Citations

We evaluated the applicability of stable isotopic tracers to the study of intramuscular fatty acid metabolism by infusing both [U-13C]palmitate and [1-13C]oleate intravenously for 4 h into fasted conscious rats. Skeletal muscles were sequentially biopsied, and the concentration and13C enrichment of fatty acids were measured by gas chromatography/combustion/isotope ratio mass spectrometry. Throughout the study, the13C enrichment of plasma palmitate and oleate remained substantially greater than intramuscular nonesterified palmitate and oleate enrichment, which in turn was greater than intramuscular triglyceride palmitate and oleate enrichment. Fractional synthesis rates of intramuscular triglycerides in gastrocnemius and soleus were 0.267 ± 0.075 and 0.100 ± 0.030/h ( P = 0.04), respectively, as determined by using [U-13C]palmitate, and were 0.278 ± 0.049 and 0.075 ± 0.013/h ( P = 0.02), respectively, by using [1-13C]oleate. We conclude that plasma free fatty acids are a source for intramuscular triglycerides and nonesterified fatty acids; the latter are likely the synthetic precursors of the former. Uniformly and singly labeled [13C]fatty acid tracers will provide an important tool to study intramuscular fatty acid and triglyceride metabolism.

We previously found that epinephrine, a mixed beta- and alpha-adrenoreceptor agonist, stimulates systemic and nonsplanchnic upper body free fatty acid (FFA) release but not lower body FFA release in healthy nonobese women. To evaluate the role of beta-adrenergic-mediated effects on this regional difference in lipolysis, we measured systemic, leg, and splanchnic FFA kinetics ([3H]palmitate) in seven healthy nonobese women before and during an intravenous isoproterenol infusion. Isoproterenol increased systemic palmitate flux (87 +/- 12 vs. 100 +/- 10 mumol/min, P < 0.05) but failed to affect leg [10.8 +/- 1.2 vs. 11.4 +/- 2.3 mumol/min, P = not significant (NS)] or splanchnic (10.8 +/- 3.2 vs. 10.0 +/- 1.8 mumol/min, P = NS) palmitate release. Upper body nonsplanchnic palmitate release increased from 56 +/- 14 to 71 +/- 10 mumol/min. Systemic O2 consumption increased (227 +/- 11 to 241 +/- 10 ml/min, P = 0.006) during isoproterenol infusion, as did leg (318 +/- 42 vs. 404 +/- 53 ml/min, P < 0.01) and splanchnic (827 +/- 104 vs. 970 +/- 108 ml/min, P < 0.05) plasma flow. These results suggest that lower body adipose tissue lipolysis in women is less sensitive or responsive than nonsplanchnic upper body adipose tissue to beta-adrenergic stimulation and that regional differences in alpha 2-adrenergic-receptor responses were not responsible for the similar regional differences we observed previously with epinephrine.

We previously reported that epinephrine stimulates leg free fatty acid (FFA) release in men but not in women. The present studies were conducted to determine whether the same is true during exercise. Six men and six women bicycled for 90 min at 45% of peak O2 consumption, during which time systemic and leg FFA kinetics ([9,10-3H]palmitate) were measured. The catecholamine and hormonal responses to exercise were not different in men and women. The baseline systemic and leg palmitate release was 94 ± 15 vs. 114 ± 5 μmol/min and 16 ± 2 and 20 ± 3 μmol/min, respectively, in men and women [ P = nonsignificant (NS)]. Systemic and leg palmitate release increased (both P < 0.001) to 251 ± 18 vs. 212 ± 16 μmol/min and 73 ± 19 vs. 80 ± 12 μmol/min in men and women, respectively, during the last 30 min of exercise ( P = NS, men vs. women). We conclude that the systemic and leg adipose tissue lipolytic response to exercise is not different in nonobese men and women.

Lungs allografts have worse long-term survival compared with other organ transplants. This is most likely due to their unique immunoregulation that may not respond to traditional immunosuppression. For example, local NO generation by inducible NOS (iNOS) is critical for lung allograft acceptance but associates with rejection of other solid organs. The source of NO in accepting lung allografts remains unknown. Here, we report that, unlike the case for other pulmonary processes in which myeloid cells control NO generation, recipient-derived eosinophils play a critical and nonredundant role in iNOS-mediated lung allograft acceptance. Depletion of eosinophils reduces NO levels to that of recipients with global deletion of iNOS and leads to a costimulatory blockade–resistant form of rejection. Furthermore, NO production by eosinophils depends on Th1 polarization by inflammatory mediators, such as IFN-γ and TNF-α. Neutralization of such mediators abrogates eosinophil suppressive capacity. Our data point to what we believe to be a unique and previously unrecognized role of eosinophil polarization in mediating allograft tolerance and put into perspective the use of high-dose eosinophil-ablating corticosteroids after lung transplantation.

Abstract Management bundles that define items or procedures strongly recommended in clinical practice have been used in many guidelines in recent years. Application of these bundles facilitates the adaptation of guidelines and helps improve the prognosis of target diseases. In Tokyo Guidelines 2013 ( TG 13), we proposed management bundles for acute cholangitis and cholecystitis. Here, in Tokyo Guidelines 2018 ( TG 18), we redefine the management bundles for acute cholangitis and cholecystitis. Critical parts of the bundles in TG 18 include the diagnostic process, severity assessment, transfer of patients if necessary, and therapeutic approach at each time point. Observance of these items and procedures should improve the prognosis of acute cholangitis and cholecystitis. Studies are now needed to evaluate the dissemination of these TG 18 bundles and their effectiveness. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.

Abstract We propose a new flowchart for the treatment of acute cholecystitis ( AC ) in the Tokyo Guidelines 2018 (TG18). Grade III AC was not indicated for straightforward laparoscopic cholecystectomy (Lap‐C). Following analysis of subsequent clinical investigations and drawing on Big Data in particular, TG 18 proposes that some Grade III AC can be treated by Lap‐C when performed at advanced centers with specialized surgeons experienced in this procedure and for patients that satisfy certain strict criteria. For Grade I, TG 18 recommends early Lap‐C if the patients meet the criteria of Charlson comorbidity index ( CCI ) ≤5 and American Society of Anesthesiologists physical status classification ( ASA ‐ PS ) ≤2. For Grade II AC , if patients meet the criteria of CCI ≤5 and ASA ‐ PS ≤2, TG 18 recommends early Lap‐C performed by experienced surgeons; and if not, after medical treatment and/or gallbladder drainage, Lap‐C would be indicated. TG 18 proposes that Lap‐C is indicated in Grade III patients with strict criteria. These are that the patients have favorable organ system failure, and negative predictive factors, who meet the criteria of CCI ≤3 and ASA ‐ PS ≤2 and who are being treated at an advanced center (where experienced surgeons practice). If the patient is not considered suitable for early surgery, TG 18 recommends early/urgent biliary drainage followed by delayed Lap‐C once the patient's overall condition has improved. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.

Abstract The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1 st edition of the Tokyo Guidelines 2007 ( TG 07) was revised in 2013. According to that revision, the TG 13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG 13 diagnostic criteria of acute cholecystitis. On the other hand, the TG 13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG 13 severity grading for acute cholecystitis was significantly associated with parameters including 30‐day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG 13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG 18/ TG 13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47 . Related clinical questions and references are also included.

Background: In individuals with a low diastolic blood pressure (DBP), the potential benefits or risks of intensive systolic blood pressure (SBP) lowering are unclear. Methods: SPRINT (Systolic Blood Pressure Intervention Trial) was a randomized controlled trial that compared the effects of intensive (target <120 mm Hg) and standard (target <140 mm Hg) SBP control in 9361 older adults with high blood pressure at increased risk of cardiovascular disease. The primary outcome was a composite of cardiovascular disease events. All-cause death and incident chronic kidney disease were secondary outcomes. This post hoc analysis examined whether the effects of the SBP intervention differed by baseline DBP. Results: Mean baseline SBP and DBP were 139.7±15.6 and 78.1±11.9 mm Hg, respectively. Regardless of the randomized treatment, baseline DBP had a U-shaped association with the hazard of the primary cardiovascular disease outcome. However, the effects of the intensive SBP intervention on the primary outcome were not influenced by baseline DBP level ( P for interaction=0.83). The primary outcome hazard ratio for intensive versus standard treatment was 0.78 (95% confidence interval, 0.57–1.07) in the lowest DBP quintile (mean baseline DBP, 61±5 mm Hg) and 0.74 (95% confidence interval, 0.61–0.90) in the upper 4 DBP quintiles (mean baseline DBP, 82±9 mm Hg), with an interaction P value of 0.78. Results were similar for all-cause death and kidney events. Conclusions: Low baseline DBP was associated with increased risk of cardiovascular disease events, but there was no evidence that the benefit of the intensive SBP lowering differed by baseline DBP. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01206062.