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Background: Few systematic reviews have examined the effects of sodium-glucose co-transporter 2 inhibitors (SGLT2is) on lipid profiles in Asian patients with type 2 diabetes mellitus. We conducted a systematic review with a meta-analysis to summarize the available literature and confirm the effects of SGLT2is on lipid profiles in these patients. Methods: We searched the electronic databases MEDLINE, CENTRAL, and Ichushi-web for studies from the dates of their earliest publication to July 2018, and there was no language restriction. Trials were included if they were randomized controlled trials (RCTs) (1) comparing the effects of SGLT2is with a placebo in Asian patients with type 2 diabetes mellitus (18 years or older), and (2) reporting HbA1c and at least one lipid parameter, such as triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). The weighted mean difference with a 95% confidence interval (CI) was calculated using a random-effects model. Results: Among the 630 studies retrieved, 17 RCTs that included 4485 patients were ultimately included in our review. Fourteen RCTs were conducted in Japan. The durations of RCTs ranged between 12 and 24 weeks. SGLT2is significantly improved HbA1c [mean difference − 0.80 (95%CI − 0.96 to − 0.64)%, p < 0.00001], TG [mean difference − 16.42 (95%CI − 22.71 to − 10.12) mg/dL, p < 0.00001], and HDL-C [mean difference 3.36 (95%CI 2.73 to 3.98) mg/dL, p < 0.00001], but significantly deteriorated LDL-C [mean difference 3.00 (95%CI 1.18 to 4.82) mg/dL, p < 0.001]. The LDL-C/HDL-C ratio was not significantly different between SGLT2is and a placebo [mean difference − 0.01 (95%CI − 0.08 to 0.06), p < 0.74].

The safety profiles of sodium-glucose co-transporter 2 (SGLT2) inhibitors may depend on races/ethnicities. We aimed to assess the safety profiles of SGLT2 inhibitors in Japanese patients with diabetes mellitus (DM). The electronic databases MEDLINE, CENTRAL, and Ichushi-web were searched for studies with no language restriction from their inception to August 2019. Trials were included in the analysis if they were randomized controlled trials (RCTs) comparing the effects of SGLT2 inhibitors with a placebo in Japanese patients with DM > 18 years and reporting HbA1c and at least 1 adverse event. We calculated risk ratios with 95% CIs and used a random-effects model. Of the 22 RCTs included in our review, only 1 included patients with type 1 DM. The durations of RCTs ranged between 4 and 24 weeks. In comparison with a placebo, SGLT2 inhibitors were associated with similar risks of hypoglycemia, urinary tract infection, genital infection, hypovolemia, and fracture. The outcomes of treatment with SGLT2 inhibitors among Japanese patients with DM suggest favorable safety profiles. However, further evidence from studies with a longer duration, involving more diverse populations, such as patients with different types of DM, or including individual SGLT2 inhibitors is needed to resolve the limitations of the present study.

Nifedipine is frequently used for patients who require an immediate reduction of blood pressure elevated temporarily by various administration techniques including sublingual route without administrating intravenous infusion of vasodilator. A cross-over clinical study was conducted to investigate the optimal administration metho of nifedipine for rapid management of hypertension. Four method of administering 10 mg nifedipine (the capsule was bitten and swallowed, sublingually with a hole in it or the contents administered orally or intranasally with a syringe) were evaluated with regarded e‹cacy, safety, and usefulness in 6 normal volunteers. Systolic and diastolic blood pressures were correlated with the nifedipine serum concentration in each method. Nifedipine pharmacokinetic parameters diŠered among the 4 administration methods. Nifedipine was absorbed rapidly by not only intestinal mucosa but also the nasal or oral mucosa. The pharmacological eŠect of intranasal or sublingual administration was superior. However, mint oil which is present in nifedipine capsules stimulates nasal mucosa when administered intranasally. For clinical usage, nifedipine capsules in which a hole is made with a needle, administered sublingually, can be eŠectively and safely used for rapid management of systemic hypertension.

Aims. To determine whether the erythrocyte phosphorylated ribavirin (RBV) level might be a useful index of EVR and risk of anemia and to determine the optimal dose of RBV in 24 patients with hepatitis C with pegylated interferon and RBV. Methodology. The RBV level was measured by a high-performance liquid chromatography. Results and Conclusion. In patients aged 50 years or over, a negative correlation (r = −0.548, P < .05) was observed between the RBV level at week 2 and rate of Hb reduction (ΔHb) at week 4. The ΔHb at week 4 was significantly greater in patients with RBV levels of ≥800 μM (−25.5 ± 10.1%) than in patients with RBV levels <800 μM (−15.6 ± 7.7%). None of the patients with RBV levels <600 μM at week 2 achieved EVR and SVR. Thus the optimal levels of erythrocyte phosphorylated RBV at week 2 of therapy in order to achieve EVR without anemia seemed to be 600–800 μM.

This pilot study found that epidural tramadol administered before incision induced a Cmax within 30 minutes of administration. The drug was detected in serum at ∼21 hours after surgery.

Abstract:In order to examine the effect of 3,5-di-tert-butyl-4-hydroxytoluene (BHT) on hepatocellular population, BHT was given orally to male rats for 7 consecutive days at dose levels of 75 or 450 mg/kg/day. BHT induced hepatocellular proliferation, increase in apoptosis, and elevated immunoreactivity for transforming growth factor (TGF)-β1 during the treatment, and hepatocellular mitoinhibition following the withdrawal. The induction of mitoinhibition, apoptosis, and TGF-β1 might be adaptive changes in response to cell proliferation; thus the homeostasis of hepatocellular population was preserved. Although both the mechanism and the biological significance of mitoinhibition observed following the withdrawal of BHT, after a 7-day treatment period, were not elucidated, its mechanism seemed to be related to the elevation of TGF-β1 immunoreactivity and its biological significance might be similar to those with non-genotoxic hepatocarcinogens in chronic treatments. (J Toxicol Pathol 2001; 14: 145-150)

Few studies have examined the relationship between the use of antidepressants and the onset of hyperglycemia and diabetes mellitus in Japan. We herein explored the possibility of this relationship using the Japanese Adverse Drug Event Report database (JADER). The present study included 20 individual antidepressants, consisting of 6 subclasses, which have been approved for use in Japan. We used Standardized MedDRA Queries 20000041 to extract patients who developed hyperglycemia/new onset diabetes mellitus (NODM) in JADER between April 2004 and September 2016. We calculated reporting odds ratios (RORs) with 95％ conˆdence intervals (CI). We also calculated odds ratios deˆned as the ratio of odds of hyperglycemia/NODM to all other adverse drug events (ADEs) by the age cut-oŠ group or sex in the cases of antidepressants. The lower limit of 95％CI of RORs for 13 antidepressants (imipramine, clomipramine, nortriptyline, amitriptyline, amoxapine, maprotiline, mianserin, sertraline, paroxetine, escitalopram, duloxetine, mirtazapine, and trazodone), which included all subclasses, exceeded 1. Younger age group was associated with hyperglycemia/ NODM for 5 antidepressants (imipramine, amitriptyline, maprotiline, duloxetine, and trazodone), and female was associated with the ADEs for trazodone, although these results should be interpreted cautiously. Healthcare personnel need to be aware that the use of antidepressants may lead to hyperglycemia/NODM.