controlling voiding function in anesthetized male rats. A simultaneous recording of the intravesical pressure (IVP), external urethral sphincter (EUS)-electromyography (EMG), and urine flow rate (UFR) during continuous cystometry was used. 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT), a 5-HT(1A) receptor agonist, significantly improved the voiding efficiency, as detected by increases in the evoked contraction amplitude, EUS burst period, and silent period, and decreases in the volume threshold, pressure threshold, and residual volume. Interestingly, the UFR during voiding was reduced by 8-OH-DPAT, as evidenced by decreases in the maximal UFR and mean UFRs of the voiding period, spike duration, and interspike interval. Conversely, treating rats with WAY-100635, a 5-HT(1A) antagonist, produced effects opposite to those produced by 8-OH-DPAT. These findings suggest that 8-OH-DPAT improved the voiding efficiency by enhancing the detrusor contractile ability and prolonging EUS burst period, which would compensate for the lower UFR, resulting from urethral smooth muscle contractions and longer EUS silent periods during voiding. The present study contributes to our understanding of the role of 5-HT(1A) receptors in controlling the urine flow rate in male rats.


Assuntos
Receptor 5-HT1A de Serotonina/metabolismo , Serotonina/metabolismo , Uretra/metabolismo , Bexiga Urinária/metabolismo , Micção , Urodinâmica , Animais , Eletromiografia , Masculino , Pressão , Ratos Sprague-Dawley , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia , Fatores Sexuais , Transdução de Sinais , Fatores de Tempo , Uretra/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Micção/efeitos dos fármacos , Urodinâmica/efeitos dos fármacos
17.
Huan Jing Ke Xue ; 35(2): 526-32, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24812943

RESUMO

With a common rail diesel engine without any modification and the engine exhaust particle number and particle size analyzer EEPS, this study used the air-fuel ratio to investigate the particulate number concentration, mass concentration and number distribution characteristics of a diesel engine fueled with butanol-diesel blends (Bu10, Bu15, Bu20, Bu30 and Bu40) and petroleum diesel. The results show: for all test fuels, the particle number distributions turn to be unimodal. With the increasing of butanol, numbers of nucleation mode particles and small accumulation mode particle decrease. At low speed and low load conditions, the number of large accumulation mode particle increases slightly, but under higher speed and load conditions, the number does not increase. When the fuels contain butanol, the total particle number concentration and mass concentration in all conditions decrease and that is more obvious at high speed load.


Assuntos
Butanóis/análise , Gasolina/análise , Material Particulado/análise , Emissões de Veículos/análise , Tamanho da Partícula
18.
Am J Physiol Renal Physiol ; 305(9): F1332-42, 2013 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-24049146

RESUMO

In this study, we examined the possibility that 5-HT1A receptors may underlie sexually dimorphic mechanisms affecting the regulation of urethral functions in anesthetized rats. Simultaneous recordings of intravesical pressure under isovolumetric conditions, external urethral sphincter-electromyography, and urethral perfusion pressure were used to examine the effects of a 5-HT1A receptor agonist [8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT)] and antagonist (WAY-100635) on bladder and urethral functions. This research also evaluated the effects of 8-OH-DPAT and α-bungarotoxin (a neuromuscular blockade agent) on urethral continence using leak point pressure testing, and the distribution of 5-HT1A receptors in the lower urinary tract was assessed by immunohistochemistry. The serotonergic mechanism that controls the urinary bladder and external urethral sphincter-electromyography activity showed no significant sexual differences, but urethral activity in urethral perfusion pressure and leak point pressure values exhibited some sexual differences. 8-OH-DPAT enhanced urethral pressure during continence in rats of both sexes, but the drug elevated the pressure during voiding in male rats and reduced it in female rats. The distribution of 5-HT1A receptors in the spinal cord also showed some sexual differences. The present study contributes to our understanding of the role of 5-HT1A receptors in physiological and immunohistochemical properties of urethral smooth muscle in rats of different sexes. These findings may be a basis for the future development of pharmacotherapies for stress urinary incontinence in men.


Assuntos
Receptor 5-HT1A de Serotonina/metabolismo , Caracteres Sexuais , Uretra/fisiologia , 8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Animais , Feminino , Masculino , Piperazinas/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT1 de Serotonina/farmacologia
19.
Neurourol Urodyn ; 32(3): 293-300, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22674809

RESUMO

AIMS: Diabetic cystopathy is typically manifested as bladder voiding dysfunction, and numerous patients are refractory to standard therapy. In this study, we determined whether electrical stimulation (ES) of the sensory branch of the pudendal nerve could engage an augmenting reflex and thereby improve bladder emptying in a diabetic animal model with cystopathy. METHODS: The efficiency of bladder emptying with ES of the sensory branch of the pudendal nerve at different stimulation intensities was measured in rats at 8 or 18 weeks after the induction of diabetes with streptozotocin. RESULTS: The voiding efficiency (VE) was reduced from 74 ± 4% to 30 ± 8% in rats with diabetes for 8 weeks and from 73 ± 6% to 20 ± 6% in rats with diabetes for 18 weeks. ES at lower intensities (0.025-0.05 mA) applied to the pudendal sensory nerve did not affect the VE in rats with diabetes for 18 weeks but increased the VE in rats with diabetes for 8 weeks. Subsequently, when the stimulation intensity was elevated to 0.1-0.3 mA, the VEs in rats with diabetes for both 8 and 18 weeks increased to 40-50%. CONCLUSIONS: The results of the present study are consistent with the essential role for pudendal sensory feedback in efficient bladder emptying, and electrical activation of the sensory branch of the pudendal nerve was efficient restoring the voiding function in diabetic animals with cystopathy. This could provide an approach to improve bladder emptying in diabetic patients with voiding dysfunction.


Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/terapia , Neuropatias Diabéticas/prevenção & controle , Terapia por Estimulação Elétrica/métodos , Nervo Pudendo/fisiopatologia , Uretra/inervação , Doenças da Bexiga Urinária/prevenção & controle , Bexiga Urinária/fisiopatologia , Micção , Animais , Diabetes Mellitus Experimental/fisiopatologia , Neuropatias Diabéticas/etiologia , Neuropatias Diabéticas/fisiopatologia , Modelos Animais de Doenças , Eletromiografia , Retroalimentação Sensorial , Masculino , Ratos , Ratos Sprague-Dawley , Reflexo , Fatores de Tempo , Uretra/fisiopatologia , Doenças da Bexiga Urinária/etiologia , Doenças da Bexiga Urinária/fisiopatologia , Urodinâmica
20.
J Formos Med Assoc ; 111(2): 67-76, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22370284

RESUMO

BACKGROUND/PURPOSE: This study examined the effects of a 5-HT(1A) receptor agonist (8-OH-DPAT) on external urethral sphincter (EUS) activity in urethane-anesthetized rats. METHODS: An EUS electromyogram (EMG) and intravesical pressure (IVP) were simultaneously recorded during continuous cystometrographic monitoring, to provide a quantitative evaluation of EUS activity and urethral urodynamics of voiding. RESULTS: When examining the EUS burst activity, durations of the active (AP) and silent periods (SP) as a function of the time axis, respectively, exhibited concave- and convex-shaped curves. The burst discharges of the EUS-EMG were divided into nonvoiding and voiding burst activities based on the oscillation waves of the IVP, which were located in Phases 1 and 2 of the IVP. After 8-OH-DPAT treatment, the entire burst period in Phases 1 to 2 of the IVP was significantly prolonged. The average SP in both Phases 1 and 2 significantly increased but the average APs were not affected. Urodynamic results showed decreases in the volume threshold, contraction amplitude, and residual volume as well as an increase in the contraction duration. In addition, the amplitude of bladder high-frequency oscillatory waves in the IVP and the average urethral flow rate were reduced, but the entire voiding efficiency increased. CONCLUSION: The influences of 8-OH-DPAT on EUS burst activity and urodynamics were exactly detected by the sophisticated EMG analytic design, and the results could be a reference for the pharmacological treatment of patients with lower urinary tract dysfunction.


Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Uretra/efeitos dos fármacos , Bexiga Urinária/efeitos dos fármacos , Micção/efeitos dos fármacos , 8-Hidroxi-2-(di-n-propilamino)tetralina/administração & dosagem , Anestésicos Intravenosos/administração & dosagem , Animais , Eletromiografia , Feminino , Pressão , Ratos , Ratos Sprague-Dawley , Agonistas do Receptor de Serotonina/administração & dosagem , Uretana/administração & dosagem , Uretra/fisiologia , Bexiga Urinária/fisiologia , Micção/fisiologia
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