Caffeine acutely activates 5'adenosine monophosphate-activated protein kinase and increases insulin-independent glucose transport in rat skeletal muscles

Caffeine (1, 3, 7-trimethylxanthine) has been implicated in the regulation of glucose and lipid metabolism including actions such as insulin-independent glucose transport, glucose transporter 4 expression, and fatty acid utilization in skeletal muscle. These effects are similar to the exercise-induced and 5′adenosine monophosphate–activated protein kinase (AMPK)–mediated metabolic changes in skeletal muscle, suggesting that caffeine is involved in the regulation of muscle metabolism through AMPK activation. We explored whether caffeine acts on skeletal muscle to stimulate AMPK. Incubation of rat epitrochlearis and soleus muscles with Krebs buffer containing caffeine (≥3 mmol/L, ≥15 minutes) increased the phosphorylation of AMPKα Thr[172], an essential step for full kinase activation, and acetyl–coenzyme A carboxylase Ser79, a downstream target of AMPK, in dose- and time-dependent manners. Analysis of isoform-specific AMPK activity revealed that both AMPKα1 and α2 activities increased significantly. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-d-glucose transport activity in the absence of insulin. These results suggest that caffeine has similar actions to exercise by acutely stimulating skeletal muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status

Unfractionated heparin versus nafamostat mesylate for anticoagulation during continuous kidney replacement therapy: an observational study

Abstract Background Unfractionated heparin sodium and nafamostat mesylate have long been used as anticoagulants in continuous kidney replacement therapy (CKRT) where citrate is unavailable. This study aimed to determine whether heparin or nafamostat mesylate used during CKRT was associated with a longer filter life. Methods In this single-centre observational study, we included adult patients who required CKRT and used heparin or nafamostat mesylate for their first CKRT in the intensive care unit from September 1, 2013, to December 31, 2020. The primary outcome was filter life (from the start to the end of using the first filter). We used propensity score matching to adjust for the imbalance in patients’ characteristics and laboratory data at the start of CKRT and compared the outcomes between the two groups. We also performed restricted mean survival time analysis to compare the filter survival times. Results We included 286 patients, 157 patients on heparin and 129 patients on nafamostat mesylate. After propensity score matching, the mean filter life with heparin was 1.58 days (N = 91, Standard deviation [SD], 1.52) and with nafamostat mesylate was 1.06 days (N = 91, SD, 0.94, p = 0.006). Multivariable regression analysis adjusted for confounding factors supported that heparin was associated with a longer filter life compared with nafamostat mesylate (regression coefficient, days, 0.52 [95% CI, 0.15, 0.89]). The between group difference of the restricted mean filter survival time in the matched cohort was 0.29 (95% CI, 0.07–0.50, p = 0.008). Conclusion Compared to nafamostat mesylate, heparin was associated with one-third to one-half a day longer filter life. Trial registration Not applicable

Severe infection including disseminated herpes zoster triggered by subclinical Cushing's disease: a case report

Background Subclinical Cushing's disease (SCD) is defined by corticotroph adenoma-induced mild hypercortisolism without typical physical features of Cushing's disease. Infection is an important complication associated with mortality in Cushing's disease, while no reports on infection in SCD are available. To make clinicians aware of the risk of infection in SCD, we report a case of SCD with disseminated herpes zoster (DHZ) with the mortal outcome. Case presentation An 83-year-old Japanese woman was diagnosed with SCD, treated with cabergoline in the outpatient. She was hospitalized for acute pyelonephritis, and her fever gradually resolved with antibiotics. However, herpes zoster appeared on her chest, and the eruptions rapidly spread over the body. She suddenly went into cardiopulmonary arrest and died. Autopsy demonstrated adrenocorticotropic hormone-positive pituitary adenoma, renal abscess, and DHZ. Conclusions As immunosuppression caused by SCD may be one of the triggers of severe infection, the patients with SCD should be assessed not only for the metabolic but also for the immunodeficient status

Use of a Compact Tripodal Tris(bipyridine) Ligand to Stabilize a Single-Metal-Centered Chirality: Stereoselective Coordination of Iron(II) and Ruthenium(II) on a Semirigid Hexapeptide Macrocycle

Fe­(II)-coordinating hexapeptides containing three 2,2′-bipyridine moieties as side chains were designed and synthesized. A cyclic hexapeptide having three [(2,2′-bipyridin)-5-yl]-d-alanine (d-Bpa5) residues, in which d-Bpa5 and Gly are alternately arranged with 3-fold rotational symmetry, coordinated with Fe­(II) to form a 1:1 octahedral Fe­(II)–peptide complex with a single <i>facial</i>-Λ configuration of the metal-centered chirality. NMR spectroscopy and molecular dynamics simulations revealed that the Fe­(II)–peptide complex has an apparent <i>C</i>₃-symmetric conformations on the NMR time scale, while the peptide backbone is subject to dynamic conformational exchange between three asymmetric β/γ conformations and one <i>C</i>₃-symmetric γ/γ/γ conformation. The semirigid cyclic hexapeptide preferentially arranged these conformations of the small octahedral Fe­(II)–bipyridine complex, as well as the Ru­(II) congener, to underpin the single configuration of the metal-centered chirality