Risk of hypoglycemia associated with repaglinide combined with clopidogrel, a retrospective cohort study.

BACKGROUND: Repaglinide is widely prescribed to reduce postprandial hyperglycemia and elevated glycated hemoglobin (HbA1c) levels associated with type 2 diabetes, and clopidogrel is a thienopyridine antiplatelet agent and widely used in cardiovascular and cerebrovascular diseases. It has been suggested that the concomitant use of repaglinide with clopidogrel may inhibit repaglinide metabolism, because repaglinide is a substrate of cytochrome P450 2C8 (CYP2C8) and the main metabolite of clopidogrel acyl-ß-D-glucuronide inhibits CYP2C8 activity. In this study, we retrospectively investigated the effect of clopidogrel with repaglinide on plasma glucose and the risk of hypoglycemia associated with the combination of both drugs. METHOD: Patients were taking clopidogrel (75 mg/day) and started taking glinide (1.5 mg/day repaglinide or 30 mg/day mitiglinide) for the first time from April 2012 to March 2017. We targeted subjects who were hospitalized at the start of glinide and whose preprandial plasma glucose was measured by a nurse. The glucose levels were collected for up to 5 days before and after the glinide start date. RESULTS: Average fasting plasma glucose levels (before breakfast) in the repaglinide and clopidogrel group before and after starting repaglinide were 180.1±35.5 and 136.5 ± 44.1 mg/dL, with a mean decrease of 43.6 ± 33.6 mg/dL. In contrast, there was only a moderate decrease of 11.6 ± 30.0 mg/dL in the mitiglinide and clopidogrel group. Minimum plasma glucose levels in the repaglinide and clopidogrel group before and after starting repaglinide were 145.2 ± 42.9 and 93.3 ± 36.3 mg/dL, respectively. Decrease in minimum levels after starting glinide in the repaglinide and clopidogrel group (51.9 ± 47.5 mg/dL) was more significant than those in the mitiglinide and clopidogrel group (only 2.1 ± 29.1 mg/dL), and the repaglinide group (without clopidogrel, 15.5 ± 20.0 mg/dL). Hypoglycemia was observed in 6 of 15 patients in the repaglinide and clopidogrel group, but only 1 of 15 patients in the mitiglinide and clopidogrel group, and no patients in the repaglinide group. CONCLUSION: These findings indicate that minimum plasma glucose levels were significantly decreased in patients taking repaglinide and clopidogrel. Considering the risk of hypoglycemia associated with taking repaglinide and clopidogrel, when a glinide is required in patients taking clopidogrel, mitiglinide may be a better choice.

Internet survey of childhood asthma and use of inhaled therapy in the home in Japan.

BACKGROUND: The aim of the present study is to undertake a survey of childhood asthma and details of the use of inhaled therapy from mothers with asthmatic children

Combined passive and active immunoprophylaxis for preventing perinatal transmission of the hepatitis B virus carrier state in Shizuoka, Japan during 1980-1994.

BACKGROUND: Efficacy and limits in preventing perinatal infection with hepatitis B virus (HBV) have been examined in a model area in Japan. METHODS: In Shizuoka (population of 3.6 million), immunoprophylaxis of perinatal HBV infection was started in 1980 in four institutions (Hamamatsu Medical College, Shimada City Hospital, Shizuoka Kodomo Hospital and Numazu City Hospital). Babies born to carrier mothers with hepatitis B e antigen (HBeAg) in serum received hepatitis B immune globulins at birth and 2 months thereafter and vaccines at 2, 3 and 5 months after birth. RESULTS: Overall, 980 of the 1030 babies born to HBeAg-positive carrier mothers were protected by the immunoprophylaxis during the 15 years from 1980 to 1994 with an efficacy of 95.1%. From 1986 to 1994 while the national immunoprophylaxis was conducted, 329,674 of the 346,637 (95.1%) expectant mothers were tested, and 2081 (0.63%) of them were positive for hepatitis B surface antigen (HBsAg). The immunoprophylaxis was given only to babies born to 764 (36.7%) of the 2081 mothers who tested positive for HBeAg. Of the 494 babies receiving immunoprophylaxis, in whom HBsAg was followed monthly after birth, 462 (93.5%) were protected. The HBV carrier state developed in the remaining 32 (6.5%) babies, 10 of whom (31.3% of the 32) turned positive for HBsAg within 1 month after birth, most likely owing to infection in utero. CONCLUSIONS: Passive-active immunoprophylasxis of high-risk babies was highly efficacious in preventing perinatal transmission of the HBV carrier state. Most failures (approximately 70%) occurred in the high-risk babies who were exposed to HBV after birth, and would have been avoided by careful and extensive execution of the immunoprophylaxis.

Theophylline suppresses IL-5 and IL-13 production, and lymphocyte proliferation upon stimulation with house dust mite in asthmatic children.

BACKGROUND: Although theophylline has long been used as a medication for bronchial asthma (BA), much remains to be elucidated about its action on Th2 cells, which play a critical role in the development of BA. OBJECTIVE: This study aimed to clarify the effect of theophylline on Th2 cells in an allergen-specific manner in children with BA. METHODS: Peripheral blood mononuclear cells (PBMCs) from 32 children with BA were stimulated with house dust mite (HDM) or a purified HDM allergen Der f 1 in the presence or absence of theophylline at a therapeutic concentration (5-20 microg/ml). The proliferation of lymphocytes and the secretion of IL-5 and IL-13 were measured to estimate the influence of theophylline. RESULTS: Theophylline at a concentration of 20 microg/ml significantly suppressed lymphocyte proliferation induced by 6-day culture with HDM or Der f 1. It also significantly reduced the production of IL-5 and IL-13 upon stimulation with HDM or Der f 1. Suppression of cytokine production and lymphocyte proliferation increased with concentrations of theopylline between 5 and 20 microg/ml. CONCLUSION: Theophylline suppresses the proliferation of lymphocytes and the production of proinflammatory Th2 cytokines, IL-5 and IL-13 induced by stimulation of PBMCs with HDM in children with BA.

Development of the capacity of peripheral blood mononuclear cells to produce IL-4, IL-5 and IFN-gamma upon stimulation with house dust mite in children with atopic dermatitis.

BACKGROUND: Imbalances of IL-4 and IFN-gamma production are widely known to increase IgE synthesis in allergic individuals, and IL-5 is known to play a critical role in the pathogenesis of various allergic diseases. However, little is known about how Th cells specific to house dust mite (HDM) develop the capacity to produce these cytokines in children with atopic dermatitis (AD). OBJECTIVE: This study aims to clarify when HDM-specific Th cells develop the capacity to produce IL-4, IL-5 and IFN-gamma in children with AD. METHODS: The production of IL-4, IL-5 and IFN-gamma by peripheral blood mononuclear cells (PBMCs) upon stimulation with HDM was measured in 91 children with AD and 37 control subjects. The changes in the cytokine production with age were analyzed transectionally and longitudinally. RESULTS: IL-4 production by HDM-stimulated PBMCs in children with AD was already increased before age 1. Thereafter, it continuously rose until reaching a near-maximum level at age 2. Growth-related changes in the production of IL-5 resembled those in the production of IL-4 and peaked at age 1. The production of these cytokines was very low in control subjects up to age 2 and then gradually increased, albeit never above the levels measured in AD children. The production of IFN-gamma in children with AD reached a near-maximum level during the first year of life and diminished after age 3. Although IFN-gamma production in controls was lower than that in AD children during infancy, it continuously rose even after age 3 and surpassed the levels measured in AD children. The level of serum HDM-specific IgE antibody began to increase after age 1 following the rise of IL-4 production. Essentially the same relationship among IL-4, IFN-gamma and IgE synthesis was seen in a longitudinal study of 6 AD infants, in whom HDM-specific IgE was initially negative but later turned positive. CONCLUSIONS: These findings suggest that the capacity of HDM-specific Th cells to produce IL-4, IL-5 and IFN-gamma develops and effectively matures during the first 3 years of life in children with AD.