Exploration of useful clinical laboratory values as diagnostic criteria for eosinophilic gastroenteritis.

BACKGROUND: Eosinophilic gastroenteritis (EGE) is a rare eosinophilic infiltrative disorder. In Japan, EGE is diagnosed using clinical symptoms as well as microscopic, haematologic and histopathological findings. In this study, we examined the usefulness of laboratory data in the diagnosis of EGE. METHODS: Patients who were diagnosed with EGE at Fujita Health University Bantane Hospital between April 2015 and December 2020 were enrolled in this study and their data was retrospectively analysed. We evaluated their medical history, laboratory data including leukocyte count, eosinophil count, immunoglobulin (Ig) E, thymus and activation-regulated chemokine (TARC), C-reactive protein (CRP), etc. and histopathological data were collected from the electronic medical records. RESULTS: One hundred twelve of 168 patients who were treated for EGE could be analysed. The peripheral eosinophil count was correlated with the duodenal or ascending colon eosinophil count; moreover, the blood lymphocyte count and the TARC were correlated with the transverse colon eosinophil count. Multivariate regression analysis showed correlations only in the oesophagus, stomach and duodenum. Specifically, correlations were noted between blood eosinophils and gastric eosinophils, blood eosinophils and duodenal eosinophils, blood lymphocytes and gastric eosinophils, blood IgE and oesophageal, gastric and duodenal eosinophils and CRP and oesophageal eosinophils. CONCLUSION: The extent of blood eosinophil count, lymphocyte count, IgE and CRP elevation together with clinical features and pathology can be incorporated into a diagnostic scoring criteria system to improve the accuracy of diagnosing this uncommon condition in the future.

Investigation of appropriate needle length considering skin thickness with the real injection posture for insulin injections in diabetic patients.

BACKGROUND: Insulin treatment is widely used not only for type 1 but also for type 2 diabetes patients. Insulin must be injected into the subcutaneous tissue to be effective. The needle length has been shortened for safety and efficiency. However, whether patients use an appropriate needle length is unclear. METHODS: Skin thickness was measured by ultrasound with patients in their usual posture during injection. Furthermore, the effect of the intervention in which the needle length was changed was investigated. RESULTS: Thirty-eight percent of the patients had fluid leakage and injected the needle intradermally. The average skin thickness was 3.3 mm while sitting, which was greater than that in a previous report including measurements taken while lying down. Consequently, the skin thickness was > 4 mm in 9.5% of the patients who used 4-mm needles. Cases of leakage and intradermal injection decreased when the needle length was changed. CONCLUSIONS: This study identified that the needle length should be considered in patients with thick skin or a lower body mass index due to possibility of intradermal injection.

A Reactive Metabolite of Clozapine Induces Hematopoietic Toxicity in HL-60 Cells Undergoing Granulocytic Differentiation through Its Effect on Glutathione Metabolism.

Clozapine is an atypical antipsychotic with several advantages over conventional antipsychotics, in addition to its well-known efficacy in treatment-resistant schizophrenia. However, the high risk of agranulocytosis associated with clozapine therapy limits its clinical application. Clozapine bioactivation to an unstable protein-reactive metabolite, identified as a nitrenium intermediate, has been implicated in cytotoxicity toward neutrophils. Clozapine affects myeloid precursor cells rather than neutrophils; however, the impact of its reactive metabolite on myeloid precursor cells undergoing granulocytic differentiation remains unclear. Herein, we used hydrogen peroxide (H2O2) to generate the reactive metabolite and compared reactive metabolite-induced cytotoxicity between HL-60 cells undergoing granulocytic differentiation and differentiated HL-60 cells. In addition, we examined the role of oxidative stress in this type of cytotoxicity. The reactive metabolite of clozapine induced rapid cytotoxicity in HL-60 cells undergoing granulocytic differentiation, but not in differentiated HL-60 cells, with the metabolite exhibiting more potent cytotoxicity than clozapine. No cytotoxicity was observed following incubation with olanzapine, a structural analog of clozapine, even after exposure of the drug to H2O2. The reactive metabolite of clozapine decreased the levels of reduced glutathione, while addition of reduced glutathione attenuated the reactive metabolite-induced cytotoxicity. These findings indicate that glutathione metabolism plays a role in the hematopoietic toxicity induced by the reactive metabolite of clozapine. Oxidative stress may potentially increase susceptibility to the hematopoietic toxicity induced by the reactive metabolite of clozapine.

Survey of chemotherapy-induced nausea and vomiting in patients with urothelial carcinoma.

Chemotherapy-induced nausea and vomiting (CINV) can cause anorexia, weight loss and deterioration of patient quality of life. It is one of the most unpleasant adverse effects of chemotherapy treatment regimens. For the optimal treatment of gastrointestinal symptoms during urothelial carcinoma chemotherapy, the present study investigated the association between gastrointestinal symptoms and therapeutic effects of gemcitabine plus platinum [cisplatin (GC) or carboplatin (GCa)] therapies. The incidence and frequency of nausea/vomiting with GC split therapy (gemcitabine, 1,000 mg/m2 on days 1 and 8; split-dose cisplatin, 35 mg/m2 on days 1 and 8; 21-day schedule) and GCa therapy [gemcitabine, 750-1,000 mg/m2 on days 1, 8 and 15; carboplatin, area under the blood concentration-time curve=5 mg min/ml (Calvert formula) on day 2; 28-day schedule] were lower compared with those of GC therapy (gemcitabine, 1,000 mg/m2 on days 1, 8 and 15; single-dose cisplatin 70 mg/m2 on day 2; 28-day schedule). However, no differences in therapeutic outcomes were observed among therapies. GCa therapy, regardless of renal function, and GC split therapy demonstrated significant increases compared with GC therapy in alleviating gastrointestinal symptoms associated with cancer chemotherapy in patients with urothelial carcinoma. Overall, these results suggested that split-dose cisplatin administration or the use of carboplatin instead of cisplatin may be useful in patients who experience CINV without compromising treatment effectiveness.

Diurnal Variation of Sitagliptin-Induced Pharmacological Effects in C57BL/6J Mice.

Chronopharmacology is the study of the varying responses of drugs to changes in biological timing and endogenous periodicities. The dipeptidyl peptidase-4 inhibitor sitagliptin is a globally prescribed anti-hyperglycemic drug. Although dipeptidyl peptidase-4 inhibitors are usually administered once, the specific intake time is generally not mentioned. Therefore, this study aimed at investigating the diurnal effects of sitagliptin-induced anti-hyperglycemia in high-fat diet (HFD)-induced obesity in mice. Five-week-old male C57BL/6J mice were fed normal (control) diet or HFD for 10 weeks. During the last 2 weeks, the mice were administered saline or sitagliptin (10 mg/kg, per os) in the light or dark phase, respectively. At the end of the experiment, the mice were euthanized after an 18 h fasting period, and plasma and tissue samples (liver, kidney, and epididymal white adipose tissues) were collected, or the oral glucose tolerance test was performed. Sitagliptin administration in the light phase significantly decreased plasma glucose levels, insulin levels, hepatic steatosis, and restored the glucose tolerance compared with the HFD group. In contrast, these parameters remained unchanged in the dark phase-treated mice. Our data therefore suggests that sitagliptin portrays definite chronopharmacology, which may provide valuable information on the importance of drug administration timing for maximum pharmacological effects.

Chronopharmacology of dapagliflozin-induced antihyperglycemic effects in C57BL/6J mice.

Chronopharmacology is the study of the varying responses of drugs to changes in biological timing and endogenous periodicities. The selective sodium-glucose cotransporter 2 inhibitor, dapagliflozin, is a globally prescribed antihyperglycemic drug. Although dapagliflozin is usually administered once a day, the specific intake time is generally not mentioned. Therefore, this study aimed at investigating the diurnal effects of dapagliflozin on high-fat diet (HFD)-induced obesity in mice. Five-week-old male C57BL/6J mice were fed a normal (control) diet or HFD for 10 weeks. During the last 2 weeks, the mice were administered olive oil/ethanol emulsion or dapagliflozin (1mg/kg, p.o.) in the light or dark phase. At the end of the experiment, the mice were euthanized after an 18h fasting period, and plasma and tissue samples (epididymal white adipose tissues, liver, and kidney) were collected. Dapagliflozin administration in the light phase significantly decreased plasma glucose levels, insulin levels, adipose adipokines, and decreased the size of adipocytes, compared with the HFD group. In contrast, these parameters remained unchanged in the mice treated during the dark phase. Our data therefore suggests that dapagliflozin portrays definite chronopharmacology, which may provide valuable information on the importance of drug administration timing for maximal pharmacological effects.