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PubMed1991

Application of free-energy decomposition to determine the relative stability of R and S oligodeoxyribonucleotide methylphosphonates.

The stereoselective stability of oligodeoxyribonucleotide methylphosphonates is examined using free-energy computer simulations. These modified phosphate linkages have the potential to be important antisense therapeutics that can be targeted on specific sequences of single- and double-stranded DNA, as well as crucial RNA messages. The stability of hybrid duplexes that contain these modified linkages is known experimentally to depend on the configuration of the chiral phosphonate center. Free-energy decomposition calculations were performed on three DNA oligomers to determine the origin of the structural interactions and physical properties that influence the relative stability of R and S methylphosphonate diastereomers. The strategy applied used free-energy decomposition methods to evaluate the free-energy contributions from selected groups. The results indicated that only three groups have a steric effect on the stability: the C2' and C3' substituents on the S diastereomer (5' side) and the C5' substituents on the R diastereomer (3' side). The balance considerably favors the R configuration in all the isomers studied and is not sequence dependent. The electrostatic effects were much more variable and were shown to be dependent on the conformation of duplex. The solvent interactions, however, were consistent and contributed favorably to the stability of the R over the S diastereomer. This favorable solvation energy for the R diastereomer was surprising (since the methyl group is more solvent exposed in this configuration) and was further supported by ab initio and associated free-energy calculations. This study concludes that oligonucleotides containing R-methylphosphonate linkages will normally form more stable duplexes than the corresponding S diastereomer irrespective of sequence, but also points that conformational changes may allow for a reversal in stability.

Base Sequence↗

PubMed1990

Comparative myocardial extraction of two technetium-labeled BATO derivatives (SQ30217, SQ32014) and thallium.

The transcapillary exchange of a new class of 99mTc-labeled compounds (BATO) were compared to 201Tl in isolated, blood perfused rabbit hearts. During variable blood flow (0.15-2.44 ml/min/g), peak and net extraction (Emax and Enet, respectively), and capillary permeability-surface area product (PScap) were determined with paired indicator-dilution techniques. Serial bolus injections of 201Tl, [111In]albumin, and [99mTc]BATO; chloro[tris(cyclohexanedionedioxime)methyl boronic acid]Tc (SQ30217, n = 8) and a hydroxy-substituted derivative (SQ32014, n = 5) were given to a total of 13 hearts. Mean (+/- s.d.) SQ30217 Emax and Enet were 0.72 +/- 0.09 and 0.55 +/- 0.18, respectively, which were higher than thallium values of 0.57 +/- 0.10 and 0.46 +/- 0.17 (p less than 0.03). Mean SQ30217 PScap was 1.1 +/- 0.4 ml/min/g and was also higher than corresponding thallium determinations (0.7 +/- 0.3; p less than 0.001). SQ32014 Emax, Enet, and PScap were all significantly less than thallium values (p less than 0.001). Thallium and SQ30217 values for Emax and PScap were closely correlated with blood flow (r greater than or equal to 0.73), whereas those for SQ32014 were weakly correlated (r = 0.09). A small clinical pilot study (n = 3) was performed, which showed that SQ32014 was a poor myocardial perfusion agent in man. In summary, transcapillary exchange of SQ30217 is greater than thallium, which in turn, is greater than SQ32014. Therefore, SQ30217 appears to have good clinical potential, but SQ32014 does not.

Adult↗

PubMed1982

Electron capture gas-liquid chromatographic determination of morantel-related residues in bovine liver.

A gas-liquid chromatographic assay has been developed to determine major residues of morantel in bovine liver, a target tissue, at levels of 0.2-0.8 ppm. The method is based on hydrolysis of the N-methyltetrahydropyrimidine portion of morantel and its metabolites to N-methyl-1,3-propanediamine, and conversion of the diamine to an N,N'-bis-(2-nitro-4-trifluoromethylphenyl) derivative. The addition of an internal standard, N-ethyl-1,3-propanediamine, to the tissue sample circumvents any potential problem that could arise from variable reaction yields, and eliminates the true recovery as a factor affecting the accuracy and precision of the procedure. The concentrations of the derivatives are determined by pulsed electron capture gas-liquid chromatography over a linear dynamic range equivalent to 0.2-0.8 ppm morantel. The method has been evaluated at 0, 0.2, 0.4, and 0.8 ppm levels in fortified bovine liver, and in a withdrawal sample containing physiologically incurred morantel residues. Mean values of 0.22 +/- 0.015, 0.40 +/- 0.033, and 0.79 +/- ppm were found for fortified samples, 0.02 ppm for control liver, and 0.56 +/- 0.050 ppm for the withdrawal sample.

Animals↗

PubMed1997

Nitric oxide contributes to surfactant-induced vasodilation in surfactant-depleted newborn piglets.

To investigate whether nitric oxide (NO) is involved in surfactant-induced systemic and pulmonary vasodilatation in newborn piglets with surfactant deficiency, 2-6-d-old piglets were subjected to repeated saline lung lavages. They were then randomly assigned to one of two groups (seven in each group): the N(omega)-nitro-L-arginine methyl ester (L-NAME) group received 3 mg/kg L-NAME i.v. 45 min before endotracheal instillation of 200 mg/kg porcine surfactant; the saline group received saline i.v. at the same time point, and instillation of 200 mg/kg surfactant. Mean arterial blood pressure, systemic vascular resistance, pulmonary arterial pressure, and pulmonary vascular resistance increased significantly after injection of L-NAME (all p < 0.01), whereas the cardiac index decreased significantly (p < 0.05). Saline injection did not change any variable. Significant decreases in mean arterial blood pressure (from a mean +/- SD of 66 +/- 10 to 53 +/- 9 mm Hg, p < 0.01), pulmonary arterial pressure (from 29 +/- 6 to 23 +/- 6 mm Hg, p < 0.01), and systemic vascular resistance (from 0.40 +/- 0.13 to 0.33 +/- 0.12 mm Hg/mL/min/kg, p < 0.05) were observed only in the saline group after surfactant instillation, whereas the decrease in pulmonary vascular resistance was not significant after surfactant instillation (p = 0.06). In contrast to the saline group, these variables were not modified in the L-NAME group after surfactant instillation. We conclude that the vasodilatory effect of porcine surfactant instillation in newborn piglets with surfactant deficiency is associated with activation of NO synthase.

Animals↗

PubMed1997

Genetics of homology-dependent gene silencing in Arabidopsis; a role for methylation.

Ninety-eight independent transformed (T1) Arabidopsis plants were generated, containing additional copies of the chalcone synthase (CHS) gene. Three T2 generation families (A, B and C) were found that showed reduced anthocyanin biosynthesis, consistent with homology-dependent gene silencing of CHS. Clonal sectors of tissue showing CHS silencing were seen in the early generations. Affected individuals in family A showed only slight silencing, in family C such plants were almost completely silenced, and in family B affected individuals were intermediate. Plants homozygous for a single silencing insert were isolated from each family. Plants homozygous or hemizygous for insert A showed variable penetrance and expressivity of silencing. Self-fertilization of plants hemizygous for the B and C-inserts suggested that these CHS-silencing inserts each behave as single Mendelian dominant traits. The CHS mRNA of the C-insert homozygotes was reduced to undetectable levels. Outcrosses of B- and C-insert homozygotes to wild-type plants resulted in F1 plants that were variegated. This variegation appears to be due to expression of the CHS allele from the wild-type parent, since use of a CHS mutant, tt4, as untransformed parent resulted in uniform green F1 plants. Southern blots revealed a correlation between DNA methylation and CHS silencing. In addition, derivative plants were generated from C-insert homozygotes that had lost the silencing inserts, and these showed a partial reversion towards wild-type phenotype and methylation of the cellular CHS gene at the TT4 locus. This result suggests that the TT4 copy of CHS became methylated during the C-insert-induced silencing and retained methylation and partial silencing after the silencing T-DNA was lost.

Acyltransferases↗

PubMed1994

Inhibition of nitric oxide biosynthesis and carotid arteriovenous anastomotic shunting in the pig.

1. The role of nitric oxide (NO) biosynthesis in the regulation of blood flow through arteriovenous anastomoses was evaluated in the carotid circulation of the anaesthetized pig. For this purpose, the effect of intracarotid (i.c.) administration of the NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME: 0.1, 0.3 and 1.0 mg kg-1; n = 6) or saline (n = 6) was studied on the distribution of common carotid blood flow, using the radioactive microsphere method. 2. Apart from the highest dose, L-NAME caused no major changes in the systemic haemodynamic variables. Both cardiac output and systemic vascular conductance were reduced by L-NAME (1 mg kg-1), being reversed partly by L-arginine (100 mg kg-1, i.c.). In both groups, L-arginine slightly reduced mean arterial blood pressure. 3. Total common carotid artery blood flow as well as its distribution over the capillary and arteriovenous anastomotic fraction remained stable after saline injection. In contrast, L-NAME caused a dose-dependent decline in common carotid artery blood flow and conductance and this decline was confined entirely to its arteriovenous anastomotic part. 4. Subsequent intracarotid injection of L-arginine (100 mg kg-1) reversed the reduction in total carotid conductance almost completely and that in the arteriovenous anastomotic region partially. Additionally, L-arginine increased capillary conductance significantly in the L-NAME--as well as the saline-treated animals. 5. These results indicate that the L-arginine-NO pathway contributes little to the regulation of tissue perfusion in the porcine carotid circulation. In contrast, NO seems to play an important role in shunting arterial blood through arteriovenous anastomoses in the anaesthetized pig.

Animals↗

PubMed2003

Glutamate receptor function in learning and memory.

The contribution of glutamate to synaptic transmission, plasticity and development is well established; current evidence is based on diverse approaches to decipher function and malfunction of this principal transmitter. With respect to learning and memory, we are now able to identify more specifically the role played by the three main glutamate receptor classes in learning and memory: centre stage is clearly the NMDA receptor, with overwhelming evidence proving its involvement in the actual learning process (encoding), throughout the animal kingdom. This is discussed with respect to many different types of learning. Evidence for the contribution of the AMPA receptors (AMPARs) is less clear-cut due to the general problem of specificity: block of AMPARs will shutdown neuronal communication, and this will affect various components essential for learning. Therefore, the role of AMPARs cannot be established in isolation. Problems of interpretation are outlined and a specific involvement of AMPARs in the regulation of neuronal excitation related to learning is proposed. Metabotropic glutamate receptors (mGluRs) may contribute very little to the actual acquisition of new information. However, memory formation appears to require mGluRs, through the modulation of consolidation and/or recall. Overall, mGluR functions seem variable and dependent on brain structure and learning task.

Animals↗

PubMed2026

The opioid receptor-ligand network in human cancers: pan-cancer multi-omics profiling and translational implications.

BACKGROUND: Opioid receptor-ligand signalling has been implicated in tumour biology and perioperative outcomes; however, its pan-cancer molecular landscape and clinical relevance remain incompletely defined. METHODS: We performed a pan-cancer multi-omics analysis of eight predefined opioid receptor-ligand genes across 33 tumour types from The Cancer Genome Atlas. Analyses included gene expression analysis using the linear models for microarray data (limma) package, genomic alterations, DNA methylation, regulatory network inference, pathway activity estimation using gene set variation analysis, and survival modelling. Multivariable Cox regression models were adjusted for age, sex, and tumour stage. RESULTS: Opioid receptor-ligand genes exhibited heterogeneous and generally low-to-moderate expression across tumour types. Genomic and epigenetic alterations were tumour-specific and variably associated with gene expression. Selected genes showed associations with overall survival in a tumour-dependent manner; however, these associations were attenuated after adjustment for clinical covariates and were accompanied by wide confidence intervals in some cohorts. Pathway analyses suggested associations with broader biological programmes, including epithelial-mesenchymal transition and immune-related pathways. Regulatory analyses identified candidate transcription factors and miRNAs, although these findings are exploratory. CONCLUSIONS: This pan-cancer analysis provides a systematic overview of opioid receptor-ligand gene features across human cancers. The observed associations are context-dependent and should be interpreted as hypothesis-generating. Further mechanistic and prospective studies are required to determine the clinical relevance of opioid signalling in cancer and perioperative settings.

Humans↗

PubMed1994

Thiopurine methyltransferase activity in a French population: h.p.l.c. assay conditions and effects of drugs and inhibitors.

1. Thiopurine methyltransferase (TPMT) is a cytosolic enzyme involved in the catabolism of thiopurine drugs, which are used to treat cancer patients and organ transplant recipients. Because TPMT activity is polymorphic and under genetic control, large interindividual variations in the immunosuppressive activity and toxicity of these drugs may, at least in part, be inherited. 2. We have developed a specific h.p.l.c. method for measuring 6-methyl mercaptopurine formed from 6-mercaptopurine (6-MP) in red blood cell lysates during the TPMT assay procedure. In blinded assays of 55 samples from adult blood donors, the results of the h.p.l.c. method correlated with those of the radiochemical reference method (r = 0.83, P < 0.001). 3. Using this h.p.l.c. assay, we tested the effect of known inhibitors of TPMT activity (syringic acid, p-anisic acid and tropolone) in vitro and showed that they were highly inhibitory. We also found that drugs often administered concomitantly with 6-MP (prednisone, prednisolone, 6-methylprednisolone, cyclophosphamide, methotrexate, and trimethoprim-sulphamethoxazole) had little or no effect on TPMT activity in vitro. 4. In a group of 300 French individuals, TMPT activity was highly variable, ranging from 4.7 to 35.3 nmol h-1 ml-1 of packed red blood cells (nmol h-1 ml-1 PRBC) with a mean value of 19.3 +/- 4.9. TMPT activity was not influenced by sex. 5. This sensitive and reproducible h.p.l.c. assay for TPMT activity in red blood cells may prove useful for prospective clinical studies designed to optimise dosage regimens of thiopurine drugs (detection limit for 6-methyl mercaptopurine is 5 ng ml-1, intra- and inter-assay variations are 6.8 and 8.2%, respectively).

Adult↗

PubMed1999

CD40 ligand expression deficiency in a female carrier of the X-linked hyper-IgM syndrome as a result of X chromosome lyonization.

We report on the case of a girl with an immune deficiency characterized by recurrent infections of the upper and lower respiratory tract, low IgG and IgA serum levels as well as deficiency of the in vivo antibody response. Since this patient is the sister of a boy affected with a hyper-IgM syndrome due to a defect in CD40 ligand (CD40L) expression, the involvement of CD40L in this phenotypic expression was investigated. A very low fraction of activated T cells (5%) in this female patient expressed CD40L. This resulted from the presence of a heterozygous CD40L nonsense mutation associated with a skewed pattern of X chromosome inactivation as determined by methylation pattern analysis. Although carriers of X-linked hyper-IgM are considered to be asymptomatic, this study indicates that extreme lyonization of the normal X can lead to a mild expression of the hyper-IgM syndrome which is similar to common variable immune deficiency (CVID). Therefore, it is possible that some cases of CVID in females represent partial deficiency of CD40L expression in carriers of the CD40L mutation.

CD40 Antigens↗

PubMed2005

UGT1A1 polymorphisms are important determinants of dietary carcinogen detoxification in the liver.

PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-f]pyridine), the most abundant heterocyclic amine in diet, is involved in the etiology of cancer. PhIP and its carcinogenic metabolite N-hydroxy-PhIP (N-OH-PhIP) are extensively conjugated by UDP-glucuronosyltransferase (UGTs) with wide variability. This study aimed to determine the genetic influence of UGTs on the hepatic detoxification of this carcinogen. The formation of N-OH-PhIP glucuronides was studied in 48 human liver samples by mass spectrometry. Liver samples were genotyped for common polymorphisms and correlated with UGT protein levels and N-OH-PhIP glucuronidation activities. The formation of four different N-OH-PhIP glucuronide metabolites was observed in all livers. The major metabolite was N-OH-PhIP-N(2)-glucuronide (N(2)G), which is the primary metabolite found in human urine, and showed a high interindividual variability (up to 28-fold). Using an heterologous expression system, the bilirubin-conjugating UGT1A1 enzyme was identified among all known UGTs (n = 16) as the predominant enzyme involved. The significant correlation between UGT1A1 protein content and formation of N(2)G (Rs = 0.87; P < .0001) suggests a critical role for UGT1A1 in the hepatic metabolism of this carcinogen. UGT1A1 expression was strongly determined by the presence of the common promoter polymorphisms, UGT1A1*28 (TATA box polymorphism) (P = .0031), -3156G/A (P = .0006) and -3279G/T (P = .0017), and rates of N(2)G were indeed correlated with these polymorphisms (P < .05), whether analyzed individually or in combination (haplotypes). In conclusion, UGT1A1 polymorphisms modulate the hepatic metabolism of the carcinogenic intermediate of PhIP and may determine the level of its exposure and potentially influence the risk of cancer through dietary exposure to HCAs.

Carcinogens↗

PubMed2000

The phosphoryl oxime-destroying activity of human plasma.

The potential of obidoxime and other pyridinium-4-aldoximes to reactivate dimethyl- and diethylphosphorylated cholinesterases is markedly restricted by the inevitable formation of rather stable phosphoryl oximes (POXs) with high anticholinesterase activity. This effect is hardly seen with very dilute enzyme preparations, but becomes significant at physiological enzyme concentrations. Human plasma with the butyrylcholinesterase irreversibly blocked by soman was able to stimulate obidoxime-induced reactivation of concentrated erythrocyte acetylcholinesterase (Ery-AChE) to the same extent as was observed with a dilute preparation, suggesting phosphoryl oxime-destroying capacity. The inactivating factor, which was tentatively termed POX-hydrolase, had (1) a molecular weight of >100 kDa; (2) required Ca2+ , which could not be substituted by Zn2+ or Mg2+; and (3) lost its catalytic activity reversibly in the presence of ethylenediamine-tetraacetic acid (EDTA). The enzyme activity varied widely (20-fold) among different subjects and did not follow the activity pattern of human serum paraoxonase (PON1). Rabbit plasma with its particularly high paraoxonase content showed only weak POX-hydrolase activity. These data suggest POX-hydrolase to be a different entity. POX-hydrolase was most active with the putative phosphoryl-obidoxime from paraoxon-ethyl, less with the product from paraoxon-methyl and least with that from diisopropylfluorophosphate. The analogue TMB-4 reacted similarly to obidoxime. The putative phosphonyl oximes arising by the reaction of obidoxime with nerve agents were apparently not cleaved. The variation in POX-hydrolase activity may additionally contribute to the variable response to oxime therapy in patients with organophosphate insecticide poisoning.

Animals↗

PubMed1988

Effects of high pressure on the single-turnover kinetics of the carbamylation of cholinesterase.

Pressure, as a perturbing variable, is one of the most powerful tools to investigate the thermodynamic parameters of chemical reactions and to study the mechanism of enzyme-catalyzed reactions. The effect of elevated hydrostatic pressure (up to 0.8 kbar) on the reaction of butyrylcholinesterase with N-methyl-(7-dimethylcarbamoxy)quinolinium was determined under single-turnover conditions at 35 degrees C. The rate of carbamylation was monitored as the accumulation of the fluorescent ion, N-methyl-7-hydroxyquinolinium, in a high-pressure stopped-flow apparatus designed for the assay of fluorescence. Elevated pressure favored formation of the enzyme-substrate complex but inhibited carbamylation of the enzyme. Because a single reaction step was recorded, it was possible to interpret the data obtained under high pressure in the form of Michaelis-Menten equations. From the pressure dependence of the dissociation constant for the enzyme-substrate complex and the rate constant for carbamylation, maximal volume changes accompanying these events were determined. The value for the binding process, delta Vb = -129 ml.mol-1, is too large to be related only to volumetric changes in the active center. Substrate-induced conformational change and change of water structure appear to be the dominant contributions to the overall volume change associated with substrate binding. The large positive activation volume measured (delta V not equal to = 119 ml.mol-1) may also reflect extended structural and hydration changes. At pressures greater than 0.4 kbar, an additional pressure effect, dependent on substrate concentration, occurred in a narrow pressure interval. This effect may have resulted from a substrate-induced pressure-sensitive enzyme conformational state.

Butyrylcholinesterase↗

PubMed2000

Excimer laser retreatment of residual myopia following photoastigmatic refractive keratectomy for compound myopic astigmatism.

PURPOSE: To prospectively evaluate the safety, efficacy, and visual performance of excimer laser enhancement following photoastigmatic refractive keratectomy (PARK) with the Summit Apex Plus. SETTING: Stanford University School of Medicine Eye Laser Clinic, Stanford, California, USA. METHODS: As part of a Food and Drug Administration clinical trial, 93 eyes of 56 patients with a mean spherical equivalent (SE) of -4.98 diopters (D) +/- 1.80 (SD) (range -1.75 to -8.50 D) had PARK for compound myopic astigmatism using the Summit Apex Plus excimer laser and a poly(methyl methacrylate) erodible mask. Seventeen eyes with a mean SE of -2.08 +/- 0.76 D required excimer laser refractive keratectomy for residual spherical myopia or compound myopic astigmatism. Patients were prospectively followed 1, 3, 6, 9, and 12+ months after the enhancement procedure. Primary outcome variables included uncorrected visual acuity (UCVA), refraction, vector analysis, best spectacle-corrected visual acuity (BSCVA) under standard ambient conditions (photopic, scotopic, and glare), corneal clarity, and contrast sensitivity function curve under photopic and scotopic conditions. RESULTS: At the last postoperative visit, the mean sphere had been corrected 82% to a residual of -0.29 +/- 1.23 D and mean SE had been corrected 65% to a residual of -0.74 +/- 1.27 D. Eighty-two percent of eyes were within +/-1.0 D of attempted correction. Eighty-eight percent had a UCVA of 20/40 or better. Vector analysis demonstrated a difference vector of within +/-1.0 D in 75% of eyes that had PARK retreatment. There was no significant loss in the contrast sensitivity curve. Late regression associated with corneal haze and loss of BSCVA occurred in 2 eyes (11.7%). CONCLUSIONS: Retreatment following PARK for compound myopic astigmatism results in effective reduction in residual spherical myopia and compound myopic astigmatism. An improvement in UCVA without loss of contrast sensitivity can be expected in most eyes. However, regression, corneal haze, and loss of BSCVA may occur. Further studies are indicated to predict risk factors for these complications.

Astigmatism↗

PubMed2004

Fabrication of poly(methyl methacrylate) microfluidic chips by atmospheric molding.

A greatly simplified method for fabricating poly(methyl methacrylate) (PMMA) separation microchips is introduced. The new protocol relies on UV-initiated polymerization of the monomer solution in an open mold under ambient pressure. Silicon microstructures are transferred to the polymer substrate by molding a methyl methacrylate solution in a sandwich (silicon master/Teflon spacer/glass plate) mold. The chips are subsequently assembled by thermal sealing of the channel and cover plates. The new fabrication method obviates the need for specialized replication equipment and reduces the complexity of prototyping and manufacturing. Variables of the fabrication process were assessed and optimized. The new method compares favorably with common fabrication techniques, yielding high-quality devices with well-defined channel and injection-cross structures, and highly smoothed surfaces. Nearly 100 PMMA chips were replicated using a single silicon master, with high chip-to-chip reproducibility (relative standard deviations of 1.5 and 4.7% for the widths and depths of the replicated channels, respectively). The relatively high EOF value of the new chips (2.12 x 10(-4) cm(2) x V(-1) x s(-1)) indicates that the UV polymerization process increases the surface charge and hence enhances the fluidic transport. The attractive performance of the new CE microchips has been demonstrated in connection with end-column amperometric and contactless-conductivity detection schemes. While the new approach is demonstrated in connection with PMMA microchips, it could be applied to other materials that undergo light-initiated polymerization. The new approach brings significant simplification of the process of fabricating PMMA devices and should lead to a widespread low-cost production of high-quality separation microchips.

Journal Article↗

PubMed1999

New Fluorinated Stannic Compounds as Precursors of F-Doped SnO(2) Materials Prepared by the Sol-Gel Route.

Dialkoxydi(beta-diketonate)tin(IV) compounds react either with difluorodi(beta-diketonate)tin(IV) or with butanoyl fluoride to yield novel tin complexes Sn(OR(1))F(R(2)COCHCOR(2))(2) 1 (R(1) = tert-amyl, isopropyl, ethyl; R(2) = methyl, tert-butyl). Multinuclear (1)H, (13)C, (19)F, and (119)Sn NMR spectroscopic characterization showed that complexes 1 are octahedral in solution with a cis configuration for the fluorine and the alkoxide group. Kinetics of configurational rearrangements were studied by variable-temperature (13)C NMR spectroscopy. The hydrolytic behavior of 1 was determined for different hydrolysis ratios h = [H(2)O]/[1]. For R(1) = tert-amyl, a dimeric fluorinated species was mainly obtained for h = 0.5, and addition of 2 mol equiv of water led to a fluorinated stannic oxopolymer soluble in CH(3)CN. In the latter case, the powder obtained after solvent elimination and treatment in air at 550 degrees C consisted of crystalline SnO(2) cassiterite particles containing the required amount (3 mol %) of doping fluorine and exhibiting electronic conductivity comparable to that of Sn-doped In(2)O(3). Complexes 1 are the first precursors of F-doped SnO(2) materials prepared by the sol-gel route.

Journal Article↗

PubMed1997

Lack of haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension induced by acute sino-aortic denervation.

1. The aims of the present experiments were to define a new experimental model of pulmonary hypertension induced by a post-capillary mechanism and to assess the haemodynamic effects of nitric oxide on post-capillary pulmonary hypertension. 2. Cardiopulmonary variables of 28 male beagle dogs, anaesthetized with chloralose, 16 spontaneous breathing and 12 with assisted ventilation, were studied before and after sino-aortic denervation (SAD). The haemodynamic effects of inhaled nitric oxide (25 p.p.m., 10 min). N(omega)-nitro-L-arginine methyl ester (20 mg kg-1, i.v.), urapidil (0.5 mg kg-1-, i.v.) and propranolol (300 micrograms kg-1, i.v.) were studied after SAD. 3. SAD induced an acute and transient pulmonary hypertension, more marked in spontaneous breathing dogs. This pulmonary hypertension involved a post-capillary mechanism, secondary to the left ventricular haemodynamic effects of the acute increase of left ventricular after-load induced by systemic hypertension. In fact, the increase of mean pulmonary arterial pressure after SAD and the decrease of this parameter after urapidil or propranolol were strongly correlated with the variations of pulmonary capillary wedge pressure. Furthermore, no significant change in pulmonary vascular resistance was found after SAD or administration of alpha or beta-adrenoceptor antagonists. 4. Inhaled nitric oxide did not reverse pulmonary hypertension induced by SAD. N(omega)-nitro-L-arginine methyl ester had no significant haemodynamic effect of pulmonary circulation. 5. In conclusion, the lack of effect of inhaled nitric oxide and nitric synthase inhibitor on pulmonary circulation parameters SAD suggest that endothelium-derived oxide is not involved in the mechanisms leading to post-capillary pulmonary hypertension.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

An evaluation of some factors affecting the detection of blood group antibodies by automated methods.

Some factors affecting the sensitivity of the automated methods for blood group antibody detection have been evaluated. The experiments revealed influencing differences between various albumin preparations. In the BMC method, one lot of albumin permitted no significant antibody detection. In the LISP technique, a plateau of maximum Polybrene activity was found. The beginning of this plateau depended on both the albumin preparation and the Polybrene lot. In the BMC method, methyl cellulose gave optimal sensitivity within a concentration range of 0.3 to 0.5 per cent. The stability of test cells stored in ACD at 4 C was studied. All test cells could be used safely up to two weeks. Cells from different donors showed variable reactivity after three weeks.

Animals↗