Nitric Oxide Signaling Pathway in Ventral Tegmental Area is Involved in Regulation of 7,8-Dihydroxyflavone on Alcohol Consumption in Rats.

We recently reported that intraperitoneal injection of 7,8-dihydroxyflavone (7,8-DHF), a brain-derived neurotrophic factor-mimicking small compound, could attenuate alcohol-related behaviors in a two-bottle choice ethanol consumption procedure (IA2BC) in rats via tropomyosin receptor kinase B in the ventral tegmental area (VTA), which is closely related to alcohol use disorder. However, the detailed mechanisms underlying the regulation of 7,8-DHF on alcohol drinking behavior remain elusive. In this study, we determined the role of nitric oxide (NO), a pleiotropic signaling molecule, in the VTA in the action of 7,8-DHF upon alcohol drinking behavior. Intermittent alcohol exposure led to the overexpression of NO in the VTA, especially 72 h after withdrawal from four weeks of ethanol exposure in IA2BC rats. A higher amount of alcohol intake was also found at the same time point, consistent with the overexpression of NO in the VTA. Microinjection of NG-Nitro-l-Arginine Methyl Ester, (NO synthase inhibitor) or 2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NO scavenger) into the VTA inhibited alcohol intake, whereas application of S-Nitroso-N-acetyl-DL-penicillamine (SNAP, the NO donor) in the VTA further enhanced alcohol consumption in IA2BC rats. Interestingly, either 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (a sGC inhibitor) or KT5823 [a selective protein kinase G (PKG) inhibitor] blocked NO's enhancing effect on ethanol intake. Intraperitoneal injection of 7,8-DHF reduced the overexpression of NO; SNAP microinjected into the VTA reversed the inhibitory effects of 7,8-DHF on alcohol consumption. Our findings suggest that NO-cGMP-PKG might be involved in regulation of 7,8-DHF on alcohol consumption in IA2BC rats.

[A dye densitometry analysis method for noninvasive measurement of cardiac output based on NIRS].

Currently, there exist technology problems in cardiac output (CO) parameter detection clinically, such as invasive and complex operation, as well as possibility of infection and death for patients. In order to solve these problems, a noninvasive and continuous method based on NIRS for CO detection was presented. In this way, the concentration changing of indocyanine green (ICG) dye in the patient's arterial blood was dynamically measured and analyzed, so that the CO could be noninvasively and continuously measured according to the characteristic parameters of dye densitometry curve. While the ICG dye was injected into the patient's body by the median cubital vein, block of photoelectric pulse dye densitometry measurement system as the lower machine acquired pulse wave data and uploaded the data to upper computer. In the scheme, two specialized light sources of LED at 940 and 805 nm were used to capture the signals of sufferer's fingertip pulse wave synchronously and successively. The CO value could then be successfully calculated through drawing complete ICG concentration variation of dye dilution and excretion process and computing mean transmission time (MTT) by upper computer. Compared with the "gold standard" method of thermodilution, the maximum relative error of this method was below 9. 76%, and the mean relative error was below 4. 39%. The result indicates that the method can be used as a kind of convenient operation, noninvasive and continuous solution for clinical CO measurement.

VEGF induces angiogenesis in a zebrafish embryo glioma model established by transplantation of human glioma cells.

Zebrafish (Danio rerio) is becoming an increasingly popular vertebrate cancer model. In this study, we established a xenotransplanted zebrafish embryo glioma model to further investigate the molecular mechanisms of tumor angiogenesis. We find that the glioma cell line U87 can survive, proliferate and induce additional SIV branches in zebrafish embryos. In addition, by the means of in situ hybridization and quantitive RT-PCR analyses we find that the transplanted U87 cells can induce the ectopic zebrafish vascular endothelial growth factor A (VEGF A) and its receptor VEGFR2/KDR mRNA expression and increase their expression levels, resulting in additional SIV branches.

Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland.

Previous studies have found a strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome in Asian areas including Taiwan, Hongkong and Thailand. This study explores the association between HLA-B*1502 allele and carbamazepine-induced cutaneous adverse reactions in Han Chinese of southern China mainland, and find the genetic marker that can predict carbamazepine-induced cutaneous adverse reactions. HLA-B*1502 allele genotyping was performed by a polymerase chain reaction-sequence specific primers (PCR-SSP) method in 48 Han Chinese subjects who had carbamazepine-induced cutaneous adverse reactions, including 9 severe cutaneous adverse reaction patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and 39 cutaneous adverse reaction patients with maculopapular eruption (MPE). Meanwhile 80 carbamazepine-tolerant controls and 62 healthy individuals were also tested. The frequency of HLA-B*1502 allele among SJS/TEN patients (100%) is significantly higher than carbamazepine-tolerant controls (13.75%, P<0.001) and healthy individuals (17.74%, P<0.001). But the frequency between MPE patients and carbamazepine-tolerant controls (25.64% vs.13.75%, P=0.110) did not have any significant difference. The data showed that HLA-B*1502 allele is strongly associated with carbamazepine-induced SJS/TEN but not MPE in Han Chinese of southern China mainland.