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Clinical features of asthmatic patients with increased urinary leukotriene E4 excretion (hyperleukotrienuria): Involvement of chronic hyperplastic rhinosinusitis with nasal polyposis.

BACKGROUND: The urinary leukotriene E4 (U-LTE4) concentration is significantly increased in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic factors of asthma and the U-LTE4 concentration remains undetermined. OBJECTIVE: We sought to examine the clinical features of asthmatic patients with increased excretion levels of U-LTE4 (hyperleukotrienuria). METHODS: We measured the U-LTE4 concentrations in 137 asthmatic patients (including 64 patients with AIA) who were in clinically stable condition. A U-LTE4 concentration of 150 pg/mg creatinine or greater (mean U-LTE4 + 3 SDs of normal healthy control subjects) was indicative of hyperleukotrienuria. RESULTS: The basal concentration of U-LTE4 was significantly higher in the patients with AIA than in those with aspirin-tolerant asthma (ATA; median, 227.2 vs 90.3 pg/mg creatinine; P <.01). Compared with normal leukotrienuria in the patients with AIA, hyperleukotrienuria in the patients with AIA was associated with older age and decrease in pulmonary function. On the other hand, compared with normal leukotrienuria in the patients with ATA, hyperleukotrienuria in the patients with ATA was associated with severe asthma and chronic hyperplastic rhinosinusitis with nasal polyposis (CHRS/NP), which are well-known symptoms of the aspirin triad, as well as hypereosinophilia and anosmia. The patients with ATA with CHRS/NP excreted U-LTE4 at significantly high concentrations. There were significant decreases in the U-LTE4 concentrations before and after the sinus surgery in both the AIA and ATA groups (P <.05). CONCLUSION: Cysteinyl leukotrienes are not strictly associated with aspirin intolerance itself but rather with clinical features, such as CHRS/NP, that are similar to those seen in AIA. CHRS/NP might be involved in cysteinyl leukotriene overproduction in asthmatic patients.

Adult↗

Effects of the number of fatty acid residues on the phase behaviors of decaglycerol fatty acid esters.

The effects of the number of fatty acid residues (n) in decaglycerol fatty acid esters, i.e., decaglycerol laurates (abbreviated to (C11)nG10), on the phase behaviors of three laurate esters, (C11)1.9G10, (C11)2.7G10, and (C11)3.4G10, were investigated. The unreacted decaglycerol remaining in each ester was removed by liquid extraction before use. (C11)1.9G10 formed hexagonal liquid crystals in aqueous solutions, while (C11)2.7G10 and (C11)3.4G10, which are more hydrophobic than (C11)1.9G10, formed lamellar liquid crystals. The cloud point in aqueous solution was measured for mixtures of these three esters. The cloud phenomenon was observed when the weight ratio of hydrophilic groups to the total surfactant (WH/WS) was around 0.6. The cloud point shifted to a markedly higher temperature, even with a slight increase in the WH/WS ratio. The solubilization abilities of (C11)nG10 for the oils m-xylene and (R)-(+)-limonene were also examined. When the WH/WS ratio was between 0.60 and 0.64, (C11)nG10 formed microemulsions and lyotropic liquid crystals in the presence of water and the oils. These self-organized structures were stable, even above 90 degrees C. It is concluded that the phase behavior of (C11)nG10 are insensitive to temperature, but strongly dependent on both the WH/WS ratio and the number of fatty acid residues (n).

Emulsions↗

Construction of a 3D model of nattokinase, a novel fibrinolytic enzyme from Bacillus natto. A novel nucleophilic catalytic mechanism for nattokinase.

A three-dimensional structural model of nattokinase (NK) from Bacillus natto was constructed by homology modeling. High-resolution X-ray structures of Subtilisin BPN' (SB), Subtilisin Carlsberg (SC), Subtilisin E (SE) and Subtilisin Savinase (SS), four proteins with sequential, structural and functional homology were used as templates. Initial models of NK were built by MODELLER and analyzed by the PROCHECK programs. The best quality model was chosen for further refinement by constrained molecular dynamics simulations. The overall quality of the refined model was evaluated. The refined model NKC1 was analyzed by different protein analysis programs including PROCHECK for the evaluation of Ramachandran plot quality, PROSA for testing interaction energies and WHATIF for the calculation of packing quality. This structure was found to be satisfactory and also stable at room temperature as demonstrated by a 300ps long unconstrained molecular dynamics (MD) simulation. Further docking analysis promoted the coming of a new nucleophilic catalytic mechanism for NK, which is induced by attacking of hydroxyl rich in catalytic environment and locating of S221.

Amino Acid Sequence↗

Decrease in acetylcholine-induced current by neomycin in PC12 cells.

The effects of neomycin, one of the aminoglycoside antibiotics, on the acetylcholine (ACh)-induced current (I(ACh)) were studied in pheochromocytoma cells by using the whole-cell clamp technique. The I(ACh) proved to be generated through neuronal nicotinic receptor. ACh (30 microM) induced an inward current at a holding potential of -80 mV. When cells were treated with neomycin (0.01-1 mM) and ACh (30 microM) simultaneously, an inhibitory effect of neomycin on the peak of I(ACh) was found. This effect was fast, reversible, and concentration dependent. Pretreatment with neomycin for 3-8 min had no effect on the inhibition of I(ACh) induced by neomycin. External application of 0.1 mM neomycin neither shifted the dose-response curve of the peak I(ACh) to the right (dissociation constant (K(d)) = 16.5 microM) nor affected its coefficient (1.8) but inhibited the curve amplitudes by approximately 33%. Stimulated protein kinase C activation by using an exogenous activator produced inhibition of I(ACh), while using protein kinase C inhibitor (PKCI 19-31) had no effect on the inhibition of I(ACh) induced by neomycin. These results suggest that neomycin has an inhibitory effect on I(ACh) without the involvement of phospholipase C. It indicates that neomycin binds to a specific site on the cell membrane, probably on the neuronal nicotinic receptor-coupled channel, and inhibits the I(ACh) in a noncompetitive manner, thus controlling the immediate catecholamine release from the sympathetic cells.

Acetylcholine↗

Liquid chromatography with amperometric detection at a nano crystalline Ce-doped lead dioxide film modified electrode for determination of (R)-Salsolinol, (R)-N-methylsalsolinol and monoamine neurotransmitters in Parkinsonian patients' cerebrospinal fluid.

The fabrication and application of a novel electrochemical detector (ED) with nano crystalline Ce-doped lead dioxide film chemically modified electrode (CME) for liquid chromatography (LC) were described. The Ce-doped PbO(2) film was characterized by X-ray diffractometer (XRD) and scanning tunnel microscope (STM). The electrochemical behaviors of (R)-Salsolinol ((R)-Sal) at the CME were investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). It was found that the CME exhibited an efficiently electrocatalytic effect on the current responses of (R)-Sal, (R)-N-methylsalsolinol ((R)-NMSal) and monoamine neurotransmitters. In LC-ED, all (R)-Sal, (R)-NMSal, dopamine (DA), norepinephrine (NE), 3-methoxy-4-hydroxyphenylglycol (MHPG), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) had good and stable current responses at the CME. The linear ranges of the nine analytes were over three orders of magnitude (R(2) > 0.995). The application of this method coupled with microdialysis sampling for the determination of (R)-Sal, (R)-NMSal and monoamine neurotransmitters in Parkinsonian patients' cerebrospinal fluid (CSF) was satisfactory.

Chromatography, Liquid↗

Insemination with sex sorted fresh bovine spermatozoa processed in the presence of antioxidative substances.

Flow cytometrically sex sorted spermatozoa are reduced in their fertilizing capacity, particularly when stored either in cooling extender or after freezing in liquid nitrogen. So far, preservation methods for sorted spermatozoa have differed only marginally from procedures used for unsorted semen. In the present study, a TRIS extender was modified to balance major cell damage caused by the sorting process and by liquid storage of the sorted spermatozoa. The new extender, containing a combination of antioxidants (AO) and bovine serum albumin (BSA), significantly increased the lifespan and fertilizing capacity of sex sorted spermatozoa. No significant differences were observed between unsorted controls and sorted samples for motility and status of sperm membranes as tested by fluorescein-isothiocyanat-peanut agglutinin/propidium iodide (FITC-PNA/PI). Acrosome integrity of spermatozoa was significantly better when semen was stored at 15 degrees C for 24 and 48 h in an extender containing AO with or without BSA as compared with controls (p < 0.05). There were no significant differences, in pregnancy rates of heifers inseminated at a natural oestrus, between unsorted controls (16/24, 66.7%) and both sorted groups (AO + BSA: 18/31, 58.1% and AO-BSA: 12/22, 54.5%). Additionally, it was shown for the first time that artificial insemination (AI) with liquid sexed bull spermatozoa stored for 72 h after sorting can result in pregnancy rates similar to AI with non-sorted semen.

Acrosome↗

DNA sequence analysis of DNA gyrase and DNA topoisomerase IV quinolone resistance-determining regions of Salmonella enterica serovar Typhi and serovar Paratyphi A.

The mutations that are responsible for fluoroquinolone resistance in the gyrA, gyrB, parC, and parE genes of Salmonella enterica serovar Typhi and serovar Paratyphi A were investigated. The sequences of the quinolone resistance-determining region of the gyrA gene in clinical isolates which showed decreased susceptibilities to fluoroquinolones had a single mutation at either the Ser-83 or the Asp-87 codon, and no mutations were found in the gyrB, parC, and parE genes.

Anti-Infective Agents↗

Resveratrol induces apoptosis in thyroid cancer cell lines via a MAPK- and p53-dependent mechanism.

Two papillary thyroid carcinoma (PTC) and two follicular thyroid carcinoma (FTC) cell lines treated with resveratrol (RV), 1-10 microM, showed activation and nuclear translocation of MAPK (extracellular signal-regulated kinase 1/2). Cellular abundance of the oncogene suppressor protein p53, serine phosphorylation of p53, and abundance of c-fos, c-jun, and p21 mRNAs were also increased by RV. Inhibition of the MAPK pathway by either H-ras antisense transfection or PD 98059, an MAPK kinase inhibitor, blocked these RV-induced effects. Addition of pifithrin-alpha, a specific inhibitor of p53, or transfection of p53 antisense oligonucleotides caused decreased RV-induced p53 and p21 expression in PTC and FTC cells. Studies of nucleosome levels estimated by ELISA and of DNA fragmentation showed that RV induced apoptosis in both papillary and follicular thyroid cancer cell lines; these effects were inhibited by pifithrin-alpha and by p53 antisense oligonucleotide transfection. PD 98059 and H-ras antisense transfection also blocked induction of apoptosis by RV. Thus, RV acts via a Ras-MAPK kinase-MAPK signal transduction pathway to increase p53 expression, serine phosphorylation of p53, and p53-dependent apoptosis in PTC and FTC cell lines.

Adenocarcinoma, Follicular↗

[Cyclosporine A and mycophenolate mofetile as prophylactics for GVHD in a murine model of H-2 haploidentical nonmyeloablative bone marrow transplantation].

In order to research the prophylactic effect of cyclosporine A (CSA) and mycophenolate mofetile (MMF) on GVHD in mice with H-2 haploidentical nonmyeloablative bone marrow transplantation, a murine model was established by using of C57BL/6J mouse as donor and (C57BL/6J x BALB/C) F(1) mouse as the recipient. The recipient mice were given CSA + MTX or CSA + MMF for prophylaxis of acute GVHD (aGVHD). The survival rate, hematopoietic recovery, and morbidity and mortality of aGVHD were observed for 50 days after transplantation. The results showed that typical aGVHD developed in the transplanted mice without prophylactic treatment during 22 to 25 days after transplantation. The morbidity of aGVHD was 75% (15/20), 40% (8/20) and 30% (6/20) and mortality was 100% (15/15), 62.5% (5/8) and 50% (3/6) respectively in unprophylactic group (control), CSA + MTX and CSA + MMF groups. In conclusion, CSA and MTX reduce the morbidity and mortality of aGVHD in mice with haploidentical nonmyeloablative bone marrow transplantation, and the effect of CSA + MMF is better than that of CSA + MTX.

Animals↗

[The anti-respiratory syncytial virus effect of an active compound (AP3) from a Chinese medicinal herb-Herba patriniae in vitro].

OBJECTIVE: To study the effect on anti-respiratory syncytial virus of an active compound (AP3) from a Chinese medicinal herb-Herba patriniae in vitro. METHODS: Active component of herba patriniae (AP3) was extracted and its anti-respiratory syncytial virus (RSV) effect was tested. A water soluble substance (AP3) was isolated from a Chinese herb Herba patriniae, by hot water extraction, ethol precipitation and gel permeation column chromatography. The cytotoxicity of AP3 was tested by adding it to HeLa cells directly. Its effect against RSV was estimated by CPEI assay while ribavirin was used as positive control. RESULTS: Chemical test showed that the nature of substance AP3 was polysaccharide. The median cytotoxic concentration (TC(50)) of AP3 was 11.45 mg/ml by morphological observation and the median effective concentration (50% effective concentration, EC(50)) of it against replication of the long strain of RSV in HeLa cells was 0.0986 mg/ml. The Therapeutic index (TI = TC(50)/EC(50)) of AP3 was 116.12, much higher than the TI of herba patriniae (AP1) (TI = 59.26) and ribavirin (TI = 53.45). Moreover, AP3 gave a dose-dependent response in inhibiting RSV. In the assay, the effect of AP3 against RSV growth was also tested. In addition, the effect of AP3 on virus growth, AP3 inhibited replication of RSV in HeLa cells, when added at 0 h, 2 h, 4 h after virus infection, were also tested. CONCLUSION: This study suggested that the AP3 exerted an obvious inhibitory effect to RSV in HeLa cell culture. This study furnished a reliable evidence for development of a new antiviral drug.

Antiviral Agents↗

[Pain control with epidural anesthesia for uterine artery embolization].

BACKGROUND: To reduce the severity of post procedure pain associated with uterine artery embolization (UAE) for leiomyomata, we used continuous infusion of low concentration ropivacaine through an epidural catheter. METHODS: Thirteen patients for UAE were evaluated. In a patient without indication for epidural anesthesia, the pain was controlled with intermittent morphine infusion. Other patients had post procedure pain managed with 10 ml bolus of 1% lidocaine and continuous infusion of 0.2% ropivacaine at 5 ml x hr-1 for 16 hours. RESULTS: The patient complained of severe pain just after UAE and required epidural lidocaine. Then, we started to infuse lidocaine or ropivacaine just before starting UAE. Among these cases, 9 patients required extra pain control using NSAIDs as a rescue. Only three patients required no medication except epidural analgesia. CONCLUSIONS: Continuous infusion of 0.2% ropivacaine at a rate of 5 ml x hr-1 is not enough for pain management after UAE.

Adult↗

Imrecoxib: a novel and selective cyclooxygenase 2 inhibitor with anti-inflammatory effect.

AIM: To investigate the inhibitory effect of imrecoxib, a synthetic compound of completely new structure, on cyclooxygenase 1 (COX-1) and 2 (COX-2) and its anti-inflammatory effect in vivo. METHODS: The inhibitory effects of imrecoxib on cyclooxygenase 1 and 2 were studied using whole cell assay with murine peritoneal macrophages induced by calcimycin and LPS. The inhibitory effects of imrecoxib on mRNA level of COX-1 and COX-2 in human macrophage cell line U937 were detected by reverse transcription polymerase chain reaction (RT-PCR) analysis. Effects of imrecoxib on acute and chronic inflammation were evaluated in rat carrageenan induced edema model and rat adjuvant-induced arthritis model, respectively. RESULTS: Imrecoxib was found to inhibit COX-1 and COX-2 with IC50 value of 115+/-28 nmol/L and 18+/-4 nmol/L, respectively. Imrecoxib was shown to selectively and dose-dependently inhibit COX-2 mRNA level. Imrecoxib effectively inhibited carrageenan-induced acute inflammation at the doses of 5, 10, and 20 mg/kg i.g. and adjuvant-induced chronic inflammation at the doses of 10 and 20 mg/kg/d i.g. CONCLUSION: Imrecoxib is a novel and moderately selective COX-2 inhibitor that possesses anti-inflammatory effect by inhibition of COX-2 mRNA expression.

Animals↗

[Infection of Penicillium marneffei].

OBJECTIVES: To elucidate the etiology, pathohistology, clinical characteristic and differential diagnosis, reduce missed diagnosis and improve the early detection and treatment of Penicillium Marneffei infection, by means of this case report and literature review. METHODS: A patient hospitalized Penicillium Marneffei infection were presented here, together with 27 cases in the literature, among which 10 patients had complications of AIDS and 5 with other diseases. RESULTS: Penicillium Marneffei is a temperature-sensitive, two-phase fungus, which can infect healthy and immunocompromised subjects. The common symptoms are lymphadenopathy and infection of the lung. The infection may be local or diffuse, involving the intestinal tract, soft tissue, bone, liver, spleen and bone marrow etc. The lesion can be classified into the granuloma type, suppurative type and anergy/necrosis type histologically. The yeast-like fungus were mainly found in the cytoplasm of macrophages, which were demonstrated by PAS and Giemsa staining. The wine red color developed on the culture confirms the diagnosis. CONCLUSIONS: The diagnosis of Penicillium Marneffei infection should be considered when tuberculosis is suspected but not confirmed, and if the patient has a history of having lived or traveled in Southeast Asia, is anemic or resistant to anti-tuberculosis treatment. The major differential diagnosis is histoplasmosis. Early administration of anti-fungus drugs is essential for recovery.

AIDS-Related Opportunistic Infections↗

Cellular toxic effects of combination of low dose of cisplatin and interstitial injection of 32P glass microspheres on mouse solid tumor S180.

BACKGROUND: Although 32P-glass microspheres (32P-GMS) have been used in internal radiotherapy for malignant tumors, it has been one of the key obstacles to improve the effect of radiotherapy. We investigated the cellular and hypersensitive effect of combined use of low dose of cisplatin and interstitial injection of 32P-GMS on mouse solid tumor S180. METHODS: The mice with solid tumor S180 were randomly divided into four groups (controls, cisplatin therapy, 32P-GMS therapy and combination therapy). The specimens of the mice were sectioned two weeks after treatment and weighed. The death rate of tumor cells and the inhibition rate of tumor were calculated respectively. The cell cycle and apoptosis rate were evaluated with flow-cytometry. The ultrastructural changes of the four groups were observed by a transmission electron microscope. The data were analyzed by the chi-square test. RESULTS: The growth of tumor was slower in the combination therapy group than in the simple therapy groups by macrography. The inhibition rate and the death rate of tumor cells of the combination therapy group were significantly higher than those of the control group and the other two simple therapy groups (P < 0.05). More cell damages were displayed in the combination therapy group than in the other groups under the light and electronic microscope. CONCLUSION: Low-dose cisplatin combined with interstitial injection of 32P glass microspheres could be used as an effective hypersensitive regimen for the internal radiotherapy of mouse solid tumor S180.

Animals↗

Efficacy of a juvenile hormone mimic, pyriproxyfen (S-31183), for mosquito control in dairy wastewater lagoons.

Pyriproxyfen (S-31183) was applied to dairy wastewater lagoons, during 1988, at 0.1 kg (AI)/ha in single and multiple applications which resulted in control of Culex spp. larvae for periods of 7 to 68 days. Length of the control period appeared to be related to water quality, with greater residual efficacy in more polluted sources. The AI apparently adsorbed onto organic debris where efficacy remained high in the lagoon even after water was pumped from the lagoon and replenished with untreated wastewater. Alternating treatments with control agents having a different mode of action is suggested to avoid selection of insecticide resistance.

Animals↗

Preclinical pharmacology of angiotensin II receptor antagonists: update and outstanding issues.

The angiotensin II receptor antagonists (AIIRA) represent a new class of antihypertensive agents, with a mechanism of action that differs from that of other classes of antihypertensive agents that also affect the renin-angiotensin system (RAS), such as the angiotensin-converting enzyme (ACE) inhibitors. The AIIRA were developed to overcome several of the deficiencies of ACE inhibitors, which include the following: 1) competitive inhibition of the ACE enzyme results in a reactive increase in renin and angiotensin I (AI) levels, which may overcome the blockade; 2) ACE is a relatively nonspecific enzyme that has substrates in addition to AI, including bradykinin and other tachykinins; thus, inhibition of ACE may also result in accumulation of these substrates; 3) production of AII can occur through non-ACE pathways, in addition to being produced by the primary ACE pathway; these alternative pathways are unaffected by ACE inhibition; and 4) specific adverse effects are associated with inhibition of the ACE enzyme. This review summarizes the preclinical pharmacology of the AIIRA class of agents and describe the means by which the deficiencies associated with ACE inhibition are overcome. The specific characteristics of the new AIIRA irbesartan are described.

Angiotensin Receptor Antagonists↗