[Safety and feasibility of indocyanine green injection through accessory incision in laparoscopic right hemicolectomy].

Objective: To explore the safety and feasibility of indocyanine green (ICG) injection through accessory incision in laparoscopic right hemicolectomy. Methods: A descriptive case series study was carried out. Clinicopathological data of 29 patients with colon cancer undergoing right hemicolectomy at Department of General Surgery, Guangdong Provincial People's Hospital were retrospectively analyzed. All the patients received ICG injection through accessory incision at the beginning of operation. Results: Among 29 patients, 13 were male and 16 were female with a mean age of (60.8±7.7) years and mean body mass index of (24.3±2.8) kg/m(2); 3 were stage I, 19 were stage II, 7 were stage III. Pericolic, intermediate and main lymph nodes could be detected under near infrared fluorescence imaging (NIRFI) in all the cases. No.6 lymph nodes were observed in 3 cases, while no lymph nodes around superior mesenteric vein (SMV) were found. The average number of fluorescent lymph node was 14.2±6.1. The average developing time of fluorescence was (36.2±3.7) minutes. The average number of harvested lymph nodes was 22.4±8.2. There was no extravasation of imaging agent during the operation, and there were no intraoperative complications such as allergies, massive abdominal bleeding, peripheral organ damage, etc. Operative time was (113.1±10.7) minutes, blood loss during operation was (22.4±3.9) ml, ambulatory time was (1.2±0.4) days, time to the first flatus was (1.7±0.7) days, time to the first fluid diet was (0.7±0.4) days, and postoperative hospital stay was (5.8±1.5) days. No operation-associated complications such as anastomotic bleeding, anastomotic leakage, peritoneal bleeding, peritoneal infection, incision infection occurred after operation. Conclusion: ICG injection through accessory incision in laparoscopic right hemicolectomy is safe and feasible.

[Current practice patterns of preoperative bowel preparation in elective colorectal surgery: a nation-wide survey of Chinese surgeons].

Objective: To understand the current practice of preoperative bowel preparation in elective colorectal surgery in China. Methods: A cross-sectional questionnaire survey was conducted through wechat. The content of the questionnaire survey included professional title of the participants, the hospital class, dietary preparation and protocol, oral laxatives and specific types, oral antibiotics, gastric intubation, and mechanical enema before elective colorectal surgery. A stratified analysis based on hospital class was conducted to understand their current practice of preoperative bowel preparation in elective colorectal surgery. Result: A total of 600 questionnaires were issued, and 516 (86.00%) questionnaires of participants from different hospitals, engaged in colorectal surgery or general surgeons were recovered, of which 366 were from tertiary hospitals (70.93%) and 150 from secondary hospitals (29.07%). For diet preparation, the proportions of right hemicolic, left hemicolic and rectal surgery were 81.59% (421/516), 84.88% (438/516) and 84.88% (438/516) respectively. The average time of preoperative dietary preparation was 2.03 days. The study showed that 85.85% (443/516) of surgeons chose oral laxatives for bowel preparation in all colorectal surgery, while only 4.26% (22/516) of surgeons did not choose oral laxatives. For mechanical enema, the proportions of right hemicolic, left hemicolic and rectal surgery were 19.19% (99/516), 30.04% (155/516) and 32.75% (169/516) respectively. Preoperative oral antibiotics was used by 34.69% (179/516) of the respondents. 94.38% (487/516) of participants were satisfied with bowel preparation, and 55.43% (286/516) of participants believed that preoperative bowel preparation was well tolerated. In terms of preoperative oral laxatives, there was no statistically significant difference between different levels of hospitals [secondary hospitals vs. tertiary hospitals: 90.00% (135/150) vs. 84.15% (308/366), χ(2)=2.995, P=0.084]. Compared with the tertiary hospitals, the surgeons in the secondary hospitals accounted for higher proportions in diet preparation [87.33% (131/150) vs. 76.78% (281/366), χ(2)=7.369, P=0.007], gastric intubation [54.00% (81/150) vs. 36.33% (133/366), χ(2)=13.672, P<0.001], preoperative oral antibiotics [58.67% (88/150) vs. 24.86% (91/366), χ(2)=12.259, P<0.001] and enema [28.67% (43/150) vs. 15.30% (56/366), χ(2)=53.661, P<0.001]. Conclusion: Although the preoperative bowel preparation practice in elective colorectal surgery for most of surgeons in China is basically the same as the current international protocol, the proportions of mechanical enema and gastric intubation before surgery are still relatively high.

Safety evaluation of subretinal injection of trypan blue in rats.

OBJECTIVE: To determine the appropriate concentration of trypan blue (TB) for subretinal injection in a rat model and to provide a safety profile that limits retinal toxicity while maintaining dye visibility. MATERIALS AND METHODS: Adult rats were subretinally injected with various concentrations of either TB or phosphate-buffered saline (PBS); rats which received sham injections served as an additional control. The injected areas were visualized under a surgical microscope. Electroretinography (ERG) was performed to measure retinal function. Animals were then sacrificed, and the eyes were sectioned and examined by light microscopy. Terminal deoxynucleotidy1 transferase dUTP nick-end labeling (TUNEL) was applied to determine retinal apoptosis. RESULTS: One day after the subretinal injection, TB stains were visible under the surgical microscope in the 0.2%, 0.08%, and 0.04% TB-injected groups, but not in the 0.02% TB-injected group. TB stain was detectable in the retina and sclera of the 0.2%, 0.08%, and 0.04% TB-injected groups for over 2 weeks after injection. However, the amplitudes of ERGa- and b-waves were affected and became significantly lower in the 0.2% TB-injected group than the amplitudes in the PBS-, or sham-injected group. Moreover, TUNEL+ cells appeared in the outer nuclear layer (ONL), ganglion cell layer (GCL), and retinal pigment epithelium (RPE) layer of the 0.2% and 0.08% TB-injected groups at 1 and 7 days after subretinal injection. In contrast, very few TUNEL+ cells were found in the 0.04% TB- or PBS-injected group. Two weeks after injection, the ONL was significantly thinner in the 0.2% TB-injected group than in the 0.04% TB-, PBS- or sham-injected group. CONCLUSIONS: TB injection induces a dose-dependent neurotoxic effect on retinal cells. Subretinal injection of 0.04% TB is relatively safe and effective for subretinal staining.

Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.

[Etiological analysis and establishment of a discriminant model for lower respiratory tract infections in hospitalized patients].

Objective: To analyze the pathogens of lower respiratory tract infection(LRTI) including bacterial, viral and mixed infection, and to establish a discriminant model based on clinical features in order to predict the pathogens. Methods: A total of 243 hospitalized patients with lower respiratory tract infections were enrolled in Fujian Provincial Hospital from April 2012 to September 2015. The clinical data and airway (sputum and/or bronchoalveolar lavage) samples were collected. Microbes were identified by traditional culture (for bacteria), loop-mediated isothermal amplification(LAMP) and gene sequencing (for bacteria and atypical pathogen), or Real-time quantitative polymerase chain reaction (Real-time PCR)for viruses. Finally, a discriminant model was established by using the discriminant analysis methods to help to predict bacterial, viral and mixed infections. Results: Pathogens were detected in 53.9% (131/243) of the 243 cases.Bacteria accounted for 23.5%(57/243, of which 17 cases with the virus, 1 case with Mycoplasma pneumoniae and virus), mainly Pseudomonas Aeruginosa and Klebsiella Pneumonia. Atypical pathogens for 4.9% (12/243, of which 3 cases with the virus, 1 case of bacteria and viruses), all were mycoplasma pneumonia. Viruses for 34.6% (84/243, of which 17 cases of bacteria, 3 cases with Mycoplasma pneumoniae, 1 case with Mycoplasma pneumoniae and bacteria) of the cases, mainly Influenza A virus and Human Cytomegalovirus, and other virus like adenovirus, human parainfluenza virus, respiratory syncytial virus, human metapneumovirus, human boca virus were also detected fewly. Seven parameters including mental status, using antibiotics prior to admission, complications, abnormal breath sounds, neutrophil alkaline phosphatase (NAP) score, pneumonia severity index (PSI) score and CRUB-65 score were enrolled after univariate analysis, and discriminant analysis was used to establish the discriminant model by applying the identified pathogens as the dependent variable. The total positive predictive value was 64.7%(77/119), with 66.7% for bacterial infection, 78.0% for viral infection and 33.3% for the mixed infection. Conclusions: The mostly detected pathogens were Pseudomonas aeruginosa, atypitcal pathogens, Klebsiella pneumoniae, influenza A virus and human cytomegalovirus in hospitalized patients with LRTI in this hospital. The discriminant diagnostic model established by clinical features may contribute to predict the pathogens of LRTI.

Brain-derived neurotrophic factor protects against tau-related neurodegeneration of Alzheimer's disease.

Reduced expression of brain-derived neurotrophic factor (BDNF) has a crucial role in the pathogenesis of Alzheimer's disease (AD), which is characterized with the formation of neuritic plaques consisting of amyloid-beta (Aß) and neurofibrillary tangles composed of hyperphosphorylated tau protein. A growing body of evidence indicates a potential protective effect of BDNF against Aß-induced neurotoxicity in AD mouse models. However, the direct therapeutic effect of BDNF supplement on tauopathy in AD remains to be established. Here, we found that the BDNF level was reduced in the serum and brain of AD patients and P301L transgenic mice (a mouse model of tauopathy). Intralateral ventricle injection of adeno-associated virus carrying the gene encoding human BDNF (AAV-BDNF) achieved stable expression of BDNF gene and restored the BDNF level in the brains of P301L mice. Restoration of the BDNF level attenuated behavioral deficits, prevented neuron loss, alleviated synaptic degeneration and reduced neuronal abnormality, but did not affect tau hyperphosphorylation level in the brains of P301L mice. Long-term expression of AAV-BDNF in the brain was well tolerated by the mice. These findings suggest that the gene delivery of BDNF is a promising treatment for tau-related neurodegeneration for AD and other neurodegenerative disorders with tauopathy.

Differential levels of p75NTR ectodomain in CSF and blood in patients with Alzheimer's disease: a novel diagnostic marker.

Alzheimer's disease (AD) is the primary cause of dementia in the elderly. The ectodomain of p75 neurotrophin receptor (p75NTR-ECD) has been suggested to play important roles in regulating beta-amyloid (Aß) deposition and in protecting neurons from the toxicity of soluble Aß. However, whether and how the serum and cerebrospinal fluid (CSF) levels of p75NTR-ECD change in patients with AD are not well documented. In the present study, we determined the concentrations of serum p75NTR-ECD in an AD group, a Parkinson disease group and a stroke group, as well as in a group of elderly controls without neurological disorders (EC). We also determined the levels of CSF p75NTR-ECD in a subset of the AD and EC groups. Our data showed that a distinct p75NTR-ECD profile characterized by a decreased CSF level and an increased serum level was present concomitantly with AD patients but not with other diseases. p75NTR-ECD levels in both the serum and CSF were strongly correlated with Mini-Mental State Examination (MMSE) scores and showed sound differential diagnostic value for AD. Moreover, when combining CSF Aß42, CSF Aß42/40, CSF ptau181 or CSF ptau181/Aß42 with CSF p75NTR-ECD, the area under the receiver operating characteristic curve (AUC) and diagnostic accuracies improved. These findings indicate that p75NTR-ECD can serve as a specific biomarker for AD and the determination of serum and CSF p75NTR-ECD levels is likely to be helpful in monitoring AD progression.

p75NTR ectodomain is a physiological neuroprotective molecule against amyloid-beta toxicity in the brain of Alzheimer's disease.

In Alzheimer's disease (AD), neurodegenerative signals such as amyloid-beta (Aß) and the precursors of neurotrophins, outbalance neurotrophic signals, causing synaptic dysfunction and neurodegeneration. The neurotrophin receptor p75 (p75NTR) is a receptor of Aß and mediates Aß-induced neurodegenerative signals. The shedding of its ectodomain from the cell surface is physiologically regulated; however, the function of the diffusible p75NTR ectodomain (p75ECD) after shedding remains largely not known. Here, we show that p75ECD levels in cerebrospinal fluid and in the brains of Alzheimer's patients and amyloid-beta precursor protein (APP)/PS1 transgenic mice were significantly reduced, due to inhibition of the sheddase-tumor necrosis factor-alpha-converting enzyme by Aß. Restoration of p75ECD to the normal level by brain delivery of the gene encoding human p75ECD before or after Aß deposition in the brain of APP/PS1 mice reversed the behavioral deficits and AD-type pathologies, such as Aß deposit, apoptotic events, neuroinflammation, Tau phosphorylation and loss of dendritic spine, neuronal structures and synaptic proteins. Furthermore, p75ECD can also reduce amyloidogenesis by suppressing ß-secretase expression and activities. Our data demonstrate that p75ECD is a physiologically neuroprotective molecule against Aß toxicity and would be a novel therapeutic target and biomarker for AD.

A study on the association between infectious burden and Alzheimer's disease.

BACKGROUND AND PURPOSE: Previous studies suggested that the overall burden of prior infections contributes to cardiovascular diseases and stroke. In the present study, the association between infectious burden (IB) and Alzheimer's disease (AD) was examined. METHODS: Antibody titers to common infectious pathogens including cytomegalovirus (CMV), herpes simplex virus type 1 (HSV-1), Borrelia burgdorferi, Chlamydophila pneumoniae and Helicobacter pylori were measured by enzyme-linked immunosorbent assay in 128 AD patients and 135 healthy controls. IB was defined as a composite serological measure of exposure to these common pathogens. RESULTS: Seropositivities toward zero-two, three and four-five of these pathogens were found in 44%, 40% and 16% of healthy controls but in 20%, 44% and 36% of AD patients, respectively. IB, bacterial burden and viral burden were independently associated with AD after adjusting for age, gender, education, APOE genotype and various comorbidities. Mini-Mental State Examination scores were negatively correlated with IB in all cases. Serum beta-amyloid protein (Aß) levels (i.e. Aß40, Aß42 and total Aß) and inflammatory cytokines (i.e. interferon-γ, tumor necrosis factor α, interleukin-1ß and interleukin-6) in individuals exposed to four-five infectious pathogens were significantly higher than those exposed to zero-two or three pathogens. CONCLUSIONS: IB consisting of CMV, HSV-1, B. burgdorferi, C. pneumoniae and H. pylori is associated with AD. This study supports the role of infection/inflammation in the etiopathogenesis of AD.

Role of cyclic nucleotides in the control of cytosolic Ca2+ levels in vascular endothelial cells.

1. Endothelial cells have a key role in the cardiovascular system. Most endothelial cell functions depend on changes in cytosolic Ca(2+) concentrations ([Ca(2+)](i)) to some extent and Ca2+ signalling acts to link external stimuli with the synthesis and release of regulatory factors in endothelial cells. The [Ca(2+)](i) is maintained by a well-balanced Ca(2+) flux across the endoplasmic reticulum and plasma membrane. 2. Cyclic nucleotides, such as cAMP and cGMP, are very important second messengers. The cyclic nucleotides can affect [Ca(2+)](i) directly or indirectly (via the actions of protein kinase (PK) A or PKG-mediated phosphorylation) by regulating Ca(2+) mobilization and Ca(2+) influx. Fine-tuning of [Ca(2+)](i) is also fundamental to protect endothelial cells against damaged caused by the excessive accumulation of Ca(2+). 3. Therapeutic agents that control cAMP and cGMP levels have been used to treat various cardiovascular diseases. 4. The aim of the present review is to discuss: (i) the functions of endothelial cells; (ii) the importance of [Ca(2+)](i) in endothelial cells; (iii) the impact of excessive [Ca(2+)](i) in endothelial cells; and (iv) the balanced control of [Ca(2+)](i) in endothelial cells via involvement of cyclic nucleotides (cAMP and cGMP) and their general effectors.

Tea polyphenols benefit vascular function.

Tea, the most popular beverage worldwide, is consumed in three basic forms; green tea, black tea and oolong tea. Tea contains over 4,000 chemicals some of which are bioactive. In recent years there has been a mounting interest in understanding the cardiovascular and metabolic benefits of polyphenolic flavonoids in tea, which can be used as a supplement among patients. Diverse cardioprotective effects of consuming tea or tea polyphenols have been described on pathological conditions, e. g. hypertension, atherosclerosis, diabetics, hypercholesterolemia, obesity, and are attributed to antioxidative, anti-thrombogenic, anti-inflammatory, hypotensive and hypocholesterolemic properties of tea polyphenols. This review focuses on cardiovascular benefits of tea polyphenols based on in vitro and in vivo studies on experimental animal models and on studies of human subjects in four areas: (1) vasorelaxant effect; (2) protective effect against endothelial dysfunction; (3) antioxidant effect and (4) hypolipidemic effect. We will briefly discuss the effects of tea on atherosclerosis and hypertension.

The alpha(1S) subunit of the L-type calcium channel is not a predisposition gene for thyrotoxic periodic paralysis.

OBJECTIVE: Thyrotoxic periodic paralysis (TTP) has been associated with genetic variations in the gene encoding the alpha 1 subunit of the L-type calcium channel (CACNA1S). Mutations in CACNA1S are known to account for the majority of cases of familial hypokalaemic periodic paralysis (HOKPP). In this study we have examined 48 genetic polymorphisms in the CACNA1S gene and genotyped a tagging set of representative polymorphisms to determine the role of this gene in TPP. DESIGN AND PATIENTS: A genetic association study was carried out with 98 TPP patients and 162 male thyrotoxic controls. Among 47 polymorphisms evaluated for linkage disequilibrium (LD) and the spectrum of haplotypes in the Chinese population, 31 were selected as tagging single-nucleotide polymorphisms (SNPs) for genotyping the whole sample. A new genotyping protocol was used to analyse an insertion/deletion (I/D) polymorphism. RESULTS: We studied the LD among 47 polymorphisms in the CACNA1S gene, which comprised a set of high-density markers with an average of one SNP every 2 kb. Subsequently, 31 tagSNPs were genotyped for all the samples. The gene is composed of three LD blocks. With this block structure, we were confident that variations of the gene were comprehensively covered by the tagSNPs. No significant association was found between the polymorphisms and TPP. CONCLUSION: We established the LD structure of this calcium channel subunit gene (CACNA1S) for the first time. However, its genetic variations are not associated with TPP in Chinese patients.

The relaxant effect of urocortin in rat pulmonary arteries.

Urocortin is a potent vasodilator, which plays physiological or pathophysiological roles in systemic circulation. However, little is known about its action on pulmonary circulation. The present study was aimed to characterize some cellular mechanisms underlying the relaxant effect of urocortin in isolated rat pulmonary arteries. Changes in isometric tension were measured on small vessel myographs. Urocortin inhibited U46619-induced contraction with reduction of the maximal response. Urocortin-induced relaxation was independent of the presence of endothelium. Inhibitors of nitric oxide (NO)-dependent dilator, NG-nitro-L-arginine methyl ester or 1H-[1,2,4]oxadizolo[4,3-a]quinoxalin-1-one, did not affect the relaxation. Astressin (100-500 nM), a corticotropin-releasing factor (CRF) receptor antagonist and KT5720, a protein kinase A (PKA) inhibitor reduced urocortin-induced relaxation. Urocortin produced less relaxant effect in 30 mM K+- than U46619-contracted arterial rings. Urocortin did not reduce CaCl2-induced contraction in 60 mM K+-containing solution. Ba2+ (100-500 microM) but not other K+ channel blockers reduced the relaxant responses to urocortin. Urocortin also relaxed the rings preconstricted by phorbol 12,13-diacetae in normal Krebs solution while this relaxation was less in a Ca2+-free solution. Our results show that urocortin relaxed rat pulmonary arteries via CRF receptor-mediated and PKA-dependent but endothelium/NO or voltage-gated Ca2+ channel-independent mechanisms. Stimulation of Ba2+-sensitive K+ channel may contribute to urocortin-induced relaxation. Finally, urocortin relaxed pulmonary arteries partly via inhibition of a PKC-dependent contractile mechanism.

No mutation in the KCNE3 potassium channel gene in Chinese thyrotoxic hypokalaemic periodic paralysis patients.

OBJECTIVES: Mutation in KCNE3 gene (Isk-related family potassium voltage-gated channel member 3 gene) was recently associated with the aetiology of thyrotoxic periodic paralysis (TPP). We studied 79 Chinese TPP patients by DNA sequencing of the entire coding sequence of KCNE3 to determine if this gene is the cause of TPP in Chinese patients. DESIGN AND MEASUREMENTS: A case-control genetic association study was carried out to determine the role of mutation/polymorphism in KCNE3 gene in the pathogenesis of TPP. Genomic DNA was extracted from peripheral blood samples. DNA sequencing was performed to cover the coding region of the KCNE3 gene for the TPP subjects. Restriction fragment length polymorphism was used to genotype specific sequence variants. subjects Seventy-nine TPP patients (cases) and 111 male thyrotoxic patients without history of paralysis (controls) were identified from thyroid clinic and during acute admission in a teaching hospital. RESULTS: No pathogenic mutation in KCNE3 was found in the TPP patients. The reported R83H mutation was also not found in the Chinese TPP patients. In addition, another silent polymorphism, 290T/C, was also not associated with TPP. CONCLUSION: The results indicate that mutation in KCNE3 is not a cause of TPP in Chinese patients.

Cardiovascular actions of berberine.

Berberine, is an alkaloid from Hydrastis canadensis L., Chinese herb Huanglian, and many other plants. It is widely used in traditional Chinese medicine as an antimicrobial in the treatment of dysentery and infectious diarrhea. This manuscript describes cardiovascular effects of berberine and its derivatives, tetrahydroberberine and 8-oxoberberine. Berberine has positive inotropic, negative chronotropic, antiarrhythmic, and vasodilator properties. Both derivatives of berberine have antiarrhythmic activity. Some cardiovascular effects of berberine and its derivatives are attributed to the blockade of K+ channels (delayed rectifier and K(ATP)) and stimulation of Na+ -Ca(2+) exchanger. Berberine has been shown to prolong the duration of ventricular action potential. Its vasodilator activity has been attributed to multiple cellular mechanisms. The cardiovascular effects of berberine suggest its possible clinical usefulness in the treatment of arrhythmias and/or heart failure.

Modulatory effect of protein kinase C activator on contractility of rat vas deferens.

The modulatory effect of the protein kinase C activator was examined on contraction of rat isolated vas deferens induced by constrictive agonists, noradrenaline (NA), ATP, BaCl2 and high K+. Phorbol 12,13-diacetate (PDA, 1 micromol/l) induced a transient extracellular Ca(2+)-dependent contraction while the inactive analogue, 4alpha-phorbol (1 micromol/l) had no effect. PDA significantly enhanced the peak amplitude of the contractile response to NA (0.1-10 micromol/l), ATP (100 micromol/l), Ba2+ (3 mmol/l) or high K+ (30 mmol/l). Staurosporine at 30 nmol/l reduced the enhancing effect of PDA on the agonist-induced contraction. NA (10 micromol/l) produced a phasic contraction followed by a sustained contraction, while ATP induced monophasic contraction. Pretreatment with nifedipine (10 nmol/l) had no effect on the phasic contraction induced by NA, but it significantly reduced ATP- or high K(+)-induced contraction. Staurosporine (30 nmol/l) alone attenuated the peak contractile response induced by NA or ATP but not by Ba2+. NA produced a transient contraction in Ca(2+)-free Krebs solution, and PDA (1 micromol/l) markedly enhanced this effect. These novel data indicate that activation of a protein kinase C-dependent mechanism not only affects contraction mediated by Ca2+ influx through voltage-sensitive Ca2+ channels, but also promotes intracellular Ca2+ release or intracellular Ca(2+)-mediated contractile mechanism in rat vas deferens.

Abolition of endothelium-dependent relaxation in the rat aorta by tetraoctylammonium ions.

Quaternary ammonium ions are common pharmacological probes used to study the kinetic properties of K+ channels in smooth muscle cells. On the other hand, some ammonium compounds cause vasorelaxation through unknown mechanisms. The main aim of this study was to examine a unique role of endothelium in the vascular response to tetraoctylammonium ions (TOA+) in the isolated rat aorta. Changes in contractile force were measured by force transducers and total tissue content of cGMP was measured by radioimmunoassay. Endothelial cytosolic Ca2+ ([Ca2+]i) was assessed by laser scanning confocal microscopy.

Potentiating effects on contractions by purified baicalin and baicalein in the rat mesenteric artery.

The effects of purified baicalin and baicalein from the traditional Chinese herb, Huangqin, on contractions induced by phenylephrine, U46619, and high extracellular K+ were investigated in isolated rat mesenteric arteries. Both baicalin (1-100 microM) and baicalein (1-50 microM) potentiated the contractile response to phenylephrine in a concentration-related manner. Both flavonoids (10 microM) also enhanced the U46619- or 40 mM K+-induced contractions. Baicalein (100-300 microM) reduced the phenylephrine-induced tone. Prazosin at 1 microM did not affect U46619-induced contraction in the absence and presence of baicalein or baicalin. Neither baicalin (1-100 microM) nor baicalein (1-100 microM) affected the basal tension. Removal of the functional endothelium abolished the potentiating effects of baicalin and baicalein in arteries preconstricted by both constrictors. Pretreatment of endothelium-intact rings with 100 microM N(G)-nitro-L-arginine also potentiated phenylephrine- or U46619-induced contraction but completely inhibited the effects of baicalin and baicalein. Pretreatment with 1 mM L-arginine reversed the enhancing effect of baicalin but not of baicalein on phenylephrine-evoked contraction. Pretreatment with 10 microM baicalin or 10 microM baicalein significantly reduced the endothelium-dependent relaxation induced by acetylcholine or ionomycin. These results indicate that both baicalin and baicalein potentiated the evoked contractile response, likely through inhibition of nitric oxide formation and/or release in the endothelium.