2a 2c Research Articles

Morphological and functional results of AcrySof intraocular lens implantation in children: prospective randomized study of age-related surgical management

Purpose To evaluate the prevalence and severity of posterior capsule opacification (PCO) in pediatric eyes with a foldable acrylic AcrySof® (Alcon) intraocular lens (IOL) and age-related surgical methods. Setting Department of Ophthalmology, University of Vienna, Medical School, Vienna, Austria. Methods This prospective randomized study comprised 50 eyes of 34 children aged between 2 and 16 years. Eyes of children between 2 and 5.9 years were consecutively randomized to Group 1a (primary posterior capsulotomy and anterior vitrectomy) or Group 1b (optic capture in addition). Eyes of children between 6 and 16 years were consecutively randomized to Group 2a (primary posterior capsulotomy without anterior vitrectomy), Group 2b (optic capture in addition), or Group 2c (in-the-bag IOL implantation without opening the posterior capsule). Main outcome parameters were the incidence and severity of PCO formation, early postoperative complications, pigmented cell deposits on the IOL surface, and cataract morphology. Results The visual axis was clear at the last follow-up in all eyes in Groups 1a, 1b, 2a, and 2b except in 1 eye in Group 1a. Sixty-percent of eyes in Group 2c had PCO. The incidence of early postoperative complications was significantly higher in eyes that developed PCO than in those that maintained a clear visual axis. There was no evidence that cataract morphology influenced PCO rates. Conclusions The AcrySof IOL was well tolerated in pediatric eyes. Optic capture was not necessary to ensure a clear visual axis. Primary posterior capsulotomy should be performed in preschool and uncooperative children and in eyes expected to have relatively high postoperative inflammation. Implanting the AcrySof in the bag and leaving the posterior capsule intact is acceptable for school children and juveniles with isolated developmental cataract.

Characterization of vesicles from ion-paired gemini surfactants by small angle neutron scattering

Detailed small angle neutron scattering (SANS) studies were carried out with the aqueous vesicular (unilamellar) suspension of dimeric ion-paired lipids (2a–2c) for spacer lengths corresponding to n-values of 2, 6 and 10 and monomeric ion-paired lipid (3) below and above the phase transition temperature of each amphiphile. The vesicular structure strongly depends on the spacer chain length. The mean vesicle size is smallest for the lipid with a short spacer, n = 3 and it increases with the increase in the spacer chain length. The bilayer thickness also decreases with the increase in the spacer chain length. The size polydispersity increases with the increase in the spacer chain length (n-value).

Identification of multicopy suppressors of cell cycle arrest at the G1-S transition in Saccharomyces cerevisiae.

Inactivation of HAL3 in the absence of SIT4 function leads to cell cycle arrest at the G(1)-S transition. To identify genes potentially involved in the control of this phase of the cell cycle, a screening for multicopy suppressors of a conditional sit4 hal3 mutant (strain JC002) has been developed. The screening yielded several genes known to perform key roles in cell cycle events, such as CLN3, BCK2 or SWI4, thus proving its usefulness as a tool for this type of studies. In addition, this approach allowed the identification of additional genes, most of them not previously related to the regulation of G(1)-S transition or even without known function (named here as VHS1-3, for viable in a hal3 sit4 background). Several of these gene products are involved in phospho-dephosphorylation processes, including members of the protein phosphatase 2A and protein phosphatases 2C families, as well as components of the Hal5 protein kinase family. The ability of different genes to suppress sit4 phenotypes (such as temperature sensitivity and growth on non-fermentable carbon sources) or to mimic the functions of Hal3 was evaluated. The possible relationship between the known functions of these suppressor genes and the progress through the G(1)-S transition is discussed.

SYNTHESES OF NOVEL SUBSTITUTED-BORANOPHOSPHATE NUCLEOSIDES

ABSTRACT A number of substituted (borano) nucleic acids, 3′-[diethylphosphite-(cyano, carboxy, or carbamoyl) borano] deoxynucleosides (3a–4c) and 5′-[diethylphosphite(cyano or carboxy) borano] deoxynucleosides (6a–7d) were prepared by a variety of synthetic procedures. The syntheses of the pyrophosphates (2a–2c), as precursors for 3a–4c, are also described.

Differential requirement for pulsatile LH during the follicular phase and exposure to the preovulatory LH surge for oocyte fertilization and embryo development in cattle

The requirement for pulsatile LH and the LH surge for the acquisition of oocyte fertilizing potential and embryo developmental competency was examined in Zebu heifers. Follicular growth was superstimulated using the GnRH agonist-LH protocol in which pulsatile LH and the preovulatory LH surge are blocked. In experiment 1, heifers were assigned on Day 7 of the estrous cycle to receive: group 1A (n=5), 1.5mg norgestomet (NOR) implant; group 1B (n=5), GnRH agonist implant. Follicular growth was superstimulated with 2× daily injections of FSH from Day 10 (a.m.) to Day 13 (p.m.), with PGF2α injection on Day 12 (a.m.). Heifers were ovariectomized on Day 15 (a.m.) and oocytes were placed immediately into fertilization, without 24h maturation. Respective cleavage and blastocyst development rates were: group 1A, 0/64 oocytes (0%) and 0/64 (0%); group 1B, 34/70 oocytes (48.6%) and 2/70 (2.9%). In experiment 2, heifers were assigned on Day 7 of the estrous cycle to receive: group 2A (n=10), 1.5mg NOR implant; group 2B (n=10), GnRH agonist implant; group 2C (n=10), GnRH agonist implant. Follicular growth was superstimulated as in experiment 1 above. Heifers in groups 2A and 2B received an injection of 25mg LH on Day 14 (p.m.) and all heifers were ovariectomized on Day 15 (a.m.); oocytes were placed immediately into fertilization without 24h maturation. Cleavage rates were similar for heifers in group 2A (84/175 oocytes, 48.0%), group 2B (61/112 oocytes, 54.5%) and group 2C (69/163, 42.3%). Blastocyst development rates were similar for heifers in group 2A (22/175 oocytes, 12.6%) and group 2B (25/112 oocytes, 22.3%) and lower (P<0.05) for heifers in group 2C (9/163 oocytes, 5.5%). Oocytes obtained from heifers treated with GnRH agonist, without injection of exogenous LH, underwent cleavage indicating that neither pulsatile LH nor the preovulatory LH surge are obligatory for nuclear maturation in cattle oocytes. Exposure to a surge-like increase in plasma LH increased embryo developmental competency indicating that the preovulatory LH surge promotes cytoplasmic maturation. The findings have important implications for controlling the in vivo maturation of oocytes before in vitro procedures including nuclear transfer.

The orthographic distinctiveness effect on direct and indirect tests of memory: delineating the awareness and processing requirements

We examined the processing and awareness requirements that mediate superior memory for distinct items in long-term memory by studying the effects of orthographic distinctiveness. Orthographically distinct words are remembered better than common words on the direct test of free recall but not on the indirect test of perceptual identification. These results suggest that the orthographic distinctiveness effect requires test awareness. But interestingly, this distinctiveness effect has also been reported in one indirect test, that of word fragment completion ( Hunt & Toth, 1990). We examined the locus of the orthographic distinctiveness effect in the indirect test of word fragment completion and the direct tests of word fragment cued recall and free recall and assessed the role of awareness (Experiment 1) and conceptual processes (Experiments 2a–2c) in mediating this effect. Our results support the proposal that the distinctiveness effect depends on direct reference to the study context and further specify that this effect is mediated, to a large extent, by comparative processes even when distinctiveness emerges from surface-level differences.

Synthesis, molecular structure, and reactivity of allenylideneosmium complexes of the half-sandwich-type

The reaction of the areneosmium(II) compunds [Os(η6-arene)(L)X2] 2a–2e, 3, 4 with propargylic alcohols HCCCR2(OH) (where R = phenyl or p-tolyl) in the presence of AgPF6 leads to the formation of the cationic osmium allenylidenes [Os(η6-arene)(CCCR2)(L)X]PF65a–5h in good to excellent yields. Salt metathesis of 5a (L = PMe3) and 5b (L = PCy3) with NaB(ArF)4 gives [Os(η6-mes)(CCCPh2)(PR3)Cl]B(ArF)46a, 6b while treatment of 5b with KBr, NaI and CF3CO2Ag affords the corresponding bromo, iodo and trifluoracetato complexes [Os(η6-mes)(CCCPh2)(PCy3)X]PF67a–7c. Compound 5a reacts with MeOH and EtOH to give the Fischer-type osmium carbenes [Os(η6-mes){C(OR)CHCPh2}(PMe3)Cl]PF68a and 8b, of which 8a has been converted by treatment with NaH to the neutral allenyl complex [Os(η6-mes){C(OMe)CCPh2}(PMe3)Cl] 9. The reaction of 5a and 5b with tertiary phosphines PR′3 yields a mixture of [Os(η6-mes){C(PR′3)CCPh2}(PR3)Cl]PF610a–10c and [Os(η6-mes)(PR3)(PR′3)Cl]PF611a–11c, which could not be separated by analytical tools. The cationic bis(phosphine) compounds 11a–11c were prepared independently from 2a–2c and PMe3 in the presence of NH4PF6. The molecular structures of 5a and 8b were determined crystallographically.

Heterocyclic quinol-type fluorophores. Part 1. Synthesis of new benzofurano[3,2-b]naphthoquinolThe IUPAC name for the parent benzofurano[3,2-b]naphthoquinone is naphtho[2,3-b]benzofuran-6,11-dione. derivatives and their photophysical properties in solution and in the crystalline stateElectronic supplementary information (ESI) available: Table S1 containing crystal data and structure refinement parameters for 2c, 3c, and 3d. See http://www.rsc.org/suppdata/p2/b1/b109198k/

Isomeric pairs of novel benzofuranonaphthoquinol-type fluorophores (2a–2c and 3a–3c) have been synthesized and their absorption and fluorescence characteristics in solution and in the crystalline state have been studied. Big differences in the absorption and fluorescence spectra were observed: the quinols 2a–2c exhibit much stronger absorption and fluorescence intensities than the quinols 3a–3c in solution. However, the two isomeric quinols exhibit similar fluorescence intensities in the crystalline state. Semi-empirical molecular orbital calculations (AM1 and INDO/S) and X-ray diffraction analysis have been carried out to elucidate the differences in the photophysical properties of the two isomers (2 and 3) both in solution and in the crystalline state. On the basis of the results of calculations and the X-ray crystal structures, the relations between the observed photophysical properties and the chemical and crystal structures of the quinol-type fluorophores are discussed.

Benzene fused monocyclic enediynyl amides: synthesis, reactivity and DNA-Cleavage activity in comparison to the corresponding sulfonamides

Monocyclic enediynyl amides 2a–2c have been synthesized via the corresponding free amine 5. Kinetic studies in chloroform revealed the reactivity of these amides towards Bergman cyclization to be less than that of the corresponding sulfonamides. However, differential scanning calorimetry (DSC) measurements in the solid state and DNA-cleavage studies in aqueous buffer showed higher reactivity for the amides than the sulphonamides.

Ovarian hormone effects on 5-hydroxytryptamine 2A and 5-hydroxytryptamine 2C receptor mRNA expression in the ventral hippocampus and frontal cortex of female rats

Alterations in female gonadal hormones are associated with anxiety and mood changes. The aim of the present study was to determine influences of chronic gonadal hormone supplementation on 5-HT 2A and 5-HT 2C receptor mRNA levels in the ventral hippocampus and the frontal cerebral cortex. Ovariectomized adult female Sprague–Dawley rats ( n=37) received implantation of subcutaneous pellets containing different dosages of 17β-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. Serotonin receptor mRNA levels were analyzed by in situ hybridization in the ventral hippocampus and 5-HT 2A receptor mRNA also in the frontal cortex. Estradiol treatment in combination with low-dose progesterone increased 5-HT 2A receptor mRNA by 43% in the CA2 region of the ventral hippocampus, while estradiol combined with high-dose progesterone increased the expression of this gene by 84% in ventral CA1. 5-HT 2A mRNA expression in the frontal cortex was not influenced by hormone manipulation. 5-HT 2C receptor gene expression was in the ventral hippocampus decreased in the CA2, ventral CA1 and the subiculum subregions by high-dose estradiol treatment (8–20% decreases). Effects on mood by gonadal hormones can be mediated, at least partly, through influences on 5-HT 2A and 5-HT 2C receptor expression.

Synthesis, structures and properties of platinum(ii) complexes of oligothiophene-functionalized ferrocenylacetylene

A series of rigid-rod alkynylferrocenyl precursors with oligothiophene (from thiophene to terthiophene) linkage units in the backbone, [(η5-C5H5)Fe(η5-C5H4)CC(C4H2S)mBr] 2a–2c, [(η5-C5H5)Fe(η5-C5H4)CC(C4H2S)mCCSiMe3] 3a–3c and [(η5-C5H5)Fe(η5-C5H4)CC(C4H2S)mCCH] 4a–4c (m = 1–3), have been prepared in moderate to good yields. The ferrocenylacetylene complexes 4a–4c can be used to form a range of stable platinum(II) alkynyl and bis(alkynyl) compounds trans-[(η5-C5H5)Fe(η5-C5H4)CC(C4H2S)mCCPt(PEt3)2Ph] 5a–5c and trans-[(η5-C5H5)Fe(η5-C5H4)CC(C4H2S)mCCPt(PBu3)2CC(C4H2S)mCC(η5-C5H4)Fe(η5-C5H5)] 6a–6c (m = 1–3). All these new compounds have been fully characterized by analytical and spectroscopic methods and the molecular structures of the bithienyl-linked complexes [(η5-C5H5)Fe(η5-C5H4)CC(C4H2S)2CC(η5-C5H4)Fe(η5-C5H5)], 2b, 4b, 5b and 6b have been established by X-ray crystallography. Structural analysis of 6b confirms its rigid-rod structural motif, featuring coplanar bithienyl rings and a trans arrangement of the two bithiophene groups. An iron–iron through-space distance of ca. 32 A is observed in 6b. Although there is no significant metallocene–metallocene interaction through the alkynyl–platinum–oligothiophene bridge, a slight negative shift of the ferrocene–ferrocenium redox potential in the platinum-containing species indicates some degree of electron delocalization into the platinum segment, in line with the results from theoretical studies. Oxidation of the thiophene units is facilitated by the presence of the platinum centre and increased conjugation in the chain.

Cyclic Analogs of Insect Oostatic Peptides: Synthesis, Biological Activity, and NMR Study

Cyclic peptides 2a–2c, derived from the sequence of the C-terminal shortened analogs of the oostatic decapeptide H-Tyr-Asp-Pro-Ala-Pro-Pro-Pro-Pro-Pro-Pro-OH (1a), were synthe sized and assayed on their effect in a reproduction of the flesh fly Neobellieria bullata. The cyclization of the N-terminal linear tetra- and pentapeptides 1b and 1c to the cyclotetra- and cyclopentapeptides 2b and 2c decreased the oostatic activity by one order of magnitude. The cyclodecapeptide 2a, which emerged spontaneously during the pentapeptide cyclization, was quite inactive. Comparative 1H and 13C NMR study on a conformation of the cyclopeptides 2a–2c, and their linear precursors 1b and 1c revealed that a space structure of the cyclic analogues 2b and 2c is too restricted to adopt a biological conformation necessary for receptor binding and therefore only minor oostatic activity is observed after their application. The lack of the oostatic activity in the case of the more flexible dimeric analogue 2a is ascribed to the size of its molecule and its overall shape that is not compatible with a receptor binding.

The Reaction of Alkenes with Triangulo-Clusters [Pt3(μ-CO)3(PR3)3

The reactions of the cluster complexes [Pt3(μ-CO)3L3], where L=PPh3 1a, PPh2Bz 1b and PCy3 1c, with activated mono-olefins have been studied under preparative and equilibrium conditions. At low temperature the olefins react quantitatively giving the adducts [Pt3(μ-CO)3L3(olefin)] (olefin=trans-dicyanoethene, DCE 2a–2c, maleic anhydride, MA 3a–3c). The stereo-chemistry of these unstable clusters has been deduced from low temperature 31P, 13C, 195Pt-NMR and I.R. spectra. At higher temperature these adducts in presence of excess of olefin convert quantitatively to stable mononuclear Pt(0) complexes [Pt(CO)L(olefin)] (olefin=DCE 4a–4c, MA 5a–5c, maleimide, MI 6a–6c and 1–4-naphthoquinone, NQ 7a, 7c).

Living coordination polymerization of end-allenyloxy poly(ethylene glycol) macromonomer by a π-allylnickel catalyst

The living coordination polymerization of end-allenyloxy poly(ethylene oxide)s (2A–2C) was carried out by [(η3-allyl)NiOCOCF3]2 (1) in the presence of PPh3 to produce narrowly dispersed polyallenes bearing poly(ethylene oxide) side chains. For instance, the polymerization of 2B (Mn = 590, [2]/[1] = 100) proceeded smoothly to give a polymer (Mn = 39 800, Mw/Mn = 1.13) in high yield. The molecular weight of poly(2) could be controlled by the ratio of 2 to 1 and by the molecular weight of 2. The block copolymers of 2B with various alkoxyallenes (3A–3C) or with 1-phenylethyl isonitrile (3D) were also obtained by the two-stage copolymerization process (i. e., the polymerization of 2, followed by that of 3A–3D). The resulting block copolymers were found to serve as polymeric surfactants in the polymer blend systems of PSt and PMMA.

Boron derivatives of dithiophosphoric acids

The reactions of tetraphosphorus decasulfide 1 with trialkyl borates 2a,b and O-isobutyl diphenylborate 2c were studied. On the basis of these studies, a novel method of synthesizing S-boron derivatives of dithiophosphoric acids was developed. The use of low frequency ultrasonic irradiation (22 kHz, power 130 W) leads to a reduction in reaction temperature and time required for completion of the reactions studied. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:102–106, 2000

Growth factor regulation of fracture repair.

Growth factor regulation of fracture repair.

Study of mechanisms of calcitonin analgesia in mice: Involvement of 5-HT 3 receptors

The analgesic effect of calcitonin when serotonin (5-HT) concentration is increased and the involvement of some 5-HT receptors were studied using the writhing test in mice. 5-hydroxytryptophan (5-HTP) administration increased both 5-HT levels in the central nervous system (CNS) and calcitonin analgesia. The 5-HT 1A agonist (±)-8-hydroxy-2-dipropylaminotetralin hydrobromide (8-OH-DPAT) diminished calcitonin analgesia, this effect being antagonised by the 5-HT 1A antagonist (WAY 100, 135). As the stimulation of 5-HT 1A autoreceptors reduces the turnover of 5-HT, the effect of 8-OH-DPAT on calcitonin analgesia may be attributed to this decrease. The 5-HT 2A–2C agonist (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) diminished calcitonin analgesia. A sub-analgesic dose of the 5-HT 2A antagonist ketanserin failed to prevent this effect. The 5-HT 3 agonist (±)-2-methyl-5-hydroxytryptamine maleate (2-methyl-5-HT) potentiated calcitonin analgesia, whereas it was significantly reduced by the 5-HT 3 antagonist tropisetron. The effect of 2-methyl-5-HT on calcitonin analgesia was also reversed by tropisetron, This result suggests that the 5-HT 3 receptor may play an important role in the relationship between calcitonin and the serotonergic system. Tropisetron also reversed the analgesia induced by calcitonin plus 5-HTP corroborating importance of the 5-HT 3 receptors.

Effects of the [formula omitted] receptor agonist and antagonist on phencyclidine-induced dopamine release in rat medial prefrontal cortex

1. 1. Systemic administration of PCP (7.5 mg/Kg I.p.) produced a greater increase in extracellular DA levels in the mPFC than in the STR and NAC, as determined by in vivo microdialysis of awake, freely moving rats. Preferential activation by PCP of prefrontal DA neurons may be, at least in part, the basis for the pathophysiology of PCP-induced psychosis as well as schizophrenia. 2. 2. Recent studies suggest a possible involvement of 5-HT 2A receptors in the pathophysiology and treatment of schizophrenia. This study was designed to examine whether and how 5-HT 2A receptors modulate PCP-induced DA release in the mPFC. 3. 3. The 5-HT 2A 2C receptor agonist (±)- DOI (2.5 mg/kg, but not 0.75 mg/Kg I.p.), administered 60 min prior to PCP, significantly attenuated the PCP-induced increase in extracellular DA levels. Pretreatment of the 5-HT 2A 2C receptor antagonist ritanserin (1.0 and 5.0 mg/Kg I.p.), administered 60 min prior to PCP, did not influence the PCP-induced increase. When administered alone, neither DOI (2.5 mg/kg) nor ritanserin (1.0 mg/kg) affected basal extracellular DA levels in the mPFC. 4. 4. The NMDA receptor antagonist MK-801 (1.0 mg/Kg I.p.) also increased extracellular DA levels in the mPFC, but this effect was unaffected by pretreatment with DOI (2.5 mg/kg). 5. 5. These results suggest that the stimulation of 5-HT 2A 2C receptors may inhibit DA release in the mPFC when it is facilitated by PCP. Other than the NMDA receptor-mediated mechanism may also be involved in the neurochemical interaction between 5-HT 2A receptors and PCP in the mPFC.

Gene substitution/knockout to delineate the role of alpha 2-adrenoceptor subtypes in mediating central effects of catecholamines and imidazolines.

Adrenergic receptors form the interface between the sympathetic nervous system and the cardiovascular system as well as many endocrine and parenchymal tissues. For the three alpha 2-adrenergic receptors (alpha 2A, alpha 2B, and alpha 2C), genetic mouse models have been developed that can be used to elucidate the physiologic function of each receptor subtype in vivo. Different strategies for homologous recombination in embryonic stem cells were applied to generate lines of mice with gene knockouts of the individual alpha 2-receptor subtypes (alpha 2A-KO, alpha 2B-KO, and alpha 2C-KO) or with a substitution of a mutant receptor at the wild-type locus (alpha 2-D79N). In these transgenic mice, the cardiovascular effects of alpha 2-agonists and imidazoline receptor agonists were tested. Stimulation of alpha 2B receptors in vascular smooth muscle produces hypertension and counteracts the clinically beneficial hypotensive effect of stimulating alpha 2A receptors in the central nervous system.

Solvent extraction of copper(II) from chloride media using N-(thiocarbamoyl)benzamidine and N-benzoylthiourea derivatives

The distribution of copper(II) between aqueous solutions and cumene solutions of N-(thiocarbamoyl)benzamidine, 2a–2c, and N-benzoylthiourea derivatives, 3a–3f, from chloride media (1 mol/l NaCl) has been studied in detail. The metal extraction was greatly influenced by extractant structure of thiourea derivatives. The extractability of Cu(II) with extractants 2a–2c and 3a–3f followed the order as: 3e>3d∼3c∼3f>3b≫3a∼2a∼2b∼2c, respectively. The N-thiocarbamoylbenzamide derivatives (2a–2c) are comparatively poor extractants than N-benzoylthiourea derivatives (3a–3f). The organic reagents 3a–3e were selected for detailed further studies owing to their better extraction behavior with copper(II). The extraction equilibria was studied as a function of total copper concentration, pH of the aqueous phase and total extractant concentration. It was shown by use of equilibrium modeling computer program LETAGROP-DISTR that the extraction of Cu(II) could be explained assuming the extraction of the species CuL 2, where L=3c. The equilibrium constants calculated by this program were also reported.