布洛芬对曲霉的体外抗真菌活性评价

目的观察布洛芬对曲霉临床分离株的体外抗真菌活性。方法分别用微量液基稀释法和纸片扩散法,测定布洛芬对10株烟曲霉、黄曲霉和土曲霉的抗菌活性。结果微量液基稀释法显示布洛芬对曲霉的最低抑菌浓度（MIC）范围为1000～2000μg/mL,最低杀菌浓度（MFC）范围为2000～8000μg/mL;纸片扩散法也显示布洛芬有体外抗曲霉活性：48h时,1000μg布洛芬对曲霉产生的抑菌圈直径为（20.1±3.89）mm。结论布洛芬有体外抗曲霉活性。     

Morphometric characterization of the first blastomeres of rainbow trout (Oncorhynchus mykiss)

Summary In the following investigation the morphometric characteristics of the first two blastomeres of rainbow trout (Oncorhynchus mykiss) were determined. Embryos were incubated at 9°C and then fixed in a Stockard solution every 30 min starting from 8.5 to 12.5 h of incubation post fertilization. Embryonic discs were extracted and microphotographs were taken with Q Capture Pro 5.0 software using a stereomicroscope Olympus SZX7. The average size of the blastodiscs was 941.22 ± 160.42 μm. The first cleavage finished after approximately 12 h of incubation. The first two blastomeres were regularly symmetrical in their morphology. Blastomere 1 had an average length (L) of 942.68 ± 105.56 μm and width (W) of 467.34 ± 64.33 μm. Blastomere 2 had an average length of 887.60 ± 101.65 and width of 454.49 ± 47.25 μm (n = 91). Significant differences were found between the length and width of blastomeres 1 and 2. The proportion between the length of blastomeres 1 and 2 was 0.94 ± 0.07 (n = 91); between the width of blastomeres 1 and 2 it was 0.88 ± 0.11 (n = 91); and the width/length ratio was 0.51 ± 0.09 (n = 182). It was concluded that rainbow trout blastomeres tend to be asymmetrical in length with a higher dispersion of widths.     

Myxobolus myleus n. sp. infecting the bile of the Amazonian freshwater fish Myleus rubripinnis (Teleostei: Serrasalmidae): morphology and pathology

Myxobolus myleus n. sp. is described from the gall-bladder of the freshwater fish Myleus rubripinnis collected near the city of Oriximiná in the Amazon System, Brazil. The spores obtained from the bile contained two equal symmetrical and smooth valves, each forming the spore wall. The spores were large, with a cone-like form, a semi spherical basal contour and measured (in μm) 19.3 ± 0.5 (n = 25) × 8.3 ± 0.5 (n = 25) × 4.0 ± 0.3 (n = 15). The apical end of the spores contained two elongate, equal and pointed conical polar capsules measuring 13.2 ± 0.4 μm (n = 25) in length and 3.0 ± 0.3 μm (n = 15) in width, each having a slightly tapering polar filament with 19 to 21 turns. The polar capsules were extended below at about 4/5 of the total length of the spores. The sporoplasm was binucleate and contained some sporoplasmosomes. All infected fish presented hypertrophy of the gall-bladder due to presence of the brownish parasite floating in the bile. In this paper we describe this new species of myxosporean based on light and ultrastructural observations, together with its associated pathology.     

Age-dependent renal cortical microvascular loss in female mice

Renal function and blood flow decline during aging in association with a decrease in the number of intrarenal vessels, but if loss of estrogen contributes to this microvascular, rarefaction remains unclear. We tested the hypothesis that the decreased renal microvascular density with age is aggravated by loss of estrogen. Six-month-old female C57/BL6 mice underwent ovariectomy (Ovx) or sham operation and then were allowed to age to 18-22 mo. Another comparable group was replenished with estrogen after Ovx (Ovx+E), while a 6-mo-old group served as young controls. Kidneys were then dissected for evaluation of microvascular density (by micro-computed tomography) and angiogenic and fibrogenic factors. Cortical density of small microvessels (20-200 μm) was decreased in all aged groups compared with young controls (30.3 ± 5.8 vessels/mm2, P < 0.05), but tended to be lower in sham compared with Ovx and Ovx+E (9.9 ± 1.7 vs. 17.2 ± 4.2 and 18 ± 3.0 vessels/mm2, P = 0.08 and P = 0.02, respectively). Cortical density of larger microvessels (200-500 μm) decreased only in aged sham (P = 0.04 vs. young control), and proangiogenic signaling was attenuated. On the other hand, renal fibrogenic mechanisms were aggravated in aged Ovx compared with aged sham, but blunted in Ovx+E, in association with downregulated transforming growth factor-β signaling and decreased oxidative stress in the kidney. Therefore, aging induced in female mice renal cortical microvascular loss, which was likely not mediated by loss of endogenous estrogen. However, estrogen may play a role in protecting the kidney by decreasing oxidative stress and attenuating mechanisms linked to renal interstitial fibrosis.     

Description of two new gill myxozoans from smallmouth (Micropterus dolomieu) and largemouth (Micropterus salmoides) bass

Two previously undescribed species of myxozoan parasites were observed in the gills of bass inhabiting the Potomac and James River basins. They are described using morphological characteristics and small-subunit (SSU) rDNA gene sequences. Both were taxonomically identified as new species of Myxobolus; Myxobolus branchiarum n. sp. was found exclusively in smallmouth bass, and Myxobolus micropterii n. sp. was found in largemouth and smallmouth bass. Small, spherical, white plasmodia of M. branchiarum from smallmouth bass were observed grossly in the gills; these plasmodia had an average length of 320.3 μm and width of 246.1 μm. The development of the plasmodia is intralamellar in the secondary lamellae of the gills. Mature spores were pyriform in shape with a length of 12.8 ± 1.4 (8.1-15.1) μm and width of 6.9 ± 1.1 (4.0-9.0) μm. Analysis of SSU rDNA identified M. branchiarum in a sister-group to 3 species of Henneguya , although morphologically caudal appendages were absent. Myxobolus micropterii observed in the gills of largemouth and smallmouth bass had larger, ovoid, cream-colored plasmodia with an average length of 568.1 μm and width of 148.1 μm. The cysts developed at the distal end of the gill filament within the primary lamellae. The mature spores were ovoid in shape with a length of 10.8 ± 0.7 (9.2-12.2) μm and width of 10.6 ± 0.6 (9.0-11.8) μm. SSU rDNA analysis placed M. micropterii in a sister group with Henneguya lobosa and Myxobolus oliveirai . The highest prevalence of M. branchiarum was observed in the gills of bass collected from the Cowpasture River (50.9%). Prevalence was 44.6% in bass from the Potomac River and only 4.3% in bass collected from the Shenandoah River. A seasonal study of M. branchiarum , which included both infected and uninfected smallmouth bass, determined that a significantly higher intensity was observed in the spring than in the summer (P < 0.001) or fall (P = 0.004). In an analysis excluding uninfected bass, a higher intensity was observed in the spring than in the summer (P = 0.001) or fall (P = 0.008). Prevalence and seasonal differences were not determined for M. micropterii .     

Effects of acetaminophen and ibuprofen on renal function in anesthetized normal and sodium-depleted dogs

In certain conditions, renal prostaglandins (PGs) are importantdeterminants of kidney function. Under these "renal PG-dependent states," pharmacological inhibition of vasodilatory PG may result inexcessive renal vasoconstriction and adversely affect kidney function.The purposes of this study were to determine whether acetaminophen(Acet), a weak PG-synthesis inhibitor, influences kidney function inthe renal PG-dependent state of anesthesia and sodium depletion.Comparisons were made with ibuprofen (Ibu). Measurements ofPGE₂ excretion were used to assessrenal PG synthesis. Acet (15 mg/kg) and Ibu (10 mg/kg) both decreasedrenal blood flow and glomerular filtration rate by ~20-30% innormal, anesthetized, sodium-replete dogs. Although Acet producedsimilar changes in renal blood flow and glomerular filtration rate inthe low-sodium dogs, Ibu caused a significantly greater renalvasoconstriction (64 ± 10%) in these animals. Both Acet and Ibuinhibited urinary PGE₂ excretionin sodium-replete and low-sodium dogs. Ibu tended to have a greater andmore prolonged effect than did Acet. These results suggest that Acetalters PGE₂ excretion and kidneyfunction under renal PG-dependent conditions; the effects, however, are less severe than those seen with Ibu.     

Production and NMR analysis of the human ibuprofen metabolite 3-hydroxyibuprofen

The anti-inflammatory drug ibuprofen (Ibu) is metabolized in the human liver to a number of metabolites including 1-hydroxyibuprofen (1-OH-Ibu), 2-OH-Ibu, and 3-OH-Ibu, respectively. The only human CYP known to produce relevant amounts of 3-OH-Ibu is CYP2C9 and as genetic polymorphisms of CYP2C9 influence the metabolization of numerous drugs, the availability of reference standards for CYP2C9-specific metabolites is of considerable interest. The aim of this study was to develop a biological production process for 3-OH-Ibu and to affirm its NMR characteristics. The recombinant fission yeast strain CAD68 coexpressing human CYP2C9 and CPR was used for the whole-cell biotransformation of Ibu to 3-OH-Ibu in 1L batch-scale for 75h. The average space-time yield for the bioproduction of 3-OH-Ibu (125±34μmol/Ld) considerably exceeded that of 2-OH-Ibu (44±10μmol/Ld). Accordingly, average biotransformation activities normalized to dry biomass weight were 5.0±0.8μmol/gd (3-OH-Ibu) and 1.9±0.7μmol/gd (2-OH-Ibu). The metabolite was prepurified on preparative TLC-plates, isolated by HPLC fractionation, and characterized by LC-MS and NMR. As expected, differential fragmentation patterns of 2-OH-Ibu and 3-OH-Ibu were detected in ESI-LC-MS analysis. 44mg of 3-OH-Ibu was efficiently purified from four 1L batch cultures and its structure was clearly confirmed by one- and two-dimensional NMR.     

Ibuprofen protects low density lipoproteins against oxidative modification

Oxidative modification of LDL by vascular cells has been proposed as the mechanism by which LDL become atherogenic. The effect of ibuprofen on LDL modification by copper ions, monocytes and endothelial cells was studied by measuring lipid peroxidation products. Ibuprofen inhibited LDL oxidation in a dose-dependent manner over a concentration range of 0.1 to 2.0 mM. Ibuprofen (2 mM, 100 microg/ml LDL) reduced the amount of lipid peroxides formed during 2 and 6 h incubation in the presence of copper ions by 52 and 28%, respectively. Weak free radical scavenging activity of ibuprofen was observed in the DPPH test. The protective effect of ibuprofen was more marked when oxidation was induced by monocytes or endothelial cells. Ibuprofen (1 mM, 100 microg/ml LDL) reduced the amount of lipid peroxides generated in LDL during monocyte-mediated oxidation by 40%. HUVEC-mediated oxidation of LDL in the absence and presence of Cu2+ was reduced by 32 and 39%, respectively. More lipid peroxides appeared when endothelial cells were stimulated by IL-1beta or TNFalpha and the inhibitory effect of ibuprofen in this case was more pronounced. Ibuprofen (1 mM, 100 microg/ml LDL) reduced the amount of lipid peroxides formed during incubation of LDL with IL-1beta-stimulated HUVEC by 43%. The figures in the absence and presence of Cu2+ for HUVEC stimulated with TNFalpha were 56 and 59%, respectively. To assess the possibility that ibuprofen acts by lowering the production rate of reactive oxygen species, the intracellular concentration of H2O2 was measured. Ibuprofen (1 mM) reduced intracellular production of hydrogen peroxide in PMA-stimulated mononuclear cells by 69%. When HUVEC were stimulated by IL-1beta or TNFalpha the reduction was 62% and 66%, respectively.     

Evidence Suggesting a Role of Iron in a Mouse Model of Nephrogenic Systemic Fibrosis

Nephrogenic systemic fibrosis is associated with gadolinium contrast exposure in patients with reduced kidney function and carries high morbidity and mortality. We have previously demonstrated that gadolinium contrast agents induce in vivo systemic iron mobilization and in vitro differentiation of peripheral blood mononuclear cells into ferroportin (iron exporter)-expressing fibrocytic cells. In the present study we examined the role of iron in a mouse model of nephrogenic systemic fibrosis. Chronic kidney disease was induced in 8-week-old male Balb/C mice with a two-step 5/6 nephrectomy surgery. Five groups of mice were studied: control (n = 5), sham surgery control (n = 5), chronic kidney disease control (n = 4), chronic kidney disease injected with 0.5 mmol/kg body weight of Omniscan 3 days per week, for a total of 10 injections (n = 8), and chronic kidney disease with Omniscan plus deferiprone, 125 mg/kg, in drinking water (n = 9). Deferiprone was continued for 16 weeks until the end of the experiment. Mice with chronic kidney disease injected with Omniscan developed skin changes characteristic of nephrogenic systemic fibrosis including hair loss, reddening, ulceration, and skin tightening by 10 to 16 weeks. Histopathological sections demonstrated dermal fibrosis with increased skin thickness (0.25±0.06 mm, sham; 0.34±+0.3 mm, Omniscan-injected). Additionally, we observed an increase in tissue infiltration of ferroportin-expressing, fibrocyte-like cells accompanied by tissue iron accumulation in the skin of the Omniscan-treated mice. The deferiprone-treated group had significantly decreased skin thickness (p<0.05) and significantly decreased dermal fibrosis compared to the Omniscan-only group. In addition, iron chelation prevented tissue infiltration of ferroportin-expressing, fibrocyte-like cells. Our in vitro experiments demonstrated that exposure to Omniscan resulted in the release of catalytic iron and this was prevented by the iron chelator deferiprone. Deferiprone inhibited the differentiation of human peripheral blood mononuclear cells into ferroportin-expressing cells by immunohistochemical staining and western blot analysis. Our studies support an important role of iron in the pathophysiology of gadolinium chelate toxicity and nephrogenic systemic fibrosis.     

Huffmanela cf. carcharhini (Nematoda: Trichosomoididae: Huffmanelinae) from skin of a sandbar shark, Carcharhinus plumbeus, in the Pacific Ocean

Eggs of Huffmanela cf. carcharhini from the skin of an aquarium-held, juvenile sandbar shark, Carcharhinus plumbeus , from the Pacific Ocean were studied using light and scanning electron microscopy. Grossly, eggs imparted a scribble-like skin marking approximately 130 × 60 mm on the right side of the shark's snout adjacent to its eye and nostril. Fresh (unfixed) eggs were elliptical, 75-95 μm long (xˉ = 85 μm, SD = ±4.5; n = 75), 48-63 μm wide (53 ± 3.4; 75), 8-10 μm in shell thickness (9 ± 1.3; 27), 45-68 μm in vitelline mass length (52 ± 6.9; 8); had a smooth shell surface and nonprotruding polar plugs 8-13 μm wide (10 ± 1.5; 73); lacked thin filaments, superficial envelope, and shell spines; sank in 35 ppt artificial seawater; and did not spontaneously hatch after 12 hr in 35 ppt artificial seawater. Formalin-fixed eggs measured 193 days postfixation were 75-95 μm long (84 ± 3.9; 150), 45-60 μm wide (50 ± 2.2; 150), 5-10 μm in shell thickness (8 ± 1.2; 87), 45-60 μm in vitelline mass length (51 ± 3.0; 92), and 30-40 μm in vitelline mass width (33 ± 2.0; 84), and had nonprotruding polar plugs that were 10-15 μm long (11 ± 1.4; 93) and 8-10 μm wide (9 ± 1.1; 108). Forcibly hatched first-stage larvae (unfixed) were filiform, 188-273 μm long (212 ± 25.5; 13), 8-13 μm wide (10 ± 1.2; 13), and had fine transverse striations. Eggs infected the epidermis only. Histology revealed intra-epithelial inflammation with eosinophilic granulocytes and hyperplasia, plus dermal lymphofollicular hyperplasia associated with the infection. The eggs of H. cf. carcharhini likely undergo considerable ex utero development before being sloughed (unhatched) from the host, along with epidermal cells.     

Luminescent complexes of terbium ion for molecular recognition of ibuprofen

The complexation behavior and luminescent properties of terbium (Tb³⁺) complexes containing bi‐dental ligands were studied: nitrogen – 1,10‐phenanthroline, and oxygen – trifluoroacetylacetone as well as acetylacetone ligands with ibuprofen (Ibu; a non‐steroidal anti‐inflammatory drug). Aqueous and aqueous alcohol microheterogeneous solutions were used as media. The effects of solubilization by various micellar solutions, pH and ligand type on luminescent properties of Tb³⁺ complexes were investigated. Sensitized luminescence of mixed ligand complex Tb(1,10‐phenanthroline)‐Ibu and dynamic quenching effect in complex Tb(trifluoroacetylacetone)₃‐Ibu allow Ibu determination with the limit of detection 5.3 × 10^–8 mol/L and 1.26 × 10^–6 mol/L, respectively. Copyright © 2013 John Wiley & Sons, Ltd.     

Oxidative stress in the developing brain: effects of postnatal glucocorticoid therapy and antioxidants in the rat

In premature infants, glucocorticoids ameliorate chronic lung disease, but have adverse effects on long-term neurological function. Glucocorticoid excess promotes free radical overproduction. We hypothesised that the adverse effects of postnatal glucocorticoid therapy on the developing brain are secondary to oxidative stress and that antioxidant treatment would diminish unwanted effects. Male rat pups received a clinically-relevant tapering course of dexamethasone (DEX; 0.5, 0.3, and 0.1 mg x kg(-1) x day(-1)), with or without antioxidant vitamins C and E (DEXCE; 200 mg x kg(-1) x day(-1) and 100 mg x kg(-1) x day(-1), respectively), on postnatal days 1-6 (P1-6). Controls received saline or saline with vitamins. At weaning, relative to controls, DEX decreased total brain volume (704.4±34.7 mm(3) vs. 564.0±20.0 mm(3)), the soma volume of neurons in the CA1 (1172.6±30.4 μm(3) vs. 1002.4±11.8 μm(3)) and in the dentate gyrus (525.9±27.2 μm(3) vs. 421.5±24.6 μm(3)) of the hippocampus, and induced oxidative stress in the cortex (protein expression: heat shock protein 70 [Hsp70]: +68%; 4-hydroxynonenal [4-HNE]: +118% and nitrotyrosine [NT]: +20%). Dexamethasone in combination with vitamins resulted in improvements in total brain volume (637.5±43.1 mm(3)), and soma volume of neurons in the CA1 (1157.5±42.4 μm(3)) and the dentate gyrus (536.1±27.2 μm(3)). Hsp70 protein expression was unaltered in the cortex (+9%), however, 4-HNE (+95%) and NT (+24%) protein expression remained upregulated. Treatment of neonates with vitamins alone induced oxidative stress in the cortex (Hsp70: +67%; 4-HNE: +73%; NT: +22%) and in the hippocampus (NT: +35%). Combined glucocorticoid and antioxidant therapy in premature infants may be safer for the developing brain than glucocorticoids alone in the treatment of chronic lung disease. However, antioxidant therapy in healthy offspring is not recommended.     

氧化应激在高原重体力劳动过程中急性高原反应发生中的作用

目的：观察氧化应激在高原重体力劳动过程中急性高原反应（AHAR）发生中的作用。方法：由低海拔（1500m）快速进入高原（3700m）并从事重体力劳动的男性官兵96名,年龄18～35岁。根据AHAR症状评分,分为重度AHAR组（A组,n=24）、轻中度AHAR组（B组,n=47）和无AHAR组（C组,n=25）,在该高度逗留50d后下撤前及返回低海拔（1500m）后12h、15d分别测定血清8．异前列腺素F2a（8-iso-PGF2a）、超氧化物歧化酶（SOD）、丙二醛（MDA）,并与低海拔（1500m）50名健康官兵（D组）比较。结果：A组血清8-iso-PGF2a、MDA[分别为（9．53±0．47）μg／L、（8．91±0．39）μmol／L]水平显著高于B组[分别为（8．34±O．42）μg／L、（7．31±0．32）μmol／L]、C组[分别为（7．02±0．48）μg／L、（6．41±0．23）μmol／L和D组[分别为（5．13±0．56）μg／L、（5．48±0．33）μmol／L]（均P〈0．01）,SOD（52．08±3．44）μ／mL水平显著低于B组（62．27±2．54）μ/mL、C组（71．99±3．35）μ/mL和D组（80．78±3．44）μ/mL,（均P〈0．01）,B组与c组之间和C组与D组之间亦有显著性差异（均P〈0．01）。海拔3700mAHAR总计分与血清8-iso-PGF2α、ⅣⅡ）A呈显著正相关（均P〈0．01）,与血清SOD显著负相关（P〈0．01）;8-iso-PGF2α、MDA与SOD显著负相关（均P〈0．01）。海拔3700m50d,血清8-iso-PGF2α、MDA水平显著高于,SOD水平显著低于海拔1500m12h、15d和D组（均P〈0．01）,海拔1500m12h与15d之间有显著性差异（均P〈0．01）,海拔1500m 15d与D组之间无显著性差异。结论：人体在高原低氧并重体力时氧化应激和氧化．抗氧化失衡与AHAR的发病和程度有密切关系,氧化应激和氧化．抗氧化失衡越严重,AHAR越重。返回低海拔后12h有显著改善,15d恢复到正常水平。     

罗格列酮对海马神经元树突发育的影响

罗格列酮(rosiglitazone,Rosig.)是噻唑烷二酮类(thiazolidinediones,TZDs)过氧化物酶体增殖物激活受体γ(peroxisome proliferator-activated receptor gamma,PPARγ)的激动剂,近年来,临床研究发现其具有神经保护作用,但对其作用机制目前仍没有完全研究清楚．利用活细胞成像的方法,观察罗格列酮对大鼠海马神经元树突丝和树突树发育的影响及其机制．结果显示,罗格列酮浓度依赖的增高神经元树突丝密度,对树突丝长度、运动速度并没有影响．此外,罗格列酮也不影响树突树的总分支、总长度以及各级分支的数目和长度．PPARγ 特异性拮抗剂GW9662完全阻断了罗格列酮介导的树突丝密度增高．结果表明罗格列酮可能通过PPARγ途径影响神经元的早期发育,这可能是罗格列酮发挥神经保护作用的潜在机制．     

Effects of corticosteroid treatment on airway inflammation, mechanics, and hyperpolarized ³He magnetic resonance imaging in an allergic mouse model

The purpose of this study was to assess the effects of corticosteroid therapy on a murine model of allergic asthma using hyperpolarized (3)He magnetic resonance imaging (MRI) and respiratory mechanics measurements before, during, and after methacholine (MCh) challenge. Three groups of mice were prepared, consisting of ovalbumin sensitized/ovalbumin challenged (Ova/Ova, n = 5), Ova/Ova challenged but treated with the corticosteroid dexamethasone (Ova/Ova+Dex, n = 3), and ovalbumin-sensitized/saline-challenged (Ova/PBS, n = 4) control animals. All mice underwent baseline 3D (3)He MRI, then received a MCh challenge while 10 2D (3)He MR images were acquired for 2 min, followed by post-MCh 3D (3)He MRI. Identically treated groups underwent respiratory mechanics evaluation (n = 4/group) and inflammatory cell counts (n = 4/group). Ova/Ova animals exhibited predominantly large whole lobar defects at baseline, with significantly higher ventilation defect percentage (VDP = 19 ± 4%) than Ova/PBS (+2 ± 1%, P = 0.01) animals. Such baseline defects were suppressed by dexamethasone (0%, P = 0.009). In the Ova/Ova group, MCh challenge increased VDP on both 2D (+30 ± 8%) and 3D MRI scans (+14 ± 2%). MCh-induced VDP changes were diminished in Ova/Ova+Dex animals on both 2D (+21 ± 9%, P = 0.63) and 3D scans (+7 ± 2%, P = 0.11) and also in Ova/PBS animals on 2D (+6 ± 3%, P = 0.07) and 3D (+4 ± 1%, P = 0.01) scans. Because MCh challenge caused near complete cessation of ventilation in four of five Ova/Ova animals, even as large airways remained patent, this implies that small airway (<188 μm) obstruction predominates in this model. This corresponds with respiratory mechanics observations that MCh challenge significantly increases elastance and tissue damping but only modestly affects Newtonian airway resistance.     

有明银鱼耳石显微结构和微化学研究

1998年从鸭绿江捕取有明银鱼成鱼 ,生物学测量后剖出耳石。每尾鱼 1对矢耳石中的 1个用于制片 ,显微镜下观察其显微结构 ,另 1个制片镀碳膜后 ,用扫描电子微探针测定Sr和Ca的浓度比率。Sr和Ca分析的标准样用SrSO4 和CaSO4 。 31尾鱼 (体长 116～ 15 7mm)耳石长半径 (Y)与鱼体长 (X)成线性关系 ,其方程式为Y =2 72 16X +9 2 2 92 ,r =0 9178,P <0 0 1。耳石中心和耳石原基的平均直径分别为 2 2 5 5± 2 88μm和6 95± 1 30 μm。 13尾鱼耳石上的日轮数为 30 5～ 35 4,大约在 45～ 70日轮处出现过渡轮。日轮间距 0 94～ 1 14μm ,最大间距在 190～ 2 2 0日轮处 ,最小间距出现在 2 80日轮之后。耳石中Sr、Ca浓度比例在第 5至第 7测点出现第 1个高峰 ,这与稚鱼为了越冬洄游到海中时间相吻合。第 2个高峰出现在 2 8～ 32测点 ,这与鱼产卵上溯洄游时间相符。个体发育过程中生理和生态条件的变化 ,可引起耳石中Sr、Ca比率的改变 ,但栖息水域盐度的突然改变是导致Sr、Ca比率显著增高的主导因素。     

Involvement of veratridine-induced increase of reverse Na(+)/Ca(2+) exchange current in intracellular Ca(2+) overload and extension of action potential duration in rabbit ventricular myocytes

The objectives of this study were to investigate the effects of veratridine (VER) on persistent sodium current (I(Na.P)), Na(+)/Ca(2+) exchange current (I(NCX)), calcium transients and the action potential (AP) in rabbit ventricular myocytes, and to explore the mechanism in intracellular calcium overload and myocardial contraction enhancement by using whole-cell patch clamp recording technique, visual motion edge detection system, intracellular calcium measurement system and multi-channel physiological signal acquisition and processing system. The results showed that I(Na.P) and reverse I(NCX) in ventricular myocytes were obviously increased after giving 10, 20 μmol/L VER, with the current density of I(Na.P) increasing from (-0.22 ± 0.12) to (-0.61 ± 0.13) and (-2.15 ± 0.14) pA/pF (P < 0.01, n = 10) at -20 mV, and that of reverse I(NCX) increasing from (1.62 ± 0.12) to (2.19 ± 0.09) and (2.58 ± 0.11) pA/pF (P < 0.05, n = 10) at +50 mV. After adding 4 μmol/L tetrodotoxin (TTX), current density of I(Na.P) and reverse I(NCX) returned to (-0.07 ± 0.14) and (1.69 ± 0.15) pA/pF (P < 0.05, n = 10). Another specific blocker of I(Na.P), ranolazine (RAN), could obviously inhibit VER-increased I(Na.P) and reverse I(NCX). After giving 2.5 μmol/L VER, the maximal contraction rate of ventricular myocytes increased from (-0.91 ± 0.29) to (-1.53 ± 0.29) μm/s (P < 0.01, n = 7), the amplitude of contraction increased from (0.10 ± 0.04) to (0.16 ± 0.04) μm (P < 0.05, n = 7), and the baseline of calcium transients (diastolic calcium concentration) increased from (1.21 ± 0.08) to (1.37 ± 0.12) (P < 0.05, n = 7). After adding 2 μmol/L TTX, the maximal contraction rate and amplitude of ventricular myocytes decreased to (-0.86 ± 0.24) μm/s and (0.09 ± 0.03) μm (P < 0.01, n = 7) respectively. And the baseline of calcium transients reduced to (1.17 ± 0.09) (P < 0.05, n = 7). VER (20 μmol/L) could extend action potential duration at 50% repolarization (APD(50)) and at 90% repolarization (APD(90)) in ventricular myocytes from (123.18 ± 23.70) to (271.90 ± 32.81) and from (146.94 ± 24.15) to (429.79 ± 32.04) ms (P < 0.01, n = 6) respectively. Early afterdepolarizations (EADs) appeared in 3 out of the 6 cases. After adding 4 μmol/L TTX, APD(50) and APD(90) were reduced to (99.07 ± 22.81) and (163.84 ± 26.06) ms (P < 0.01, n = 6) respectively, and EADs disappeared accordingly in 3 cases. It could be suggested that: (1) As a specific agonist of the I(Na.P), VER could result in I(Na.P) increase and intracellular Na(+) overload, and subsequently intracellular Ca(2+) overload with the increase of reverse I(NCX). (2) The VER-increased I(Na.P) could further extend the action potential duration (APD) and induce EADs. (3) TTX could restrain the abnormal VER-induced changes of the above-mentioned indexes, indicating that these abnormal changes were caused by the increase of I(Na.P). Based on this study, it is concluded that as the I(Na.P) agonist, VER can enhance reverse I(NCX) by increasing I(Na.P), leading to intracellular Ca(2+) overload and APD abnormal extension.     

Ibuprofen attenuates early lung injury in endotoxemic, neutropenic rats.

The objective of our study was to determine the role of ibuprofen in protecting neutropenic rats from cardiopulmonary injury due to endotoxemia. We hypothesized that ibuprofen would offer pulmonary protection by altering cytokine production. Neutropenic rats received E. coli lipopolysaccharide (LPS) alone or ibuprofen and LPS. After 4 h, arterial blood gases, heart rate and blood pressure were measured. Blood and bronchoalveolar lavage fluid (BALF) were collected for TNF- alpha and MIP-2 concentrations. Lung tissue for iNOS mRNA and myeloperoxidase were obtained. The ibuprofen group had decreased heart rate and better oxygenation. Ibuprofen suppressed TNF- alpha and MIP-2 production in blood and MIP-2 concentrations in BALF. Lung mRNA for iNOS was higher in the ibuprofen group. Neutrophil infiltration in the lung was similar in both groups. Ibuprofen attenuated cardiopulmonary dysfunction by decreasing the early cytokine response. The balance of vasodilator to vasoconstrictor production in the lung may favor vasodilation as shown by increased iNOS mRNA and suppression of thromboxane.     

Ibuprofen attenuates plasma tumor necrosis factor activity during sepsis-induced acute lung injury.

Plasma tumor necrosis factor (TNF) activity, cardiac index, extravascular lung water, systemic and pulmonary arterial pressures, pulmonary vascular resistance index, and arterial PO2 were monitored for 300 min in four groups of anesthetized pigs: saline-infused animals (n = 5), saline-infused animals given ibuprofen (12.5 mg/kg iv) at 0 and 120 min (n = 4), animals infused for 60 min with live Pseudomonas aeruginosa (Ps, 5 x 10(8) organisms/ml at 0.3 ml.20 kg-1.min-1, n = 6), and animals infused for 60 min with Ps plus ibuprofen administered at 0 and 120 min (n = 4). Infusion of Ps induced significant elevations (greater than 4-fold increase in units/ml of TNF by 60 min, P less than 0.05) in plasma TNF activity (L929 cytolysis assay) and alterations (P less than 0.05) in all hemodynamic and pulmonary parameters within 30-60 min. Ibuprofen administration in sepsis significantly decreased peak TNF activity by 2 units/ml and attenuated many of the physiological alterations due to sepsis. These results show that ibuprofen attenuates sepsis-induced injury and that alterations of acute septic insult are correlated with reduced plasma TNF activity in septic animals given ibuprofen.