[Effect of obstructive sleep apnea on cardiopulmonary function in patients with chronic obstructive pulmonary disease].

Objective: To study the characteristics of cardiopulmonary function in patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) overlapping syndrome (OS). Methods: A total of 149 COPD patients, who were on stable treatment, were enrolled from the Second Affiliated Hospital of Soochow University from December 2017 to December 2019. The patients were divided into the OS group (n=56) and the COPD only group (n=93) according to their apnea hypopnea index (AHI) measured by the Apnealink device. Data were gathered from polysomnograph (PSG), spirometry, arterial blood gas and N-terminal pro-brain natriuretic peptide (NT-proBNP) assay to assess the cardiopulmonary function of patients. Partial correlation analysis was used to analyze the correlation between AHI and various factors, to study the characteristic changes in the cardiopulmonary function of these OS patients. Results: There were no significant cross-group differences in age and gender (all P>0.05). In the OS group, the forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC), the forced expiratory volume in the first second expressed as percent predicted (FEV1%pred), pH[M (Q1, Q3)], partial pressure of oxygen (PaO2) and oxygen saturation (SaO2) were lower than those in the COPD group [(49.46±12.98)% vs (54.38±11.72)%, (47.86±14.78)% vs (57.78±15.81)%, 7.37(7.34, 7.39) vs 7.40(7.39, 7.41), (80.75±10.20) vs (84.28±8.43) mmHg (1 mmHg=0.133 kPa), (94.46±2.52)% vs (95.74±2.28)%], whereas partial pressure of carbon dioxide (PaCO2) [M (Q1, Q3)] was higher than that in the COPD group [55.00 (45.50, 60.00) vs 44.00(40.00, 48.00)mmHg] (all P<0.05). Pulmonary arterial pressure and plasma NT-proBNP levels [M (Q1, Q3)] in the OS group were significantly higher than those in the COPD group [38.90 (28.60, 49.05) vs 28.60 (24.95, 32.60) mmHg, 434.00 (273.75, 631.00) vs 136.00 (86.00, 205.00) pg/ml] (P<0.05). Partial correlation analysis showed that AHI was positively correlated with PaCO2, pulmonary artery pressure, NT-proBNP, and acute exacerbation events (r values: 0.496, 0.544, 0.628, 0.446), and negatively correlated with FEV1/FVC, FEV1%pred, pH, PaO2, and SaO2 (r values:-0.309, -0.346, -0.410, -0.289, -0.267) (all P<0.05). Conclusion: Patients with OS suffer from more severe hypoxemia, hypercapnia and pulmonary function damage, and their pulmonary arterial pressure and NT-proBNP are significantly higher than those with COPD only.

The metabolic regulation of fenofibrate is dependent on dietary protein content in male juveniles of Nile tilapia (Oreochromis niloticus).

The fenofibrate functions in mammals could be affected by many factors such as dietary nutrient levels and physiological status. However, this phenomenon has not been well studied in fish. The goal of our study was to investigate the effect of dietary protein contents on metabolic regulation of fenofibrate in Nile tilapia. An 8-week experiment was conducted to feed fish with four diets at two protein levels (28 and 38 %) with or without the supplementation of fenofibrate (200 mg/kg body weight per d). After the trial, the body morphometric parameters, plasma biochemical parameters and quantitative PCR data were examined. These results showed that fenofibrate significantly reduced the feeding intake and weight gain rate, increased the oxidative stress (increased plasma methane dicarboxylic aldehyde) and liver : body ratio (increased hepatosomatic index) in the low protein (LP)-fed fish. In contrast, fenofibrate exhibited a lipid-lowering (reduced hepatic lipid) effect and up-regulated the expressions of the genes related to lipid catabolism, transport and anabolic metabolism in the high protein (HP)-fed fish. The present study suggested that lipid-lowering effect of fenofibrate would be strengthened in the fish fed with the HP diet containing high energy, but in the fish fed with the LP diet containing low energy, the fenofibrate treatment would cause adverse effects for metabolism. Taking together, our study showed that the metabolic regulation of fenofibrate in Nile tilapia was dependent not only on feed energy content but also on dietary nutrient composition, such as dietary protein and/or lipid levels.

[Risk factor analysis of the patients with solitary pulmonary nodules and establishment of a prediction model for the probability of malignancy].

Objective: This study aims to analyze the relationship among the clinical features, radiologic characteristics and pathological diagnosis in patients with solitary pulmonary nodules, and establish a prediction model for the probability of malignancy. Methods: Clinical data of 372 patients with solitary pulmonary nodules who underwent surgical resection with definite postoperative pathological diagnosis were retrospectively analyzed. In these cases, we collected clinical and radiologic features including gender, age, smoking history, history of tumor, family history of cancer, the location of lesion, ground-glass opacity, maximum diameter, calcification, vessel convergence sign, vacuole sign, pleural indentation, speculation and lobulation. The cases were divided to modeling group (268 cases) and validation group (104 cases). A new prediction model was established by logistic regression analying the data from modeling group. Then the data of validation group was planned to validate the efficiency of the new model, and was compared with three classical models(Mayo model, VA model and LiYun model). With the calculated probability values for each model from validation group, SPSS 22.0 was used to draw the receiver operating characteristic curve, to assess the predictive value of this new model. Results: 112 benign SPNs and 156 malignant SPNs were included in modeling group. Multivariable logistic regression analysis showed that gender, age, history of tumor, ground -glass opacity, maximum diameter, and speculation were independent predictors of malignancy in patients with SPN(P<0.05). We calculated a prediction model for the probability of malignancy as follow: p=e(x)/(1+ e(x)), x=-4.8029-0.743×gender+ 0.057×age+ 1.306×history of tumor+ 1.305×ground-glass opacity+ 0.051×maximum diameter+ 1.043×speculation. When the data of validation group was added to the four-mathematical prediction model, The area under the curve of our mathematical prediction model was 0.742, which is greater than other models (Mayo 0.696, VA 0.634, LiYun 0.681), while the differences between any two of the four models were not significant (P>0.05). Conclusions: Age of patient, gender, history of tumor, ground-glass opacity, maximum diameter and speculation are independent predictors of malignancy in patients with solitary pulmonary nodule. This logistic regression prediction mathematic model is not inferior to those classical models in estimating the prognosis of SPNs.

[Comparison of contrast sensitivity and wavefront aberrations with myopic].

Objective: Correlation analysis of visual acuity, wavefront aberrations and contrast sensitivity in myopia. Methods: Retrospective study. One hundred and twelve patients with myopia(209 eyes) from April 2013 to August 2015 were enrolled in our study. All subjects were divided into various groups to investigate the relationship between wavefront aberrations and contrast sensitivity in myopic eyes.The correlations between ocular aberrations and contrast sensitivity(4 spatial frequency) in myopia eyes were analyzed using multivariate stepwise regression. Results: The AULCSF in the BCVA 1.2 were 1.32±0.10,1.30±0.12 respectively in the light and dark conditions,, which were higher than those in the BCVA 1.0 (t=-3.58 and-2.48, P<0.05). There was no significant difference between AULCSF in dark glare condition.At 4mm and 6mm pupil diameters,The difference in Z(-)(33) of ocular higher-order aberrations between the BCVA 1.0 and the BCVA 1.2 was statistically significant (t=2.09, P=0.04; t=-2.05, P=0.04). Differences between the other ocular higher-order aberrations and corneal aberrations were not statistically significant.The spherical aberrations of the low contrast sensitivity group were (0.019±0.010), (0.136±0.117) and(0.006±0.003)µm separately under the condition of bright light, dark light and dark glare light, which were higher than other groups (0.013±0.006) , (0.083±0.054) , (0.004±0.002) µm (t=1.10, 2.65, 2.44, P<0.05). The values of AULCSF for the larger spherical aberrations under dark light and dark glare light conditions were 1.281±0.126 and 1.216±0.154 respectively which were lower than the AULCSF 1.281±0.126, 1.216±0.154 of the another spherical aberrations group (t=2.14, 1.98, P<0.05). It was found that the S(All) RMS and spherical aberrations under different frequencies and illuminating conditions were negatively correlated with CS.Vertical coma was positively correlated with CS. Conclusions: Better BCVA may achieve better visual quality.In the case of the same BCVA, there are differences in visual quality.Higher order aberrations are the main factor affecting this result, especially the spherical aberrations.Total aberrations and spherical aberration had a negative correlation with visual quality.Vertical coma had a positive affects with visual quality. (Chin J Ophthalmol, 2018, 54: 748-755).

A QTL with Major Effect on Reducing Stripe Rust Severity Detected From a Chinese Wheat Landrace.

Stripe rust, a devastating disease of wheat worldwide, can be controlled by use of diverse wheat resistance resources. To find new quantitative trait loci (QTL) for resistance to stripe rust, Qing Shumai (a Chinese winter wheat landrace possessing slow rusting resistance) was crossed with the susceptible line Mingxian 169. The parents and 276 recombinant inbred lines (RILs) from the cross were evaluated in five environments involving two locations (Gansu and Shandong provinces, China) and four autumn-sown wheat seasons (2008 to 2012). Disease severities on Qing Shumai were lower than 25%, contrasting with approximately 90% on Mingxian 169. The RILs varied in rust intensity in a continuous and monomodal distribution. A bulked segregant analysis approach using 2,344 simple sequence repeat (SSR) markers mapped a major QTL to the long arm of chromosome 6D (hereby designated as QYr.cau-6DL). An SSR marker (gpw5179, https://wheat.pw.usda.gov/GG2/index.shtml ) was identified as being tightly linked with QYr.cau-6DL. Combination between QYr.cau-6DL and the stripe rust-resistance gene Yr18 was examined using 160 F2:3 families of Qing Shumai × RL6058 (a near-isogenic line for Yr18 in the genetic background of the spring wheat Thatcher). The combination elevated the resistance consistently across both winter and spring wheat backgrounds, acting synergistically without undesired epistasis.

Enhanced immunity and antiviral effects of an HBV DNA vaccine delivered by a DC-targeting protein.

DNA vaccine targeting delivery to DC represents one effective strategy to improve the immunogenicity of the vaccine. In a previous study, we developed a novel DC-targeting recombinant protein that can deliver plasmid DNA to DCs by an electrostatic coupling effect and can thus improve the uptake efficiency of DCs, improving the expression of plasmid DNA in DCs. In this study, we coupled the protein with the HBV DNA vaccine pSVK-HBVA and investigated whether the immunogenicity and antiviral ability of the vaccine can be improved in HBV transgenic mice. The results show that a stronger specific immune response can be induced in mice after immunization with the coupling vaccine. The HBV DNA copy number and circulating antigen HBsAg in the serum of HBV transgenic mice were significantly decreased. Therefore, this study has demonstrated that the DC-targeting protein has the ability to improve the immunogenicity and the antiviral activity of the HBV DNA vaccine pSVK-HBVA. These findings indicate that this DC-targeting protein can be a potential method for the delivery of DNA vaccines directly to DCs.

Comparison study of three laparoscopic ligation procedures for pediatric inguinal hernia: a multicenter cohort of 5523 cases.

PURPOSE: Single-site laparoscopic percutaneous extraperitoneal ligation (SLPEL) for pediatric inguinal hernia has gained popularity worldwide. However, complications associated with extraperitoneal knotting are not rare. This study evaluated the effectiveness of a modified SLPEL (M-SLPEL) to decrease adverse events associated with ligation knotting by comparing it with two other methods: classical SLPEL (C-SLPEL) and intracorporeal purse-string suturing (IPS). METHODS: A multicenter retrospective comparative study was conducted among 5523 pediatric inguinal hernia patients. Cases were divided into three groups according to the surgical procedure: the M-SLPEL, C-SLPEL, and IPS groups. Data describing the clinical characteristics, operative time, and complications were collected. RESULTS: All procedures were performed uneventfully. There were no significant differences in the age at operation (mean 2.62 ± 1.38 years). The operative time was shorter in the M-SLPEL group both for unilateral hernias (12.5 ± 1.8 min in C-SLPEL, 11.7 ± 1.3 min in M-SLPEL, and 17.6 ± 2.9 min in IPS) and for bilateral hernias (15.1 ± 2.1 min, 14.6 ± 1.7 min, and 23.9 ± 2.3 min, respectively). The overall incidence of adverse events in the inguinal region was 0% for M-SLPEL, 2.2% for C-SLPEL, and 0.5% for IPS. All patients were followed up for 12-93 months (mean 54 months). Recurrence occurred in 8 cases in the C-SLPEL group, 1 case in the M-SLPEL group, and 8 cases in the IPS group, with no significance between groups. No scrotal hematoma, testicular atrophy, or iatrogenic cryptorchidism occurred in any group. CONCLUSION: The M-SLPEL procedure has time-consumption efficiency equivalent to that of C-SLPEL and even fewer adverse events in the inguinal region than IPS and C-SLPEL.

Inhibition of p38 MAPK during cellular activation modulate gene expression of head kidney leukocytes isolated from Atlantic salmon (Salmo salar) fed soy bean oil or fish oil based diets.

Head kidney leukocytes isolated from Atlantic salmon fed either a diet based on fish oil (FO) or soy bean oil (VO) were used in order to evaluate if different lipid sources could contribute to cellular activation of the salmon innate immune system. A specific inhibitor of p38 MAPK, SB202190, was used to investigate the effect of lipopolysaccharide (LPS) signalling in the head kidney leukocytes. The results show that LPS up regulate IL-1ß, TNF-α, Cox2 expression in leukocytes isolated from fish fed either diet. The p38 MAPK inhibitor, SB202190, reduced the LPS induced expression of these genes in both dietary groups. In LPS stimulated leukocytes isolated from VO fed fish, SB202190 showed a clear dose dependent inhibitory effect on IL-1ß, TNF-α and Cox2 expression. This effect was also observed for Cox2 in leukocytes isolated from FO fed fish. Furthermore, there was a stronger mean induction of Cox2 in LPS stimulated leucocytes isolated from the VO-group compared to LPS stimulated leukocytes isolated from the FO-group. In both dietary groups, LPS stimulation of salmon head kidney leukocytes increased the induction of CD83, a dendrite cell marker, while the inhibitor reduced CD83 expression in the VO fed fish only. The inhibitor also clearly reduced hsp27 expression in VO fed fish. Indicating a p38 MAPK feedback loop, LPS significantly inhibited the expression of p38MAPK itself in both diets, while SB202190 increased p38MAPK expression especially in the VO diet group. hsp70 expression was not affected by any treatment or feed composition. There were also differences in p38MAPK protein phosphorylation comparing treatment groups but no obvious difference comparing the two dietary groups. The results indicate that dietary fatty acids have the ability to modify signalling through p38 MAPK which may have consequences for the fish's ability to handle infections and stress. Signalling through p38MAPK is ligand dependent and affects gene and protein expression differently.

Electronic structure, bonding and phonon modes in the negative thermal expansion materials of Cd(CN)(2) and Zn(CN)(2).

The disordered configuration, band structures, density of states, Mulliken population, elastic constants, zone center optic phonon modes and their Grüneisen parameters of M(CN)(2) (M =  Cd, Zn) have been studied for possible cyanide-ordering patterns by the first-principles plane-wave pseudopotential method based on density functional theory. Total energy calculations predict that MC(2)N(2)-MC(2)N(2) is the most favorable configuration for Cd(CN)(2) whereas all three possible configurations are near equally favorable for Zn(CN)(2). Effective charges and bond order analyses reveal that the M(CN)(2) (M =  Cd, Zn) frameworks include much stiffer [Formula: see text] and weaker M-C/N bonds, which account for the flexing of the M-CN-M linkage during the transverse motion of the cyanide-bridge. The transverse translational and the librational modes give rise to negative Grüneisen parameters and therefore contribute to the negative thermal expansion. Transverse vibrations of the C and N atoms in the same (transverse translational modes) or opposite (librational modes) directions have the same effect of drawing the anchoring metal atoms closer. Among all the optical phonon modes, the lowest-energy transverse translational optical modes which are neither Raman nor infrared active in Cd(CN)(2) and Zn(CN)(2) give rise to the largest contribution to the negative thermal expansion.

Cardioprotective effects of pinacidil pretreatment and lazaroid (U74500A) preservation in isolated rat hearts after 12-hour hypothermic storage.

BACKGROUND: Two important processes in the preservation of the function of donor hearts are the maintenance of ATP-sensitive potassium channel activity during myocardial ischemia and the scavenging of reactive oxygen species formed during reperfusion. The aim of this study was to compare the effect of three protocols on the preservation of hemodynamic function in isolated rat hearts after hypothermic storage. These protocols were: (1) pretreatment of the heart with a potassium channel opener (200 microM pinacidil); (2) storage of the heart in an aspartate-enriched extracellular cardioplegic solution containing the lazaroid antioxidant, U74500A (30 microM); and (3) a combination of protocols 1 and 2. METHODS: Hearts from Wistar rats were perfused on a Langendorff apparatus. After stabilization in working mode, baseline measurements of heart rate, coronary and aortic flow, and cardiac output were performed. Hearts (n=6 in each group) were then randomized to protocols 1-3, untreated controls, or vehicle-treated controls. Hearts were stored in extracellular-based preservation solution for 12 hr at 2-3 degrees C, remounted on the perfusion apparatus, and stabilized as before; hemodynamic measurements were then repeated. RESULTS: Recovery of hemodynamic function was enhanced by pinacidil pretreatment or incorporation of lazaroid in the storage solution, but the combination of these two treatments produced the best results. CONCLUSIONS: Combined pharmacological activation of ATP-sensitive potassium channels before cardioplegia and the addition of U74500A to the preservation solution is associated with significantly enhanced hemodynamic function in the isolated rat heart after 12 hr of hypothermic storage. These data suggest a novel use for these agents in the transplantation context.

Selective inhibition of nitric oxide production during cardiac allograft rejection causes a small increase in graft survival.

Nitric oxide production is increased in allograft rejection and may have both beneficial and deleterious effects on graft function and survival. In animal models, conventional immunosuppressive agents have been shown to decrease nitric oxide production. The aim of our study was to determine what effect augmentation and selective inhibition of nitric oxide production may have on graft survival by using the model of heterotopic cardiac transplantation in the rat. L-Arginine, the naturally occurring substrate for nitric oxide production, was administered subcutaneously at 200 mg/kg/day. L-NG-monomethyl-L-arginine (L-NMMA) is a selective inhibitor of nitric oxide synthase and was administered at 500 mg/kg/day to allograft recipients from the day of operation. Endogenous nitric oxide production was quantified by analysis of urinary nitrate excretion, and time to rejection was determined by graft palpation. L-Arginine did not significantly alter urinary nitrate excretion by iso- or allografts, suggesting that nitric oxide production is not a substrate-limited process in this model. Graft survival in this group was unchanged. L-NMMA produced a small increase in graft survival from 5.1 +/- 0.1 to 6.3 +/- 0.3 days compared with control allografts (P = 0.001) and abolished the rise in urinary nitrate excretion seen with control allografts. Lower doses of L-NMMA produced dose-related decrements in urinary nitrate excretion, but did not alter graft survival. We found that allograft rejection can proceed to graft loss despite complete inhibition of the increase in nitric oxide production that occurs during untreated rejection. The small increase in graft survival suggests that nitric oxide plays a minor role as a cytotoxic effector molecule in this model of acute rejection.

Urinary nitrate excretion is a noninvasive indicator of acute cardiac allograft rejection and nitric oxide production in the rat.

Cytokine induction of calcium-independent nitric oxide synthase is associated with production of large amounts of nitric oxide (NO). NO is a free radical that is rapidly degraded to nitrite and nitrate. Measurement of plasma and urinary nitrate is an indirect marker of NO production and previous studies have demonstrated that plasma nitrate rises with allograft rejection. The purpose of this study was to examine the temporal relationship between the rise in urinary nitrate excretion and the onset of graft rejection, and to determine the effect of conventional immunosuppression on nitrate excretion. The heterotropic model of cardiac transplantation in the rat was used, with Brown-Norway to Lewis allografts and Lewis to Lewis isograft controls. Twenty-four-hour urine specimens were collected before and after transplantation. Urinary nitrate excretion was measured by gas chromatography/mass spectrometry. Each group was treated with (1) no immunosuppression, (2) dexamethasone (3 mg/kg), or (3) CsA (10 mg/kg) on days 0, 1, and 2. Time to rejection for untreated allografts was 5.1 +/- 0.1 days, extending to 8.4 +/- 0.5 and 9.6 +/- 0.4 days with dexamethasone and CsA treatment, respectively. There was a significant rise in nitrate excretion on days 4, 7, and 9 for control, dexamethasone-treated, and CsA-treated allografts, respectively, preceding evidence of rejection. Untreated allograft rejection was associated with a peak in nitrate excretion 8 times that of basal excretion by isografts. Treatment of the allografts with dexamethasone and CsA significantly attenuated peak nitrate excretion compared with untreated allografts with a only a 2- to 3-fold rise preceding rejection. Results indicate that allograft rejection is associated with a dramatic increase in peak urinary nitrate excretion that is attenuated by standard immunosuppressive therapy. An increase in nitrate excretion precedes evidence of graft rejection, and may serve as a noninvasive marker of graft rejection.

Tolerance to glyceryl trinitrate in isolated human internal mammary arteries.

The purpose of this study was to examine the vascular reactivity of segments of internal mammary artery removed from patients undergoing coronary artery bypass operations. Responses to relaxant and contractile agents were compared in arteries removed from patients who had or had not been treated with glyceryl trinitrate after admission to the hospital until operation. Segments of mammary artery were removed from 13 patients who underwent coronary artery bypass grafting. Endothelium-containing rings of artery, 3 to 5 mm long, were suspended in physiologic saline solution in 20 ml organ baths. Responses to the endothelium-dependent relaxant acetylcholine and the endothelium-independent relaxants glyceryl trinitrate and sodium nitroprusside were compared. In addition, contractile responses to phenylephrine and 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (U46619) were examined. Glyceryl trinitrate-induced relaxation was significantly impaired in mammary artery segments from patients treated with that nitrate before operation; the responses to acetylcholine and sodium nitroprusside were not affected. Previous treatment with glyceryl trinitrate also reduced the contractile responses to both phenylephrine and U46619. These studies indicate that treatment of patients with glyceryl trinitrate before operation induces significant tolerance to this agent in the mammary artery; however, there was no evidence of cross tolerance to sodium nitroprusside or the endothelium-dependent vasodilator acetylcholine. Glyceryl trinitrate may therefore not always be effective in dilating mammary artery grafts and sodium nitroprusside may be a more effective dilator of the internal mammary artery in patients who have been treated with glyceryl trinitrate before operation.

Ischemic preconditioning enhances donor lung preservation in the rat.

BACKGROUND: Ischemic preconditioning achieved by brief periods of ischemia and reperfusion before a prolonged period of ischemia can significantly reduce the extent of cardiac damage in many mammalian species and human beings. In this study we used a rat model of single lung transplantation to show that ischemic preconditioning also occurs in the lung. METHODS: Rats randomly selected for ischemic preconditioning had their left main bronchus and pulmonary artery occluded for 5 minutes, followed by 10 minutes of reperfusion and ventilation. Lungs of control rats were ventilated for 15 minutes. The lungs were perfused with University of Wisconsin solution, then heart and lungs were excised en bloc and stored in University of Wisconsin solution at 0 degree C for 6 or 12 hours. After left pneumonectomy, the left lung of the donor was then implanted into the recipient via left thoracotomy. After 1 hour of ventilation and reperfusion, a right pneumonectomy was performed making the animal completely dependent on the transplanted lung. Samples of arterial blood from the left ventricle were then taken for arterial oxygen tension and arterial carbon dioxide tension determination. Water contents of the donor lungs were measured before and after reperfusion. Thiobarbituric acid reactive substances were measured in the right donor lung after storage. RESULTS: Lungs transplanted after 12 hours of storage had profoundly impaired gas exchange (arterial oxygen tension = 34 +/- 5; arterial carbon dioxide tension = 69 +/- 7 mm Hg) compared with the normal levels in the 6-hour storage group (arterial oxygen tension = 308 +/- 22; arterial carbon dioxide tension = 17 +/- 1 mm Hg). Ischemic preconditioning significantly improved gas exchange in the 12-hour storage group (arterial oxygen tension = 83 +/- 11; arterial carbon dioxide tension = 40 +/- 4 mm Hg). Ischemic preconditioning also significantly decreased thiobarbituric acid reactive substances formation at both 6- and 12-hour storage. CONCLUSIONS: These results show that the phenomenon of ischemic preconditioning occurs in the lung and that it may reduce injury to the donor lung during prolonged cold ischemic storage.

The nitric oxide donor, diethylamine NONOate, enhances preservation of the donor rat heart.

BACKGROUND: Ischemia/reperfusion injury to transplanted organs may be associated with loss of endothelial release of nitric oxide. The aim of this study was to determine whether supplementation of an extracellular-based cardioplegic solution in routine clinical use at our institution with nitric oxide (as diethylamine NONOate) enhanced poststorage functionality of an isolated working heart model. METHODS: Excised hearts were ligated to an aortic cannula and immediately perfused retrogradely with oxygenated Krebs solution at a hydrostatic pressure of 100 cm H2O at 37 degrees C. This preparation was then converted to a working system by switching the supply of perfusate from the aorta to a left atrial cannula at a filling pressure of 15 cm H2O. After a 1-minute stabilization period, baseline measurements of heart rate, aortic flow, coronary artery flow, and cardiac output were performed. Oxygenated cardioplegic solution (0.1 micromol/L), with or without NONOate, was then infused into the coronary circulation. Hearts were then stored in the same solutions for 6 or 12 hours at 2 degrees to 3 degrees C. The hearts were then remounted on the perfusion apparatus and reperfused as before, and hemodynamic measurements were repeated. Water content of the hearts were then determined. RESULTS: Addition of the nitric oxide donor significantly improved all hemodynamic parameters measured after 12 hours storage and aortic flow at 6 hours storage compared with the untreated control groups. There was no significant difference between the water contents of the NONOate-treated and control groups. CONCLUSIONS: The presence of the nitric oxide donor diethylamine NONOate was associated with significantly better preservation of coronary artery flow and cardiac function in the isolated rat heart after a 12-hour period of hypothermic storage and suggests a novel use for this family of compounds in the transplantation context.

Three types of liver cell dysplasia (LCD) in small cirrhotic nodules are distinguishable by karyometry and PCNA labelling, and their features resemble distinct grades of hepatocellular carcinoma.

We have studied the occurrence and specific features of liver cell dysplasia (LCD) in Chinese patients showing liver cirrhosis with or without hepatocellular carcinoma (HCC). Three types of LCD (SLCD, LLCDo, LLCDe) were morphologically defined, and these types were further analyzed using karyometry, estimation of nucleic acid content and density, and PCNA immunostaining. Features found for three types of LCD were compared with those of normal hepatocytes (NLC), simple regenerating hepatocytes (SRLC), and cells of HCCs covering different grades. The results show that 1) karyometry and nucleic acid parameters allow an objective separation of LCD types both from NLC and SRLC; 2) karyometric features of LLCDe are most close to those of highly differentiated HCCs, whereas nuclear size and chromatin composition of SLCD closely reflect those of poorly differentiated HCCs; 3) the frequency of LCD clusters was higher in cirrhotic livers carrying HCC, being about double for all three LCD types; 4) the highest PCNA labelling occurred in the small cell group of LCD (SLCD), still, however, being smaller than that of simple regenerating hepatocytes. Based on these findings it is suggested that, similar to atypical adenomatous hyperplasia, LCDs of distinct morphotypes may represent precursor lesions for HCC, and some cellular forms may mimick cell types known to occur in experimental carcinogenesis.

The effect of hypercholesterolaemia and atherosclerosis on alpha-adrenoceptor-mediated vasoconstriction in conscious rabbits and rabbit aorta.

Rabbits were fed a diet containing 1% cholesterol for 4 or 8 weeks and the constrictor responses to alpha-adrenoceptor agonists, as well as endothelium-dependent and endothelium-independent dilatation, were examined both in vivo and in vitro. The high cholesterol diet caused a significant elevation of plasma cholesterol concentration but no macroscopic evidence of atherosclerosis after 4 weeks whereas after 8 weeks there was a significant development of atherosclerotic lesions in the thoracic and abdominal aorta. In conscious rabbits pressor responses to the non-selective alpha-adrenoceptor agonist noradrenaline and the selective alpha 1-adrenoceptor agonist phenylephrine were enhanced after 4 weeks but returned to control levels after 8 weeks on the diet. The pressor responses to the alpha 2-adrenoceptor agonist B-HT 920 were reduced by the development of atherosclerosis. In the isolated thoracic aorta from these rabbits contractile responses to noradrenaline were impaired by hypercholesterolaemia whereas responses to phenylephrine were unaffected. Endothelium-dependent relaxation was impaired by hypercholesterolaemia both in vivo and in vitro after 4 and 8 weeks on the diet whereas endothelium-independent relaxation was not affected. These results indicate that the effect of hypercholesterolaemia on alpha-adrenoceptor-mediated constriction is dependent on: (1) the absence or presence of atherosclerotic lesions, (2) the size of the artery and (3) the subtype of alpha-adrenoceptor involved in the response. There does not appear to be any relationship between the loss of endothelium-dependent relaxation in hypercholesterolaemia and the observed changes in adrenergic vasoconstriction.

Baroreceptor reflexes and vascular reactivity during inhibition of nitric oxide synthesis in conscious rabbits.

The effect of the nitric oxide (NO) synthase inhibitor N-nitro-L-arginine (NOLA) on vascular reactivity and the baroreceptor heart rate reflex was examined in chronically instrumented conscious rabbits. NOLA (15 mg/kg i.v.) significantly increased mean arterial pressure and hindlimb vascular resistance and decreased heart rate. Increases and decreases in arterial pressure were produced by the intravenous injection of phenylephrine and sodium nitroprusside respectively and the values obtained relating mean arterial blood pressure to heart rate were fitted to a sigmoid curve. NOLA significantly reduced the lower plateau of the arterial pressure--heart rate curve but did not significantly affect baroreceptor sensitivity. Depressor and hindlimb vasodilator responses to acetylcholine were significantly impaired by NOLA whereas responses to sodium nitroprusside were significantly enhanced. The pressor and hindlimb vasoconstrictor responses to phenylephrine were significantly enhanced in the presence of NOLA. We conclude that the bradycardia produced by NOLA does not result from a change in baroreceptor sensitivity. The continuous generation of NO appears to be important in regulating basal vascular resistance and in modulating vascular reactivity to both vasodilator and vasoconstrictor agents.

HDV (delta factor) infection complicated with subacute fulminant hepatitis B. A morphological and immunohistochemical observation.

In 75 patients with subacute fulminant hepatitis B (SAFH), HDAg positive liver cells were observed in 14 cases (18.67%) by direct enzyme labelled method. It was found further that HDV (delta factor) infection was an important cause in producing massive necrosis of liver cells and superinfection of HDV with hepatitis B was identified as one of the causes of SAFH. This experiment also showed that the number of HDAg positive cells was in direct proportion to the area of liver necrosis. No obvious lymphocytic infiltrations and cytotoxic phenomena around the necrotic foci and HDAg positive cells could be found, while the cytoplasmic type HDAg positive cells showed distinct degeneration or even atrophy. Hence it was suggested that HDV could be a direct pathogenesis. No obvious characteristic changes in morphology of HDV infection could be found.

Decolorization of Direct Black 22 by Aspergillus ficuum.

The decolorization of Direct Black 22 by Aspergillus ficuum has been studied. It was found that Aspergillus ficuum could effectively decolorize Direct Black 22 especially when grown as pelleted mycelia. Results showed that the media containing Direct Black 22 at 50 mg/L could be decolorized by 98.05% of the initial color in 24 h. The optimum pH and temperature of decolorization are 4.0 and 33 degrees C respectively. Aeration was quite beneficial to decolorization. Medium composition and the concentration of Direct Black 22 could affect the rate of decolorization. The dye degraded products assayed by UV-visible spectrophotometer and macroscopic observation showed that the decolorization of Direct Black 22 by mycelial pellets includes two important processes: bioadsorption and biodegradation. The degradation experiment agree with the Michaelis-Menten kinetics equation.