Shigehiro Shibata

Properties of the delayed rectifier potassium current in porcine sino-atrial node cells

1 Whole‐cell currents were recorded in single, spontaneously active cells dissociated from porcine sino‐atrial node, and the conductance and gating properties of the delayed rectifier K+ current (IK) were investigated. 2 The isolated cells exhibited spontaneous action potentials at a rate of 80.5 ± 5.4 min−1 (mean ± s.e.m., n= 11). Under Ca2+ current block, depolarization from ‐40 mV to various potentials activated a time‐dependent outward current (IK). The activation curve of IK showed a half‐activation potential (V½) of 20.5 ± 2.1 mV and a slope factor (S) of 16.4 ± 1.2 mV (n= 8). 3 As the duration of the depolarizing pulse to either +10 or +60 mV was prolonged, the amplitude of the tail current increased in proportion to that of the activated outward current during depolarization. 4 E4031 (2‐5 μM), a selective blocker for the rapidly activating component of IK (IK,r), hardly affected IK, but chromanol 293B, a selective blocker for the slowly activating component (IK,s), inhibited IK with an IC50 of 8.79 μM. 5 The reversal potential of IK was ‐75.2 ± 2.3 mV with 5.4 mM external and 150 mM internal K+. The time courses of activation and deactivation of IK were fitted by the sum of two exponential functions at various potentials. The relationship between the time constants and membrane potential showed a bell‐shaped curve with a peak at around ‐10 mV for both fast and slow components. 6 The results indicate that in porcine sino‐atrial node cells IK is largely derived from IK,s and that IK,s plays a functional role in the slow diastolic depolarization. IK,s may, in part, account for the relatively slower heart rate of pigs than that of rabbit in which IK,r is a functionally dominant component of IK.

Inhibition by genistein of the hyperpolarization‐activated cation current in porcine sino‐atrial node cells

The hyperpolarization‐activated cation current (If) was recorded in single pacemaker cells of the porcine sino‐atrial node, and the effects of genistein, an isoflavone inhibitor of tyrosine‐specific protein kinases was investigated by the whole‐cell patch clamp technique. Genistein (20–500 μM) decreased If in a dose‐dependent manner with an IC50 value of 62.3 μM and a maximum inhibition of 45.3%. The effect on If appeared without altering the half‐activation potential (control, −88.3±2.8 mV; genistein, −87.0±1.8 mV) and the slope factor (control, 8.0±0.3 mV; genistein, 8.6±0.7 mV) of the steady‐state activation curve. No significant voltage‐dependency was detected in the fully‐activated current‐voltage relation measured by the double‐pulse protocols. The inactive form of genistein analogue, daidzein (500 μM) or genistin (200 μM), were without effect. If was not affected by another tyrosine kinase inhibitor, tryphostin‐47 (100 μM), but tyrphostin‐25 (100–200 μM) suppressed If in an irreversible manner. Neither bath nor intracellular application of the tyrosine phosphatase inhibitor, orthovanadate, affected If, and subsequent application of genistein inhibited If significantly. These data indicate that the inhibition of If by genistein is not mediated through tyrosine kinase inhibition but through nonselective block of the If channels.

Green Urine Discoloration due to Propofol Infusion: A Case Report

We present a 19-year-old man who excreted green urine after propofol infusion. The patient was admitted to our hospital for injuries sustained in a traffic accident and underwent surgery. After starting continuous infusion of propofol for postoperative sedation, his urine became dark green. Serum total bilirubin and urine bilirubin were both elevated. We believe that the green discoloration of the urine was caused by propofol infusion and was related to impaired enterohepatic circulation and extrahepatic glucuronidation in the kidneys.

Presepsin in the prognosis of infectious diseases and diagnosis of infectious disseminated intravascular coagulation: a prospective, multicentre, observational study.

BACKGROUND Few prospective studies have described the prognostic accuracy of presepsin for 28-day mortality during days 0 to 7, or its role in the diagnosis of disseminated intravascular coagulation (DIC) in patients with infection. OBJECTIVE We aimed to evaluate the clinical usefulness of presepsin levels by comparing infection markers such as procalcitonin, interleukin-6 and C-reactive protein, as well as markers of DIC such as fibrin degradation products (FDPs) and D-dimer, from days 0 to 7. DESIGN A prospective, multicentre, observational study. SETTING Four medical institutions between June 2010 and June 2011. PATIENTS A total of 191 patients who fulfilled at least one of the systemic inflammatory response syndrome (SIRS) criteria were enrolled in the study. MAIN OUTCOME MEASURES The presepsin levels were evaluated for their diagnostic accuracy in discriminating between SIRS and sepsis, the prognostic accuracy for 28-day mortality from days 0 to 7 and the diagnostic accuracy for DIC in patients with infection by comparison with other infection markers. RESULTS The diagnostic accuracy for discriminating between SIRS and sepsis from combining the presepsin and procalcitonin measurements [area under the curve (AUC), 0.91; likelihood ratio, 4.96] was higher than that of presepsin (AUC, 0.89; likelihood ratio, 4.75) or procalcitonin (AUC, 0.85; likelihood ratio, 3.18) alone. Not only the correlation coefficient between the presepsin level and the sequential organ failure assessment (SOFA) score but also the prognostic accuracy of presepsin for 28-day mortality increased with the elapsed time, and both were highest at day 7. The diagnostic accuracy for DIC generated by combining presepsin and FDP (AUC, 0.84; likelihood ratio, 3.57) was higher than that of FDP (AUC, 0.82; likelihood ratio, 2.64) or presepsin (AUC, 0.80; likelihood ratio, 2.94) alone. CONCLUSION The prognosis and severity of infection may be assessed more accurately by measuring the presepsin levels until day 7. Presepsin is a useful diagnostic tool for DIC with infection.

Multiple Transverse Colonic Perforations Associated with Slow-Release Nonsteroidal Anti-Inflammatory Drugs and Corticosteroids: A Case Report

The patient was a 36-year-old woman with sarcoidosis and Sjogrens syndrome, and had been prescribed slow-release diclofenac sodium and prednisolone for the treatment of pain associated with uveitis and erythema nodosum. She was admitted to our emergency center with abdominal pain and distention. A chest X-ray showed free air under the diaphragm on both sides, and an emergency laparotomy was performed for suspected panperitonitis associated with intestinal perforation. Laparotomy revealed several perforations on the antimesenteric aspect of the transverse colon. The resected specimen showed 11 punched-out ulcerations, many of which were up to 10 mm in diameter. The microscopic findings were non-specific, with leukocytic infiltration around the perforations. She showed good postoperative recovery, as evaluated on day 42. The present case highlights the need for exercising caution while prescribing slow-release nonsteroidal anti-inflammatory drugs with corticosteroids to patients with autoimmune diseases, as such treatment may exacerbate intestinal epithelial abnormalities.

Eicosanoids as Risk and Prognostic Factors for Acute Respiratory Distress Syndrome in Sepsis Patients

Although a number of studies have reported elevated levels of eicosanoids in acute lung injury with sepsis, the possibility that eicosanoids may act as risk and prognostic factors for sepsis patients who develop acute respiratory distress syndrome (ARDS) remains poorly studied. To clarify this aspect, we measured the levels of eicosanoids and used logistic regression analysis and receiver operating characteristic (ROC) curves to investigate whether eicosanoids could act as risk and prognostic factors for sepsis patients who develop ARDS. We conducted a casecontrol study comparing 13 sepsis patients with ARDS and 23 sepsis patients without ARDS. The plasma levels of leukotriene B4 (LTB4), 6-keto-prostaglandin F1α (6-keto-PGF1α) and thromboxane B2 (TXB2) were measured by radioimmunoassays as substitutes for the plasma levels of PGI2 and TXA2, which are unstable. The levels of eicosanoids in sepsis patients with ARDS were significantly higher than those in sepsis patients without ARDS. Logistic regression analysis revealed that LTB4 was the only risk factor for sepsis patients with ARDS (odds ratio, 1.10; P=0.02). The area under the ROC curve values for all eicosanoids were significantly greater than 0.5 (P<0.001), and the likelihood value for the TXB2 levels was higher than those of the other eicosanoids. We conclude that LTB4 may be an important risk factor for sepsis patients with ARDS, while TXA2 may be an important prognostic factor for sepsis patients with ARDS.