The presence of baseline SMI and MA are associated with future CHD events in asymptomatic patients with T2D and may be of practical use in risk stratification.

Resveratrol is a dietary phytochemical that has been shown to inhibit proliferation of a number of cell lines, and it behaves as a chemopreventive agent in assays that measure the three stages of carcinogenesis. We tested for its chemopreventive potential against gastric cancer by determining its interaction with signaling mechanisms that contribute to the proliferation of transformed cells. Low levels of exogenous reactive oxygen (H(2)O(2)) stimulated [(3)H]thymidine uptake in human gastric adenocarcinoma SNU-1 cells, whereas resveratrol suppressed both synthesis of DNA and generation of endogenous O(2)(-) but stimulated nitric oxide (NO) synthase (NOS) activity. To address the role of NO in the antioxidant action of resveratrol, we measured the effect of sodium nitroprusside (SNP), an NO donor, on O(2)(-) generation and on [(3)H]thymidine incorporation. SNP inhibited DNA synthesis and suppressed ionomycin-stimulated O(2)(-) generation in a concentration-dependent manner. Our results revealed that the antioxidant action of resveratrol toward gastric adenocarcinoma SNU-1 cells may reside in its ability to stimulate NOS to produce low levels of NO, which, in turn, exert antioxidant action. Resveratrol-induced inhibition of SNU-1 proliferation may be partly dependent on NO formation, and we hypothesize that resveratrol exerts its antiproliferative action by interfering with the action of endogenously produced reactive oxygen. These data are supportive of the action of NO against reactive oxygen and suggest that a resveratrol-rich diet may be chemopreventive against gastric cancer.

Objective: Somatostatin (SST) analogues are a key option in the management of a variety of conditions, including acromegaly. Tachyphylaxis to SST analogues is not documented in acromegaly. We describe such a phenomenon. Design and methods: A 74-year-old female with acromegaly previously treated with 90 Y implant, external radiotherapy and thrice daily s.c. octreotide had stable GH levels of 19 mU/l. GH progressively rose following switches to lanreotide and depot octreotide as Sandostatin LAR: from 29 to 126 mU/l. Magnetic resonance imaging and 111 In-pentetreotide scanning revealed no tumour growth or alteration in SST receptor (SSTR) status. Tachyphylaxis to SST analogues was considered. Therapy was discontinued and re-introduced in daily 200 mg/24 h increments by continuous s.c. infusion, to a maximum of 1000 mg/24 h, and maintained over 3 weeks with daily, followed by weekly, GH profiles. Competitive 125 I-octreotide radioligand binding assays measured in vitro bio-activity of anti-SST analogue antibodies. In vitro SSTR binding studies utilised SSTR-expressing rat cortex membrane. Results: Median GH fell by 93% from 504 to 39.5 mU/l and rose reproducibly on continued infusion to 120 mU/l. Octreotide withdrawal for 16 h produced a 64% increase in sensitivity. High-affinity IgG anti-lanreotide ðIC 50 ¼ 187 pmol=lÞ and anti-octreotide ðIC 50 ¼ 82 nmol=lÞ antibody, with no crossreactivity with natural SST, was demonstrated. In vitro inhibition of 125 I-octreotide SSTR binding by anti-SST analogue crossreacting antibody was observed at 1:1 serum dilution. Conclusions: This is the first report of tachyphylaxis to SST analogues in acromegaly. We believe that the short time course of resensitisation following acute octreotide withdrawal is suggestive of an effect(s) on receptor function or on the receptor signal transduction cascade at sites further downstream, rather than an immune-mediated phenomenon.

Our observations show that withholding an antithyroid drug in excess of just over 2 weeks prior to administering a fixed administered activity of radioiodine in patients with thyrotoxicosis leads to the lowest reported failure rate, irrespective of the underlying cause. One possible mechanism for this could be the avoidance of drug induced radio-resistance.