Minimal impact of low-density lipoprotein apheresis on vancomycin serum concentration: A case report.

Low-density lipoprotein apheresis (LDL-A) is a blood purification therapy used to treat refractory ulcers in patients with arteriosclerosis obliterans. We describe a case of vancomycin treatment in a patient undergoing maintenance hemodialysis and LDL-A therapy and assess its impact on serum vancomycin concentration. The patient underwent LDL-A twice a week (Mondays and Fridays) and maintenance dialysis three times a week (Tuesdays, Thursdays, and Saturdays) for diabetic nephropathy associated with type 1 diabetes mellitus. Following the wound culture results, vancomycin was initiated with a 1.75 g administration post-dialysis. Serum vancomycin levels before and after LDL-A, measured on the subsequent day, exhibited only slight fluctuations within the intermeasurement variability range. Despite continuing vancomycin administration at the standard dose in patients undergoing hemodialysis, the serum concentration remained consistent, suggesting a minimal impact of LDL-A on vancomycin pharmacokinetics.

A novel test for type-I allergy based on crosslink formation of immunoglobulin-E receptors by allergen-specific immunoglobulin-E antibodies and an allergen.

Detection of allergen-specific immunoglobulin E (IgE) antibodies (Abs) in serum would allow for screening of the causative allergen in patients with type-I allergy. In this study, we developed a new assay method to detect allergen-specific IgE Abs, which involved crosslinking the plural FcεRIα molecules with an allergen and detection using an amplified luminescence proximity homogeneous assay (AlphaCL). First, the allergen concentration, bead concentrations, and incubation time were optimized for the detection of anti-2,4-dinitrophenyl (DNP) IgE Abs in buffer. Under optimal conditions, AlphaCL was able to detect DNP-specific IgE Abs in simulated human serum at levels comparable to those in serum from type-I allergic patients. When AlphaCL was used to detect anti-DNP IgE Abs, no signal counts were obtained with the monovalent allergen 2,4-dinitrophenylated poly-γ-glutamic acid, whereas high signal counts were obtained with the multivalent allergen DNP-BSA. This confirmed that AlphaCL could specifically detect allergen-specific IgE Abs with the ability to crosslink a multivalent allergen. In summary, we have established a new assay model using AlphaCL to detect allergen-specific IgE Abs with FcεRIα crosslinking ability in human serum. This simple and practical assay model may be applied as a new diagnostic tool for patients with type-I allergy.

Extravasation of Noncytotoxic Agents: Skin Injury and Risk Classification.

Extravasations are common manifestations of iatrogenic injuries associated with intravenous therapy. Cytotoxic agents are already subject to a relatively well-defined management strategy in healthcare institutions and classified into three groups according to the extent of damage from extravasation: vesicants, irritants, and non-tissue-damaging agents. Therefore, careful monitoring and initial treatment according to the severity of the skin injury decreases the incidence of extravasation injury. In contrast, high osmolarity, acidic or alkaline, and/or vasoconstrictive activity have all been suggested as possible causes of tissue injury due to the extravasation of noncytotoxic agents. However, the severity of the injuries has not been classified. Therefore, due to a lack of awareness, case reports of severe extravasation injury caused by noncytotoxic agents are increasing. In this paper, we review case reports and animal experiments and classify the severity of extravasation injury by noncytotoxic agents into three categories. Parallel to cytotoxic agents, the classification provides appropriate warning of possible injury severity, helping medical personnel better understand the severity of tissue damage and prevent injury severity during extravasation.

A Narrative Mini Review on Current Status of Hypoallergenic Wheat Development for IgE-Mediated Wheat Allergy, Wheat-Dependent Exercise-Induced Anaphylaxis.

Immunoglobulin E (IgE)-mediated food allergies to wheat that develop after school age typically shows a type of wheat-dependent exercise-induced anaphylaxis (WDEIA). At present, avoidance of wheat products or postprandial rest after ingesting wheat is recommended for patients with WDEIA, depending on the severity of the allergy symptoms. ω5-Gliadin has been identified as the major allergen in WDEIA. In addition, α/ß-, γ-, and ω1,2-gliadins, high and low molecular weight-glutenins, and a few water-soluble wheat proteins have been identified as IgE-binding allergens in a small proportion of patients with IgE-mediated wheat allergies. A variety of approaches have been manufactured to develop hypoallergenic wheat products that can be consumed by patients with IgE-mediated wheat allergies. In order to analyze such approaches, and to contribute to the further improvement, this study outlined the current status of these hypoallergenic wheat productions, including wheat lines with a reduced allergenicity that are mostly constructed for the patients sensitized to ω5-gliadin, hypoallergenic wheat by enzymic degradation/ion exchanger deamidation, and hypoallergenic wheat by thioredoxin treatment. The wheat products obtained by these approaches significantly reduced the reactivity of Serum IgE in wheat-allergic patients. However, either these were not effective on some populations of the patients, or low-level IgE-reactivity to some allergens of the products was observed in the patients. These results highlight some of the difficulties faced in creating hypoallergenic wheat products or hypoallergenic wheat lines through either traditional breeding or biotechnology approaches in developing hypoallergenic wheat completely safe for all the patients allergic to wheat.

Influence of discontinuation of prophylactic antimicrobial agent for trabeculectomy.

BACKGROUND: There is no unified view of the necessity of prophylactic antimicrobial agents in trabeculectomy. Preoperative prophylactic antimicrobial agent injection and cefazolin sodium (CEZ) for trabeculectomy were discontinued at the Hiroshima University Hospital. In this study, we evaluated whether discontinuation of preoperative administration of CEZ in ophthalmology affects the incidence of postoperative infections. METHODS: We retrospectively investigated patient background, concomitant medications, subconjunctival dexamethasone sodium phosphate (DEX) injection at the end of the surgery, and the incidence of infective endophthalmitis within 6 weeks after surgery in the CEZ and non-CEZ groups. We also performed propensity score matching for background matching. Statistical analysis was performed using the Mann-Whitney U-test and Fisher's exact test. RESULTS: The incidence of postoperative endophthalmitis was not significantly different between 629 and 751 patients in the CEZ and no-CEZ groups, respectively (0 in the CEZ group and 2 in the no-CEZ group, P = 0.504). More patients in the CEZ group were taking diabetes drugs preoperatively (P = 0.028) and fewer patients were receiving subconjunctival DEX at the end of surgery (P < 0.001) than those in the non-CEZ group. Propensity scores were calculated using the risk factors for postoperative infection as covariates, and matching (580 patients in the CEZ group and 580 patients in the non-CEZ group) showed no significant difference in the incidence of postoperative endophthalmitis (P = 0.500). CONCLUSIONS: There was no significant difference in the incidence of endophthalmitis after trabeculectomy between the CEZ and non-CEZ groups, suggesting a decreased need for CEZ injections before trabeculectomy.

Classification of Skin Injury Risk Caused by Extravasation of Electrolyte Solutions or Infusions in a Rat Model.

Cytotoxic agents are classified according to the severity of skin injury after extravasation. However, injuries caused by extravasation of noncytotoxic agents have not been sufficiently investigated, although the risk of extravasation is mentioned in medical safety information published by the Japan Council for Quality Health Care. Therefore, in this study, we focused on noncytotoxic electrolyte solutions and infusions and evaluated skin injuries during leakage using extravasation model rats. Rats were anesthetized and intradermally injected with 100 µL of an electrolyte solution or infusion. Injection lesions were macroscopically and histopathologically evaluated for extravasation injuries. Each electrolyte solution and infusion were classified into three categories (vesicants, irritants, and non-tissue-damaging agents) depending on the degree of skin injury. Similar to saline, 0.3% potassium chloride and 0.6% magnesium sulfate showed almost no injury, and 3% sodium chloride and BFLUID® caused erythema and induration. Erythema, induration, and ulceration were observed with the following: 10% sodium chloride, 2% calcium chloride, 8.5% calcium gluconate, 12.3% magnesium sulfate, MAGSENT®, FESIN®, and Intralipos®. The duration of damage with these agents was markedly prolonged. Electrolyte solutions and infusions can be classified into vesicants (10% sodium chloride, 2% calcium chloride, 8.5% calcium gluconate, 12.3% magnesium sulfate, MAGSENT®, FESIN®, and Intralipos®), irritants (3% sodium chloride and BFLUID®), and non-tissue-damaging agents (0.3% potassium chloride and 0.6% magnesium sulfate) according to their composition. The characteristic symptoms and severity of each drug extravasation revealed in this study will provide basic information for preparation of guidelines for treatment of extravasation.

Hypoallergenic Wheat Line (1BS-18H) Lacking ω5-Gliadin Induces Oral Tolerance to Wheat Gluten Proteins in a Rat Model of Wheat Allergy.

The early ingestion of food can prevent the onset of food allergy related to inducing oral tolerance (OT). We developed the Hokushin wheat line as a hypoallergenic wheat (1BS-18H) lacking ω5-gliadin, a major allergen of wheat-dependent exercise-induced anaphylaxis (WDEIA). The 1BS-18H wheat had lower ability of sensitization for ω5-gliadin compared with Hokushin wheat. Here, we evaluated the induction of OT to gluten and ω5-gliadin by the early consecutive ingestion of 1BS-18H gluten using a rat model of wheat allergy. Rats were subcutaneously immunized with commercial gluten or native ω5-gliadin following the daily oral administration of gluten. The daily oral administration of 1BS-18H gluten for 5 days before immunization suppressed the increase in gluten- or ω5-gliadin-specific IgE and IgG1 antibodies induced by immunization to a level similar to Hokushin gluten. Intravenous challenge with gluten or ω5-gliadin did not decrease the rectal temperature in rats with OT induced by 1BS-18H or Hokushin gluten, although it was decreased in non-OT rats. In conclusion, the early consecutive ingestion of 1BS-18H wheat before sensitization induced OT to gluten and ω5-gliadin. These findings support the benefit of 1BS-18H wheat to prevent wheat allergy including WDEIA by consecutive ingestion in humans.

A novel detection method for cross-linking of IgE-receptors by autoantibodies in chronic spontaneous urticaria.

BACKGROUND: Autoantibodies (AAbs) against immunoglobulin E (IgE) antibodies (Abs) and their high-affinity receptor alpha subunits (FcεRIα) are key factors in the elicitation of type IIb autoimmune chronic spontaneous urticaria (type IIb aiCSU). In this study, we aimed to develop a new method to detect functional anti-FcεRIα and anti-IgE AAbs, which can crosslink the plural FcεRІα molecules and IgE Abs on the surface of mast cells and basophils, in sera from aiCSU patients using the amplified luminescence proximity homogeneous assay (Alpha). METHODS: Sera were obtained from 14 aiCSU patients, as diagnosed by recurrent chronic spontaneous urticaria episodes and positive results for the autologous serum skin test and/or histamine release test (HRT). The AAbs to FcεRIα and IgE Abs were determined in sera from aiCSU patients using enzyme-linked immunosorbent assay (ELISA) and Alpha by cross-linking (AlphaCL) of IgE Abs and/or FcεRІα. RESULTS: Serum anti-FcεRIα and anti-IgE AAb levels were not significantly different between aiCSU patients and healthy subjects in ELISA. Anti-FcεRIα AAbs were detected in 10 of 14 aiCSU patients who displayed positive (5/5) and negative (5/9) results in the HRT for anti-FcεRIα AAbs by AlphaCL, whereas no signals were observed in healthy subjects. Additionally, anti-IgE AAbs were detected in two of four aiCSU patients who displayed positive results in the HRT for anti-IgE AAbs. CONCLUSIONS: A new assay method using AlphaCL can detect anti-FcεRIα and anti-IgE AAbs with FcεRIα- and IgE-crosslinking abilities in sera from aiCSU patients. This simple and practical assay method may be available as a diagnostic tool for urticaria patients.

Differences in Pharmaceutical Intervention Triggers for the Optimization of Medication by Patient Age: A University Hospital Study.

Optimization of medication therapy for the elderly is a matter of rapidly growing importance, which is addressed by pharmacists through comprehensive reviews. In this study, the impact of medication review by pharmacists on medication optimization and avoidance of adverse drug events (ADE) was investigated, as well as differences in the triggers for pharmaceutical intervention to allow for optimization of medication by patient age. Data for this study were collected from reports recorded between April 2013 and March 2019 for patients admitted to the Hiroshima University Hospital. In response to pharmacists' proposals, prescriptions were modified in 18932 cases, comprising 17% of the total 111479 patients during hospitalization. The frequency of such intervention was higher in elderly patients aged ≥65 years than in those <65 years (20 vs. 14%, p < 0.01). The reasons for pharmacists' intervention were primarily (67%) medication history or clinical symptoms in all age groups. Patient complaint was a minor reason in patients aged ≥75 years, accounting for only 2% of all interventions; laboratory results were a more typical reason, accounting for 24% of all interventions. These findings reveal the importance of pharmacists' interventions for optimizing medication and preventing ADEs, particularly in elderly patients. Thus, pharmacists must evaluate the medications and conditions, including laboratory results, in the medical records of elderly patients more carefully than those of younger patients as elderly patients might be unable to communicate about subjective symptoms.

Identification of allergens for food-dependent exercise-induced anaphylaxis to shrimp.

Shrimp is a causative food that elicits food-dependent exercise-induced anaphylaxis (FDEIA). In this study, we sought to identify IgE-binding allergens in patients with shrimp-FDEIA. Sera were obtained from eight patients with shrimp-FDEIA and two healthy control subjects. Proteins were extracted from four shrimp species by homogenization in Tris buffer. Immunoblot analysis revealed that IgE from patient sera bound strongly to a 70-kDa and a 43-kDa protein in a preparation of Tris-soluble extracts from Litopenaeus vannamei. Mass spectrometry identified the 70-kDa and 43-kDa proteins as a P75 homologue and fructose 1,6-bisphosphate aldolase (FBPA), respectively. To confirm that the putative shrimp allergens were specifically recognized by serum IgE from shrimp-FDEIA patients, the two proteins were purified by ammonium sulfate precipitation followed by reversed-phase HPLC and/or anion-exchange hydrophobic interaction chromatography and then subjected to immunoblot analysis. Purified P75 homologue and FBPA were positively bound by serum IgE from one and three, respectively, of the eight patients with shrimp-FDEIA, but not by sera from control subjects. Thus, P75 homologue and FBPA are identified as IgE-binding allergens for shrimp-FDEIA. These findings could be useful for the development of diagnostic tools and desensitization therapy for shrimp-FDEIA patients.

Low Serum Albumin Level Is a Risk Factor for Delayed Methotrexate Elimination in High-Dose Methotrexate Treatment.

BACKGROUND: In high-dose methotrexate (HD-MTX) therapy, delayed elimination of MTX from plasma leads to severe adverse effects. However, the risk factors for the delayed elimination of plasma MTX are still unclear. OBJECTIVE: The purpose of this study was to investigate the factors related to the delayed MTX elimination in HD-MTX monotherapy. METHODS: This retrospective study was performed on patients who received HD-MTX monotherapy between April 2009 and March 2019 at the Hiroshima University Hospital. Patients were divided into a "Normal" and a "Delayed" group according to their MTX plasma concentration at 48 or 72 hours after administration. Patient characteristics, dose of HD-MTX, MTX plasma concentration, and adverse effects were analyzed and compared between the 2 groups. RESULTS: A total of 74 patients were included in this study. Logistic analysis of patient baseline characteristics was performed to identify risk factors for delayed MTX elimination. Serum albumin (ALB) was detected as a risk factor. Univariate and multivariate analysis revealed that low ALB level (<3.7 g/dL) and type of cancer were associated with delayed MTX elimination (univariate analysis: odds ratio [OR] = 6.00, P = 0.004, and OR = 4.33, P = 0.039, respectively; multivariate analysis: adjusted OR [AOR] = 6.45, P = 0.006, and AOR = 8.11, P = 0.018, respectively). Adverse effects were not significantly different between the 2 groups, excluding renal impairment. CONCLUSIONS AND RELEVANCE: Our study showed that low ALB is a risk factor for delayed MTX elimination in HD-MTX monotherapy. Pharmacokinetic analysis is needed to establish the dose of HD-MTX in patients with a low ALB level.

Identification of peroxidase-1 and beta-glucosidase as cross-reactive wheat allergens in grass pollen-related wheat allergy.

BACKGROUND: Some patients with wheat-dependent exercise-induced anaphylaxis (WDEIA) or wheat allergy showed negative ω-5 gliadin-specific IgE test and high level of grass pollen-specific IgE. It was presumed that these patients developed allergic reaction upon cross-reaction of their IgE antibodies raised against grass pollen allergens to wheat allergens. This study aimed to clarify clinical characteristics and wheat allergens of this phenotype of WDEIA/wheat allergy, which were tentatively diagnosed as grass pollen-related wheat allergy (GPWA). METHODS: A total of six patients with GPWA were enrolled, and controls were 17 patients with grass pollen allergy but no episode of wheat allergy, and 29 patients with other wheat allergies: 18 with conventional WDEIA and 11 with hydrolyzed wheat protein allergy. Sensitization to wheat proteins was determined by basophil activation test (BAT). IgE-binding proteins in wheat flour were identified by immunoblotting followed by mass spectrometry. Wheat allergen-specific IgE tests were established by CAP-FEIA system. RESULTS: All the six patients with GPWA were sensitized to water-soluble wheat proteins in BAT and IgE-immunoblotting, and peroxidase-1 (35 kDa) and beta-glucosidase (60 kDa) were identified as specific IgE-binding wheat proteins. The binding of patient IgE to these proteins was inhibited by pre-incubation of patient sera with grass pollen. The peroxidase-1- and beta-glucosidase-specific IgE tests identified three and four of six patients with GPWA, respectively, but only two of 29 controls, indicating high specificity of these tests. CONCLUSIONS: Peroxidase-1 and beta-glucosidase are specific wheat allergens for GPWA among grass pollen allergy and other types of wheat-induced food allergies.

Impact of systemic steroid treatment on talc pleurodesis: a report of six cases.

BACKGROUND: Instillation of sterile graded talc in the pleural space is performed to prevent reaccumulation of malignant pleural effusion after drainage. Talc is thought to encourage pleural adhesions as part of the repair process by provoking inflammation, suggesting that adhesions are less likely to form in patients taking corticosteroids or other drugs with anti-inflammatory effects. However, the relationship between steroid therapy and pleurodesis efficacy remains unclear. CASE PRESENTATION: We report the outcomes of six patients who underwent pleurodesis at Hiroshima University Hospital while being treated with systemic steroid therapy for non-cancer-related illnesses. Talc pleurodesis was successful at the first attempt in five of the six patients. The five successful cases were receiving low-dose oral prednisolone or methyl prednisolone (range, 1-20 mg/day) at the time of pleurodesis and had serum albumin levels ranging from 2.2 to 3.0 g/dL. In contrast, the patient in whom pleurodesis was unsuccessful was receiving a higher dose of prednisolone (40 mg/day) intravenously and had a relatively low serum album level (1.7 g/dL). CONCLUSIONS: The outcome of pleurodesis may be affected by the dose and/or route of systemic steroid therapy. Further analysis with more patients will be necessary to clarify the relationship between steroid dosage and talc pleurodesis success rate.

Exercise-induced allergic reactions on desensitization to wheat after rush oral immunotherapy.

BACKGROUND: The effect of oral immunotherapy (OIT) on wheat allergy is promising in terms of the potential to obtain desensitization; however, the frequency of exercise-induced allergic reactions on desensitization (EIARDs) and the associated risk factors remain to be determined. METHODS: Twenty-five patients underwent rush OIT for wheat allergy, and 21 achieved the full-dose intake of wheat products (5 g of wheat protein). Exercise-provocation tests were repeatedly performed after the ingestion of a full-dose wheat product. The time-course of the levels of the specific IgEs (sIgE) to wheat extract, total gliadin, deamidated gliadin, recombinant gliadin components (α/ß-, γ- and ω-5-), and glutenin (high and low molecular weight) components was analyzed using ImmunoCAP® , ELISA, or IgE immunoblotting. RESULTS: Fourteen patients (66.7%) were diagnosed as EIARD+, which remained 5 years after rush OIT in 11 patients (52.4%). There were no differences in the clinical backgrounds of the EIARD+ and EIARD- patients. However, EIARD+ patients showed significantly higher sIgE levels to all gliadin and glutenin components than EIARD- patients before OIT. The sIgE levels to each component decreased equally after 1 and 2 years of OIT. On IgE immunoblotting, sera from all patients reacted to the multiple gluten bands, and some reacted to the water-soluble bands. The intensity of all IgE-reactive bands also became equally lighter after OIT. CONCLUSIONS: EIARDs were frequently observed and remained for a long period after successful OIT for wheat allergy. None of the specific wheat components were found to contribute to EIARDs.

Aspirin enhances sensitization to the egg-white allergen ovalbumin in rats.

Enhancement of oral absorption of food allergens by non-steroidal anti-inflammatory drugs (NSAIDs), especially aspirin, is considered an exacerbating factor in the development of food allergies. In this study, we examined the effect of aspirin on oral sensitization to and absorption of the egg-white allergen ovalbumin (OVA) in rats. The absorption of OVA was evaluated by measuring the plasma concentration of OVA after oral administration by gavage. To evaluate oral sensitization to OVA, plasma levels of immunoglobulin (Ig) E and IgG1 antibodies (Abs) specific to OVA were determined by enzyme-linked immunosorbent assay after initiation of sensitization. High-dose aspirin (30 mg/kg) increased oral OVA absorption and plasma levels of OVA-specific IgE and IgG1 Abs compared with those observed in vehicle-treated rats. In contrast, low-dose aspirin (3 mg/kg) exerted no changes in either absorption or sensitization. Spermine, an absorption enhancer, increased the oral absorption of OVA to nearly the same extent as high-dose aspirin, whereas the plasma levels of OVA-specific IgE and IgG1 Abs exhibited no significant differences between spermine- and vehicle-treated rats. Among the NSAIDs, diclofenac and indomethacin increased sensitization to OVA, similar to high-dose aspirin, but meloxicam exerted no effects on Ab levels. In conclusion, we showed that high-dose aspirin enhanced oral sensitization to OVA. Our study suggests that enhanced oral sensitization to OVA cannot be ascribed to increased absorption of OVA from the intestinal tract. Although the mechanisms underlying this enhancement of sensitization are still controversial, our study suggests that modification of cytokine production due to impairment of the intestinal barrier function and inhibition of cyclooxygenase-1 activity by aspirin may be involved.

Evaluation of the allergenicity of ω5-gliadin-deficient Hokushin wheat (1BS-18) in a wheat allergy rat model.

We previously developed Hokushin wheat line as a hypoallergenic wheat lacking ω5-gliadin (1BS-18), a major allergen for wheat-dependent exercise-induced anaphylaxis. However, the allergenicity of 1BS-18 has not been understood completely. In this study, we evaluated the allergenicity of 1BS-18 such as anaphylactic elicitation ability and sensitization ability using rats sensitized with ω5-gliadin or glutens prepared from Hokushin (Hokushin gluten) or 1BS-18 (1BS-18 gluten). Rats were sensitized by intraperitoneal administration of ω5-gliadin, Hokushin gluten or 1BS-18 gluten. Immunoglobulin E-mediated systemic anaphylaxis was evaluated by measuring changes in rectal temperature for 30 min after intravenous challenge with ω5-gliadin or the test glutens in unsensitized rats or rats sensitized with ω5-gliadin or the test glutens. In ω5-gliadin-sensitized rats, intravenous challenge with ω5-gliadin or Hokushin gluten significantly decreased the rectal temperature at 30 min after challenge while challenge with 1BS-18 gluten did not reduce the rectal temperature. Furthermore, intravenous challenge with ω5-gliadin significantly decreased the rectal temperature in rats sensitized with Hokushin gluten or 1BS-18 gluten. However, the reduced degree observed in 1BS-18 gluten-sensitized rats was smaller than that in Hokushin gluten-sensitized rats. In conclusion, 1BS-18 elicited no allergic reaction in ω5-gliadin-sensitized rats and had less sensitization ability for ω5-gliadin than that of Hokushin wheat.

Blockade of multiple monoamines receptors reduce insulin secretion from pancreatic ß-cells.

Clinical use of olanzapine frequently causes severe hyperglycemia as an adverse effect. In this study, we elucidated mechanisms by which olanzapine reduced insulin secretion using the hamster pancreatic ß-cell line HIT-T15. Reverse transcriptional-PCR analysis revealed expression of dopamine (D2, D3 and D4), serotonin (5-HT2A, 5-HT2B, 5-HT2C, and 5-HT6), and histamine (H1 and H2) receptors in HIT-T15 cells. Olanzapine decreased insulin secretion from HIT-T15 cells at clinically relevant concentrations (64-160 nM). A dopamine D2 agonist, D3 antagonist, and D4 antagonist suppressed insulin secretion, whereas a D2 antagonist and D3 agonist increased it. A serotonin 5-HT2B agonist slightly increased insulin secretion, while a 5-HT2C antagonist slightly decreased it. Other agonists and antagonists for serotonin receptors did not affect insulin secretion. A histamine H1 agonist increased insulin secretion, whereas an H1 antagonist and H2 agonist suppressed it. Our results suggest that dopamine (D2, D3 and D4), serotonin (5-HT2B and 5-HT2C), and histamine (H1 and H2) receptors, which are expressed on pancreatic ß-cells, directly modulate insulin secretion from pancreatic ß-cells. Thus, olanzapine may induce hyperglycemia in clinical settings by suppressing insulin secretion from pancreatic ß-cells through inhibition of dopamine D3, serotonin 5-HT2B and 5-HT2C, and histamine H1 receptors.

Protective effect of phosphatidylcholine on lysophosphatidylcholine-induced cellular senescence in cholangiocyte.

BACKGROUND: Pancreaticobiliary maljunction and intrahepatic gallstones are at a high risk for biliary malignancy. Lysophosphatidylcholine (LPC) is increased in the bile of these patients, and we have previously reported that LPC-induced cytotoxicity causes senescence-associated secretory phenotype (SASP) in cholangiocytes. We aimed to determine the protective effect of phosphatidylcholine (PC) on LPC-induced cholangiocyte cytotoxicity. METHODS: MMNK-1, a human immortalized cholangiocyte cell line was treated with LPC with or without PC. To assess the biological effects of SASP components on cholangiocarcinoma, HuH28 and HuCCT1 (human cholangiocarcinoma cell lines) were cultured in the conditioned media where MMNK-1 cells treated with LPC. RESULTS: The presence of PC reduced reactive oxygen species generation and oxidative DNA damage in MMNK-1 treated with LPC. Moreover, SA-ß-gal activity was markedly downregulated by PC. The secretion of SASP components, including interleukin (IL)-8, IL-6, and C-C motif chemokine ligand 2 was also substantially reduced in the presence of PC. Cellular proliferation and migration were enhanced in HuCCT1 and HuH28 cells when cultured in the conditioned media, and these observations were suppressed by simultaneous addition of PC. CONCLUSION: PC protects cholangiocytes against LPC-induced cytotoxicity and cellular senescence, suggesting its potential as a target for inhibiting LPC-related carcinogenesis and its promotion.

[Comparison of Pegfilgrastim and Filgrastim for the Primary Prophylactic Effect for Preventing Febrile Neutropenia in Patients Undergoing Rituximab with Dose-adjusted EPOCH Chemotherapy].

The combination of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin with rituximab (DA-EPOCH-R) is used for non-Hodgkin lymphoma patients. Febrile neutropenia (FN) is a common complication of treatment with myelo-suppressive chemotherapy, so preventing FN is important for maintaining chemotherapy dosage. Recently, pegfilgrastim has been used as the primary prophylaxis of FN in Japan, but there have been few cases reported using pegfilgrastim for the primary prophylaxis in DA-EPOCH-R. In this study, we retrospectively compared the efficacy of pegfilgrastim with that of filgrastim in patients receiving DA-EPOCH-R in Hiroshima University Hospital. Efficacy assessment was based on incidence of FN and serious neutropenia (neutrophil count <500/µL), hospitalization days and chemotherapy dosage level. Ten patients met the inclusion criteria: pegfilgrastim (n=5, 30 cycles) or filgrastim (n=5, 16 cycles). No difference in efficacy existed between pegfilgrastim and filgrastim in the first cycle; however, 2 of 5 patients in filgrastim group reduced dose level in the total cycles of chemotherapy, no patients in pegfilgrastim group reduced. In conclusion, pegfilgrastim seemed better than filgrastim for the primary prophylaxis in DA-EPOCH-R.