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Facet cysts in the subaxial cervical spine are a relatively rare cause of neuropathy. This case series aimed to investigate the radiological and histopathological features and surgical results of these lesions, and provide possible mechanisms of cyst development.Thirteen subaxial cervical facet cysts in 12 patients were diagnosed on the basis of magnetic resonance imaging and computed tomography with facet arthrography. Surgical outcomes were evaluated according to the Japanese Orthopaedic Association scores for cervical myelopathy, or Tanaka's scores for cervical radiculopathy. These results were presented in combination with a scoping review of the literature.Seven cysts were found in the posteromedial region, and six in the posterolateral portion of the spinal canal. Computed tomography revealed degeneration of all involved facet joints. All patients underwent decompression, and the mean recovery rates of Japanese Orthopaedic Association scores and Tanaka's scores were 57.1% and 87.5%, respectively. Histopathologically, all cysts were continuous with the degenerated ligamentum flavum. In the scoping review, the patients' mean age was 65.1 years. The cysts were distributed as follows: 3.6% at C2-3, 10.7% at C3-4, 14.3% at C4-5, 5.4% at C5-6, 7.1% at C6-7, and 58.9% at C7-T1. The presenting symptoms were myelopathy (49.4%) and radiculopathy (50.0%). Radiologically, 55% and 45% of the cysts were of the posteromedial and posterolateral types. Of the patients, 76.9% underwent decompression only, and 23.1% had concomitant fusion. Cyst recurrence was not observed in the mean follow-up period of 15.1 months.The pathogenesis of cysts is closely related to degenerative changes in the facet joint and ligamentum flavum, and rupture in degenerated ligaments can develop into a cavity, which contributes to cyst formation. The scoping review suggests that cyst resection generally results in positive outcomes without recurrence in either decompression alone or concomitant fusion.

SUMMARY Unzen volcano, located on Shimabara Peninsula, Nagasaki, Japan, is an active volcano that has been intensively monitored since 1989, one year before the most recent eruption in 1990–1995. Previous earthquake and surface deformation studies have revealed that magma is transported obliquely from a magma reservoir beneath Tachibana Bay, to the west of Shimabara Peninsula. Here, we conduct broad-band magnetotelluric (MT) surveys at 99 sites around Shimabara Peninsula to investigate the crustal structure beneath Unzen volcano that is related to magma migration. A 3-D resistivity model that is constructed from 25 broad-band MT sites and 45 telluric sites shows a broad high-resistivity zone beneath Shimabara Peninsula and low-resistivity zones to the west and east of the peninsula. An unexpected observation is the spatial alignment of the high-resistivity zone with a seismic low-velocity zone (LVZ) at 3–15 km depth. Quantitative analysis indicates this high-resistivity zone contains

Objective: The association between high sugar-sweetened beverages (SSB) intake during pregnancy and offspring overweight/obesity has been reported only from Western countries. The objective of this study was to examine the association between SSB intake before and during pregnancy and offspring overweight/obesity among Japanese women. Design: Japanese prospective birth cohort study. Setting: We analysed mother–offspring pairs who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017. SSB intake during pregnancy was evaluated using the FFQ and classified into three groups: none (0 g/d), medium (195 g/d). Overweight or obesity at 1 year of age in offspring was defined as having a BMI Z-score greater than 2 sd, calculated based on the BMI reference data for Japanese children. Multiple logistic regression analyses were performed to examine the associations between SSB intake before and during pregnancy and offspring overweight/obesity, after adjusting for covariates. Participants: Japanese mother–offspring pairs (n 7114). Results: The overweight/obesity rate of the offspring was 8·8 %. Pregnant women with a high intake of SSB in early to mid-pregnancy had a higher risk of overweight/obesity in their offspring compared with those who did not; the OR was 1·52 (95 % CI (1·09, 2·12)). Conclusions: High SSB intake in early to mid-pregnancy was associated with an increased risk of offspring overweight/obesity at 1 year of age.

Purpose : This study aimed to reveal the clinical features requiring sacroiliac joint (SIJ) arthrodesis, which was performed for patients who complain of severe SIJ pain. Methods : The differences in clinical features between a surgical treatment group (n = 20) and a conservative treatment group (n = 66) were investigated. All patients were definitively diagnosed with SIJ pain by the use of SIJ injections. Results : Six significant features were identified in the surgical treatment group, namely, sitting tolerance (< 15 minutes), walking with a cane, pain in the supine position, pain while lying on the painful side, numbness in the lower limbs, and any accident that induced SIJ pain (P < 0.01). Univariate logistic regression analysis revealed that sitting tolerance < 15 minutes (odds ratio : 31.73), pain in the supine position (13.07), and pain while lying on the painful side (18.30) showed a high odds ratio. Conclusions : Sitting tolerance (< 15 minutes), walking with a cane, pain in the supine position, pain while lying on the painful side, numbness in the lower limbs, and a history of any accident that induced SIJ pain may be considered as indicators for surgery after > 6 months of continued substantial conservative treatment.

Hintergrund: Die chronische myeloische Leukämie ist eine hämatologische Malignität, die mit der Fusion von zwei Genen einhergeht: BCR und ABL1. Diese Fusion resultiert aus einer Translokation zwischen den Chromosomen 9 und 22, auch als Philadelphia Chromosom bekannt. Obwohl das Philadelphia-Chromosom bei mehr als 90% der Patienten mit chronischer myeloischer Leukämie vorhanden ist, weisen 5-8% der Patienten mit chronischer myeloischer Leukämie komplexe Translokationsvarianten auf. Wir berichten hier über einen Fall einer dreifachen Translokationsvariante bei chronischer myeloischer Leukämie in der chronischen Phase. Vorstellung des Falles: Bei einem 40-jährigen asiatischen Mann, der sich mit Leukozytose vorstellte, wurde eine chronische myeloischen Leukämie in chronischer Phase diagnostiziert. Die zytogenetische Karyotypisierungsanalyse ergab 46,XY,t(4;9;22)(q21;q34;q11.2). Er wurde behandelt mit Bosutinib und dann wegen Unverträglichkeit auf Dasatinib umgestellt, und nach 17 Monaten kontinuierlicher Behandlung wurde MR4,5 (BCR-ABL/ABL ≤ 0,0032%, internationale Skala) erreicht. Schlussfolgerung: Dies war der 14. Fall von t(4;9;22), im Speziellen einer neue Variante der Ph-Translokation, bei der das Chromosom 4q21 beteiligt ist, und der erste weltweit erfolgreiche Fall, der mit Tyrosinkinase-Inhibitoren behandelt wurde. Wir fassen frühere Fallberichte über die dreifache Chromosomenverschiebung t(4;9;22) zusammen und erörtern, wie diese seltene Verschiebung mit der Prognose zusammenhängt.

It seems obvious to laypeople that neurotypical humans experience color equivalently across their entire visual field. To some neuroscientists, psychologists, and philosophers, though, this claim has been met with skepticism, as neurophysiological evidence indicates the mechanisms that support color perception degrade with eccentricity. However, the argument that this entails altered color experience in peripheral vision is not universally accepted. Here, we address whether color experience is essentially equivalent between central and peripheral vision. To assess this, we will obtain similarity relationships between color experiences across the visual field using both online and laboratory-based far-field displays, while removing the confounds of saccades, memory, and expectation about color experiences. Our experiment was designed to provide clear evidence that would favor either unchanged or altered color experience relationships in the periphery. Our results are consistent with lay people's phenomenological reports: Color experiences, as probed by similarity relationships in central vision and the far field (60°), are equivalent when elicited by large stimuli. These findings challenge the widespread view in philosophy and cognitive science that peripheral color experiences are illusory, and are discussed in the context of their related neurophysiological, psychophysical, and philosophical literature.

Background/Aim: Concomitant nonalcoholic fatty liver disease (NAFLD)/hepatic steatosis (HS) is suggested to increase the risk of hepatocellular carcinoma (HCC) in hepatitis virus B (HBV)-infected patients. Patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 gene single-nucleotide polymorphism (SNP) is well-known to be associated with the development of NAFLD/HS; however, it is still unclear whether this SNP is related to the development of HCC in HBV-infected patients. Patients and Methods: We investigated a total of 202 HBV-infected patients who received percutaneous liver biopsy, and simultaneously assessed biopsy-proven HS, insulin resistance, and the PNPLA3 SNP status. We further investigated the relationships of these factors with the development of HCC in HBV-infected patients. Results: Most of the enrolled cases (196/202: 97.0%) were non-cirrhotic patients. One hundred seventy-three patients (85.6%) received antiviral therapy. A Kaplan-Meier analysis showed that the incidence of HCC development in patients with HS was higher than that in patients without HS (p

Schwannoma is an uncommon benign tumor in the oral and maxillofacial region, and development of schwannoma in the lower lip is rare. Herein, we present the case of a 68-year-old woman who visited Nihon University Itabashi Hospital complaining of a painless mass in the lower lip. The lesion was surgically resected under local anesthesia. On histopathological examination, the resected specimen was a mixture of Antoni types A and B schwannoma. No recurrence has been seen over a postoperative follow-up period of 58 months. In the schwannoma of the lower lip, the mean tumor volume was compared for type A and the mixed type, which tended to be larger in the mixed type. No previous reports have described the relationship between the size of schwannoma in the lower lip and Antoni classification. Therefore, this report discusses the possibility of a relationship between tumor size and Antoni classification for schwannomas in the lower lip.

The aim of this study was to compare the difference in bone formation between hydroxyapatite (HAp) and β-tricalcium phosphate (β-TCP) ceramics with similar porous structure. Porous HAp and β-TCP ceramics (total porosity: ~70%) with highly-interconnected structure were fabricated by firing calcium-phosphate fiber mixed with carbon beads (~150 μm). The size of highly-interconnected pores was measured by mercury intrusion technique. Each sample (ϕ4 mm × 8 mm) was implanted into the tibial bone defect (ϕ4.2 mm × 8 mm) of a pig (2 years old, male). After 6 weeks of implantation, undecalcified section was prepared and stained with hematoxylin and eosin (HE) stain. New bone area and remaining material area were evaluated.Interconnection sizes of HAp and β-TCP ceramics were 23.0 µm and 15.6 µm, respectively. New bone area of β-TCP ceramics was significantly higher compared to HAp ceramics. Remaining material ratio was 77.1 ± 3.3% for β-TCP ceramics whereas HAp ceramics remained stable. Bone formation in HAp ceramics was inhomogeneous compared to β-TCP ceramics in HE stained section. Although the β-TCP ceramics interconnection size was smaller, higher resorption may have played a positive role in homogeneous bone formation. According to the result of the study, it is suggested that highly-interconnected porous ceramics made by β-TCP could be a suitable material for bone regeneration.

Purpose Depending on its histological subtype, salivary gland carcinoma (SGC) may have a poor prognosis. Due to the scarcity of preclinical experimental models, its molecular biology has so far remained largely unknown, hampering the development of new treatment modalities for patients with these malignancies. The aim of this study was to generate experimental human SGC models of multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques. Methods Tumor specimens from surgically resected SGCs were processed for the preparation of PDXs and patient-derived organoids (PDOs). Specimens from SGC PDXs were also processed for PDX-derived organoid (PDXO) generation. In vivo tumorigenicity was assessed using orthotopic transplantation of SGC organoids. The pathological characteristics of each model were compared to those of the original tumors using immunohistochemistry. RNA-seq was used to analyze the genetic traits of our models. Results Three series of PDOs, PDXs and PDXOs of salivary duct carcinomas, one series of PDOs, PDXs and PDXOs of mucoepidermoid carcinomas and PDXs of myoepithelial carcinomas were successfully generated. We found that PDXs and orthotopic transplants from PDOs/PDXOs showed similar histological features as the original tumors. Our models also retained their genetic traits, i.e., transcription profiles, genomic variants and fusion genes of the corresponding histological subtypes. Conclusion We report the generation of SGC PDOs, PDXs and PDXOs of multiple histological subtypes, recapitulating the histological and genetical characteristics of the original tumors. These experimental SGC models may serve as a useful resource for the development of novel therapeutic strategies and for investigating the molecular mechanisms underlying the development of these malignancies.

This trial evaluated the superiority of intraoperative wound irrigation (IOWI) with aqueous povidone-iodine (PVP-I) compared to that with saline for reducing the incidence of surgical site infection (SSI).IOWI with aqueous PVP-I is recommended for the prevention of SSI by the World Health Organization and Centers for Disease Control and Prevention, although the evidence level is low.This single-institute in Japan, prospective, randomized, blinded-endpoint trial was conducted to assess the superiority of IOWI with aqueous PVP-I in comparison to IOWI with saline for reducing the incidence of SSI in clean-contaminated wounds after gastroenterological surgery. Patients ≥20 years old were assessed for eligibility, and eligible participants were randomized at a 1:1 ratio using a computer-generated block randomization. In the study group, IOWI was performed for one minute with 40 mL of aqueous 10% PVP-I before skin closure. In the control group, the procedure was performed with 100 mL of saline. Participants, assessors, and analysts were masked to the treatment allocation. The primary outcome was the incidence of incisional SSI in the intention-to-treat set.Between June 2019 and March 2022, 941 patients were randomized to the study group (473 patients) or the control group (468 patients). The incidence of incisional SSI was 7.6% in the study group and 5.1% in the control group (risk difference 0.025, 95% CI -0.006 to 0.056; risk ratio 1.484, 95% CI 0.9 to 2.448; P=0.154).The current recommendation of IOWI with aqueous PVP-I should be reconsidered.

We develop a general framework to compute photometric variations induced by the oblique rotation of a star with an axisymmetric inhomogeneous surface. We apply the framework to compute lightcurves of white dwarfs adopting two simple models of their surface inhomogeneity. Depending on the surface model and the location of the observer, the resulting lightcurve exhibits a departure from a purely sinusoidal curve that are observed for a fraction of white dwarfs. As a specific example, we fit our model to the observed phase-folded lightcurve of a fast-spinning white dwarf ZTF J190132.9+145808.7 (with the rotation period of 419s). We find that the size and obliquity angle of the spot responsible for the photometric variation are $\dts \approx 60^\circ$ and $\thetaS \approx 60^\circ$ or $90^\circ$, respectively, implying an interesting constraint on the surface distribution of the magnetic field on white dwarfs., 25 pages, 9 figures, accepted for publication in PASJ

Proton pump inhibitors (PPIs) are potent inhibitors of gastric acid secretion, used as first-line agents in treating peptic ulcers. However, we have previously reported that PPIs may diminish the therapeutic effect of anti-vascular endothelial growth factor (VEGF) drugs in patients with cancer. In this study, we explored the effects of vonoprazan, a novel gastric acid secretion inhibitor used for the treatment of peptic ulcers, on the secretion of VEGF in cancer cells and attempted to propose it as an alternative PPI for cancer chemotherapy. The effects of PPI and vonoprazan on VEGF expression in cancer cells were compared by real-time reverse transcription-polymerase chain reaction and ELISA. The interaction of vonoprazan and PPIs with transcriptional regulators by docking simulation analysis. In various cancer cell lines, including the human colorectal cancer cell line (LS174T), PPI increased VEGF messenger RNA expression and VEGF protein secretion, while this effect was not observed with vonoprazan. Molecular docking simulation analysis showed that vonoprazan had a lower binding affinity for estrogen receptor alpha (ER-α), one of the transcriptional regulators of VEGF, compared to PPI. Although the PPI-induced increase in VEGF expression was counteracted by pharmacological ER-α inhibition, the effect of vonoprazan on VEGF expression was unchanged. Vonoprazan does not affect VEGF expression in cancer cells, which suggests that vonoprazan might be an alternative to PPIs, with no interference with the therapeutic effects of anti-VEGF cancer chemotherapy.

Twinning and detwinning behavior of a commercial AZ31 magnesium alloy during cyclic compression–tension deformation with a total strain amplitude of 4% (±2%) was evaluated using the complementary techniques of in-situ neutron diffraction, identical area electron backscatter diffraction, and transmission electron microscopy. In-situ neutron diffraction demonstrates that the compressive deformation was dominated by twin nucleation, twin growth, and basal slip, while detwinning dominated the unloading of compressive stresses and subsequent tension stage. With increasing number of cycles from one to eight: the volume fraction of twins at -2% strain gradually increased from 26.3% to 43.5%; the residual twins were present after 2% tension stage and their volume fraction increased from zero to 3.7% as well as a significant increase in their number; and the twinning spread from coarse grains to fine grains involving more grains for twinning. The increase in volume fraction and number of residual twins led to a transition from twin nucleation to twin growth, resulting in a decrease in yield strength of compression deformation with increasing cycles. A large number of -component dislocations observed in twins and the detwinned regions were attributed to the dislocation transmutation during the twinning and detwinning. The accumulation of barriers including twin boundaries and various types of dislocations enhanced the interactions of migrating twin boundary with these barriers during twinning and detwinning, which is considered to be the origin for increasing the work hardening rate in cyclic deformation of the AZ31 alloy.

Introduction: As the high mortality rate of gastric cancer (GC) is due to delayed diagnosis, early detection is vital for improved patient outcomes. Metabolic deregulation plays an important role in GC. Although various metabolite-level biomarkers for early detection have been assessed, there is still no unified early detection method. We conducted a plasma metabolome study to assess metabolites that may distinguish GC samples from non-GC samples. Methods: Blood samples were collected from 72 GC patients and 29 control participants (non-GC group) at the Tokyo Medical University Hospital between March 2020 and November 2020. Hydrophilic metabolites were identified and quantified using liquid chromatography-time-of-flight mass spectrometry. Differences in metabolite concentrations between the GC and non-GC groups were evaluated using the Mann-Whitney test. The discrimination ability of each metabolite was evaluated by the area under the receiver operating characteristic curve. A radial basis function (RBF) kernel-based support vector machine (SVM) model was developed to assess the discrimination ability of multiple metabolites. The selection of variables used for the SVM utilized a step-wise regression method. Results: Of the 96 quantified metabolites, 8 were significantly different between the GC and non-GC groups. Of these, N1-acetylspermine, succinate, and histidine were used in the RBF-SVM model to discriminate GC samples from non-GC samples. The area under the curve (AUC) of the RBF-SVM model was higher (0.915; 95% CI: 0.865–0.965, p < 0.0001), indicating good performance of the RBF-SVM model. The application of this RBF-SVM to the validation dataset resulted from the AUC of the RBF-SVM model was (0.885; 95% CI: 0.797–0.973, p < 0.0001), indicating the good performance of the RBF-SVM model. The sensitivity of the RBF-SVM model was better (69.0%) than those of the common tumor markers carcinoembryonic antigen (CEA) (10.5%) and carbohydrate antigen 19-9 (CA19-9) (2.86%). The RBF-SVM showed a low correlation with CEA and CA19-9, indicating its independence. Conclusion: We analyzed plasma metabolomics, and a combination of the quantified metabolites showed high sensitivity for the detection of GC. The independence of the RBF-SVM from tumor markers suggested that their complementary use would be helpful for GC screening.

In general, randomly oriented ice crystallites are formed by heating amorphous solid water (ASW) films at ∼160 K via homogeneous nucleation. Here, we demonstrate that monolayers of methanol and 1-propanol additives incorporated in the multilayer ASW film lead to heterogeneous nucleation at the substrate interface of Pt(111), as evidenced by the occurrence of epitaxial ice growth. The mobility of water in direct contact with the Pt(111) substrate is decreased relative to that in the bulk, but it can be increased via interactions with hydrophobic moieties of alcohols that are segregated to the interfacial region. As a result, heterogeneous nucleation occurs at ca. 160 K along with homogeneous nucleation in the film interior. However, the template effect is quenched when the alcohols are in direct contact with the substrate. The methanol adspecies deposited onto the ASW film surface induces heterogeneous nucleation at a temperature as low as 145 K, but the 1-propanol adspecies has no such an effect. Their different ability of heterogeneous nucleation at the free ASW film surface, as well as their uptake behaviors in the near surface region, is associated with the hydrophobic hydration of the alcohols resulting from different lengths of the aliphatic moiety.

Background/Aim: Treatment options for unresectable cholangiocarcinoma are limited. The aim of the study was to evaluate the clinical outcomes of definitive external-beam radiation therapy (EBRT) for patients with unresectable cholangiocarcinoma. Patients and Methods: Patients with unresectable primary cholangiocarcinoma, or local recurrent cholangiocarcinoma after primary surgery, without distant metastasis who received definitive EBRT (≥45 Gy) between January 2006 and December 2020 at our Institution were analyzed retrospectively. EBRT was basically performed using conventional fractionation (1.8-2 Gy per fraction). Prophylactic nodal irradiation was not performed. Results: A total of 21 consecutive patients were analyzed: 7 primary and 14 recurrent cases. The median age was 70 (range=38–85) years at initiation of EBRT. A median dose of 54 (range=45-60) Gy comprising 1.8 (range=1.8-3) Gy per fraction was administered to the primary/recurrent local tumor site. The median follow-up period was 21.6 months. The 2-year overall survival, cause-specific survival, progression-free survival, and local recurrence-free rates were 35.7, 35.7, 16.1, and 32.7%, respectively. Long-term local control (>2 years after EBRT) was achieved in 19.0%. Grade 3 toxicities related to EBRT were observed in 4.8% (duodenum hemorrhage). No grade 4 or higher toxicities were observed. Conclusion: Definitive EBRT for unresectable cholangiocarcinoma was feasible and achieved long-term local control in a subset of patients. As the avoidance of local recurrence may lead to the benefits of prolonging biliary patency and subsequently alleviating the need for an invasive procedure for biliary drainage, EBRT could be one sustainable therapeutic option for patients with unresectable cholangiocarcinoma.

Potassium (K) fertilizer consumption in rice production has increased in developing countries where negative K balance was observed, but it has recently decreased in Japan. This situation raises a question of how K fertilization is managed in Japanese paddy fields and how it affects soil K balance and soil K status. Rice straw (RS) is a good source of K, and RS recycling after harvesting is a common practice in Japan. However, in mixed crop–livestock systems, RS is taken at harvesting time to use as the feed for cows and substituted with the application of cow dung compost (CDC) to the fields. We investigated soil K balance and soil K status in 8 (2017) and 10 (2018) pairs of adjacent RS- and CDC-treated fields in Mamurogawa, Yamagata, Japan. The K balance was calculated from K inputs (RS or CDC, fertilizer, and irrigation water) and K outputs (plant uptake and leaching). K fertilizer application varied widely in both treatments, with no significant difference between RS and CDC fields. K fertilizer was applied in amounts lower than those recommended for paddy rice in the study area in 56% of the fields in both treatments. The K balance was positive in most fields with RS recycling even if K fertilizer application was lower than recommended, but it was negative in half of the fields where RS was substituted with CDC. Most fields in the RS treatment had higher soil exchangeable K than the standard value for fertile soil. Therefore, K input through RS is sufficient for maintaining positive K balance, whereas K input in the CDC treatment from CDC or fertilizer may need to be increased to ensure positive K balance.

Lipopolysaccharide (LPS) treatment induced hemophagocytic lymphohistiocytosis in senescence-accelerated mice (SAMP1/TA-1), but not in senescence-resistant control mice (SAMR1). SAMP1/TA-1 treated with LPS exhibited functional impairment of the hematopoietic microenvironment, which disrupted the dynamics of hematopoiesis. Macrophages are a major component of the bone marrow (BM) hematopoietic microenvironment, which regulates hematopoiesis. Qualitative and quantitative changes in activated macrophages in LPS-treated SAMP1/TA-1 are thought to contribute to the functional deterioration of the hematopoietic microenvironment. Thus, we examined the polarization of pro-inflammatory (M1) and anti-inflammatory (M2) macrophages, and the dynamics of macrophage production in the BM of SAMP1/TA-1 and SAMR1 after LPS treatment. After LPS treatment, the proportions of M1 and M2 macrophages and the numbers of macrophage progenitor (CFU-M) cells increased in both SAMP1/TA-1 and SAMR1. However, compared to the SAMR1, the increase in the M1 macrophage proportion was prolonged, and the increase in the M2 macrophage proportion was delayed. The increase in the number of CFU-M cells was prolonged in SAMP1/TA-1 after LPS treatment. In addition, the levels of transcripts encoding an M1 macrophage-inducing cytokine (interferon-γ) and macrophage colony-stimulating factor were markedly increased, and the increases in the levels of transcripts encoding M2 macrophage-inducing cytokines (interleukin (IL)-4, IL-10, and IL-13) were delayed in SAMP1/TA-1 when compared to SAMR1. Our results suggest that LPS treatment led to the severely imbalanced polarization of activated M1/M2 macrophages accompanied by a prolonged increase in macrophage production in the BM of SAMP1/TA-1, which led to the impairment of the hematopoietic microenvironment, and disrupted the dynamics of hematopoiesis.

Cetirizine, a second-generation antihistamine, and diphenhydramine, a first-generation antihistamine, are among the most widely used anti-allergic drugs. In addition to longer duration of action and less incidence of sedative side effects, recent clinical studies also indicate a higher potency of cetirizine than diphenhydramine in the treatment or prevention of allergic disorders. In the present study, using the differential-interference contrast (DIC) microscopy, we examined the effects of cetirizine and diphenhydramine (1 μM to 1 mM) on the degranulation from rat peritoneal mast cells. Using fluorescence imaging of a water-soluble dye, lucifer yellow, we also examined their effects on the deformation of the plasma membrane. At relatively higher concentrations (100 μM, 1 mM), both cetirizine and diphenhydramine significantly reduced the numbers of degranulating mast cells. Of note, at 1 mM, cetirizine more markedly reduced the number than diphenhydramine, almost entirely suppressing the degranulation of mast cells. Additionally, 1 mM cetirizine and levocetirizine, another second-generation antihistamine, almost totally inhibited the process of exocytosis in mast cells and washed out the trapping of the lucifer yellow on the cell surface, while diphenhydramine and chlorpheniramine, another first-generation antihistamine, did not. This study provided in vitro evidence for the first time that cetirizine more potently inhibited the process of exocytosis in mast cells than diphenhydramine, indicating its higher potency as a mast cell-stabilizer. Such mast cell-stabilizing property of cetirizine could be ascribed to its counteracting effect on the plasma membrane deformation in degranulating mast cells.