Backdoor Attack on Deep Neural Networks Triggered by Fault Injection Attack on Image Sensor Interface.

A backdoor attack is a type of attack method that induces deep neural network (DNN) misclassification. The adversary who aims to trigger the backdoor attack inputs the image with a specific pattern (the adversarial mark) into the DNN model (backdoor model). In general, the adversary mark is created on the physical object input to an image by capturing a photo. With this conventional method, the success of the backdoor attack is not stable because the size and position change depending on the shooting environment. So far, we have proposed a method of creating an adversarial mark for triggering backdoor attacks by means of a fault injection attack on the mobile industry processor interface (MIPI), which is the image sensor interface. We propose the image tampering model, with which the adversarial mark can be generated in the actual fault injection to create the adversarial mark pattern. Then, the backdoor model was trained with poison data images, which the proposed simulation model created. We conducted a backdoor attack experiment using a backdoor model trained on a dataset containing 5% poison data. The clean data accuracy in normal operation was 91%; nevertheless, the attack success rate with fault injection was 83%.

Development of an Interactive Touchless Technology Based on Static-Electricity-Induced Luminescence.

Touchless technology has garnered significant interest in recent years because of its effectiveness in combating infectious diseases such as the novel coronavirus (COVID-19). The goal of this study was to develop an inexpensive and high-precision touchless technology. A base substrate was coated with a luminescent material that emitted static-electricity-induced luminescence (SEL), and it was applied at high voltage. An inexpensive web camera was used to verify the relationship between the non-contact distance to a needle and the applied-voltage-triggered luminescence. The SEL was emitted at 20-200 mm from the luminescent device upon voltage application, and the web camera detected the SEL position with an accuracy of less than 1 mm. We used this developed touchless technology to demonstrate a highly accurate real-time detection of the position of a human finger based on SEL.

Area-Efficient Post-Processing Circuits for Physically Unclonable Function with 2-Mpixel CMOS Image Sensor.

In order to realize image information security starting from the data source, challenge-response (CR) device authentication, based on a Physically Unclonable Function (PUF) with a 2 Mpixel CMOS image sensor (CIS), is studied, in which variation of the transistor in the pixel array is utilized. As each CR pair can be used only once to make the CIS PUF resistant to the modeling attack, CR authentication with CIS can be carried out 4050 times, with basic post-processing to generate the PUF ID. If a larger number of authentications is required, advanced post-processing using Lehmer encoding can be utilized to carry out authentication 14,858 times. According to the PUF performance evaluation, the authentication error rate is less than 0.001 ppm. Furthermore, the area overhead of the CIS chip for the basic and advanced post-processing is only 1% and 2%, respectively, based on a Verilog HDL model circuit design.

Identification of Veterans With PTSD Based on EEG Features Collected During Sleep.

Background: Previously, we identified sleep-electroencephalography (EEG) spectral power and synchrony features that differed significantly at a population-average level between subjects with and without posttraumatic stress disorder (PTSD). Here, we aimed to examine the extent to which a combination of such features could objectively identify individual subjects with PTSD. Methods: We analyzed EEG data recorded from 78 combat-exposed Veteran men with (n = 31) and without (n = 47) PTSD during two consecutive nights of sleep. To obviate the need for manual assessment of sleep staging and facilitate extraction of features from the EEG data, for each subject, we computed 780 stage-independent, whole-night features from the 10 most commonly used EEG channels. We performed feature selection and trained a logistic regression model using a training set consisting of the first 47 consecutive subjects (18 with PTSD) of the study. Then, we evaluated the model on a testing set consisting of the remaining 31 subjects (13 with PTSD). Results: Feature selection yielded three uncorrelated features that were consistent across the two consecutive nights and discriminative of PTSD. One feature was from the spectral power in the delta band (2-4 Hz) and the other two were from phase synchronies in the alpha (10-12 Hz) and gamma (32-40 Hz) bands. When we combined these features into a logistic regression model to predict the subjects in the testing set, the trained model yielded areas under the receiver operating characteristic curve of at least 0.80. Importantly, the model yielded a testing-set sensitivity of 0.85 and a positive predictive value (PPV) of 0.31. Conclusions: We identified robust stage-independent, whole-night features from EEG signals and combined them into a logistic regression model to discriminate subjects with and without PTSD. On the testing set, the model yielded a high sensitivity and a PPV that was twice the prevalence rate of PTSD in the U.S. Veteran population. We conclude that, using EEG signals collected during sleep, such a model can potentially serve as a means to objectively identify U.S. Veteran men with PTSD.

Mechanism-based identification of plasma metabolites associated with liver toxicity.

Early diagnosis of liver injuries caused by drugs or occupational exposures is necessary to enable effective treatments and prevent liver failure. Whereas histopathology remains the gold standard for assessing hepatotoxicity in animals, plasma aminotransferase levels are the primary measures for monitoring liver dysfunction in humans. In this study, using Sprague Dawley rats, we investigated whether integrated analyses of transcriptomic and metabolomic data with genome-scale metabolic models (GSMs) could identify early indicators of injury and provide new insights into the mechanisms of hepatotoxicity. We obtained concurrent measurements of gene-expression changes in the liver and kidneys, and expression changes along with metabolic profiles in the plasma and urine, from rats 5 or 10 h after exposing them to one of two classical hepatotoxicants, acetaminophen (2 g/kg) or bromobenzene (0.4 g/kg). Global multivariate analyses revealed that gene-expression changes in the liver and metabolic profiles in the plasma and urine of toxicant-treated animals differed from those of controls, even at time points much earlier than changes detected by conventional markers of liver injury. Furthermore, clustering analysis revealed that both the gene-expression changes in the liver and the metabolic profiles in the plasma induced by the two hepatotoxicants were highly correlated, indicating commonalities in the liver toxicity response. Systematic GSM-based analyses yielded metabolites associated with the mechanisms of toxicity and identified several lipid and amino acid metabolism pathways that were activated by both toxicants and those uniquely activated by each. Our findings suggest that several metabolite alterations, which are strongly associated with the mechanisms of toxicity and occur within injury-specific pathways (e.g., of bile acid and fatty acid metabolism), could be targeted and clinically assessed for their potential as early indicators of liver damage.

Alterations in sleep electroencephalography synchrony in combat-exposed veterans with post-traumatic stress disorder.

STUDY OBJECTIVES: We assessed whether the synchrony between brain regions, analyzed using electroencephalography (EEG) signals recorded during sleep, is altered in subjects with post-traumatic stress disorder (PTSD) and whether the results are reproducible across consecutive nights and subpopulations of the study. METHODS: A total of 78 combat-exposed veteran men with (n = 31) and without (n = 47) PTSD completed two consecutive laboratory nights of high-density EEG recordings. We computed a measure of synchrony for each EEG channel-pair across three sleep stages (rapid eye movement [REM] and non-REM stages 2 and 3) and six frequency bands. We examined the median synchrony in 9 region-of-interest (ROI) pairs consisting of 6 bilateral brain regions (left and right frontal, central, and parietal regions) for 10 frequency-band and sleep-stage combinations. To assess reproducibility, we used the first 47 consecutive subjects (18 with PTSD) for initial discovery and the remaining 31 subjects (13 with PTSD) for replication. RESULTS: In the discovery analysis, five alpha-band synchrony pairs during non-REM sleep were consistently larger in PTSD subjects compared with controls (effect sizes ranging from 0.52 to 1.44) across consecutive nights: two between the left-frontal and left-parietal ROIs, one between the left-central and left-parietal ROIs, and two across central and parietal bilateral ROIs. These trends were preserved in the replication set. CONCLUSION: PTSD subjects showed increased alpha-band synchrony during non-REM sleep in the left frontoparietal, left centro-parietal, and inter-parietal brain regions. Importantly, these trends were reproducible across consecutive nights and subpopulations. Thus, these alterations in alpha synchrony may be discriminatory of PTSD.

Genome-Scale Model-Based Identification of Metabolite Indicators for Early Detection of Kidney Toxicity.

Identifying early indicators of toxicant-induced organ damage is critical to provide effective treatment. To discover such indicators and the underlying mechanisms of toxicity, we used gentamicin as an exemplar kidney toxicant and performed systematic perturbation studies in Sprague Dawley rats. We obtained high-throughput data 7 and 13 h after administration of a single dose of gentamicin (0.5 g/kg) and identified global changes in genes in the liver and kidneys, metabolites in the plasma and urine, and absolute fluxes in central carbon metabolism. We used these measured changes in genes in the liver and kidney as constraints to a rat multitissue genome-scale metabolic network model to investigate the mechanism of gentamicin-induced kidney toxicity and identify metabolites associated with changes in tissue gene expression. Our experimental analysis revealed that gentamicin-induced metabolic perturbations could be detected as early as 7 h postexposure. Our integrated systems-level analyses suggest that changes in kidney gene expression drive most of the significant metabolite alterations in the urine. The analyses thus allowed us to identify several significantly enriched injury-specific pathways in the kidney underlying gentamicin-induced toxicity, as well as metabolites in these pathways that could serve as potential early indicators of kidney damage.

Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats.

BACKGROUND: Although numerous reports have shown that α1-adrenoceptor (α1-AR) antagonists, which are used to treat benign prostatic hyperplasia (BPH), can cause ejaculatory disorders, few studies have investigated whether the phosphodiesterase 5 (PDE5) inhibitor tadalafil has such adverse effects. In this study, we compared the effects of tadalafil and α1-AR antagonists on seminal emission and their mechanisms of action. AIM: To evaluate in normal rats the possible effects of tadalafil on spontaneous seminal emission (SSE) and seminal contraction evoked by hypogastric nerve stimulation. METHODS: Male Sprague-Dawley rats were used. To assess SSE, plastic corsets were fitted around the thorax and upper abdomen of male Sprague-Dawley rats to prevent genital autogrooming. Rats were treated orally with tadalafil or an α1-AR antagonist (silodosin, naftopidil, or tamsulosin) for 3 days and housed in wire-bottomed cages. Ejaculatory plugs dropped on the bottoms of the cages were counted and weighed. To assess the intraluminal pressure of seminal vesicles, the hypogastric nerve of urethane-anesthetized rats was isolated and electrically stimulated. After stabilization of seminal vesicle contraction, the rats were intravenously administered test drugs. The expression of PDE5, endothelial nitric oxide synthetase (eNOS), and neuronal NOS (nNOS) in the seminal vesicle and vas deferens were measured by reverse-transcription polymerase chain reaction. MAIN OUTCOME MEASURE: The number and weight of the ejaculatory plugs produced by corset-fitted rats and the intraluminal pressure of the seminal vesicle were evaluated. RESULTS: Tadalafil did not affect the number or weight of the ejaculatory plugs of corset-fitted rats, whereas all α1-AR antagonists decreased both in a dose-dependent manner. The α1-AR antagonists, but not tadalafil, inhibited the seminal vesicle contraction evoked by electrical stimulation of the hypogastric nerve. The seminal vesicle and vas deferens expressed higher levels of PDE5 and eNOS mRNA and lower levels of nNOS mRNA relative to the urethra. CLINICAL IMPLICATIONS: Tadalafil can be a treatment option in cases where there is concern about negative effects on seminal emission. STRENGTHS AND LIMITATIONS: We demonstrated different effects of tadalafil and 3 α1-AR antagonists on rat SSE and their mechanisms of action by measuring seminal vesicle contractility in vivo. A limitation is that we used normal rats, not BPH model rats, and so our results might not apply to human BPH patients. CONCLUSION: Tadalafil did not inhibit spontaneous seminal emission or electrical field stimulation-induced seminal vesicle contraction in normal rats. The NO-cyclic guanosine monophosphate pathway is unlikely to be involved in the inhibition of seminal vesicle contraction in normal rats. Yoshinaga R, Fukui T, Yoshifuji M, et al. Comparison of the Effects of Tadalafil and α1-Adrenoceptor Antagonists on Spontaneous Seminal Emission and Electrical Field Stimulation-Induced Seminal Vesicle Contraction in Rats. J Sex Med 2019;16:680-690.

Individualized estimation of human core body temperature using noninvasive measurements.

A rising core body temperature (Tc) during strenuous physical activity is a leading indicator of heat-injury risk. Hence, a system that can estimate Tc in real time and provide early warning of an impending temperature rise may enable proactive interventions to reduce the risk of heat injuries. However, real-time field assessment of Tc requires impractical invasive technologies. To address this problem, we developed a mathematical model that describes the relationships between Tc and noninvasive measurements of an individual's physical activity, heart rate, and skin temperature, and two environmental variables (ambient temperature and relative humidity). A Kalman filter adapts the model parameters to each individual and provides real-time personalized Tc estimates. Using data from three distinct studies, comprising 166 subjects who performed treadmill and cycle ergometer tasks under different experimental conditions, we assessed model performance via the root mean squared error (RMSE). The individualized model yielded an overall average RMSE of 0.33 (SD = 0.18)°C, allowing us to reach the same conclusions in each study as those obtained using the Tc measurements. Furthermore, for 22 unique subjects whose Tc exceeded 38.5°C, a potential lower Tc limit of clinical relevance, the average RMSE decreased to 0.25 (SD = 0.20)°C. Importantly, these results remained robust in the presence of simulated real-world operational conditions, yielding no more than 16% worse RMSEs when measurements were missing (40%) or laden with added noise. Hence, the individualized model provides a practical means to develop an early warning system for reducing heat-injury risk. NEW & NOTEWORTHY A model that uses an individual's noninvasive measurements and environmental variables can continually "learn" the individual's heat-stress response by automatically adapting the model parameters on the fly to provide real-time individualized core body temperature estimates. This individualized model can replace impractical invasive sensors, serving as a practical and effective surrogate for core temperature monitoring.

A strategy for evaluating pathway analysis methods.

BACKGROUND: Researchers have previously developed a multitude of methods designed to identify biological pathways associated with specific clinical or experimental conditions of interest, with the aim of facilitating biological interpretation of high-throughput data. Before practically applying such pathway analysis (PA) methods, we must first evaluate their performance and reliability, using datasets where the pathways perturbed by the conditions of interest have been well characterized in advance. However, such 'ground truths' (or gold standards) are often unavailable. Furthermore, previous evaluation strategies that have focused on defining 'true answers' are unable to systematically and objectively assess PA methods under a wide range of conditions. RESULTS: In this work, we propose a novel strategy for evaluating PA methods independently of any gold standard, either established or assumed. The strategy involves the use of two mutually complementary metrics, recall and discrimination. Recall measures the consistency of the perturbed pathways identified by applying a particular analysis method to an original large dataset and those identified by the same method to a sub-dataset of the original dataset. In contrast, discrimination measures specificity-the degree to which the perturbed pathways identified by a particular method to a dataset from one experiment differ from those identifying by the same method to a dataset from a different experiment. We used these metrics and 24 datasets to evaluate six widely used PA methods. The results highlighted the common challenge in reliably identifying significant pathways from small datasets. Importantly, we confirmed the effectiveness of our proposed dual-metric strategy by showing that previous comparative studies corroborate the performance evaluations of the six methods obtained by our strategy. CONCLUSIONS: Unlike any previously proposed strategy for evaluating the performance of PA methods, our dual-metric strategy does not rely on any ground truth, either established or assumed, of the pathways perturbed by a specific clinical or experimental condition. As such, our strategy allows researchers to systematically and objectively evaluate pathway analysis methods by employing any number of datasets for a variety of conditions.

A rat long-lasting cystitis model induced by intravesical injection of hydrogen peroxide.

Novel longer lasting inflammatory bladder animal models are needed to better understand the pathophysiology of chronic cystitis. We previously developed a relatively long-lasting mouse cystitis model by intravesical injection of hydrogen peroxide (H2O2). To further evaluate its pathophysiology, in this study, we established and analyzed a rat cystitis model. Under anesthesia, 1.5% H2O2 solution was introduced transurethrally into the bladder of female rats, and kept for 30 min. The H2O2 injection significantly increased the number of micturition events up to day 14 and decreased urine volume per micturition, with the smallest volumes on day 3, compared with the vehicle-treated group. Cystometric analysis on day 7 revealed that intercontraction intervals were significantly shortened without affecting the baseline, threshold, or maximum pressures. Intravesical resiniferatoxin-evoked nociceptive behaviors, such as freezing, were significantly enhanced on days 7 and 14. Furthermore, histopathology revealed hemorrhage, edema, infiltration of neutrophils into the lamina propria, and urothelial denudation in the early phase (day 1). These damages were gradually repaired, while hyperplasia of the urothelium, vascularization, increases in fibroblast counts, and infiltration of mast cells and eosinophils were observed through the later phase (days 7 and 14). These results suggest that intravesical H2O2 injection induces relatively long-lasting cystitis with enhanced bladder activity and pain sensation in rats. This approach thus provides a novel rat long-lasting cystitis model that allows us to analyze detailed symptoms and pathophysiology of H2O2-induced cystitis model than the mouse model and may be used to investigate the pathophysiology and treatment of chronic bladder hypersensitive disorders, such as bladder pain syndrome/interstitial cystitis.

Effects of chalcogen atom substitution on the optoelectronic and charge-transport properties in picene-type π-systems.

A series of π-conjugated 3,10-dialkyl-dinaphtho[1,2-b:2',1'-d]chalcogenophenes incorporating S, Se, and Te as the central chalcogen atom was newly synthesized, and their optoelectronic and charge-transport properties were systematically investigated. High carrier mobilities of up to 4.7 cm2 V-1 s-1 were achieved for solution-processed organic field-effect transistors using these materials as p-channel organic semiconductors.

Effects of the phosphodiesterase 5 inhibitor Tadalafil on bladder function in a rat model of partial bladder outlet obstruction.

AIMS: To investigate the effect of the phosphodiesterase 5 (PDE5) inhibitor Tadalafil on bladder blood flow and bladder function in a rat model of partial bladder outlet obstruction (BOO). METHODS: Female 14-15-week-old Sprague-Dawley rats were divided into three groups. BOO was surgically induced in rats by placing a rubber ring around the urethra. BOO rats were administered daily oral Tadalafil (BOO-Tadalafil) or vehicle (BOO-Vehicle), while sham-operated animals were treated with vehicle (Sham). On the 14th day after surgery, micturition behavior was recorded for 24 hr by using a metabolic cage. On the 15th day after surgery, bladder blood flow and bladder weight were measured. The expression of PDE5 mRNA in the vesical and iliac arteries of intact rats was measured by reverse transcriptase-polymerase chain reaction. RESULTS: BOO led to a significant decrease in bladder blood flow and a significant increase in bladder weight. These changes were partially suppressed by Tadalafil treatment. The number of micturitions in the BOO group was significantly increased and the average micturition volume was significantly decreased, without affecting the total micturition volume. Repeated Tadalafil treatment markedly inhibited the increase in micturition frequency and the decrease in average micturition volume. PDE5 mRNA was expressed in the vesical and iliac arteries. CONCLUSION: Tadalafil suppressed the reduction in bladder blood flow caused by BOO in rats and improved urinary function. This action of Tadalafil may contribute to its amelioration of bladder function. Neurourol. Urodynam. 35:444-449, 2016. © 2015 Wiley Periodicals, Inc.

[Drug-induced liver injury caused by a dietary supplement (Kin-toki Shoga(®)) made from ginger].

A 70-year-old woman who took a dietary supplement, Kin-toki Shoga(®) made from ginger for peripheral psychroesthesia and numbness, experienced an epigastric sense of incongruity and appetite loss and passed brown urine for 2 months. Although she had stopped taking the supplement, her symptoms had not improved. She was admitted to our hospital because of jaundice and liver dysfunction. After an investigation of causes, she was diagnosed with drug-induced liver injury caused by Kin-toki Shoga(®). Liver dysfunction gradually improved with conservative treatment. She was discharged on the 25th day of illness. Liver biopsy findings were compatible with drug-induced liver injury.

Effect of a single treatment with tadalafil on blood flow in lower urinary tract tissues in rat models of bladder overdistension/emptying and abdominal aorta clamping/release.

Impaired blood flow in lower urinary tract (LUT) tissues is a pathophysiological cause of LUT symptoms. We investigated the effects of the phosphodiesterase 5 (PDE5) inhibitor tadalafil on the sustained decrease in bladder blood flow (BBF) and time-dependent changes in BBF and prostate blood flow (PBF) resulting from ischemia/reperfusion in two rat models. In a rat model of bladder overdistension/emptying (O/E), the bladder was overdistended by saline infusion and emptied after 2h. Tadalafil was administered intraduodenally immediately after emptying. In a rat model of clamping/release (C/R), the abdominal aorta was clamped for 2h after a single oral dose of tadalafil and then the clamp was released. BBF in O/E and C/R rats and PBF in C/R rats were measured by laser Doppler flow imaging. BBF decreased on overdistension and partially recovered after emptying. A progressive decrease in BBF was observed after O/E, and this was prevented by tadalafil treatment. Both BBF and PBF decreased during clamping of the abdominal aorta and partially recovered after clamp removal. Oral pretreatment with tadalafil partially or completely prevented the decreases in BBF and PBF not only after clamp removal but also during clamping. PDE5 mRNA was highly expressed in the bladder and the supporting vasculature. Tadalafil inhibited the O/E-induced decrease in BBF and the C/R-induced time-dependent decreases in BBF and PBF. PDE5 inhibition by tadalafil may improve both BBF and PBF.

The analgesic effect of tramadol in animal models of neuropathic pain and fibromyalgia.

(±)-Tramadol hydrochloride (tramadol) is a widely used analgesic for the treatment of cancer pain and chronic pain. Although many animal studies have shown antinociceptive effects of tramadol in both acute and chronic pain, little is known about the effect of tramadol in putative animal models of fibromyalgia. In this study, we compared the antiallodynic effects of oral administration of tramadol in two kinds of rat chronic pain models, neuropathic pain induced by partial sciatic nerve ligation (PSL) and reserpine-induced myalgia (RIM). In PSL rats, the threshold for responses induced by tactile stimulation with von Frey filaments was significantly decreased seven days after the operation, suggesting that the operation induced tactile allodynia. Orally administered tramadol showed a potent and dose-dependent antiallodynic effect on PSL-induced allodynia. In RIM rats, the threshold was significantly decreased five days after reserpine treatment. Orally administered tramadol also attenuated reserpine-induced tactile allodynia. To explore the mechanism of the antiallodynic effect of tramadol in RIM rats, we investigated the effect of the opioid antagonist naloxone on the tramadol-induced analgesic effect in these rats. The effect of tramadol was partially antagonized by naloxone, suggesting that the opioid receptor is involved at least in part in the antiallodynic effect of tramadol in RIM rats. These data indicate that orally administered tramadol produced improvement in both PSL rats and RIM rats at similar doses and provide evidence that the opioid system is partly involved in the analgesic effect of tramadol in RIM rats.

Acamprosate {monocalcium bis(3-acetamidopropane-1-sulfonate)} reduces ethanol-drinking behavior in rats and glutamate-induced toxicity in ethanol-exposed primary rat cortical neuronal cultures.

Acamprosate, the calcium salt of bis(3-acetamidopropane-1-sulfonate), contributes to the maintenance of abstinence in alcohol-dependent patients, but its mechanism of action in the central nervous system is unclear. Here, we report the effect of acamprosate on ethanol-drinking behavior in standard laboratory Wistar rats, including voluntary ethanol consumption and the ethanol-deprivation effect. After forced ethanol consumption arranged by the provision of only one drinking bottle containing 10% ethanol, the rats were given a choice between two drinking bottles, one containing water and the other containing 10% ethanol. In rats selected for high ethanol preference, repeated oral administration of acamprosate diminished voluntary ethanol drinking. After three months of continuous access to two bottles, rats were deprived of ethanol for three days and then presented with two bottles again. After ethanol deprivation, ethanol preference was increased, and the increase was largely abolished by acamprosate. After exposure of primary neuronal cultures of rat cerebral cortex to ethanol for four days, neurotoxicity, as measured by the extracellular leakage of lactate dehydrogenase (LDH), was induced by incubation with glutamate for 1h followed by incubation in the absence of ethanol for 24h. The N-methyl-D-aspartate receptor blocker 5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine, the metabotropic glutamate receptor subtype 5 antagonist 6-methyl-2-(phenylethynyl)pyridine and the voltage-gated calcium-channel blocker nifedipine all inhibited glutamate-induced LDH leakage from ethanol-exposed neurons. Acamprosate inhibited the glutamate-induced LDH leakage from ethanol-exposed neurons more strongly than that from intact neurons. In conclusion, acamprosate showed effective reduction of drinking behavior in rats and protected ethanol-exposed neurons by multiple blocking of glutamate signaling.

Increased mRNA expression of genes involved in pronociceptive inflammatory reactions in bladder tissue of interstitial cystitis.

PURPOSE: We assayed mRNA expression of the TRP family of channels and ASIC1 in bladder tissue from patients with interstitial cystitis. MATERIALS AND METHODS: Bladder biopsies of 1) nonclassic interstitial cystitis, 2) nonulcerative portions of classic interstitial cystitis, 3) ulcerative portions of classic interstitial cystitis and 4) noncancerous portions of bladder cancer as the control were placed immediately in ice-cold RNAlater® and subjected to real-time reverse transcriptase-polymerase chain reaction. We compared the mRNA expression of TRP channels, ASIC1, NGF, CXCL9 and UPK3A with that of controls, and correlated expression with symptom severity. RESULTS: We analyzed specimens from 17 patients with nonclassic interstitial cystitis, 22 with classic interstitial cystitis and 11 controls. In nonclassic interstitial cystitis samples TRPV2 and NGF showed significantly increased expression. In classic interstitial cystitis samples nonulcerative portions demonstrated a significant increase in the expression of TRPA1, TRPM2 and 8, TRPV1 and 2, ASIC1, NGF and CXCL9, and a significant decrease in UPK3A and TRPV4. Ulcerative portions showed similar changes for TRPM2, TRPV1, 2 and 4, CXCL9 and UPK3A. Increased expression of TRPM2, first noted in interstitial cystitis tissue, was the most pronounced one of the TRP family. All symptom measures correlated with TRPM2 and TRPV2 expression, and partially with that of the other genes. CONCLUSIONS: This study showed increased expression of the genes involved in pronociceptive inflammatory reactions in interstitial cystitis, including TRPV1, 2 and 4, ASIC1, NGF and CXCL9, and to our knowledge TRPM2 for the first time. The different expression patterns suggest distinct pathophysiologies for classic and nonclassic interstitial cystitis. The genes and their products are potential candidates for use as biomarkers or novel therapy targets.

Bladder function in 17ß-estradiol-induced nonbacterial prostatitis model in Wistar rat.

OBJECTIVES: To investigate bladder function in a model of nonbacterial prostatitis (NBP) induced in castrated rats by 17ß-estradiol injection. METHODS: Ten-month-old male Wistar rats were divided into two groups, sham and NBP (both N = 8). NBP was induced by castration followed by daily subcutaneous injection of 17ß-estradiol for 30 days. On the 31st day after surgery, we investigated (1) voiding behavior, (2) bladder blood flow (BBF), (3) prostate and bladder weight, and proinflammatory cytokines (TNF-α and CXCL1) levels and (4) bladder contractile responses to electrical field stimulation (EFS), carbachol and KCl. RESULTS: (1) Voiding behavior (average micturition volume, total urine volume and number of micturitions) and (2) BBF were not significantly different between the sham and NBP groups. (3) NBP led to a significant decrease in prostatic weight and increase in proinflammatory cytokine levels in the prostate, but NBP did not cause a significant change in bladder weight or proinflammatory cytokine levels in the bladder. (4) Bladder contractile forces in response to EFS, carbachol and KCl were not significantly affected by NBP. CONCLUSIONS: In this rat model, NBP did not cause a significant change in the level of proinflammatory cytokines in the bladder and affect bladder function.

Novel mouse model of chronic inflammatory and overactive bladder by a single intravesical injection of hydrogen peroxide.

There is so far no generally accepted animal model of chronic cystitis by which potential therapies can be evaluated. In this study, we aimed to establish a new mouse model of cystitis based on the proinflammatory effects of reactive oxygen species. A single intravesical injection of 1.5% hydrogen peroxide (H2O2) significantly increased the numbers of voids by 1 day after injection in female mice, which lasted up to 7 days. The H2O2 injection rapidly increased the bladder weight by 3 h in parallel with the histological damage and hyperpermeability of urothelial barrier. Although the urothelial dysfunction was recovered to normal by 7 days, increase in bladder weight, edematous thickening of the submucosa, and vascular hyperpermeability were apparent even 7 days after injection. During the time course, massive infiltration of neutrophils and increased expression of inflammatory cytokines were observed in the bladder. An intraperitoneal administration of oxybutynin, amitriptyline, indomethacin, or morphine attenuated the H2O2-induced frequent urination. These findings suggest that an intravesical injection of H2O2 induces relatively long-lasting inflammatory and overactive bladder, compared with existing cystitis models. The intravesical H2O2 injection model may be a simple and useful tool in the pathological study and drug discovery for chronic cystitis.