Adipose tissue expansion during obesity is associated with increased macrophage infiltration. Macrophage-derived factors significantly alter adipocyte function, inducing inflammatory responses and decreasing insulin sensitivity. Identification of the major factors that mediate detrimental effects of macrophages on adipocytes may offer potential therapeutic targets. IL-1β, a proinflammatory cytokine, is suggested to be involved in the development of insulin resistance. This study investigated the role of IL-1β in macrophage-adipocyte cross-talk, which affects insulin signaling in human adipocytes. Using macrophage-conditioned (MC) medium and human primary adipocytes, we examined the effect of IL-1β antagonism on the insulin signaling pathway. Gene expression profile and protein abundance of insulin signaling molecules were determined, as was the production of proinflammatory cytokine/chemokines. We also examined whether IL-1β mediates MC medium-induced alteration in adipocyte lipid storage. MC medium and IL-1β significantly reduced gene expression and protein abundance of insulin signaling molecules, including insulin receptor substrate-1, phosphoinositide 3-kinase p85α, and glucose transporter 4 and phosphorylation of Akt. In contrast, the expression and release of the proinflammatory markers, including IL-6, IL-8, monocyte chemotactic protein-1, and chemokine (C-C motif) ligand 5 by adipocytes were markedly increased. These changes were significantly reduced by blocking IL-1β activity, its receptor binding, or its production by macrophages. MC medium-inhibited expression of the adipogenic factors and -stimulated lipolysis was also blunted with IL-1β neutralization. We conclude that IL-1β mediates, at least in part, the effect of macrophages on insulin signaling and proinflammatory response in human adipocytes. Blocking IL-1β could be beneficial for preventing obesity-associated insulin resistance and inflammation in human adipose tissue.
Patients with ATAD who are operated on by lower-volume surgeons experience higher levels of in-hospital mortality. Directing these patients to higher-volume surgeons may be a strategy to reduce in-hospital mortality.
The result of surgical treatment of 21 infected femoral pseudoaneurysms in 19 intravenous drug addicts was evaluated. Eight pseudoaneurysms involved only the common or superficial femoral artery and 13 involved the femoral bifurcation. Excision and ligation was performed as the sole procedure in 19 instances, and revascularization by bypass through the obturator route was carried out in two. The mean follow-up was 12.3 months. One patient required an above-knee amputation. The resultant ischaemia was greater after triple vessel ligation (mean ankle:brachial pressure index (ABPI) 0.41) than single vessel ligation (mean ABPI 0.58). Postoperative bleeding occurred in one patient. Intermittent claudication was present in 14 patients after excision and ligation. Claudication was universal and more severe after triple than after single vessel ligation. There was no subsequent limb loss. Excision and ligation is safe and is the treatment of choice for infected femoral pseudoaneurysm in drug addicts.
A total of 611 patients with carcinoma of the oesophagus or gastric cardia were operated on between July 1982 and December 1989. Resection was performed in 491 patients (one-stage, 483; two-stage, eight), bypass operation in 97, and 23 had exploration alone. The anastomoses of 580 patients with one-stage resection and bypass operations were evaluated. Hand-sewn anastomosis using a single layer of continuous absorbable monofilament suture was performed in 304 patients (221 resections and 83 bypasses). A stapled anastomosis was performed on 276 patients (262 resections and 14 bypasses). Following resection, there were 11 (5 per cent) anastomotic leaks in the hand-sewn group and ten (3.8 per cent) in the stapled anastomosis group (P = 0.69). Excluding anastomotic leaks, hospital mortality and anastomotic recurrence, stricture occurred in 18 of 172 hand-sewn anastomoses (10.5 per cent) and in 57 of 195 stapled anastomoses (29.2 per cent) (P less than 0.001). In patients who had bypass operations there were 12 anastomotic leaks, ten in the hand-sewn group (12.0 per cent) and two in the stapled anastomosis group (14.3 per cent). Only two of the discharged patients with bypass developed anastomotic strictures, a low incidence probably because of short survival. In addition, there were 245 subsidiary anastomoses made in the abdomen by the hand-sewn method as part of the reconstructive procedure, and there was one leak. The results of this non-randomized study suggest that hand-sewn anastomosis using a single layer continuous technique for the oesophagus is as safe as the use of circular staplers; hand-sewn anastomosis is less likely to become stenotic.
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