Azeliragon ameliorates Alzheimer's disease via the Janus tyrosine kinase and signal transducer and activator of transcription signaling pathway

OBJECTIVES: TTP488, an antagonist of the receptor for advanced glycation end-products, was evaluated as a potential treatment for patients with mild-to-moderate Alzheimer's disease (AD). However, the mechanism underlying the protective action of TTP488 against AD has not yet been fully explored. METHODS: Healthy male rats were exposed to aberrant amyloid β (Aβ) 1-42. Lipopolysaccharide (LPS) and the NOD-like receptor family pyrin domain containing 1 (NLRP1) overexpression lentivirus were injected to activate the NLRP1 inflammasome and exacerbate AD. TTP488 was administered to reverse AD injury. Finally, tofacitinib and fludarabine were used to inhibit the activity of Janus tyrosine kinase (JAK) and signal transducer and activator of transcription (STAT) to prove the relationship between the JAK/STAT signaling pathway and TTP488. RESULTS: LPS and NLRP1 overexpression significantly increased the NLRP1 levels, reduced neurological function, and aggravated neuronal damage, as demonstrated by the impact latency time of, time spent by, and length of the platform covered by, the mice in the Morris water maze assay, Nissl staining, and immunofluorescence staining in rats with AD. CONCLUSIONS: TTP488 administration successfully reduced AD injury and reversed the aforementioned processes. Additionally, tofacitinib and fludarabine administration could further reverse AD injury after the TTP488 intervention. These results suggest a new potential mechanism underlying the TTP488-mediated alleviation of AD injury.

Full-information Force Sensor for Pulse Condition Diagnose / 中国医疗器械杂志

According to the collection principles and characteristics of the pulse physiological signals of traditional Chinese medicine, combined with the international standard requirements of the pulse graph force transducer (ISO 19614:2017-05), a special force sensor component that can be used for a complete and objective collection of pulse signals has been developed, this sensor meets the requirements of industrialization. The sensor can measure the pulse amplitude and width signals of the cunpart of the human body. In addition, three sensors can be placed at the cun, guan, chi part at the same time, so that the "three body parts and nine pulse-taking sites" can be realized synchronously. After the sensor has been verified, the results meet the relevant requirements of international standard. The consistency of the result can be reached to 92.3% compared with the diagnosis result of clinical TCM experts.

Neuroprotective potential of imatinib in global ischemia-reperfusion-induced cerebral injury: possible role of Janus-activated kinase 2/signal transducer and activator of transcription 3 and connexin 43

The present study was aimed to explore the neuroprotective role of imatinib in global ischemia-reperfusion-induced cerebral injury along with possible mechanisms. Global ischemia was induced in mice by bilateral carotid artery occlusion for 20 min, which was followed by reperfusion for 24 h by restoring the blood flow to the brain. The extent of cerebral injury was assessed after 24 h of global ischemia by measuring the locomotor activity (actophotometer test), motor coordination (inclined beam walking test), neurological severity score, learning and memory (object recognition test) and cerebral infarction (triphenyl tetrazolium chloride stain). Ischemia-reperfusion injury produced significant cerebral infarction, impaired the behavioral parameters and decreased the expression of connexin 43 and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in the brain. A single dose administration of imatinib (20 and 40 mg/kg) attenuated ischemia-reperfusion-induced behavioral deficits and the extent of cerebral infarction along with the restoration of connexin 43 and p-STAT3 levels. However, administration of AG490, a selective Janus-activated kinase 2 (JAK2)/STAT3 inhibitor, abolished the neuroprotective actions of imatinib and decreased the expression of connexin 43 and p-STAT3. It is concluded that imatinib has the potential of attenuating global ischemia-reperfusion-induced cerebral injury, which may be possibly attributed to activation of JAK2/STAT3 signaling pathway along with the increase in the expression of connexin 43.

Variabilidad de micrófonos utilizados para análisis acústico de la voz en los últimos veinte años / Variability of microphones used for acoustic analysis of the voice in the last twenty years

Se realizó una reflexión sobre la selección, durante los últimos 20 años, de los micró-fonos utilizados en estudios científicos que consideran análisis acústico y que son he-chos por profesionales de la voz. Se revisaron los equipos escogidos en 21 artículos ­a través del motor de búsqueda de Google, principalmente Google Scholar­ en los que la metodología consideraba el análisis acústico. Solo 4 de los 21 documentos elegidos realizaron una selección acertada según los estándares actuales de microfonía para fines de muestreo. Se determinó que los procesos de estandarización deben continuar con su perfeccionamiento

A reflection was made on the selection of microphones used in scientific studies, per-formed in the last 20 years, that consider acoustic analysis and are made by voice spe-cialists. The selected equipment was reviewed in 21 articles ­found through the Goo-gle engine, mainly Google Scholar­ in which the methodology considered acoustic analysis. Only 4 of the 21 chosen articles made an accurate selection according to the most recent microphone standards for sampling purposes. It was determined that the standardization processes should continue to be refined

Ultrafast Imaging of Coherent Plane-wave Compouding Based on a Small Size Ultrasound Transducer / 中国医疗器械杂志

The ultrasound endoscopic probes with very small size transducers are normally imaging by focused ultrasound beamforming technology. So the imaging frame rate is not very high, which cannot meet the needs of some clinical applications based on high imaging rate. In recent years, plane-wave ultrafast imaging technology can obtain high image frame rate and guarantee the image quality. In this paper, a plane wave ultra-fast imaging technique based on a home-made small line array ultrasound transducer is presented. Feasibility of the method is verified by simulation estimations and phantom experiments. The results show that for the small size transducer design of plane wave ultrafast imaging, it is necessary to fully consider the combination of the array element width and the number of array elements. So that a good plane wave imaging quality can be obtained. It lays a foundation for the ultra-fast imaging of plane wave in the interventional ultrasound imaging and ultrasound endoscopy.

Measurement of Tumor Pressure and Strategies of Imaging Tumor Pressure for Radioimmunotherapy / 대한핵의학회잡지

Tumor interstitial pressure is a fundamental feature of cancer biology. Elevation in tumor pressure affects the efficacy of cancer treatment and results in the heterogenous intratumoral distribution of drugs and macromolecules. Monoclonal antibodies (mAb) play a prominent role in cancer therapy and molecular nuclear imaging. Therapy using mAb labeled with radionuclides—also known as radioimmunotherapy (RIT)—is an effective form of cancer treatment. RIT is clinically effective for the treatment of lymphoma and other blood cancers; however, its clinical use for solid tumor was limited because their high interstitial pressure prevents mAb from penetrating into the tumor. This pressure can be decreased using anti-cancer drugs or additional external therapy. In this paper, we reviewed the intratumoral pressure using direct tumor-pressure measurement strategies, such as the wick-in-needle and pressure catheter transducer method, and indirect tumor-pressure measurement strategies via magnetic resonance.

Cryptotanshinone Inhibits Lipid Accumulation in Differentiating 3T3-L1 Preadipocytes by Down-regulating C/EBP-α, PPAR-γ, FAS, Perilipin A, and STAT-3 / 계명의대학술지

Differentiation of preadipocyte, also named adipogenesis, leads to the phenotype of mature adipocyte that is filled with many lipid droplets. Excessive lipid accumulation in adipocytes leads to the development of obesity. In this study, we investigated the effect of 11 different natural compounds on lipid accumulation during the differentiation of 3T3-L1 preadipocytes into 3T3-L1 adipocytes. Strikingly, among the natural compounds, cryptotanshinone at 10 µM most strongly reduced triglyceride (TG) contents in 3T3-L1 cells after 8 days of the differentiation. Furthermore, cryptotanshinone at 10 µM significantly suppressed lipid accumulation in 3T3-L1 cells after 8 days of the differentiation. Cryptotanshinone at 1 to 10 µM tested did not affect the survival of 3T3-L1 cells after 8 days of the differentiation. On mechanistic levels, cryptotanshinone time-differentially decreased the expression levels of CCAAT/enhancer-binding protein-α (C/EBP-α), peroxisome proliferator-activated receptor-γ (PPAR-γ), fatty acid synthase (FAS), and perilipin A but also the phosphorylation levels of signal transducer and activator of transcription-3 (STAT-3) during the 3T3-L1 cell differentiation. Taken together, these findings demonstrate that cryptotanshinone inhibits lipid accumulation in differentiating 3T3-L1 cells, which appears to be mediated through the reduced expression and/or phosphorylation levels of C/EBP-α, PPAR-γ, FAS, Perilipin A, and STAT-3.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

Effect of STAT3 on Lysophosphatidic Acid-Induced Oral Cancer Cell Invasion / 치위생과학회지

BACKGROUND: Oral cancer has a high incidence worldwide and has been closely associated with smoking, alcohol, and infection by the human papillomavirus. Metastasis is highly important for oral cancer survival. Lysophosphatidic acid (LPA) is a bioactive lipid mediator that promotes various cellular processes, including cell survival, proliferation, metastasis, and invasion. Signal transducer and activator of transcription (STATs) are transcription factors that mediate gene expression. Among the seven types of STATs in mammals, STAT3 is involved in invasion and metastasis of numerous tumors. However, little is known about the role of STAT3 in oral tumor invasion. In the present study, we hypothesized that STAT3 mediates LPA-induced oral cancer invasion. METHODS: Immunoblotting was performed to analyze LPA-induced STAT3 activation. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was performed to assess the survival rates of YD-10B cells. STAT3 levels in LPA-treated oral tumor cells were evaluated by performing in vitro invasion assay. RESULTS: To the best of our knowledge, this is the first study to demonstrate that LPA enhances STAT3 phosphorylation in oral cancer. In addition, treatment with WP1066, a selective inhibitor of STAT3, at a concentration that does not cause severe reduction in cell viability, significantly attenuated LPA-induced YD-10B cancer cell invasion. CONCLUSION: The results suggested that LPA induces oral tumor cells with greater invasive potential via STAT3 activation. Our findings provided important insights into the mechanisms underlying mouth neoplasms.

Anticancer Activity of Tubulosine through Suppression of Interleukin-6-Induced Janus Kinase 2/Signal Transducer and Activation of Transcription 3 Signaling / 한국유방암학회지

PURPOSE: The chemical structure of tubulosine has been known since the mid-1960s. However, little is known about its biological and pharmacological functions. The aim of this study was to investigate the novel functions of tubulosine in cancer treatment, specifically in breast cancer. METHODS: An Unpaired (Upd)-induced Drosophila cell line and interleukin (IL)-6-stimulated human breast cancer cell lines were used to investigate the biological and pharmacological activities of tubulosine in vitro. To investigate the activities of tubulosine, we performed molecular and cellular experiments such as Western blot and reverse transcription polymerase chain reaction analyses, immunoprecipitation and terminal deoxynucleotidyl transferase dUTP nick end labeling assays, and immunofluorescence staining using breast cancer cell lines. RESULTS: Tubulosine exhibited anticancer activity in IL-6-stimulated human breast cancer cells. Moreover, tubulosine reduced the tyrosine phosphorylation level and transcriptional activity of signal transducer and activator of transcription (STAT) protein at 92E in Upd-induced Drosophila cells. Additionally, tubulosine suppressed IL-6-induced Janus kinase 2 (JAK2)/STAT3 signaling, resulting in decreased viability and induction of apoptotic cell death in breast cancer cells. Interestingly, inhibition of IL-6-induced JAK2/STAT3 signaling by tubulosine was associated with the blocking of IL-6 receptor (IL-6R) and glycoprotein 130 (gp130) binding. CONCLUSION: Tubulosine exhibits anticancer activity through functional inhibition of IL-6-induced JAK2/STAT3 signaling by targeting IL-6Rα/gp130 binding in breast cancer cells. These findings suggest that tubulosine may hold promise for the treatment of inflammation-associated cancers, including breast cancer.

Porphyromonas gingivalis lipopolysaccharide stimulates vascular smooth muscle cell migration through signal transducer and activator of transcription 3-mediated matrix metalloproteinase-9 expression

Periodontal diseases have been associated with the development of cardiovascular diseases. Accumulating evidences have indicated that Porphyromonas gingivalis, a major periodontopathic pathogen, plays a critical role in the pathogenesis of atherosclerosis. In the present study, we demonstrated that P. gingivalis lipopolysaccharide (LPS) increases the mRNA and protein expression of matrix metalloproteinase-9 (MMP-9) in rat vascular smooth muscle cells. We showed that the MMP-9 expression induced by P. gingivalis LPS is mediated by the activation of signal transducer and activator of transcription 3 (STAT3) in vascular smooth muscle cells. Furthermore, the inhibition of STAT3 activity reduced P. gingivalis LPS-induced migration of vascular smooth muscle cells. Overall, our findings indicate that P. gingivalis LPS stimulates the migration of vascular smooth muscle cells via STAT3-mediated MMP-9 expression.

Thermometry and interpretation of body temperature

This article reviews the historical development and up-to-date state of thermometric technologies for measuring human body temperature (BT) from two aspects: measurement methodology and signifi cance interpretation. Since the fi rst systematic and comprehensive study on BT and its relation to human diseases was conducted by Wunderlich in the late 19th century, BT has served as one of the most fundamental vital signs for clinical diagnosis and daily healthcare. The physiological implication of BT set point and thermoregulatory mechanisms are briefl y outlined. Infl uential determinants of BT measurement are investigated thoroughly. Three types of BT measurement, i.e., core body temperature, surface body temperature and basal body temperature, are categorized according to its measurement position and activity level. With the comparison of temperature measurement in industrial fi elds, specialties in technological and biological aspects in BT measurement are mentioned. Methodologies used in BT measurement are grouped into instrumental methods and mathematical methods. Instrumental methods utilize results of BT measurements directly from temperature-sensitive transducers and electronic instrumentations by the combination of actual and predictive measurement, invasive and noninvasive measurement. Mathematical methods use several numerical models, such as multiple regression model, autoregressive model, thermoregulatory mechanism-based model and the Kalman fi lter-based method to estimate BT indirectly from some relevant vital signs and environmental factors. Thermometry modalities are summarized on the dichotomies into invasive and noninvasive, contact and noncontact, direct and indirect, free and restrained, 1-D and n-D. Comprehensive interpretation of BT has an equal importance as the measurement of BT. Two modes to apply BT are classifi ed into real-time applications and long-term applications. With rapid advancement in IoT infrastructure, big data analytics and AI platforms, prospects for future development in thermometry and interpretation of BT are discussed.

A universal ultrasound diagnostic system developed to support urology and coloproctological applications

In this study, we sought to describe a novel imaging apparatus that is lightweight, inexpensive, and highly eff ective for use in colorectal diagnostic and treatment settings. Typical probes for use in colorectal ultrasonic imaging applications are developed for surgeons to diagnose and stage rectal tumors and image the rectum and anus. Here we outline a new technique and use it for colorectal imaging in an animal. This technique involves use of an ultrasound array module positioned along the axis of rotation such that improved rotation is possible. This module is in the shape of a linear rod with a rotary linear component that allows for emission of focused ultrasonic echo signals from a linear section of the probe. The usability of the transducer and rectal image quality are satisfactory in a porcine model with the technique proposed here, axial/lateral resolution as 0.96/2.24 mm with 6 dB applied through the contour map using the point spread function. When compared to currently available methods, this technique provides superior diagnostic 3D volumetric image quality with reduced acquisition time. Given this, the ultrasound device proposed here may prove a viable and preferable method to those currently available for urology and colorectal imaging applications.

Development of a multi-channel NIRS-USG hybrid imaging system for detecting prostate cancer and improving the accuracy of imaging-based diagnosis: a phantom study

PURPOSE: This study aimed to develop a multi-channel near-infrared spectroscopy (NIRS) and ultrasonography (USG) fusion imaging system for imaging prostate cancer and to verify its diagnostic capability by applying the hybrid imaging system to a prostate cancer phantom. METHODS: A multi-channel NIRS system using the near-infrared 785-nm wavelength with 12 channels and four detectors was developed. After arranging the optical fibers around a USG transducer, we performed NIRS imaging and grayscale USG imaging simultaneously. Fusion imaging was obtained by processing incoming signals and the spatial reconstruction of NIRS, which corresponded with grayscale USG acquired at the same time. The NIRS-USG hybrid system was applied to a silicone-based optical phantom of the prostate gland containing prostate cancer to verify its diagnostic capability qualitatively. RESULTS: The NIRS-USG hybrid imaging system for prostate cancer imaging simultaneously provided anatomical and optical information with 2-dimensional registration. The hybrid imaging system showed more NIR attenuation over the prostate cancer model than over the model of normal prostate tissue. Its diagnostic capability to discriminate a focal area mimicking the optical properties of prostate cancer from the surrounding background mimicking the optical properties of normal prostate tissue was verified by applying the hybrid system to a silicone-based optical phantom of prostate cancer. CONCLUSION: This study successfully demonstrated that the NIRS-USG hybrid system may serve as a new imaging method for improving the diagnostic accuracy of prostate cancer, with potential utility for future clinical applications.

Tomographic density imaging using modified DF–DBIM approach

Ultrasonic computed tomography based on back scattering theory is the most powerful and accurate tool in ultrasound based imaging approaches because it is capable of providing quantitative information about the imaged target and detects very small targets. The duple-frequency distorted Born iterative method (DF–DBIM), which uses density information along with sound contrast for imaging, is a promising approach for imaging targets at the level of biological tissues. With two frequencies f₁ (low) and f₂ (high) through Nf₁ and Nf₂ iterations respectively, this method is used to estimate target density along with sound contrast. The implications of duple-frequency fusion for the image reconstruction quality of density information along with sound contrast based ultrasound tomography have been analyzed in this paper. In this paper, we concentrate on the selection of parameters that is supposed to be the best to improve the reconstruction quality of ultrasound tomography. When there are restraints imposed on simulated scenarios to have control of the computational cost, the iteration number Nf₁ is determined resulting in giving the best performance. The DF–DBIM is only effective if there are a moderate number of iterations, transmitters and receivers. In case that the number of transducers is either too large or too small, a result of reconstruction which is better than that of the single frequency approach is not produced by the implementation of DF–DBIM. A fixed sum N(iter) of Nf₁ and Nf₂ was given, the investigation of simulation results shows that the best value of Nf₁ is [N(iter)/2 − 1]. The error, when applying this way of choosing the parameters, will be normalized with the reduction of 56.11%, compared to use single frequency as used in the conventional DBIM method. The target density along with sound contrast is used to image targets in this paper. It is a fact that low-frequency offers fine convergence, and high-frequency offers fine spatial resolution. Wherefore, this technique can effectively expand DBIM's applicability to the problem of biological tissue reconstruction. Thanks to the usage of empirical data, this work will be further developed prior to its application in reality.

Recent Advances in Biosensors for Nucleic Acid and Exosome Detection / 전남의대학술지

Biosensors are analytical devices for biomolecule detection that compromise three essential components: recognition moiety, transducer, and signal processor. The sensor converts biomolecule recognition to detectable signals, which has been applied in diverse fields such as clinical monitoring, in vitro diagnostics, food industry etc. Based on signal transduction mechanisms, biosensors can be categorized into three major types: optical biosensors, electrochemical biosensors, and mass-based biosensors. Recently, the need for faster, more sensitive detection of biomolecules has compeled researchers to develop various sensing techniques. In this review, the basic structure and sensing principles of biosensors are introduced. Additionally, the review discusses multiple recent works about nucleic acid and exosome sensing.

Magnetic Resonance-Guided Focused Ultrasound : Current Status and Future Perspectives in Thermal Ablation and Blood-Brain Barrier Opening

Magnetic resonance-guided focused ultrasound (MRgFUS) is an emerging new technology with considerable potential to treat various neurological diseases. With refinement of ultrasound transducer technology and integration with magnetic resonance imaging guidance, transcranial sonication of precise cerebral targets has become a therapeutic option. Intensity is a key determinant of ultrasound effects. High-intensity focused ultrasound can produce targeted lesions via thermal ablation of tissue. MRgFUS-mediated stereotactic ablation is non-invasive, incision-free, and confers immediate therapeutic effects. Since the US Food and Drug Administration approval of MRgFUS in 2016 for unilateral thalamotomy in medication-refractory essential tremor, studies on novel indications such as Parkinson's disease, psychiatric disease, and brain tumors are underway. MRgFUS is also used in the context of blood-brain barrier (BBB) opening at low intensities, in combination with intravenously-administered microbubbles. Preclinical studies show that MRgFUS-mediated BBB opening safely enhances the delivery of targeted chemotherapeutic agents to the brain and improves tumor control as well as survival. In addition, BBB opening has been shown to activate the innate immune system in animal models of Alzheimer’s disease. Amyloid plaque clearance and promotion of neurogenesis in these studies suggest that MRgFUS-mediated BBB opening may be a new paradigm for neurodegenerative disease treatment in the future. Here, we review the current status of preclinical and clinical trials of MRgFUS-mediated thermal ablation and BBB opening, described their mechanisms of action, and discuss future prospects.

The Feasibility Study of Contrast-enhanced Ultrasound Using a 3 Dimension Transducer for Tumor Volume Measurement in Rabbit Hepatic VX2 Carcinoma Comparison with 2 Dimension Ultrasound and 3 Dimension Ultrasound without Contrast: Preliminary Results

BACKGROUND/AIMS: To investigate the feasibility of tumor volume measurement using contrastenhanced ultrasound (US) with 3 dimension transducer (3D CEUS) in rabbit hepatic VX2 carcinoma. METHODS: Three different tumor volume measurements, including 2D US using the equation, 4/3(π)(abc), 3D US without contrast, and 3D CEUS were performed in 35 rabbit hepatic VX2 carcinomas. With the tumor volume from computerized tomography (CT) as a reference standard, we compared difference between CT volume and each different US tumor volume. The mean difference and correlation coefficient between each US volume measurement and CT volume were analyzed. RESULTS: Tumor volume measurement using 3D CEUS and 2D US using equation showed no statistical difference compared to CT volume (0.276 cm3, 0.212 cm3, and 0.263 cm3 vs. 0.306 cm3, 0.247 cm3, 0.276 cm3, P>0.05). However, 3D CEUS provided the highest correlation coefficient with CT volume (R=0.835 and 0.720) and the highest intraclass correlation (0.973 and 0.993). 3D CEUS provided a smaller mean difference with CT volume (0.016 cm3 and 0.033 cm3) than 2D US, showing 3D CEUS's accurate measurement of tumor volume. CONCLUSIONS: Due to its highly accurate, reliable, and reproducible measurements of tumor volume, 3D CEUS may be useful for predicting the therapeutic response evaluation after treatment.

Feline Interstitial Cystitis Enhances Mucosa-Dependent Contractile Responses to Serotonin / 대한배뇨장애요실금학회지

PURPOSE: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). METHODS: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response (0.01–10μM) was determined for each strip with the mucosa intact or denuded. RESULTS: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by 1μM atropine in both control and FIC bladder strips. CONCLUSIONS: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.