Although adipocytes are major targets of insulin, the influence of impaired insulin action in adipocytes on metabolic homeostasis remains unclear. We here show that adipocyte-specific PDK1 (3′-phosphoinositide–dependent kinase 1)-deficient (A-PDK1KO) mice manifest impaired metabolic actions of insulin in adipose tissue and reduction of adipose tissue mass. A-PDK1KO mice developed insulin resistance, glucose intolerance, and hepatic steatosis, and this phenotype was suppressed by additional ablation of FoxO1 specifically in adipocytes (A-PDK1/FoxO1KO mice) without an effect on adipose tissue mass. Neither circulating levels of adiponectin and leptin nor inflammatory markers in adipose tissue differed between A-PDK1KO and A-PDK1/FoxO1KO mice. Lipidomics and microarray analyses revealed that leukotriene B4(LTB4) levels in plasma and in adipose tissue as well as the expression of 5-lipoxygenase (5-LO) in adipose tissue were increased and restored in A-PDK1KO mice and A-PDK1/FoxO1KO mice, respectively. Genetic deletion of the LTB4receptor BLT1 as well as pharmacological intervention to 5-LO or BLT1 ameliorated insulin resistance in A-PDK1KO mice. Furthermore, insulin was found to inhibit LTB4production through down-regulation of 5-LO expression via the PDK1−FoxO1 pathway in isolated adipocytes. Our results indicate that insulin signaling in adipocytes negatively regulates the production of LTB4via the PDK1−FoxO1 pathway and thereby maintains systemic insulin sensitivity.
High CXCL10 expression is an independent prognostic factor and has the potential to serve as a clinically useful marker of the need for adjuvant chemotherapy after surgery in patients with advanced thoracic ESCC.
Background: Poor oral health is a risk factor for causing upper aerodigestive tract tumors, including esophageal cancer. Our aim was to determine the periodontitis rate in our cohort of esophageal cancer patients. We also analyzed whether preoperative dental examination and care reduces the likelihood of severe pneumonia after esophagectomy. Study Design: Between 2003 and 2014, 529 esophageal cancer patients received esophagectomy at Akita University Hospital. We studied 232 patients who had preoperative dental examinations and care (dental care group) retrospectively and assessed the severity of their periodontitis. The dental care group was compared to 297 patients who did not have preoperative dental care (control group) with respect to the incidence of severe pneumonia after esophagectomy. Results: Ninety-one patients (39.2%) in the dental care group were diagnosed with slight periodontitis and 69 (29.7%) were diagnosed with severe periodontitis. Among all the patients, 69 patients (13.0%) were diagnosed with grade 3B postoperative severe pneumonia. The dental care group had a significantly lower incidence of severe pneumonia than the control group. Moreover, multivariable logistic regression analysis revealed that anastomotic leakage, preoperative dental care, gender and %VC were correlated significantly with the occurrence of postoperative severe pneumonia. Conclusion: Preoperative dental examination and care by a dentist are essential to reduce the likelihood of postoperative severe pneumonia in esophageal cancer patients.
The case of a 2-month-old boy with a congenital fistula of the dural carotid-cavernous sinus is presented. This is a rare vascular anomaly in infancy, and it may cause acute changes in vision. The child was initially followed up for 1 year to see if spontaneous thrombosis would occur. The symptoms persisted, however, and intravascular surgery using platinum coils was performed for closure. After treatment, the symptoms completely resolved. Literature pertaining to this anomaly has been reviewed with particular emphasis on dural fistulas of the cavernous, transverse, sigmoid, and straight sinuses in infancy.
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