Probiotics and synbiotics for preventing postoperative infectious complications in colorectal cancer patients: a systematic review and meta-analysis.

BACKGROUND: The health benefits of probiotics and synbiotics in healthy adults are well established, but their role in preventing infectious complications after surgery for colorectal cancer remains controversial. The aim of this meta-analysis was to assess the impact of probiotics/synbiotics on the incidence of infectious complications in patients who had surgery for colorectal cancer. METHODS: A comprehensive literature search of all randomized control trials (RCTs) was conducted using PubMed, Embase, World Health Organization (WHO) Global Index Medicus, WHO clinical trial registry, and Clinicaltrials.gov. Inclusion criteria included RCTs comparing the use of any strain or dose of a specified probiotic/synbiotic with placebo or a "standard care" control group. The incidence of postoperative infectious complications was analyzed. RESULTS: Fourteen RCTs involving 1566 patients (502 receiving probiotics, 273 receiving synbiotics, and 791 receiving placebo) were analyzed. Overall, probiotic or synbiotic administration significantly reduced the risk of developing postoperative infectious complications by 37% (relative risk (RR) = 0.63, 95% confidence interval (CI) 0.54-0.74, p < 0.001). Furthermore, when considering the six different types of postoperative infectious complications (septicemia, incision infection, central line infection, pneumonia infection, urinary infection, and incidence of diarrhea), probiotic or synbiotic administration was beneficial in reducing the incidence of each one of them. The quality of evidence was listed below: incidence of diarrhea (high), septicemia (moderate), incision infection (moderate), pneumonia infection (moderate), urinary infection (moderate), and central line infection (low). However, for the main outcome of infectious complications, we found evidence of possible publication bias, although estimates still showed a reduction following trim-and-fill analysis (RR = 0.72, 95% CI 0.62-0.84, p < 0.001). CONCLUSIONS: The use of probiotic/synbiotic supplementation is associated with a significant reduction in the risk of developing postoperative infectious complications in patients who had surgery for colorectal cancer. Additional studies are needed to confirm the findings due to publication bias and low quality of evidence.

Syphilis-related rapidly progressive glomerulonephritis: a case presentation.

BACKGROUND: Syphilis is a multisystemic infection that causes a wide variety of symptoms and thus has been dubbed one of the great medical mimickers. Due to recent global re-emergence of syphilis, it has become important to recognize its various presentations. Relative to the kidney, syphilitic infections generally present themselves with nephrotic range proteinuria, and are most often associated with pathological features of a membranous glomerulonephritis with subepithelial immune complex deposition. However, other rare renal presentations have been reported. One of these includes a rapidly progressive glomerulonephritis picture. All described cases have been successfully resolved with the treatment of the underlying syphilis infection. CASE PRESENTATION: The patient was an elderly woman of Caribbean descent who presented with lower extremity weakness, anasarca and proteinuria, hematuria with progressive renal failure. On kidney biopsy, she was found to have a pauci-immune crescentic glomerulonephritis pattern and a concomitant acute tubulointerstitial nephritis. She had a positive Treponema pallidum particle agglutination test and a negative syphilis rapid plasma reagin test with clinical evidence of polyneuropathy suggestive chronic syphilis infection. CONCLUSION AND DISCUSSION: It is important in the context of pauci-immune crescentic glomerulonephritis to explore all differential diagnoses. Given the positive syphilis serologies, clinical context and presence of tubulointerstitial nephritis, she was determined to have syphilitic glomerulonephritis that resolved with a course of both penicillin and steroids.

Evaluating Inoculation Methods to Infect Sugar Beet with Fusarium oxysporum f. betae and F. secorum.

Minnesota and North Dakota combined contain 55% of the sugar beet production area in the United States, contributing to 49% of the nation's sugar beet production in 2018. Fusarium diseases caused by Fusarium oxysporum f. betae and F. secorum on sugar beet can cause significant reduction in both root yield and sucrose concentration and purity. The objective of this research was to identify an alternative artificial inoculation method to induce Fusarium diseases on sugar beet leaves and roots caused by both Fusarium spp. in greenhouse conditions to better aid in research efforts. We tested four inoculation methods, including barley to seed, barley to root, drenching, and cutting. and compared them with the conventional root-dipping inoculation method. The inoculation method of placing Fusarium-colonized barley seed close to sugar beet seed (barley to seed) caused levels of symptom severities on both leaves and roots similar to the root-dipping method. Because the traditional root-dipping method involves a laborious transplant process, use of infected barley seed as inoculum may serve as an alternative method in the evaluation of host resistance and pathogen virulence among Fusarium diseases by Fusarium spp. on sugar beet at the seed or seedling stage.

[Comparative study on changes of ginsenosides and activities of American ginseng before and after steaming].

The chemical fingerprints of American ginseng were established by high performance liquid chromatography(HPLC) coupled with similarity evaluation system for chromatographic fingerprint of traditionanl Chinese medicine. The results were analyzed with use of stoichiometry methods(cluster analysis, principal component analysis, and orthogonal partial least squares discriminant analysis), and meanwhile, a preliminary study on the antioxidant and anti-proliferation activity of colorectal cancer cells was conducted. By comparing the fingerprints of American ginseng before and after processing, the contents of five components in the eight ginseno-sides quantified in this paper increased, including ginsenoside Rc, Rg_2, Rb_2, Rb_3 and Rd, respectively, and a new component was produced after steaming. The activity study showed that steamed American ginseng had better antioxidant activity and anti-proliferation activity of colorectal cancer cells than raw American ginseng. The research results show that the steaming method of American ginseng used in this experiment has good stability and reproducibility, and the steaming of American ginseng produces similar changes as artificial red ginseng, which provides a certain reference for expanding the application range of American ginseng.

Genetic diversity and population structure of Kazakh horses (Equus caballus) inferred from mtDNA sequences.

The Kazakh horse is an important old horse breed in Xinjiang. They have contributed greatly to the breeding and improvement of other local horse breeds, yet their genetic diversity and population structure are not well understood. In the present study, we evaluated the genetic diversity of Kazakh horses and their relationship with other horse breeds using the mtDNA D-loop region, Cyt b gene, and a DNA fragment (nps 7974-9963, containing COX3, tRNA-Gly, ND3, and tRNA-Arg). A total of 130 Kazakh horses from 8 populations in China and Kazakhstan were analyzed. A total of 88 haplotypes (haplotype diversity: 0.9895) were identified, in which 3 haplotypes were shared by groups in the two countries. In a median-joining network, 6 haplogroups were found, in which most haplogroups included haplotypes from different populations. Neighbor-joining analysis revealed similar results in that haplotypes in different populations were admixed in most of the 6 clusters. In conclusion, a high level of genetic diversity was found in the Kazakh horses. However, no clear correspondence between haplogroups and geographic origin and no significant differentiation between populations in the two countries were observed. This might have resulted from the frequent contact between the two countries through the Silk Road in the past, or due to long-term outcrossing and hybridization with the introduced horses.

Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL).

BACKGROUND: We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation. PROCEDURE: This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 [9-36.1] years) with age- and gender-specific LS-BMD Z-scores <0 to receive nutritional counseling with supplementation of 1,000 mg/day calcium and 800 International Unit cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes. RESULTS: Pre-randomization LS-BMD below the mean was associated with male gender (P = 0.0024), White race (P = 0.0003), lower body mass index (P < 0.0001), and cumulative glucocorticoid doses of ≥ 5,000 mg (P = 0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33 ± 0.57) or placebo (0.28 ± 0.56). Participants aged 9-13 years and those 22-35 years had the greatest mean increases in LS-BMD (0.50 ± 0.66 and 0.37 ± 0.23, respectively). Vitamin D insufficiency (serum 25[OH]D <30 ng/ml) found in 296 (75%), was not associated with LS-BMD outcomes (P = 0.78). CONCLUSION: Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry).

Comparative Pathogenicity and Virulence of Fusarium Species on Sugar Beet.

In all, 98 isolates of three Fusarium spp. (18 Fusarium oxysporum, 30 F. graminearum, and 50 Fusarium sp. nov.) obtained from sugar beet in Minnesota were characterized for pathogenicity and virulence on sugar beet in the greenhouse by a bare-root inoculation method. Among the 98 isolates tested, 80% of isolates were pathogenic: 83% of the F. oxysporum isolates, 57% of the F. graminearum isolates, and 92% of the Fusarium sp. nov. isolates. Symptoms varied from slight to moderate wilting of the foliage, interveinal chlorosis and necrosis, and vascular discoloration of the taproot without any external root symptoms. Among the pathogenic isolates, 14% were highly virulent and 12% were moderately virulent. Most of the highly virulent isolates (91%) and moderately virulent isolates (89%) were Fusarium sp. nov. All pathogenic isolates of F. graminearum and most pathogenic isolates (87%) of F. oxysporum were less virulent. In general, more-virulent isolates induced first foliar symptoms earlier compared with less-virulent isolates. This study indicates that both F. oxysporum and Fusarium sp. nov. should be used in greenhouse and be present in field studies used for screening and developing sugar beet cultivars resistant to Fusarium yellows complex for Minnesota and North Dakota.

[Predicting postoperative recurrence of stage â -â ¢ renal clear cell carcinoma based on preoperative CT radiomics feature nomogram].

OBJECTIVE: To explore the preoperative radiomics features (RFs) and construct a nomogram for predicting postoperative recurrence of stage Ⅰ-Ⅲ clear cell renal carcinoma (ccRCC). METHODS: The clinicopathological data and preoperative enhanced CT images collected from 256 patients with ccRCC were used as the training dataset (175 patients) and test dataset (81 patients). The enhanced CT images of the tumor were segmented using ITK-SNAP software, and the RFs were extracted using the PyRadiomics computing platform. In the training dataset, the RFs were screened based on Lasso-CV algorithm, and the Rad_score was calculated. The Clinic factors were screened by univariate and multivariate logistic regression analysis of the clinical and pathological factors and CT characteristics. The Rad_score, Clinic、Rad_score + Clinic nomograms were constructed and verified using the test dataset. The performance, discrimination power and calibration of the nomograms were compared, and their clinical value was evaluated using decision curve analysis. RESULTS: Six RFs were retained to calculate the Rad_score. The Clinic factors included Rad_score, KPS score, platelet, calcification and TNM clinical stage. In terms of discrimination, the Rad_score + Clinic nomogram showed better performance (AUC=0.84 for training set; AUC=0.85 for test set) than the Rad_score nomogram (AUC=0.78 for training set, P=0.029; AUC=0.77 for Test set, P=0.025) and Clinic nomogram (AUC=0.77 for training set, P=0.014; AUC=0.77 for test set, P=0.011). In terms of calibration, the P value for goodness of fit test of the Rad_score+Clinic nomogram was 0.065 for the training set and 0.628 for the test set. Decision curve analysis showed a greater clinical value of the Rad_score+Clinic nomogram with Rad_score than the Clinic nomogram without Rad_score. CONCLUSION: The nomogram based on preoperative CT RFs has a high value for predicting postoperative recurrence of stage Ⅰ-Ⅲ ccRCC to facilitate individualized treatment of RCC.

Capture and use of solar radiation, water, and nitrogen by sugar beet (Beta vulgaris L.).

Sugar beet is spring-sown for sugar production in most sugar beet-growing countries. It is grown as a vegetative crop and it accumulates yield (sugar) from very early in its growth cycle. As long as the sugar beet plants do not flower, the sugar accumulation period is indefinite and yield continues to increase. This paper reviews the success of the sugar beet crop in capturing and using solar radiation, water and mineral nitrogen resources. The prospects for improved resource capture and therefore increased sugar yield are also considered, particularly the potential to increase solar radiation interception in the future by sowing the crop in the autumn.

Fluctuations in number of Cercospora beticola conidia in relationship to environment and disease severity in sugar beet.

Cercospora leaf spot, caused by Cercospora beticola, is the most damaging foliar disease of sugar beet in Minnesota (MN) and North Dakota (ND). Research was conducted to characterize the temporal progression of aerial concentration of C. beticola conidia in association with the environment and disease severity in sugar beet. In 2003 and 2004, volumetric spore traps were placed within inoculated sugar beet plots to determine daily dispersal of conidia at Breckenridge, MN, and St. Thomas, ND. Plots were rated weekly for disease severity. At both locations, conidia were first collected in early July 2003 and late June in 2004. Peaks of conidia per cubic meter of air were observed with maxima in late August 2003 and in early September 2004 at both locations. Peaks of airborne conidium concentration were significantly correlated with the average temperature of daily hours when relative humidity was greater than 87%. Weekly mean hourly conidia per cubic meter of air was significantly (P < 0.01) associated with disease severity during both years and across locations. This study showed that C. beticola conidial numbers may be used to estimate potential disease severity that, with further research, could be incorporated in a disease forecasting model to rationalize Cercospora leaf spot management.

Computational analysis of alternative splicing in plant genomes.

Computational analyses play crucial roles in characterizing splicing isoforms in plant genomes. In this review, we provide a survey of computational tools used in recently published, genome-scale splicing analyses in plants. We summarize the commonly used software and pipelines for read mapping, isoform reconstruction, isoform quantification, and differential expression analysis. We also discuss methods for analyzing long reads and the strategies to combine long and short reads in identifying splicing isoforms. We review several tools for characterizing local splicing events, splicing graphs, coding potential, and visualizing splicing isoforms. We further discuss the procedures for identifying conserved splicing isoforms across plant species. Finally, we discuss the outlook of integrating other genomic data with splicing analyses to identify regulatory mechanisms of AS on genome-wide scale.

Effectiveness of Rlm7 resistance against Leptosphaeria maculans (phoma stem canker) in UK winter oilseed rape cultivars.

The Rlm7 gene in Brassica napus is an important source of resistance for control of phoma stem canker on oilseed rape caused by the fungus Leptosphaeria maculans. This study shows the first report of L. maculans isolates virulent against Rlm7 in the UK. Leptosphaeria maculans isolates virulent against Rlm7 represented 3% of the pathogen population when cultivars with the Rlm7 gene represented 5% of the UK oilseed rape area in 2012/13. However, the Rlm7 gene has been widely used since then, representing >15% of the UK oilseed rape area in 2015/16. Winter oilseed rape field experiments included cultivars with the Rlm7 gene, with the Rlm4 gene or without Rlm genes and took place at five sites in the UK over four cropping seasons. An increase in phoma leaf spotting severity on Rlm7 cultivars in successive seasons was observed. Major resistance genes played a role in preventing severe phoma leaf spotting at the beginning of the cropping season and, in addition, quantitative resistance (QR) in the cultivars examined made an important contribution to control of phoma stem canker development at the end of the cropping season. Deployment of the Rlm7 resistance gene against L. maculans in cultivars with QR in combination with sustainable disease management practices will prolong the use of this gene for effective control of phoma stem canker epidemics.

Negative emotions affect postoperative scores for evaluating functional knee recovery and quality of life after total knee replacement.

This study aimed to determine whether psychological factors affect health-related quality of life (HRQL) and recovery of knee function in total knee replacement (TKR) patients. A total of 119 TKR patients (male: 38; female: 81) completed the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), State Trait Anxiety Inventory (STAI), Eysenck Personality Questionnaire-revised (EPQR-S), Knee Society Score (KSS), and HRQL (SF-36). At 1 and 6 months after surgery, anxiety, depression, and KSS scores in TKR patients were significantly better compared with those preoperatively (P<0.05). SF-36 scores at the sixth month after surgery were significantly improved compared with preoperative scores (P<0.001). Preoperative Physical Component Summary Scale (PCS) and Mental Component Summary Scale (MCS) scores were negatively associated with extraversion (E score) (B=-0.986 and -0.967, respectively, both P<0.05). Postoperative PCS and State Anxiety Inventory (SAI) scores were negatively associated with neuroticism (N score; B=-0.137 and -0.991, respectively, both P<0.05). Postoperative MCS, SAI, Trait Anxiety Inventory (TAI), and BAI scores were also negatively associated with the N score (B=-0.367, -0.107, -0.281, and -0.851, respectively, all P<0.05). The KSS function score at the sixth month after surgery was negatively associated with TAI and N scores (B=-0.315 and -0.532, respectively, both P<0.05), but positively associated with the E score (B=0.215, P<0.05). The postoperative KSS joint score was positively associated with postoperative PCS (B=0.356, P<0.05). In conclusion, for TKR patients, the scores used for evaluating recovery of knee function and HRQL after 6 months are inversely associated with the presence of negative emotions.

Multi-walled carbon nanotubes as a solid-phase extraction adsorbent for the determination of chlorophenols in environmental water samples.

Multi-walled carbon nanotubes (MWCNs) are used as adsorbent for solid-phase extraction (SPE) of several chlorophenols (CPs). CPs were adsorbed on MWCNs cartridge, then desorbed with pH 10.0 methanol, finally determined by HPLC. Under the optimized conditions, detection limits of 0.08-0.8 ng mL(-1) were obtained. The method had been applied to analyze the five CPs in tap water and river water.

Nonsustained ventricular tachycardia arising from the right ventricular outflow tract.

Characteristics of left bundle branch block morphology, inferiorly directed frontal plane QRS axis and repetitive nonsustained salvos were used to define a discrete subgroup of patients with ventricular tachycardia (VT). The origin of this tachycardia was thought to be the right ventricular outflow tract. Twenty-six patients with this definition (group 1) were compared with 29 consecutive patients with all other forms of VT (group 2). When compared with patients in group 2, group 1 patients were younger (average age 37 vs 51 years, p less than 0.005), had less structural heart disease (2 of 26 vs 25 of 29 patients, p less than 0.005) and had a better prognosis (no deaths) after an average follow-up time of 28 months in comparison with 5 deaths after an average follow-up of 35 months (p less than 0.05). Induction of VT was possible using isoproterenol infusion in 14 of 20 group 1 patients, but no VT could be induced in 9 group 2 patients (p less than 0.05). Exercise stress testing induced VT in 11 of 21 group 1 patients and 2 of 9 group 2 patients (p greater than 0.05). Programmed electrical stimulation failed to induce VT in 9 group 1 patients, but did induce it in 15 of 20 group 2 patients (p less than 0.005). Successful therapy in group 1 patients was achieved by beta blockers alone (7 patients), beta blockers plus type 1A antiarrhythmic drugs (9 patients), procainamide alone (2 patients), sotalol (3 patients) and amiodarone (2 patients). Three patients were not treated.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation by extracellular ATP of L-type calcium channels in guinea-pig single sinoatrial nodal cell.

1. The effects of extracellular adenosine 5'-triphosphate ([ATP]zero) on the L-type Ca2+ channel currents in guinea-pig single sinoatrial nodal (SAN) cells, isolated by enzymatic dissociation, were investigated by use of whole-cell patch-clamp techniques. 2. The application of [ATP]zero (2 microM-1 mM) produced an inhibitory effect on the L-type Ca2+ channel current peak amplitude (10 mM Ba2+ as charge carrier) in a concentration-dependent and reversible manner with an IC50 of 100 microM and a Hill coefficient of 1.83. 3. The presence of the adenosine receptor antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.1 microM) and 8-phenyltheophylline (10 microM) did not affect the [ATP]zero-induced inhibition of the Ca2+ channel currents. Adenosine (100 microM) had little effect on the basal Ca2+ channel currents. Adenosine 500 microM, caused 23% inhibition of the Ca2+ channel current, which was abolished by 0.1 microM DPCPX. 4. The presence of the P2-purinoceptor antagonists, suramin (1, 10 and 100 microM), reactive blue 2 (1 and 10 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 50 and 100 microM) failed to affect the inhibitory action of [ATP]zero on Ca2+ channel currents. 5. The relative rank order of potency of different nucleotides and nucleosides, at a concentration of 100 microM, on the inhibition of the Ca2+ channel currents is as follows: adenosine 5'-triphosphate (ATP) = alpha,beta-methylene-ATP (alpha,beta MeATP) > > 2-methylthioATP (2-MeSATP) > or = adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S) > > uridine 5'-triphosphate (UTP) = adenosine 5'-diphosphate (ADP) > adenosine 5'-monophosphate (AMP) > or = adenosine. 6. These results suggest that [ATP]zero may play an important role in the heart beat by inhibiting the L-type Ca2+ channel currents in single SAN cells. This inhibitory effect is not due to the formation of adenosine resulting from the enzymatic degradation of [ATP]zero. Based on the relative order of inhibitory potency of different nucleotides and nucleosides on the L-type Ca2+ channel currents and the ineffectiveness of the purinoceptor antagonists tested, a novel type of purinoceptor may be involved.

Differential coupling of the human P2Y(11) receptor to phospholipase C and adenylyl cyclase.

1. The human P2Y(11) (hP2Y(11)) receptor was stably expressed in two cell lines, 1321N1 human astrocytoma cells (1321N1-hP2Y(11)) and Chinese hamster ovary cells (CHO-hP2Y(11)), and its coupling to phospholipase C and adenylyl cyclase was assessed. 2. In 1321N1-hP2Y(11) cells, ATP promoted inositol phosphate (IP) accumulation with low microM potency (EC(50)=8.5+/-0.1 microM), whereas it was 15 fold less potent (130+/-10 microM) in evoking cyclic AMP production. 3. In CHO-hP2Y(11) cells, ATP promoted IP accumulation with slightly higher potency (EC(50)=3.6+/-1.3 microM) than in 1321N1-hP2Y(11) cells, but it was still 15 fold less potent in promoting cyclic AMP accumulation (EC(50)=62.4+/-15.6 microM) than for IP accumulation. Comparable differences in potencies for promoting the two second messenger responses were observed with other adenosine nucleotide analogues. 4. In 1321N1-hP2Y(11) and CHO-hP2Y(11) cells, down regulation of PKC by chronic treatment with phorbol ester decreased ATP-promoted cyclic AMP accumulation by 60--80% (P<0.001) with no change in its potency. Likewise, chelation of intracellular Ca(2+) decreased ATP-promoted cyclic AMP accumulation by approximately 45% in 1321N1-hP2Y(11) cells, whereas chelation had no effect on either the efficacy or potency of ATP in CHO-hP2Y(11) cells. 5. We conclude that coupling of hP2Y(11) receptors to adenylyl cyclase in these cell lines is much weaker than coupling to phospholipase C, and that activation of PKC and intracellular Ca(2+) mobilization as consequences of inositol lipid hydrolysis potentiates the capacity of ATP to increase cyclic AMP accumulation in both 1321N1-hP2Y(11) and CHO-hP2Y(11) cells.

The first clinical results of "wide-focus and low-pressure" ESWL.

A clinical study of the concept "wide-focus and low-pressure" extracorporal shock-wave lithotripsy (ESWL) was performed in a scientific cooperation between the Physical Institute of the University of Stuttgart and the Xixin Medical Instruments Co. Ltd. in Wuxian-Suzhou, China. In this cooperation, self-focusing electromagnetic shock-wave generator systems from the University of Stuttgart were integrated into Xixin lithotripters and installed in seven hospitals in China. A total of 297 detailed patient protocols revealed an average of 1532 shock pulses for successful treatment with no necessity for pain medication and auxiliary measures, and a stone-free rate of 86% after a follow-up of 3 months. These results are discussed in terms of the wide-focus low-pressure conditions and the mechanism of binary fragmentation by squeezing.

Inhibition by extracellular ATP of L-type calcium channel currents in guinea-pig single sinoatrial nodal cells: involvement of protein kinase C.

It is generally accepted that ATP is costored and coreleased with noradrenaline from the sympathetic nerve terminals. The pacemaker region of the mammalian heart is highly innervated with the sympathetic nervous system. It is possible, therefore, that ATP released from nerve terminals can act on pacemaker cells and modulate heart beat activity. However, the physiological role(s) of extracellular ATP in mammalian heart beat has been little evaluated, even though the effect of extracellular ATP observed in in vivo studies has been attributed to the formation of adenosine, the catabolic product of ATP, which is a cardiodepressant. The present study investigated the effect of extracellular ATP on L-type calcium channel currents of guinea-pig single sinoatrial nodal cells, by using the whole cell patch clamp technique. Application of extracellular ATP caused a concentration-dependent and reversible inhibition of calcium channel currents with a 50% inhibitory concentration of 100 microM. The presence of the P2-purinoceptor antagonist suramin (1, 10 and 100 microM), reactive blue 2 (1 and 10 microM) and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 50 and 100 microM) or the adenosine receptor antagonists 8-cyclopentyl-1,3-dipropyl-xanthine (DPCPX, 0.1 microM) and 8-phenyltheophylline (10 microM) failed to affect the inhibitory action of extracellular ATP on calcium channel currents. The relative rank order of potency of different nucleotides and nucleosides, at a concentration of 100 microM, on the inhibition of calcium channel currents was as follows: ATP = alpha, beta-methylene-ATP >> 2-methylthioATP > or = adenosine 5'-O-(3-thiotriphosphate) >> UTP = ADP > AMP > or = adenosine. Dialysis, by way of the patch pipette, of the cell interior with specific protein kinase C inhibitor staurosporine (70 nM) or calphostin C (500 nM) abolished extracellular ATP-induced inhibition of calcium channel currents. Therefore, extracellular ATP-mediated inhibition of calcium channel currents in guinea-pig single sinoatrial nodal cells involves activation of protein kinase C.

[Effects of arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on tension of rabbit aortic strips].

The purpose of the investigation was to determine the effects of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) on the isolated rabbit aortic strips. The results showed that (1) the rabbit aortic strips with intact endothelium contracted in a dose-dependent manner to exogenous AA between the concentrations of 2.5 x 10(-6) mol/L and 4 x 10(-5) mol/L. EPA did not affect the tension of the relaxing strips, but inhibited the contractile response to AA (2 x 10(-5) mol/L), IC50 = 9.94 x 10(-6) mol/L. DHA showed no significant effect on the contractile response to AA. (2) In the endothelium-damaged rabbit aorta, the contraction of strips to AA was drastically diminished. The inhibitory effect of EPA on the contraction to AA was almost vanished. (3) The contraction of rabbit aortic strips to AA was shown to be abolished by indomethacin (1.5 x 10(-5) mol/L), a cyclooxygenase inhibitor. (4) Radioimmunoassay showed that exogenous AA increased the tissue levels of 6-keto-PGF1 alpha, TXB2 and their ratio. Lower dose of EPA (1.5 x 10(-6) or 1.5 x 10(-5) mol/L) did not affect the tissue levels of 6-keto-PGF1 alpha and TXB2. However, EPA at higher concentrations decreased the metabolites of AA significantly. These findings suggest that exogenous AA induces the contraction of rabbit aortic strips in vitro, which is related to the endothelial cells and mediated by the metabolites(s) of cyclooxygenase, likely endothelium-derived contracting factor (EDCF).(ABSTRACT TRUNCATED AT 250 WORDS)