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At least 469 records · Page 26Linked to original sources
PubMed1996

Effect of selective and non-selective muscarinic blockade on baclofen inhibition of gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine in Wistar rats.

The effects of baclofen, a gamma-amino-n-butyric acid receptor B agonist, on gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine and how its effects are influenced by selective (M1) and non-selective (M1 and M2) pharmacological blockade of muscarinic receptors were investigated in inbred Wistar rats. Rats were given s.c. injections of 8 mg/kg body wt baclofen with and without 0.5 mg/kg body wt atropine (non-selective M1 and M2 muscarinic receptor antagonist) or 1.0 mg/kg body wt pirenzepine (selective M1 muscarinic receptor antagonist) every other day after a 25 week carcinogen treatment. At week 52 baclofen significantly decreased the incidence of gastric cancers. Concomitant treatment with atropine significantly attenuated the inhibition by baclofen of gastric carcinogenesis, but combined use with pirenzepine had no significant effect on the inhibition by baclofen of gastric carcinogenesis. Baclofen also significantly decreased the labeling index of the antral mucosa. Baclofen plus atropine attenuated the decrease in the labeling index of the antral mucosa due to baclofen, but baclofen plus pirenzepine had no significant effect on the labeling index. These results suggest that the inhibition of gastric carcinogenesis by baclofen is mediated through muscarinic receptors and M2 receptors, but not M1 receptors, are involved in this response.

Adenocarcinoma↗
PubMed1976

Selective versus non-selective His bundle pacing.

His bundle pacing was achieved in 10 anaesthetized open chest dogs by stimulation from bipolar electrode catheters positioned in the aortic root and right heart. Recordings were taken directly through plunge wires from the right atrium, high ventricular septum, and epicardial sites on the right and left ventricles. Six types of response were seen during A-V junctional stimulation: (1) low atrial pacing; (2) combined atrial and His bundle pacing; (3) His bundle pacing; (4) combined atrial, ventricular septal, and His bundle pacing; (5) combined septal and His bundle pacing; and (6) ventricular pacing. Pacing of the His bundle in combination with the atrium and/or ventricular septum is designated as non-selective, whereas stimulation of the His bundle alone is considered selective pacing. Non-selective His bundle pacing can be recognized from the surface leads by changes in onset and amplitude of the QRS with appreciable T-wave alterations. Although electrode position was an important determinant of the type of pacing achieved, a variety of patterns of stimulation resulted from variation in the modalities of the pacing stimulus, ie, polarity, intensity, and duration. Unless these factors are considered, selective His bundle pacing may not be achieved.

Animals↗
PubMed1998

Intracytoplasmic sperm injection, results in women older than 39, according to age and the number of embryos replaced in selective or non-selective transfers.

The aim of this study was to assess the results of intracytoplasmic sperm injection (ICSI) in a large cohort of women older than 39 according to age and to embryo transfer policy. In all, 736 ICSI cycles were analysed retrospectively. In 576 (78.3%) cycles an embryo transfer was carried out. The embryo transfer was defined as non-selective when all the available embryos were transferred, and as selective when fewer than the available number of embryos were replaced. A statistically significant gradual decrease in the number of embryos available for transfer, the number of good or excellent quality embryos available for transfer, the pregnancy rates, the clinical pregnancy rates, the implantation rates and the viable pregnancy rates was found with advancing age. No viable pregnancies ensued in women from 45 years old onwards. There was a statistically significant gradual increase in the pregnancy rates, the clinical pregnancy rates, the implantation rates and the viable pregnancy rates from non-selective to selective transfers. The results were similar in women with five or more embryos available, irrespective of the embryo transfer policy. It seems, therefore, that the ovarian reserve and the chances for a successful pregnancy decrease gradually with advancing age, and it is pointless to treat women from 45 years old onwards. A subgroup of patients with better ovarian response and more embryos available for transfer have higher chances of conception. Conception and implantation rates depend mainly on the quality of the transferred embryos. However, the implantation capacity of the embryos is generally lower irrespective of their good morphology.

Adult↗
PubMed1995

The positively selected T cell repertoire: is it exclusively restricted to the selecting MHC?

Transgenic lines of mice showing compartmentalized expression of MHC I-E in different thymic microenvironments and nearly normal expression in the periphery were used to ask whether the mature T cell repertoire is restricted exclusively to the selecting MHC molecules expressed on thymic cortical epithelial cells. We show that upon in vivo priming, mice with a T cell repertoire selected in the thymic cortex on MHC I-A, in the absence of MHC I-E, display a clearly significant T cell response to two I-E-restricted peptides. Our results suggest that expression of one isotype or allele of class II MHC molecules in the appropriate thymic environment enables the selection of a polyclonal repertoire restricted in part to non-selecting class II MHC molecules. Thus, although the requirement for interaction with the MHC by the TCR on developing thymocytes exists, the available adult repertoire need not be solely faithful to the specific MHC expressed on the thymic cortical epithelium: it can also be restricted to other isotypes and alleles of this same class of MHC molecule.

Animals↗
PubMed2006

In vitro selection using a dual RNA library that allows primerless selection.

High affinity target-binding aptamers are identified from random oligonucleotide libraries by an in vitro selection process called Systematic Evolution of Ligands by EXponential enrichment (SELEX). Since the SELEX process includes a PCR amplification step the randomized region of the oligonucleotide libraries need to be flanked by two fixed primer binding sequences. These primer binding sites are often difficult to truncate because they may be necessary to maintain the structure of the aptamer or may even be part of the target binding motif. We designed a novel type of RNA library that carries fixed sequences which constrain the oligonucleotides into a partly double-stranded structure, thereby minimizing the risk that the primer binding sequences become part of the target-binding motif. Moreover, the specific design of the library including the use of tandem RNA Polymerase promoters allows the selection of oligonucleotides without any primer binding sequences. The library was used to select aptamers to the mirror-image peptide of ghrelin. Ghrelin is a potent stimulator of growth-hormone release and food intake. After selection, the identified aptamer sequences were directly synthesized in their mirror-image configuration. The final 44 nt-Spiegelmer, named NOX-B11-3, blocks ghrelin action in a cell culture assay displaying an IC50 of 4.5 nM at 37 degrees C.

Animals↗
PubMed1988

Adrenaline-induced amplification of sympathetic activity during rest and stress: inhibition by non-selective and beta 1-selective beta-adrenoceptor blockade.

In a placebo-controlled randomized cross-over trial the effects of non-selective (bopindolol, 1 mg once daily for 1 week) and of beta 1-selective beta-adrenoceptor blockade (atenolol, 50 mg once daily for 1 week) on adrenaline-induced enhancement of basal and stimulated sympathetic activity were studied in 10 hypertensive subjects. During infusion of adrenaline (20 ng/kg per min) venous plasma adrenaline levels increased into the high physiological range. Resting concentrations of arterial plasma noradrenaline and of the basal production of noradrenaline in the forearm increased significantly (P less than 0.01) during infusion of adrenaline. The increases in these two indices of sympathetic activity were abolished by bopindolol and by atenolol. Arterial noradrenaline, but not noradrenaline production, also increased in response to isometric exercise, cold provocation and mental stress during infusion of adrenaline (P less than 0.05). These amplifications were also abolished by both beta-adrenoceptor antagonists. Our findings provide further evidence in man for a stimulatory effect of adrenaline in the physiological range on sympathetic activity. This effect, which is supposed to be mediated by prejunctional beta-adrenoceptors, can be blocked not only by non-selective, but also by beta 1-selective beta-adrenoceptor antagonists.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Selectivity of prenalterol for adrenergic receptor subtypes: a potential mechanism of inotropic selectivity.

To address the hypothesis that myocardial adrenergic receptors mediating chronotropy may be distinguishable from receptors mediating inotropy on the basis of existing subtype classifications, the binding properties of the inotropically selective adrenergic agonist prenalterol to receptor populations of known subtype were characterized. In competitive binding assays, prenalterol exhibited higher affinity for beta 1- than for beta 2-receptors, and a low affinity for both alpha 1- and alpha 2-receptors, in comparison with non-subtype-selective agonists. In addition, log molar displacement curves for prenalterol binding to beta 1-receptors, but not to beta 2- or alpha 2-receptors, were steepened and shifted rightward by guanine nucleotide, suggesting that prenalterol is a beta 1-agonist, but may have antagonist properties at beta 2- and alpha 2-receptors. This receptor subtype profile is similar to that of dobutamine, another inotropically selective adrenergic agonist. This concordance lends further support to the hypothesis that chronotropic responses to exogenous adrenergic agonists may be mediated selectively through beta 2-receptors.

Adrenergic beta-Agonists↗
PubMed2003

Rationally selected basis proteins: a new approach to selecting proteins for spectroscopic secondary structure analysis.

Protein basis sets have been extensively used as reference data for the determination of protein structure with optical methods such as circular dichroism and infrared spectroscopies. We have taken a new approach to basis protein selection by utilizing three crystal structure classification databases: CATH, SCOP, and PDB_SELECT. Through the use of the information available in these and other online resources, we identified 115 commercially available proteins as potential basis set candidates. By carefully screening the quality of the crystal structures and commercial protein preparations, we obtained a final set of 50 rationally selected proteins (RaSP50) that has been optimized for use in spectroscopic protein structure determination studies. These proteins span the full range of known protein folds as well as alpha-helix and beta-sheet contents, and they represent a more comprehensive variety of fold types than any previous reference set. This report includes a detailed presentation of the reasoning behind the rational protein selection process, a description of the properties of the RaSP50 set, and a discussion of the types of structural and spectral variations that are represented in the set.

Circular Dichroism↗
PubMed1982

Effects of cold exposure on blood pressure, heart rate and forearm blood flow in normotensives during selective and non-selective beta-adrenoceptor blockade.

Haemodynamic effects of a cold pressor test (foot immersion for 6 min in water at 5 degrees C) without medication and after the non-selective beta-adrenoceptor blocker propranolol and the selective beta-adrenoceptor blocker metoprolol were studied in 17 volunteers. In the control study as well as in the study with the beta-adrenoceptor blockers cold exposure caused comparable changes, namely a blood pressure rise and a reduction of forearm blood flow. The increase in heart rate during cold exposure was clearly and equally reduced by both beta-adrenoceptor blockers. Plasma noradrenaline rose significantly by 47%, plasma adrenaline did not change. It is concluded, that as to this kind of stress, beta 1-selective-adrenoceptor blockade confers no important advantage over non-selective beta-adrenoceptor blockade.

Adolescent↗
PubMed2005

Selective sparing of hippocampal CA3 cells following in vitro ischemia is due to selective inhibition by acidosis.

A brief global ischemic insult to the brain leads to a selective degeneration of the pyramidal neurons in the hippocampal CA1 region while the neurons in the neighbouring CA3 region are spared. The reason for this difference is not known. The selective vulnerability of CA1 neurons to ischemia can be reproduced in vitro in murine organotypic slice cultures, if the ion concentrations in the medium during the anoxic/aglycemic insult are similar to that in the brain extracellular fluid during ischemia in vivo. As acidosis develops during ischemia, we studied the importance of extracellular pH for selective vulnerability. We found that cell death in the CA1 and CA3 regions was equally prevented by removal of calcium from the medium or following blockade of the N-methyl-D-aspartate (NMDA) receptor by D-2 amino-5-phosphonopentanoic-acid (D-APV). On the other hand, damage to the CA3 neurons markedly decreased with decreasing pH following in vitro ischemia, while the degeneration of CA1 neurons was less pH dependent. Patch-clamp recordings from pyramidal neurons in the CA1 and CA3 regions, respectively, revealed a pronounced inhibition of NMDA-receptor mediated excitatory postsynaptic currents (EPSCs) at pH 6.5 that was equally pronounced in the two regions. However, when changing pH from 6.5 to 7.4 the recovery of the EPSCs was significantly slower in the CA3 region. We conclude that acidosis selectively protects CA3 pyramidal neurons during in vitro ischemia, and differentially affects the kinetics of NMDA receptor activation, which may explain the difference in vulnerability between CA1 and CA3 pyramidal neurons to an ischemic insult.

Acidosis↗
PubMed1975

Selection of early treatment of myelomeningocele: a retrospective analysis of selection procedures.

In an attempt to formulate a procedure for the selection of those children with open myelomeningocele most likely to benefit from early surgery, the records of 163 children have been reviewed. No physical findings, either singly or in combination, were found to distinguish accurately between children with good and poor prognoses, and an alternative selection procedure is proposed which takes into consideration the absence or presence of lacunar skull deformity (a finding strongly associated with mental retardation). Early surgery is not recommended for children with lacunar skull deformity and at least two of Lorber's major adverse neonatal criteria, or children with associated gross congenital anomalies. This selection procedure has been applied retrospectively to the 163 children reviewed and has been shown to predict the (known) outcome of these children much more reliably than existing selection criteria.

Follow-Up Studies↗
PubMed2005

Bifidobacterium-selective isolation and enumeration from chicken caeca by a modified oligosaccharide antibiotic-selective agar medium.

AIMS: To determine the efficacy and selectivity of an acidified, antibiotic-selective, oligosaccharide-containing media for enumerating Bifidobacterium spp. from chicken caeca samples. METHODS AND RESULTS: Transoligosaccharide propionate agar medium (TOS) modified by addition of mupirocin (50 microg ml-1) and glacial acetic acid (1%, v/v), did not inhibit the growth of bifidobacteria compared with the control media yet inhibited the growth of Lactobacillus acidophilus, Lactobacillus gallinarum, Lactobacillus helveticus and Streptococcus gordonii. CONCLUSIONS: Addition of mupirocin (50 microg ml-1) and glacial acetic acid (1%, v/v) to TOS (TOS-AM50), is an effective selective medium for isolation and enumeration of Bifidobacterium spp. from chicken caeca samples. SIGNIFICANCE AND IMPACT OF THE STUDY: The development of an intestinal bifidobacteria-selective media contributes to the study of probiotics and prebiotics in poultry and potentially other species.

Animals↗
PubMed1986

Effect of beta 1-selective and non-selective beta-blockade on work capacity and muscle metabolism.

Six well-trained men were studied while performing a maximal bicycle exercise. The seven experiments included in this study were randomized in a double-blind cross-over fashion. On each occasion the subjects were given either placebo or 40, 80, or 160 mg propranolol (non-selective blockade) or 25,50, or 100 mg atenolol (beta 1-selective blockade). After completion of the study each subject had performed once under each of the seven treatments. Heart rate, maximal oxygen uptake (Vo2max), blood lactate and performance time to exhaustion were measured. A muscle biopsy from vastus lateralis was taken at exhaustion after placebo, 80 mg propranolol and 50 mg atenolol trials, for analysis of ATP, creatine phosphate (CP), glucose-6-phosphate (G-6-P), glucose and lactate. The performance time was reduced (P less than 0.05-0.001) with both blockers compared to placebo. At an equal heart rate reduction, Vo2max was equally reduced by both blockers. Performance time, on the other hand, was reduced to a greater extent (P less than 0.05) with propranolol. ATP and CP levels were decreased (P less than 0.05) by both drugs. G-6-P, however, was lower (P less than 0.05) with propranolol than with either placebo or atenolol. No difference was observed between placebo and atenolol. In conclusion, both beta1-selective and non-selective blockade reduced short-term maximal exercise capacity. The major limiting factor seems to be the reduction in oxygen transport. The finding that at an equivalent reduction in Vo2max propranolol reduced performance time to a greater extent than atenolol suggests that beta 2-blockade may reduce performance by mechanisms additional to those that affect oxygen transport.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1988

Behavioural responses to the selective D1-dopamine receptor agonist R-SK&F 38393 and the selective D2-agonist RU 24213 in young compared with aged rats.

1. In aged male Sprague-Dawley rats (22 months) with a selective loss of D2- but not of D1-dopamine receptors, stereotyped behaviour induced by 0.5 mg kg-1 apomorphine was increased and prolonged in comparison with young (4 month) counterparts. This suggested a pharmacokinetic effect rather than a pharmacodynamic change. 2. The syndrome of non-stereotyped behavioural responses to the selective D1-agonist R-SK&F 38393, 1.25-20.0 mg kg-1, was unchanged in aged vs young animals, but the topography of individual behaviours constituting this overall syndrome was altered with aging. 3. Neither the overall syndrome of low intensity stereotyped behaviour nor the topography of individual behaviours induced by the selective D2-agonist RU 24213, 1.25-20.0 mg kg-1, were altered in aged vs young animals. 4. Loss of D2- but not D1-receptors with aging was therefore found to be associated with no change in responsivity to a D2-receptor agonist. The decreased intense grooming and increased vacuous chewing responses to the D1-agonist with aging parallel the previously demonstrated effects of selective D2-antagonists on these D1-stimulated behaviours. 5. It is suggested that age-related decline in D2-receptor activity may have greater functional consequences in relation to D1-:D2-interactions than in simply influencing responsivity to a D2-agonist. Such interactive effects should be taken into account when considering the pathophysiology and treatment of age-related extrapyramidal movement disorders.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Renal selective N-acetyl-L-gamma-glutamyl prodrugs: studies on the selectivity of some model prodrugs.

1. In this study, a number of structurally different N-acetyl-L-gamma-glutamyl prodrugs were investigated with respect to selective uptake by the kidney in male Wistar rats. 2. All prodrugs were tested in vitro in rat kidney slices and kidney homogenate to study their uptake and conversion. It was found that the prodrugs of para-nitroaniline (agPNA), aminophenyl acetic acid (agAFA), sulphamethoxazole (agSM), sulphadimethoxine (agSDM), propranolol (agPP) and metoprolol (agMP) were accumulated by a probenecid-sensitive carrier. The prodrug of 4'-aminoantipyrine (agAAP) was not accumulated by a probenecid- or buthionine sulphoximine-sensitive carrier. Unlike all other prodrugs, agAAP and agMP were not, or only a very limited extent converted to the parent compound in vitro. 3. agPNA, agAFA and agPP were also investigated in vivo. The tissue distribution of the prodrugs and the parent drugs was established, as was their urinary excretion and pharmacokinetic behaviour. agPNA and agAFA showed selective uptake by the kidney, in contrast to agPP which accumulated in the liver. The distribution of the parent compounds following prodrug administration was as follows: agPNA was found in kidney and plasma: agAFA in kidney only; agPP in liver only. 4. The factors which determine the selectivity of N-acetyl-L-gamma-glutamyl prodrugs are discussed. The main factors are: the transport into the kidney, the conversion rate, the residence time of the prodrug in the kidney and the presence or absence of competition for uptake and conversation by other tissues, e.g. the liver. It is concluded that this prodrug approach offers the possibility of delivering drugs selectively to the kidney, but also that it is not universally applicable.

Ampyrone↗
PubMed1984

Non-selective conductance in calcium channels of frog muscle: calcium selectivity in a single-file pore.

Voltage-clamp studies were carried out to compare currents through Ca2+ channels (ICa) with Na+ currents (Ins) through a non-selective cation conductance blocked by micromolar concentrations of external Ca2+. The gating of both currents was found to have similar time and voltage dependence. The amplitudes of ICa and Ins varied widely, but Ins was always large in fibres with large ICa, and small in fibres with small ICa. Both ICa and Ins were blocked by the specific Ca2+ channel blocker nifedipine, with half-blockage concentrations that were virtually identical (KD = 0.9 microM for ICa and 0.7 microM for Ins). ICa and Ins were also equally sensitive to block by diltiazem (KD = 80 microM). These parallels between Ins and ICa are most easily explained if Ins flows through Ca2+ channels. Apparently, Ca2+ channels bear high-affinity Ca2+-binding sites, and are highly permeable to monovalent cations when Ca2+ is absent. Ba2+ currents (IBa) and ICa were measured in external solutions containing mixtures of Ba2+ and Ca2+. IBa is blocked by Ca2+, as is Ins. Adding Ba2+ to Ca2+ produces only small or no increases in current, as if Ba2+ is only sparingly permeant when Ca2+ is present. Membrane currents in Ba2+/Ca2+ mixtures show anomalous mole-fraction behaviour, suggesting that Ca2+ channels are single-file, multi-ion pores. Complex current transients are observed under maintained depolarizations in Na+/Ca2+ and Ba2+/Ca2+ mixtures. They suggest that in ion mixtures, Ca2+ channels transport Ca2+ in preference to Na+ and Ba2+. Hence Ca2+ channels are selective for Ca2+, even though current amplitudes suggest that the Na+ or Ba2+ permeabilities in the absence of Ca2+ are as high as, or higher than, the Ca2+ permeability. We conclude that the selective permeability of Ca2+ channels depends on the presence of Ca2+. In model calculations, our observations are explained as a consequence of Ca2+ channels being single-file pores. It is proposed that Ca2+ channels derive much of their ion selectivity from high-affinity Ca2+ binding sites located in an otherwise unselective aqueous pore.

Action Potentials↗
PubMed2002

Beta(1)-selective agonist (-)-1-(3,4-dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] differentially interacts with key amino acids responsible for beta(1)-selective binding in resting and active states.

(-)-1-(3,4-Dimethoxyphenetylamino)-3-(3,4-dihydroxy)-2-propanol [(-)-RO363] is a highly selective beta(1)-adrenergic receptor (beta(1)AR) agonist. To study the binding site of beta(1)-selective agonist, chimeric beta(1)/beta(2)ARs and Ala-substituted beta(1)ARs were constructed. Several key residues of beta(1)AR [Leu(110) and Thr(117) in transmembrane domain (TMD) 2], and Phe(359) in TMD 7] were found to be responsible for beta(1)-selective binding of (-)-RO363, as determined by competitive binding. Based on these results, we built a three-dimensional model of the binding domain for (-)-RO363. The model indicated that TMD 2 and TMD 7 of beta(1)AR form a binding pocket; the methoxyphenyl group of N-substituent of (-)-RO363 seems to locate within the cavity surrounded by Leu(110), Thr(117), and Phe(359). The amino acids Leu(110) and Phe(359) interact with the phenyl ring of (-)-RO363, whereas Thr(117) forms hydrogen bond with the methoxy group of (-)-RO363. To examine the interaction of these residues with beta(1)AR in an active state, each of the amino acids was changed to Ala in a constitutively active (CA)-beta(1)AR mutant. The degree of decrease in the affinity of CA-beta(1)AR for (-)-RO363 was essentially the same as that of wild-type beta(1)AR when mutated at Leu(110) and Thr(117). However, the affinity was decreased in Ala-substituted mutant of Phe(359) compared with that of wild-type beta(1)AR. These results indicated that Leu(110) and Thr(117) are necessary for the initial binding of (-)-RO363 with beta(1)-selectivity, and interaction of Phe(359) with the N-substituent of (-)-RO363 in an active state is stronger than in the resting state.

Adrenergic beta-1 Receptor Agonists↗
PubMed1983

Selective photothermolysis: precise microsurgery by selective absorption of pulsed radiation.

Suitably brief pulses of selectively absorbed optical radiation can cause selective damage to pigmented structures, cells, and organelles in vivo. Precise aiming is unnecessary in this unique form of radiation injury because inherent optical and thermal properties provide target selectivity. A simple, predictive model is presented. Selective damage to cutaneous microvessels and to melanosomes within melanocytes is shown after 577-nanometer (3 x 10(-7) second) and 351-nanometer (2 x 10(-8) second) pulses, respectively. Hemodynamic, histological, and ultrastructural responses are discussed.

Animals↗