Caffeine-induced impairment of insulin action but not insulin signaling in human skeletal muscle is reduced by exercise

We investigated the effects of caffeine ingestion on skeletal muscle glucose uptake, glycogen synthase (GS) activity, and insulin signaling intermediates during a 100-min euglycemic-hyperinsulinemic (100 microU/ml) clamp. On two occasions, seven men performed 1-h one-legged knee extensor exercise at 3 h before the clamp. Caffeine (5 mg/kg) or placebo was administered in a randomized, double-blind fashion 1 h before the clamp. During the clamp, whole-body glucose disposal was reduced (P < 0.05) in caffeine (37.5 +/- 3.1 micromol x min(-1) x kg(-1)) vs. placebo (54.1 +/- 2.9 micromol x min(-1) x kg(-1)). In accordance, the total area under the curve over 100 min (AUC(0--100 min)) for insulin-stimulated glucose uptake in caffeine was reduced (P < 0.05) by approximately 50% in rested and exercised muscle. Caffeine also reduced (P < 0.05) GS activity before and during insulin infusion in both legs. Exercise increased insulin sensitivity of leg glucose uptake in both caffeine and placebo. Insulin increased insulin receptor tyrosine kinase (IRTK), insulin receptor substrate 1-associated phosphatidylinositol (PI) 3-kinase activities, and Ser(473) phosphorylation of protein kinase B (PKB)/Akt significantly but similarly in rested and exercised legs. Furthermore, insulin significantly decreased glycogen synthase kinase-3alpha (GSK-3alpha) activity equally in both legs. Caffeine did not alter insulin signaling in either leg. Plasma epinephrine and muscle cAMP concentrations were increased in caffeine. We conclude that 1) caffeine impairs insulin-stimulated glucose uptake and GS activity in rested and exercised human skeletal muscle; 2) caffeine-induced impairment of insulin-stimulated muscle glucose uptake and downregulation of GS activity are not accompanied by alterations in IRTK, PI 3-kinase, PKB/Akt, or GSK-3alpha but may be associated with increases in epinephrine and intramuscular cAMP concentrations; and 3) exercise reduces the detrimental effects of caffeine on insulin action in muscle.     

Characterization of intensive care unit acquired hyponatremia and hypernatremia following cardiac surgery

Purpose

Although intensive care unit (ICU) acquired sodium disturbances are common in critically ill patients, few studies have examined sodium disturbances in patients following cardiac surgery. The objective of this study was to describe the epidemiology of ICU-acquired hyponatremia and hypernatremia in patients following cardiac surgery.

Methods

We identified 6,727 adults (≥18 yr) who were admitted consecutively to a regional cardiovascular intensive care unit (CVICU) from January 1, 2000 to December 31, 2006 and were documented as having normal serum sodium levels (133 to 145 mmol·L^?1) during the first day of ICU admission. ICU-acquired hyponatremia and hypernatremia were defined as a change in serum sodium concentration to <133 mmol·L^?1 or >145 mmol·L^?1, respectively, following ICU day one.

Results

A first episode of ICU-acquired hyponatremia and hypernatremia developed in 785 (12%) and 242 (4%) patients, respectively, (95% confidence interval [CI] 11-12% and 95% CI 3-4%, respectively), with a respective incidence density of 4.2 and 1.3 patients per 100 days of ICU admission (95% CI 4.0-4.5 and 95% CI 1.2-1.5). The incidence of ICU-acquired sodium disturbances varied according to the patients’ demographic and clinical variables for both hyponatremia (age, diabetes, Acute Physiology and Chronic Health Evaluation [APACHE II] score, mechanical ventilation, length of ICU stay, serum glucose level, and serum potassium level) and hypernatremia (APACHE II score, mechanical ventilation, length of hospital stay prior to ICU admission, length of ICU stay, serum glucose level, and serum potassium level). Compared with patients with normal serum sodium levels, hospital mortality was increased in patients with ICU-acquired hyponatremia (1.6% vs 10%, respectively; P < 0.001) and ICU-acquired hypernatremia (1.6% vs 14%, respectively; P < 0.001).

Conclusion

ICU-acquired hyponatremia and hypernatremia are common complications in critically ill patients following cardiac surgery. They are associated with patient demographic and clinical characteristics and an increased risk of hospital mortality.     

Emergency Medical Service (EMS) systems in developed and developing countries

OBJECTIVES: To compare patient- and injury-related characteristics of trauma victims and pre-hospital trauma care systems among different developed and developing countries. METHOD: We collated de-identified patient-level data from national or local trauma registries in Australia, Austria, Canada, Greece, Germany, Iran, Mexico, New Zealand, the Netherlands, the United Kingdom and the United States. Patient and injury-related characteristics of trauma victims with injury severity score (ISS) >15 and the pre-hospital trauma care provided to these patients were compared among different countries. RESULTS: A total of 30,339 subjects from one or several regions in 11 countries were included in this analysis. Austria (51%), Germany (41%) and Australia (30%) reported the highest proportion of air ambulance use. Monterrey, Mexico (median 10.1min) and Montreal, Canada (median 16.1min) reported the shortest and Germany (median: 30min) and Austria (median: 26min) reported the longest scene time. Use of intravenous fluid therapy among advanced EMS systems without physicians as pre-hospital care providers, varied from 30% (in the Netherlands) to 55% (in the US). The corresponding percentages in advanced EMS systems with physicians actively involved in pre-hospital trauma care, excluding Montreal in Canada, ranged from 63% (in London, in the UK) to 75% in Germany and Austria. Austria and Germany also reported the highest percentage of pre-hospital intubation (61% and 56%, respectively). CONCLUSION: This study provides an early look at international variability in patient mix, process of care, and performance of different pre-hospital trauma care systems worldwide. International efforts should be devoted to developing a minimum standard data set for trauma patients.     

The Rab GTPase-activating protein AS160 integrates Akt, protein kinase C, and AMP-activated protein kinase signals regulating GLUT4 traffic

Insulin-dependent phosphorylation of Akt target AS160 is required for GLUT4 translocation. Insulin and platelet-derived growth factor (PDGF) (Akt activators) or activation of conventional/novel (c/n) protein kinase C (PKC) and 5' AMP-activated protein kinase (AMPK) all promote a rise in membrane GLUT4 in skeletal muscle and cultured cells. However, the downstream effectors linking these pathways to GLUT4 traffic are unknown. Here we explore the hypothesis that AS160 is a molecular link among diverse signaling cascades converging on GLUT4 translocation. PDGF and insulin increased AS160 phosphorylation in CHO-IR cells. Stimuli that activate c/n PKC or AMPK also elevated AS160 phosphorylation. We therefore examined if these signaling pathways engage AS160 to regulate GLUT4 traffic in muscle cells. Nonphosphorylatable AS160 (4P-AS160) virtually abolished the net surface GLUT4myc gains elicited by insulin, PDGF, K(+) depolarization, or 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside but partly, yet significantly, inhibited the effects of 4-phorbol-12-myristate-13-acetate. However, the hypertonicity or 2,4-dinitrophenol-dependent gains in surface GLUT4myc were unaffected by 4P-AS160. RK-AS160 (GTPase-activating protein [GAP] inactive) or 4PRK-AS160 (GAP inactive, nonphosphorylatable) had no effect on surface GLUT4myc elicited by all stimuli. Collectively, these results indicate that activation of Akt, c/n PKC, or alpha2-AMPK intersect at AS160 to regulate GLUT4 traffic, as well as highlight the potential of AS160 as a therapy target to increase muscle glucose uptake.     

Laparoscopic ureteroureterostomy for the management of obstructive uropathy caused by congenital ureteric entrapment in the iliac bone

A rare case of congenital entrapment of the left ureter in an iliac bone canal causing left side hydroureteronephrosis is reported. The patient represented a case of congenital ureteral entrapment in a reversed C-shaped iliac bone canal that was missed before his laparoscopy. The ureter also had a retro-iliac course. The patient was successfully managed by laparoscopic ureteroureterostomy. Interestingly, in our experience, laparoscopy provided a minimally invasive milieu for both diagnosis and correction of this rare cause of obstructive uropathy.     

Does liberal use of bone wax increase the risk of mediastinitis?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether bone wax increases the risk of mediastinitis in patients undergoing cardiac surgery. Altogether 276 papers were found using the reported search, of which five presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these papers are tabulated. We conclude that animal studies indicate that there are strong reasons for concern over the liberal usage of bone wax.     

Endovascular management of an arteriovenous fistula and concomitant pseudoaneurysm in an intravenous drug abuser

An interesting case of an intravenous drug abuser who had endovascular management of an arteriovenous fistula and concomitant pseudoaneurysm, resulting from recurrent puncture of the femoral artery is reported in this study.     

Laser-induced thermal injury to dermal blood vessels: analysis of wavelength (585 nm vs. 595 nm), cryogen spray cooling, and wound healing effects

BACKGROUND AND OBJECTIVES: Successful laser treatment of cutaneous hyper-vascular lesions requires appropriate laser irradiation parameters for selective photothermolysis of ectatic dermal blood vessels as well as appropriate cooling parameters for epidermal protection based on an individual patient basis. Using the rabbit ear as an in vivo model for dermal vasculature, we investigated the influences of laser wavelength (585 nm vs. 595 nm) and cryogen spray cooling with various spurt durations on the laser-induced thermal injury to dermal blood vessels. Wound healing response was also evaluated in 2 hours and 4 days. STUDY DESIGN/MATERIALS AND METHODS: Flashlamp-pumped pulsed dye laser ScleroPlus (operated at the wavelength of 585 or 595 nm) was used for the comparison between the influences of two wavelengths (585 nm vs. 595 nm). R134-a cryogen spurts with the durations from 50 to 300 milliseconds were sprayed onto the sites to be irradiated and terminated 20 milliseconds before the onset of the laser pulses. In vivo rabbit ear was used as the model for cutaneous hyper-vascular lesions. Totally 10 New Zealand Albino white rabbits were experimented and in each rabbit ear six to seven sites were irradiated. Five animals were sacrificed 2 hours after the irradiation, and the remaining five sacrificed 4 days after the irradiation. Thermal injury to the blood vessel was assessed by hematoxylin and eosin stained histological sections and confirmed by an apoptosis assay. RESULTS: When the radiant exposures were above 10 J/cm2, 595 nm wavelength induced equivalent or more severe thermal injury to dermal blood vessels than 585 nm. Cryogen spray cooling with the spurt durations above 100 milliseconds resulted in increased depth of the most superficial thermal injury to dermal blood vessels than without cooling, indicating that superficial blood vessels were non-specifically cooled by the cryogen spurts applied at these parameters. Laser-induced thermal injury was significantly healed in the rabbit ear vasculature at 4 days post irradiation. CONCLUSIONS: Given sufficient radiant exposure, 595 nm wavelength can induce equivalent or more severe vascular injury compared with 585 nm. Cryogen spray cooling with the spurt durations above 100 ms may impair the photocoagulation of superficial blood vessels. Irreversible thermal injury to blood vessel can be achieved only when the basement membrane of blood vessel wall is irreversibly damaged.     

Remote ischemic preconditioning in major vascular surgery

Remote ischemic preconditioning is a physiologic mechanism in mammalian species whereby brief exposure to nonlethal ischemia in one tissue confers protection against a prolonged ischemic insult in a distant tissue. First described almost 15 years ago, it has been slow to translate into clinical practice. Several clinical trials have recently reported that remote ischemic preconditioning reduces myocardial injury after major cardiovascular surgery. In addition, a randomized trial in patients undergoing open abdominal aortic aneurysm repair reported a significant reduction in perioperative myocardial infarctions. Remote ischemic preconditioning is easily performed and likely to prove highly cost-effective. large-scale trials of the technique are warranted in patients undergoing major vascular surgery.