Roles of phosphatidylinositol 3-kinase-Akt and NADPH oxidase in adenosine 5'-triphosphate-sensitive K+ channel function impaired by high glucose in the human artery

The present study was designed to examine roles of the phosphatidylinositol 3-kinase-Akt pathway and reduced nicotinamide-adenine dinucleotide phosphate oxidases in the reduced ATP-sensitive K(+) channel function via superoxide produced by high glucose in the human artery. We evaluated the activity of the phosphatidylinositol 3-kinase-Akt pathway, as well as reduced nicotinamide-adenine dinucleotide phosphate oxidases, the intracellular levels of superoxide and ATP-sensitive K(+) channel function in the human omental artery without endothelium. Levels of the p85-alpha subunit and reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits, including p47phox, p22phox, and Rac-1, increased in the membrane fraction from arteries treated with D-glucose (20 mmol/L) accompanied by increased intracellular superoxide production. High glucose simultaneously augmented Akt phosphorylation at Ser 473, as well as Thr 308 in the human vascular smooth muscle cells. A phosphatidylinositol 3-kinase inhibitor LY294002, as well as tiron and apocynin, restored vasorelaxation and hyperpolarization in response to an ATP-sensitive K(+) channel opener levcromakalim. Therefore, it can be concluded that the activation of the phosphatidylinositol 3-kinase-Akt pathway, in combination with the translocation of p47phox, p22phox, and Rac-1, contributes to the superoxide production induced by high glucose, resulting in the impairment of ATP-sensitive K(+) channel function in the human visceral artery.     

Does lidocaine provoke clinically significant vasospasm?

Two cases with peripheral vasoconstriction possibly caused by topical application of lidocaine were reported. A potential risk of vasospasm provoked by lidocaine may be a pitfall for anesthesiologists because lidocaine is commonly considered a vasodilator.     

G6PD enzyme activity in normal term Malaysian neonates and adults using a OSMMR2000-D kit with Hb normalization

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is one of the commonest causes of neonatal jaundice in Malaysia. Screening of cord blood for G6PD deficiency by the semiquantitative fluorescent spot test (FST) is performed in Malaysia but this test can miss cases of partial G6PD deficiency. The OSMMR-D kit assay measures G6PD activity and hemoglobin (Hb) concentration, allowing direct expression of results in U/gHb. We evaluated this method and established the normal range for G6PD activity in normal term neonates and adults. EDTA blood from 94 neonates and 295 adults (age 15-59 years old) with normal Hb and FST were selected. The normal means for G6PD activity for neonates and adults were 12.43 +/- 2.28 U/gHb and 9.21 +/- 2.6 U/gHb, respectively; the reference ranges for normal G6PD activity in neonates and adults were 10.15-14.71 U/gHb and 6.61-11.81 U/gHb respectively. There were no significant differences in mean normal G6PD activity between the Malays and Chinese racial groups or between genders. The upper and lower limit cut-off points for partial deficiency in neonates were 7.4 U/gHb (60% of the normal mean) and 2.5 U/gHb (20% of the normal mean), respectively. For adults, the upper and lower limit cut-off points for partial deficiency in adults were 5.52 U/gHb (60% of the normal mean) and 1.84 U/gHb (20% of the normal mean), respectively. The quantitation of G6PD enzymes using this OSMMR-D kit with Hb normalization was simple since the Hb was analyzed simultaneously and the results were reproducible with a CV of less than 5%.     

Molecular Characterisation of α‐ and β‐Thalassaemia among Indigenous Senoi Orang Asli Communities in Peninsular Malaysia

Thalassaemia is a public health problem in Malaysia, with each ethnic group having their own common mutations. However, there is a lack on data on the prevalence and common mutations among the indigenous people. This cross‐sectional study was performed to determine the common mutations of α‐ and β‐thalassaemia among the subethnic groups of Senoi, the largest Orang Asli group in Peninsular Malaysia. Blood samples collected from six Senoi subethnic groups were analysed for full blood count and haemoglobin analysis (HbAn). Samples with abnormal findings were then screened for α‐ and β‐globin gene mutations. Out of the 752 samples collected, 255 showed abnormal HbAn results, and 122 cases showing abnormal red cell indices with normal HbAn findings were subjected to molecular screening. DNA analysis revealed a mixture of α‐ and β‐globin gene mutations with 25 concomitant cases. The types of gene abnormalities detected for α‐thalassaemia were termination codon (T>C) Hb CS (α^CSα), Cd59 (G>A) haemoglobin Adana (Hb Adana) (α^Cd59α), initiation codon (ATG>A‐G) (α^IniCdα), two‐gene deletion (–^SEA), and single‐gene 3.7‐kb deletion (‐α^3.7). For β‐thalassaemia, there were Cd26 (G>A) Hb E (β^E), Cd19 (A>G) Haemoglobin Malay (Hb Malay) (β^Cd19), and IVS 1–5 (G>C) (β^{IVS 1–5}).     

Use of the laryngeal mask airway in combination with regional anesthesia facilitates induction and emergence from general anesthesia in patients undergoing colorectal surgery

The laryngeal mask airway (LMA) is selected as an alternative to the endotracheal tube (ETT) when rapid recovery from general anesthesia is considered. However, the clinical significance of this airway for abdominal surgery is unclear. Thus, we evaluated whether the LMA, in combination with regional anesthesia, facilitates the induction of and emergence from general anesthesia in patients undergoing elective colorectal surgery. Anesthesia-controlled time in a ETT/Epidural Anesthesia (EA) group [n = 11; general anesthesia, combined with epidural anesthesia, was maintained by sevoflurane (< 3%) supplemented with a fixed rate of propofol (3 mg/kg/h) under controlled ventilation using the ETT] was compared with that in a LMA/Combined Spinal-Epidural Anesthesia (CSEA) group [n = 10; in combination with spinal-epidural anesthesia, general anesthesia was maintained as the same protocol as the ETT/EA under spontaneous ventilation using the LMA]. Time for airway placement in the LMA/CSEA group was significantly shorter than that in the ETT/EA group. Intervals from the end of surgery until the removal of the airway or the decision to exit the operating room in the LMA/CSEA group were shorter than those in the ETT/EA group. No practical sign of aspiration pneumonia and/or atelectasis was found in patients in either group. Under the circumstance of regional anesthesia being requested for post-surgical pain management, we concluded that the LMA facilitated the emergence from as well as the induction of anesthesia without any practical complication when used for patients in colorectal surgery.     

Prothrombotic roles of substance-P, neurokinin-1 receptors and leukocytes in the platelet-dependent clot formation in whole blood

A number of types of non-neuronal cells including leukocytes have been confirmed to possess substance-P and its specific neurokinin-1 receptor (NK1R), while the pathophysiological roles of substance-P in these cells remain to be established. Effects of substance-P through NK1R on platelet-dependent clot formation were evaluated by using an oscillating-probe viscoelastometer. The clot signal, indicative of the clot strength in blood-derived samples, was measured after the stimulation with celite and Ca²⁺. Substance-P (10 nM) increased the clot signal of whole blood obtained from healthy volunteers, especially modulating the platelet-dependent distinctive peak in traces of the signal. A NK1R antagonist Spantide (500 nM) blocked such substance-P derived change, suggesting the involvement of platelets in the action of substance-P. In contrast, substance-P did not increase the clot signal of platelet-containing but leukocyte-removed plasma. From these, we conclude that substance-P promotes platelet-dependent clot formation through NK1R, in which leukocytes appear to be involved.     

32‐channel phased‐array receive with asymmetric birdcage transmit coil for hyperpolarized xenon‐129 lung imaging

Hyperpolarized xenon‐129 has the potential to become a noninvasive contrast agent for lung MRI. In addition to its utility for imaging of ventilated airspaces, the property of xenon to dissolve in lung tissue and blood upon inhalation provides the opportunity to study gas exchange. Implementations of imaging protocols for obtaining regional parameters that exploit the dissolved phase are limited by the available signal‐to‐noise ratio, excitation homogeneity, and length of acquisition times. To address these challenges, a 32‐channel receive‐array coil complemented by an asymmetric birdcage transmit coil tuned to the hyperpolarized xenon‐129 resonance at 3 T was developed. First results of spin‐density imaging in healthy subjects and subjects with obstructive lung disease demonstrated the improvements in image quality by high‐resolution ventilation images with high signal‐to‐noise ratio. Parallel imaging performance of the phased‐array coil was demonstrated by acceleration factors up to three in 2D acquisitions and up to six in 3D acquisitions. Transmit‐field maps showed a regional variation of only 8% across the whole lung. The newly developed phased‐array receive coil with the birdcage transmit coil will lead to an improvement in existing imaging protocols, but moreover enable the development of new, functional lung imaging protocols based on the improvements in excitation homogeneity, signal‐to‐noise ratio, and acquisition speed. Magn Reson Med 70:576–583, 2013. © 2012 Wiley Periodicals, Inc.