Anti-SARS-CoV-2 IgG antibody after the second and third mRNA vaccinations in staff and residents in a nursing home with a previous COVID-19 outbreak in Niigata, Japan.

This study measured IgG antibody titers against spike (S) and nucleocapsid (N) proteins of SARS-CoV-2 before vaccination and after the second and third doses of an mRNA vaccine in staff and residents of a nursing home in Niigata, Japan. The study included 52 staff members, of whom six (11.5%) were previously infected with SARS-CoV-2, and 32 older residents, of whom 22 (68.8%) were previously infected. All participants received the first two doses in April-July 2021 and a third dose in January-March 2022. In staff, the median anti-S antibody titers (interquartile range) in previously infected and SARS-CoV-2-naïve individuals before vaccination were 960 (592-1,926) and 0.5 (0.0-2.1) arbitrary units (AU)/mL. Anti-S antibody titers 5 months after the second and third doses in previously infected staff were 7,391 (5,230-7,747) and 10,195 (5,582-13,886) AU. In residents, the median anti-S antibody titers in previously infected and naïve individuals before vaccination were 734 (425-1,934) and 1.1 (0.0-3.1) AU/mL. Anti-S antibody titers at 5 months after the second and third doses in previously infected residents were 15,872 (9,683-21,557) and 13,813 (6,689-20,839) AU/mL; however, there were no significant differences in titers between the second and third doses in previously infected residents. Anti-N antibody titers were higher in previously infected than naïve individuals, and titers decreased chronologically.

Comparisons of Hepatobiliary Phase Imaging Using Combinations of Parallel Imaging and Variable Degrees of Compressed Sensing With Use of Parallel Imaging Alone.

OBJECTIVE: This study aimed to compare the image quality in the hepatobiliary phase images of gadoxetic acid-enhanced liver magnetic resonance imaging using parallel imaging (PI) and compressed sensing (CS) reconstruction, using variable CS factors with the standard method using the PI technique. METHODS: In this study, 64 patients who underwent gadoxetic acid-enhanced liver magnetic resonance imaging at 3.0 T were enrolled. Hepatobiliary phase images were acquired 6 times using liver acquisition with volume acceleration (LAVA) and CS reconstruction with 5 CS factors 1.4, 1.6, 1.8, 2.0, and 2.5 (LAVA-CS 1.4, 1.6, 1.8, 2.0, and 2.5) and standard LAVA (LAVA-noCS). For objective analysis, the signal intensity ratios (SIRs) of the liver-to-spleen (SIR liver/spleen ), liver-to-portal vein (SIR liver/portal vein ), and liver-to-fat (SIR liver/fat ) were estimated. For subjective analysis, 2 radiologists independently evaluated the quality of all the images. RESULTS: The objective analysis demonstrated no significant difference in all evaluation parameters of all the images. Subjective analysis revealed that the scores of all evaluation items were higher for LAVA-noCS images than for LAVA-CS images, and only LAVA-CS 1.4 did not significantly differ from LAVA-noCS in all evaluation items ( P = 1.00 in 2 readers). CONCLUSIONS: A CS factor of 1.4 in the hepatobiliary phase image with combined PI and CS can reduce the scan time without degrading the image quality compared with the standard method.

Sports activity participation and subjective health status of patients after total hip arthroplasty via the anterolateral-supine approach: a case series study.

BACKGROUND: No reports have been published about participation in sports activity and subjective health status after total hip arthroplasty via the anterolateral approach in the supine position (ALS-THA) in Japanese patients. This study assessed sports activity participation and subjective health status, as well as factors potential associated with these variables, in patients who underwent ALS-THA. METHODS: Of 698 patients who underwent total hip arthroplasty at our institution between 2013 and 2018, questionnaires were sent to 355 patients under 80 years old who had undergone ALS-THA and 242 responded. Patients were asked about their subjective health status, participation in sports activity, the EuroQol 5-dimensions 5-level (EQ-5D-5L), the University of California Los Angeles (UCLA) activity scale score and the Forgotten Joint Score (FJS). Patient characteristics and hospitalization information were also collected. Patients' subjective health status was categorized as "healthy" or "unhealthy". Univariate and multivariate logistic regression analyses were performed to determine factors associated with participation in sports activity after ALS-THA and a "healthy" status. RESULTS: The pre- and postoperative sports activity participation rates were 54.0% and 57.8%, respectively. Most patients (76.8%, n = 182) were considered "healthy". Age (P = .019) and UCLA activity score (P < .001) were significantly associated with sports activity after ALS-THA. FJS (P = .002) and EQ-5D-5L (P = .004) were significantly associated with a "healthy" status. CONCLUSION: Patients participating in sports activity after ALS-THA are older and have higher UCLA activity scores and patients considered "healthy" have higher FJS and EQ-5D-5L scores.

Multijurisdictional Outbreak of Enterohemorrhagic Escherichia coli O157 Caused by Consumption of Ready-to-Eat Grilled Skewered Meat in Niigata, Japan.

Enterohemorrhagic Escherichia coli O157 (EHEC) causes severe complications such as hemolytic uremic syndrome. Contaminated ready-to-eat (RTE) food is one of the vehicles of multijurisdictional outbreaks of foodborne disease worldwide. Multijurisdictional (covering cities, towns, and villages) outbreaks of EHEC are usually linked to an increase in cases, and here we describe such an outbreak involving 29 cases in October 2017 in the Niigata Prefecture. After prefecture-wide active case finding, we conducted a case-control study of 29 cases with eligible data who tested positive for EHEC. To determine the association of the outbreak with risk factors, we compared these cases with 38 controls selected from family and acquaintances who were both symptom free and tested negative for EHEC. The largest number of cases was in the 20-29-year age group (7/29; 24%) and most were women (20/29; 69%). All 29 cases had an identical or similar multilocus variable number tandem-repeat analysis (MLVA) profile. Of these, 76% (22/29) had consumed some type of grilled skewered meat. Also, 69% (20/29) had consumed grilled skewered meat produced by company X. EHEC infection was strongly associated with the consumption of grilled skewered meat produced by any food processing company (odds ratio [OR] = 11.8, confidence interval [95% CI]: 3.7-37.4) and by company X (OR = 9.8, 95% CI: 3.2-30.7). At company X, the skewered meat was grilled to 95°C and then removed from the grilling area to meat trays. The meat trays were not sufficiently washed and disinfected. Testing indicated that the facility was negative for EHEC but four asymptomatic employees tested positive for EHEC. Company X was temporarily closed and voluntarily recalled the foods. We recommend that all employees sufficiently wash and disinfect meat trays to prevent contamination of RTE food, avoid cross-contamination of grilled skewered meat through the environment by regularly cleaning the facility, and appropriately practice self-health care.

Sports activity participation after curved periacetabular osteotomy for acetabular dysplasia.

BACKGROUND: Curved periacetabular osteotomy (CPO) was developed to treat acetabular dysplasia. Given that CPO can improve physical function in the early post-operative period, patients might be able to participate in sports activities post-operatively. Therefore, this study examined the post-operative sports activity participation and characteristics of acetabular dysplasia patients who have undergone CPO. METHODS: A total of 52 patients who underwent CPO for acetabular dysplasia were given a questionnaire on pre- and post-operative sports activities; 43 patients responded. We surveyed patients' sports activities, satisfaction, and physical function. Patients were divided according to whether they participated in sports activities after CPO. Physical function was compared before and after CPO. RESULTS: The pre- and post-operative sports activity participation rates were 55.8 and 72.1%, respectively. Patients mostly performed low-impact sports activities. Moreover, patients who participated in sports activities post-operatively had smaller pre-operative range of motion of hip flexion and returned to full weight bearing earlier. CONCLUSIONS: Among acetabular dysplasia patients who underwent CPO, 72.1% participated in sports activities post-operatively. Post-operatively, patients participated not only in low-impact sports activities, but also in high-impact ones. These findings might be useful for advising patients who are concerned about participating in sports activities after CPO.

Effects of forefoot arthroplasty on plantar pressure, pain, gait and disability in rheumatoid arthritis.

Objectives: The purpose of this study was to clarify the effect of forefoot arthroplasty on plantar pressure, pain, gait, and disability within 1 year after arthroplasty in patients with RA.Methods: Eleven patients with RA who underwent forefoot arthroplasty completed this quasi-experimental study. Outcome measures were in-shoe plantar pressure, visual analog scale (VAS) for pain, temporal gait parameters, and modified Health Assessment Questionnaire (mHAQ), obtained preoperatively and at 4 and 12 months postoperatively.Results: The average peak plantar pressure under the 2nd metatarsal head decreased at 4 months postoperatively, compared to preoperative values (p < .05) and the decreased plantar pressure was sustained at 12 months postoperatively. Similar changes were observed under the 3rd to 5th metatarsal heads. The median VAS for foot pain decreased from 25 mm preoperatively to 1 mm at 4 months postoperatively and the lower score was sustained at 12 months postoperatively (p < .05). The median mHAQ score remained lower (<1.0) at all measurement points. Regarding gait, there were no significant differences from the preoperative assessment to postoperative follow-up.Conclusion: Plantar pressure and forefoot pain decreased at 4 and 12 months after forefoot arthroplasty in patients with RA. No adverse effects on gait parameters or disability were observed.

Effects of Tissue Flossing and Dynamic Stretching on Hamstring Muscles Function.

Tissue flossing aims to improve range of motion (ROM), reduce pain, and enhance injury prevention. However, evidence is lacking regarding its effects. Therefore, this study examined the effects of flossing on hamstring muscles function in comparison to dynamic stretching (DS). Seventeen healthy young men ([mean ± SD] age, 23.2 ± 1.1 years; height, 1.72 ± 0.08 m; body mass, 63.5 ± 9.3 kg) volunteered as subjects in this randomized crossover trial. The subjects received flossing, DS, and control interventions in random order at least 1 week apart to eliminate the influence of the previous intervention. Flossing involved passive twisting and active movement using a floss band (Sanctband COMPRE Floss Blueberry, Sanct Japan Co., Ltd.). DS was performed for 4 minutes in 30-second sets consisting of 15 repetitions of 2 seconds stretching. The following were measured before and after each intervention: straight leg raise (SLR) test, passive knee extension (KE) test, passive torque, passive stiffness, fascicle length in the biceps femoris long head as an indication of hamstring muscles flexibility, and maximal isometric knee flexion contraction, maximal eccentric knee extension/flexion contraction, rate of force development, and muscle activity. Flossing yielded significant improvements in the SLR test (mean difference in post-intervention changes between interventions: 5.4°, percentage change from pre- to post-value: 13.4%, p = 0.004), passive KE test (6.2°, 4.5%, p < 0.001), passive torque at end-ROM (3.8 Nm, 4.7%, p = 0.03), and maximal eccentric knee flexion contraction (14.9% body weight, 8.2%, p = 0.03) than control. Moreover, flossing yielded 2.1-fold greater improvements in the passive KE test (3.8°, 4.5%, p = 0.03) and yielded significant improvements in the maximal eccentric knee extension contraction (29.9% body weight, 13.8%, p = 0.02) than DS. Therefore, flossing on hamstring muscles is more beneficial than DS with respect to increasing ROM and muscle exertion.

Effect of Devised Simultaneous Physical Function Improvement Training and Posture Learning Exercises on Posture.

Poor posture in young adults and middle-aged people is associated with neck and back pain which are among the leading causes of disability worldwide. Training posture maintenance muscles and learning about ideal posture are important for improving poor posture. However, the effect of using both approaches simultaneously has not been verified, and it is unclear how long the effects persist after the intervention. Forty female university students were randomly and evenly assigned to four groups: physical function improvement training, posture learning, combination, and control groups. Four weeks of intervention training was conducted. Postural alignment parameters were obtained, including trunk anteroposterior inclination, pelvic anteroposterior inclination, and vertebral kyphosis angle. Physical function improvement training for improving crossed syndrome included two types of exercises: "wall-side squatting" and "wall-side stretching". The posture learning intervention consisted of two types of interventions: "standing upright with their back against the wall" and "rolled towel". A multiple comparison test was performed after analysis of covariance to evaluate the effect of each group's postural change intervention on postural alignment. Only the combination group showed an effective improvement in all posture alignments. However, it was found that a week after the 4-week intervention, the subjects' postures returned to their original state.

Evaluation of the efficacy and safety of intravenous ciprofloxacin versus meropenem in the treatment of postoperative infection.

Therapeutic options for postoperative infection in gastrointestinal surgery are limited. To identify new treatment alternatives, the Japan Society for Surgical Infection conducted a multicenter prospective, randomized, controlled clinical trial comparing the efficacy of intravenous ciprofloxacin (CIP IV) and intravenous meropenem (MEM IV). Between July 2005 and May 2008, the trial recruited patients who developed postoperative infection or had suspected infectious systemic inflammatory response syndrome after elective clean-contaminated gastrointestinal surgery. All patients had received prophylactic postoperative antibiotic treatment. Patients received either intravenous CIP IV 300 mg b.i.d. or MEM IV 500 mg b.i.d. A total of 205 patients from 31 institutions were enrolled. Of these, 101 were randomized to CIP IV and 104 to MEM IV. There were 100 and 102 in the intent-to-treat (ITT)/safety population and 75 and 77 in the per-protocol (PP) population. There was no significant difference between CIP IV and MEM IV in terms of clinical efficacy, bacteriological efficacy, incidence of adverse drug reactions, duration of antimicrobial treatment, or relapse/reactivation. Overall clinical success PP population) was high in both treatment groups: 85.3% (64/75) for CIP IV and 89.6% (69/77) for MEM IV, although the non-inferiority of CIP IV was not demonstrated (difference -4.3%, 95% CI -14.8, 6.2). In patients who had undergone upper gastrointestinal surgery, success was 88.5% (23/26) for CIP IV and 85.2% (23/27) for MEM IV. Intravenous ciprofloxacin is as effective as intravenous meropenem in the empiric therapy of postoperative infection after gastrointestinal surgery.

Time to initiation of treatment with polymyxin B cartridge hemoperfusion in septic shock patients.

BACKGROUND: We investigated whether early initiation of hemoperfusion with a polymyxin B cartridge (PMX) after the diagnosis of septic shock could improve the clinical outcome. METHODS: A prospective, open-labeled, multicenter cohort study was performed at intensive care units in Japan. 41 patients received PMX within 6 h after the diagnosis of septic shock (early group) and 51 patients were treated after 6 h (late group). RESULTS: The early group had a significantly shorter duration of ventilator support and also had a lower catecholamine requirement. PMX was effective for improvement of hypotension, hypoperfusion, the sequential organ failure assessment score, and pulmonary oxygenation regardless of the timing of its initiation. The 28-day mortality rate did not differ between the two groups. CONCLUSIONS: Early initiation of PMX shortened the duration of ventilator support and also reduced the catecholamine requirement, so early treatment of septic shock should achieve a better outcome.

Assessing the Pre-Vaccination Anti-SARS-CoV-2 IgG Seroprevalence among Residents and Staff in Nursing Home in Niigata, Japan, November 2020.

An outbreak of coronavirus disease 2019 (COVID-19) occurred in a nursing home in Niigata, Japan, November 2020, with an attack rate of 32.0% (63/197). The present study was aimed at assessing the pre-vaccination seroprevalence almost half a year after the COVID-19 outbreak in residents and staff in the facility, along with an assessment of the performance of the enzyme-linked immunosorbent assay (ELISA) and the chemiluminescent immunoassay (CLIA), regarding test seropositivity and seronegativity in detecting immunoglobulin G (IgG) anti-severe acute respiratory syndrome 2 (SARS-CoV-2) antibodies (anti-nucleocapsid (N) and spike (S) proteins). A total of 101 people (30 reverse transcription PCR (RT-PCR)-positive and 71 RT-PCR-negative at the time of the outbreak in November 2020) were tested for anti-IgG antibody titers in April 2021, and the seroprevalence was approximately 40.0-60.0% for residents and 10.0-20.0% for staff, which was almost consistent with the RT-PCR test results that were implemented during the outbreak. The seropositivity for anti-S antibodies showed 90.0% and was almost identical to the RT-PCR positives even after approximately six months of infections, suggesting that the anti-S antibody titer test is reliable for a close assessment of the infection history. Meanwhile, seropositivity for anti-N antibodies was relatively low, at 66.7%. There was one staff member and one resident that were RT-PCR-negative but seropositive for both anti-S and anti-N antibody, indicating overlooked infections despite periodical RT-PCR testing at the time of the outbreak. Our study indicated the impact of transmission of SARS-CoV-2 in a vulnerable elderly nursing home in the pre-vaccination period and the value of a serological study to supplement RT-PCR results retrospectively.

A case of rectal obstruction caused by bilateral internal iliac artery aneurysms.

In this article, we report a rare case of rectal obstruction caused by bilateral internal iliac artery aneurysms that required open surgical repair. A 73-year-old man was admitted to our hospital complaining of abdominal pain and persistent constipation for >1 month. Computed tomography demonstrated bilateral internal iliac artery aneurysms, 5.0 and 7.0 cm each in diameter, which occupied the intrapelvic space. An urgent surgery was performed to reduce the volume of the aneurysms and release the obstructed rectum. The postoperative course was uneventful, in which he had good evacuation. Aneurysms in the iliac region can be a good indication for the use of newly developed endovascular devices; however, open surgery should be considered without delay to avoid ileus or subileus symptoms when the aneurysms cause space-occupying complications.

Alpha-fetoprotein producing ovarian clear cell carcinoma with a neometaplasia to hepatoid carcinoma arising from endometriosis: a case report.

We present a rare case of alpha-fetoprotein (AFP) producing ovarian clear cell carcinoma. This is the first report of a clear cell ovarian carcinoma with hepatoid carcinoma arising from endometriosis. A 54-year-old menopausal woman had a primary ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IIIc. Serum level of AFP was 4195 ng/mL. Histological examination revealed clear cell adenocarcinoma arising from endometriosis with hepatoid carcinoma. Metastatic liver and lymph node tumors were found after 25 months from the first surgery. However, the patient's serum AFP was within normal limits. The recurrent and metastatic tumors disappeared in response to combined liposomal doxorubicin and carboplatin chemotherapy. She has had a disease-free survival of 4 years. In conclusion, the patient had a clear cell ovarian carcinoma with hepatoid carcinoma arising clearly from endometriosis. The recurrent tumors did not show a component of hepatoid carcinoma. Therefore, it is possible to expect better survival with good sensitivity to chemotherapy.

Adjuvant combined paclitaxel and carboplatin chemotherapy for glassy cell carcinoma of the uterine cervix: report of three cases with clinicopathological analysis.

Glassy cell carcinoma of the uterine cervix (GCC) is a rare form of cervical carcinoma that is characterized by aggressiveness and poor prognosis. We reviewed a variety of clinicopathological features, treatment strategies, and outcomes in three women with GCC. The three patients were successfully treated by radical hysterectomy with pelvic/para-aortic lymphadenectomy. The patients had stage Ib1, stage IIa, and stage Ib2 tumors without lymph node metastases. A 44-year-old woman with stage Ib1 tumor did not undergo adjuvant chemotherapy or radiation therapy. She had recurrent pelvic tumors 12 months after surgery, and died 6 months after the recurrent disease. The histological findings of her cervix, which were different from the other two patients, did not show the marked infiltration of eosinophils. The other two patients with stage Ib2 and IIa tumors underwent adjuvant chemotherapy with paclitaxel and carboplatin, and had disease-free survival for 4.5 and 9 years. We think that all patients with GCC of stage Ib1 or more should undergo adjuvant chemotherapy of paclitaxel and carboplatin or other adjuvant therapies.

Genomic Epidemiology Reveals Multiple Introductions of Severe Acute Respiratory Syndrome Coronavirus 2 in Niigata City, Japan, Between February and May 2020.

The coronavirus disease 2019 (COVID-19) has caused a serious disease burden and poses a tremendous public health challenge worldwide. Here, we report a comprehensive epidemiological and genomic analysis of SARS-CoV-2 from 63 patients in Niigata City, a medium-sized Japanese city, during the early phase of the pandemic, between February and May 2020. Among the 63 patients, 32 (51%) were female, with a mean (±standard deviation) age of 47.9 ± 22.3 years. Fever (65%, 41/63), malaise (51%, 32/63), and cough (35%, 22/63) were the most common clinical symptoms. The median C t value after the onset of symptoms lowered within 9 days at 20.9 cycles (interquartile range, 17-26 cycles), but after 10 days, the median C t value exceeded 30 cycles (p < 0.001). Of the 63 cases, 27 were distributed in the first epidemic wave and 33 in the second, and between the two waves, three cases from abroad were identified. The first wave was epidemiologically characterized by a single cluster related to indoor sports activity spread in closed settings, which included mixing indoors with families, relatives, and colleagues. The second wave showed more epidemiologically diversified events, with most index cases not related to each other. Almost all secondary cases were infected by droplets or aerosols from closed indoor settings, but at least two cases in the first wave were suspected to be contact infections. Results of the genomic analysis identified two possible clusters in Niigata City, the first of which was attributed to clade S (19B by Nexstrain clade) with a monophyletic group derived from the Wuhan prototype strain but that of the second wave was polyphyletic suggesting multiple introductions, and the clade was changed to GR (20B), which mainly spread in Europe in early 2020. These findings depict characteristics of SARS-CoV-2 transmission in the early stages in local community settings during February to May 2020 in Japan, and this integrated approach of epidemiological and genomic analysis may provide valuable information for public health policy decision-making for successful containment of chains of infection.

A portable pneumatic compression device to prevent venous thromboembolism in orthopedic patients with the highest risks of both venous thrombosis and bleeding: A case series study.

PURPOSE: There is a pressing need for safe venous thromboembolism (VTE) prophylaxis in orthopedic patients with the highest risks of both venous thrombosis and bleeding. Portable intermittent pneumatic compression device (IPCD) has proven to be effective and safe in patients with a high risk of venous thrombosis and low bleeding risk. Therefore, this study examined the effectiveness, safety, and wearing compliance of portable IPCD for postoperative VTE prophylaxis in patients with the highest risks of both venous thrombosis and bleeding. METHODS: The cases consisted of 38 patients who had used a portable IPCD and had the highest risks of both venous thrombosis and bleeding. We examined the incidence of VTE to assess the effectiveness of the portable IPCD, the presence of hemorrhagic adverse events to assess safety, and the wearing rate to assess wearing compliance. RESULTS: The incidences of asymptomatic and symptomatic deep vein thrombosis were 5.3% and 2.6%, respectively. The incidence of hemorrhagic adverse events was 21.1% in patients who received anticoagulants and wore an IPCD simultaneously and 0% in patients who wore an IPCD but did not receive anticoagulants. The wearing rate (i.e. ≥18 h/day) was 100%. CONCLUSION: Portable IPCD has the potential for safe VTE prophylaxis in patients at high risks for both venous thrombosis and bleeding. Therefore, we suggest that such patients use a portable IPCD for VTE prophylaxis.

MEMS-based wearable eyeglasses for eye health monitoring.

A large number of world population suffer from vision related diseases/defects. Visual health supervision is important for detection, prevention and treatment of eyes disorders. Images of retina/fundus are important for diagnosis of eye diseases. In this paper we report on design and development of a wearable eyeglass type retinal imaging system using a 2D MEMS scanner for ocular health monitoring. Several wearability criteria for instance weight and size factor should be taken into account while designing a wearable health monitoring system. The 2D-MEMS scanner used in the system is small in size, that helps to fabricate an easy to use and lightweight wearable imaging device. The net weight of fabricated system including optical components is 150 g. Sensitivity of the system was estimated by measuring the signal-to-noise ratio for high and low reflectance materials. Signal-to-noise ratio was 7 for high reflectance material and about 4 for biological samples. Imaging results were obtained by scanning a model eye, ham slice and enucleated swine eye in real time by custom made LabVIEW program. The fabricated system has adequate sensitivity and resolution for the observation of retinal arteries and optic disc for detection of eye diseases.

Role of cyclin-dependent kinase 5 in capsaicin-induced cough.

The role of cyclin-dependent kinase 5 (Cdk5) in the capsaicin-induced cough reflex was examined in mice. Pretreatment with inhaled roscovitine, a selective Cdk5 inhibitor, at concentrations of 0.3 to 3 mM inhibited the number of capsaicin-induced coughs in a concentration-dependent manner. Pretreatment with inhaled roscovitine, at a concentration of 3 mM also slightly but significantly inhibited the number of citric acid-induced coughs. The number of capsaicin-induced coughs was significantly reduced when C-fibers were desensitized by the pretreatment with capsaicin. The number of citric acid-induced coughs was slightly but significantly reduced in capsaicin-pretreated mice as compared with that in naive mice. Although the inhalation of roscovitine at a concentration of 3 mM significantly reduced the number of citric acid-induced coughs in naive mice to the level observed in capsaicin-pretreated mice, roscovitine had no effect on the number of citric acid-induced coughs in capsaicin-pretreated mice. These results suggest that Cdk5-dependent factors are involved in C-fiber-mediated cough signaling.

Involvement of ionotropic purinergic receptors in the histamine-induced enhancement of the cough reflex sensitivity in guinea pigs.

We examined the effect of inhaled histamine on citric acid-induced coughs and clarified the role of ionotropic purinergic receptors in the resulting changes. Although the inhalation of 0.1 M citric acid by itself produced only a few coughs in guinea pigs, exposure to histamine, at concentrations of 0.3 to 1 mM, for 2 min concentration dependently increased the number of citric acid-induced coughs. This histamine-induced increase in the number of citric acid-induced coughs was dose dependently and significantly reduced when animals were pretreated with fexofenadine, a histamine H1 receptor antagonist. The histamine-induced increase in the number of citric acid-induced coughs was completely reduced when animals were co-pretreated with 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP, 50 microM), a P2X receptor antagonist, and reactive blue 2, a P2Y receptor antagonist, for 2 min. Furthermore, the ATP-induced increase in the number of citric acid-induced coughs was dose dependently and significantly decreased when animals were pretreated with fexofenadine, at doses of 0.3, 1 and 3 mg/kg, p.o. These results suggest that histamine enhances the excitability of rapidly adapting receptors to tussive stimuli via modulation of ATP release in the airways. Furthermore, ATP might act not only on P2X receptors to directly activate rapidly adapting receptors, but also on P2Y receptors to increase histamine release, indirectly increasing the cough reflex sensitivity.

Novel gender-related regulation of CYP2C12 gene expression in rats.

The expression of CYP2C12 by GH occurs in female but not in male rat livers. Direct injection of the CYP2C12 promoter-luciferase gene into male rat livers showed that the CYP2C12 promoter was active in both male and female rats. Thus, to further examine one or more factors that regulate the gender-related expression of CYP2C12, male rats were treated with trichostatin A, a specific inhibitor of histone deacetylase capable of condensing the chromatin structure. Interestingly, the expression of CYP2C12 by GH was seen even in the livers of male rats, indicating that histone deacetylase contributes to the suppression of CYP2C12 expression in male rats. Deoxyribonuclease I hypersensitive assay using nuclei from the livers of male or female rats revealed that the chromatin structure of the CYP2C12 gene was gender specific: a hypersensitive site at a position -4.2 kb containing GH-responsive element that bound to signal transducer and activator of transcription 5 (STAT5), termed as HS (hypersensitive site) 1, was specific for female rat livers, whereas a hypersensitive site at a position -3 kb, designated as HSm (male-specific hypersensitive site), was characteristic of male rat livers. A -3425/-3275 region within HSm functioned as a negative regulatory region, when the region was inserted in front of simian virus 40 promoter. Gel shift assay demonstrated that both CCAAT/enhancer-binding protein alpha and beta bound to the -3425/-3275 region. Based on these results, we conclude that the gender-related expression of the CYP2C12 gene results from the inaccessibility of to STAT5 to the GH-responsive element by chromatin condensation seen in male rat livers, and from the presence of the male-specific HSm that acts as a silencer.