Effects of insulin resistance on endothelial function: possible mechanisms and clinical implications.

Insulin resistance (IR) is defined as a reduced responsiveness of peripheral tissues to the effects of the hormone, referring to abated ability of insulin in stimulating glucose uptake in peripheral tissues and in inhibiting hepatic glucose output. Insulin has both a vasodilatory effect, which is largely endothelium dependent through the release of nitric oxide, and a vasoconstrictory effect through the stimulation of the sympathetic nervous system and the release of endothelin-1. IR and endothelial dysfunction (ED) are not only linked by common pathogenetic mechanisms, involving deranged insulin signalling pathways, but also by other, indirect to the hormone's actions, mechanisms. Different treatment modalities have been proposed to affect positively both the metabolic effects of insulin and ED. Weight loss has been shown to improve sensitivity to insulin as a result of either altered diet or exercise. Exercise has favourable effects on endothelial function in normal states and in states of disease, in men and women, and throughout the age spectrum and, hence, in IR states. Metformin improves sensitivity to insulin and most likely affects positively ED. Studies have shown that inhibitors of the renin-angiotensin system alter IR favourably, while Angiotensin converting enzyme (ACE) inhibitors and Angiotensin receptor type II (ATII) inhibitors improve ED. Ongoing studies are expected to shed more light on the issue of whether treatment with the thiazolidinediones results in improvement of endothelial function, along with the accepted function of improving insulin sensitivity. Finally, improved endothelial function by such treatments is not in itself proof of reduced risk for atherosclerosis; this remains to be directly tested in clinical trials.

Liver metallothionein expression in thioacetamide-intoxicated rats.

Metallothioneins (MT), a group of ubiquitous low molecular weight proteins, implicated primarily in metal ion detoxification, are known to be expressed during hepatocellular proliferation after partial hepatectomy in rats. In the present study, we investigated the expression of MT in a rat model of liver injury and regeneration, induced by intraperitoneal administration of thioacetamide (TAA). The animals were killed at 0, 12, 24, 36, 48, 60, 72, 84, 96, 108 and 120 hours after TAA administration. The rate of tritiated thymidine incorporation into hepatic DNA, the enzymatic activity of thymidine kinase, and the assessment of the mitotic index in hepatocytes were used as indices of liver regeneration. Liver MTs were detected immunohistochemically. TAA administration caused severe hepatic injury, followed by regeneration. MT expression became prominent in hepatocytes as early as 12 hours post-TAA administration. At 24 and 36 hours post-TAA administration intense nuclear and cytoplasmic staining of hepatocytes was found in the vicinity of necrotic areas. The maximal nuclear and cytoplasmic MT expression coincides with the peak of hepatocyte proliferative capacity, occurring at 48 and 60 hours post-TAA administration. MT expression correlated positively with the Zn content of liver tissue, but negatively with serum one, at the time of maximum hepatocyte proliferative capacity. This study suggests that MT participates in hepatocyte replication after toxin-induced liver injury.

Serum concentrations of lignocaine before, during and after fiberoptic bronchoscopy.

BACKGROUND: Lignocaine is commonly used for local anesthesia during fiberoptic bronchoscopy (FOB). Several studies have reported the peak serum concentration of lignocaine in relation to time, but most of them did not specify the administered dose of lignocaine gel and its possible correlation with peak serum concentration. OBJECTIVE: The aim of our study was to record the plasma concentrations of lignocaine before, during and after FOB and to evaluate whether the doses for nasal and tracheobronchial anesthesia have any correlation with the peak serum concentrations of the drug. METHODS: Twelve patients with no comorbid conditions undergoing FOB were studied. Lignocaine was administered as a 2% solution using a larynx syringe, 2% gel (mean dose 182.5 +/- 15 mg) and finally 2% solution through the bronchoscope (mean dose 339 +/- 12 mg). Total dose was 622 +/- 20 mg. Venous blood samples were taken before the beginning of local anesthesia and then at 5, 10, 20, 60, 90 and 120 min thereafter. RESULTS: Our results showed that peak plasma concentrations of lignocaine were observed in 8 patients 20 min after the beginning of local anesthesia, in 3 patients 30 min afterwards and in 1 patient 60 min afterwards (2.15 +/- 0.4 microg/ml, 1.9 +/- 0.3 microg/ml, 1. 81 microg/ml, respectively). None of our patients exceeded the critical level of toxicity (5 microg/ml). Both the total and tracheobronchial doses of lignocaine were significantly correlated with peak serum concentration (r = 0.63, p = 0.05 and r = 0.64, p = 0.02, respectively). No correlation was found between the dose for nasal anesthesia and peak serum concentration. No adverse reactions were observed. CONCLUSIONS: In conclusion our data show that although the amount of lignocaine used in this study exceeded the recommended highest dose (400 mg) in all patients, no toxic levels were observed. Peak plasma concentrations were found within 20-30 min from the beginning of local anesthesia. The dose for the anesthesia of nasal mucosa represented a significant percentage of the total dose, but did not correlate with the peak serum concentration of the drug.