Theoretical Models of Chronotherapy: I. Periodic Perturbations in Oscillating Chemical Reactions

Dynamics resulting from periodic perturbations in oscillating chemical reaction, as theoretical models of chronotherapy techniques are studied. Replication reactions and fluctuations take place in these models giving rise to new species with autocatalitic properties. Oscillating chemical reaction models due to Hanusse (H) with three intermediaries and Bourceanu (E₁, E₂, E₃) with four, five and six intermediaries, respectively, are taken for this study and are manipulated numerically using a Gear algorithm. The bifurcation diagrams are obtained applying non-linear dynamic techniques, such as, power spectrum, stroboscopic method, Lyapunov exponents and correlation dimension D 2 . The dynamics of Hanusse and Bourceanu perturbed models are very similar. The main dynamic behaviours observed after perturbation are quasiperiodicity, entrainment, some Arnold tongues and situations without chemical meaning. Chaos is not observed. This study contributes to understand theoretical and practical aspects of the chronotherapy techniques.     

Synthesis of “Reversed” Methylenecyclopropane Analogues of Antiviral Phosphonates

Synthesis of “reversed” methylenecyclopropane analogues of nucleoside phosphonates 6a,7a, 6b, and 7b is described. 1-Bromo-1-bromomethylcyclopropane 8 was converted to the bromocyclopropyl phosphonate 9 by Michaelis-Arbuzov reaction with triisopropyl phosphite. Base-catalyzed β-elimination and deacetylation gave the key Z- and E-hydroxymethylcyclopropyl phosphonates 10 and 11 separated by chromatography. The Mitsunobu type of alkylation of 10 or 11 with adenine or 2-amino-6-chloropurine afforded phosphonates 12a, 12b, 13a, and 13b. Acid hydrolysis furnished the adenine and guanine analogues 6a, 7a, 6b, and 7b. The E and Z configuration was assigned on the basis of NOE experiments with phosphonates 6b and 7b. All Z- and E-isomers were also distinguished by different chemical shifts of CH₂O or CH₂N (H₄ or H_4′). Significant differences of the chemical shifts of the cyclopropane C_3(3’) carbons and coupling constants ³J_P,C2(2’) or ³J_P,C3(3’) selective for the Z- or E-isomers were also noted. Phosphonates 6a, 7a, 6b, and 7b are devoid of significant antiviral activity.     

Applications of the ETS-NOCV method in descriptions of chemical reactions

The present study characterizes changes in the electronic structure of reactants during chemical reactions based on the combined charge and energy decomposition scheme, ETS-NOCV (extended transition state–natural orbitals for chemical valence). Decomposition of the activation barrier, ΔE ^#, into stabilizing (orbital interaction, ΔE _orb, and electrostatic, ΔE _elstat) and destabilizing (Pauli repulsion, ΔE _Pauli, and geometry distortion energy, ΔE _dist) factors is discussed in detail for the following reactions: (I) hydrogen cyanide to hydrogen isocyanide, HCN → CNH isomerization; (II) Diels-Alder cycloaddition of ethene to 1,3-butadiene; and two catalytic processes, i.e., (III) insertion of ethylene into the metal-alkyl bond using half-titanocene with phenyl-phenoxy ligand catalyst; and (IV) B–H bond activation catalyzed by an Ir-containing catalyst. Various reference states for fragments were applied in ETS-NOCV analysis. We found that NOCV-based deformation densities (Δρ _i) and the corresponding energies ΔE _orb(i) obtained from the ETS-NOCV scheme provide a very useful picture, both qualitatively and quantitatively, of electronic density reorganization along the considered reaction pathways. Decomposition of the barrier ΔE^# into stabilizing and destabilizing contributions allowed us to conclude that the main factor responsible for the existence of positive values of ΔE ^# for all processes (I, II, III and IV) is Pauli interaction, which is the origin of steric repulsion. In addition, in the case of reactions II, III and IV, a significant degree of structural deformation of the reactants, as measured by the geometry distortion energy, plays an important role. Depending on the reaction type, stabilization of the transition state (relatively to the reactants) originating either from the orbital interaction term or from electrostatic attraction can be of vital importance. Finally, use of the ETS-NOCV method to describe catalytic reactions allows extraction of information on the role of catalysts in determination of ΔE ^#.     

A coupled model of photosynthesis-transpiration based on the stomatal behavior for maize (Zea mays L.) grown in the field

The study presents a theoretical basis of a stomatal behavior-based coupled model for estimating photosynthesis, A, and transpiration, E. Outputs of the model were tested against data observed in a maize (Zea mays L.) field. The model was developed by introducing the internal conductance, g _ic, to CO₂ assimilation, and the general equation of stomatal conductance, g _sw, to H₂O diffusion, into models of CO₂ and H₂O diffusion through the stomata of plant leaves. The coupled model is easier for practical use since the model only includes environmental variables, such as ambient CO₂ concentration, leaf temperature, humidity and photosynthetic photon flux received at the leaves within the canopy. Moreover, concept of g _ic, and factors controlling A and E were discussed, and applicability of the model was examined with the data collected in the maize field.     

Quantum chemical study of the inhibition of the corrosion of mild steel in H2SO4 by some antibiotics

The inhibition efficiency of some antibiotics against mild steel corrosion was studied using weight loss and quantum chemical techniques. Values of inhibition efficiency obtained from weight loss measurements correlated strongly with theoretical values obtained through semi empirical calculations. High correlation coefficients were also obtained between inhibition efficiency of the antibiotics and some quantum chemical parameters, including frontier orbital (E _HOMO and E _LUMO), dipole moment, log P, TNC and LSER parameters (critical volume and dipolar-polarisability factor), which indicated that these parameters affect the inhibition efficiency of the compounds. It was also found that quantitative structure activity relation can be used to adequately predict the inhibition effectiveness of these compounds.     

男性内源性性激素水平与冠心病范围及左心室射血分数的相关性

摘要 目的：探究男性内源性性激素水平与冠心病范围及左心室射血分数（LVEF）的相关性。方法：将2018年6月至2020年6月于我院接受治疗的96例经冠状动脉造影术（CAG）确诊为冠心病的96例患者纳入研究,按照临床分型将其区分为稳定型心绞痛（SAP,30例）、不稳定型心绞痛（UAP,30例）、急性心肌梗死（AMI,36例）,另选同期CAG检测结果提示冠状动脉管腔直径狭窄率<50 %的50例个体为对照组,检测入组对象的睾酮（Ts）、雌二醇（E₂）水平,评估计算入组对象的Gensini积分以及LVEF,对比不同组别之间Ts、E₂、Gensini积分以及LVEF差异,Spearman相关分析探究Ts、E₂与Gensini积分、LVEF的相关性,最后将患者按照Genisini评分区分为狭窄轻型组与严重组,Logistic回归分析影响冠脉狭窄的危险因素。结果：（1）比较显示,冠心病各组间Ts、E₂、Gensini积分以及LVEF差异明显,以AMI组患者Ts、E₂和LVEF水平最低,Gensini积分最高（P<0.05）;（2）Spearman相关性分析显示,Ts、E₂均与Gensini积分呈负相关,与LVEF呈正相关（P<0.05）;（3）多因素Logistic回归分析显示Ts、E₂水平是影响冠脉狭窄程度的独立危险因素（P<0.05）。结论：男性内源性性激素水平同其冠心病范围和LVEF呈现密切相关性,是影响冠脉狭窄程度的独立危险因素,可以考虑将其应用于临床冠脉狭窄的诊断与鉴别中。     

Complement-Dependent Phagocytosis of Liposomes: Suppression by “Stealth” Lipids

Abstract

Liposomes containing either ganglioside G_M1, phosphatidylinositol, sulfogalactosyl ceramide, certain other anionic phospholipids, prostaglandin E₂, or thromboxane B₂ have a reduced ability to undergo complement-dependent phagocytosis by cultured macrophages. We propose that this phenomenon is partially responsible for the prolonged circulation time that is observed after intravenous injection of certain liposomes that are said to have “stealth” properties.     

A simplified method for study of RNA conformation--reaction of formylmethionine transfer RNA with [14C]methylamine-bisulfite

A new chemical method for radioactive labeling of single-stranded regions of RNA has been used to probe the three-dimensional structure of E. coli tRNA^fMet in solution. The procedure involves conversion of cytosine residues to N⁴-[¹⁴C]methylcytosines by treatment with ¹⁴CH₃NH₂ and sodium bisulfite at pH7. Ribonuclease digestion of the modified tRNA produces ¹⁴C-labeled oligonucleotides which comigrate with the corresponding unlabeled oligonucleotides, facilitating structural analysis. By this procedure, E. coli tRNA^fMet has been found to contain only six reactive cytosines: C₁, C₁₆, C₁₇, C₃₅, C₇₅ and C₇₆. In addition, slow reaction at C^m₃₃ was observed. These results are in excellent agreement with previously reported data on the sites of exposed cytosine residues in tRNA^fMet obtained by two other chemical methods. The methylamine-bisulfite procedure is recommended for studying the ordered structure of more complex polyribonucleotides such as viral and ribosomal RNAs.     

Differences between CTP and ATP as substrates for the (Na + K)-ATPase

CTP was a poorer substrate than ATP when substituted in the (Na + K)-ATPase reaction assay, not only in terms of K_m but also of V. CDP was a poorer inhibitor than ADP, so product inhibition cannot account for CTP being a poorer substrate. In the Na-ATPase reaction, which the enzyme also catalyzes, substituting CTP for ATP resulted in greater activity, arguing against CTP being less effective than ATP in forming the enzyme-phosphate intermediate common to both reactions. Ligands that favor the E₂ conformational state of the enzyme, K⁺, Mg²⁺, and Mn₂⁺, inhibited the (Na + K)-CTPase reaction more than the (Na + K)-ATPase. Conversely, Triton X-100, which favors the E₁ conformational state of the enzyme, K⁺, Mg²⁺, and Mn²⁺, inhibited the (Na + K)-CTPase ATPase reaction but stimulated the (Na + K)-CTPase. Although the (Na + K)-ATPase reaction sequence probably involves cyclical interconversion between E₁ and E₂ conformational states (and is thus inhibitable by ligands favoring either state), the K-phosphatase reaction catalyzed by the enzyme apparently functions entirely in the E₂ state. This reaction is better stimulated by CTP plus Na⁺ than by ATP plus Na⁺; moreover, CTP lessens inhibition by Triton X-100, and ATP lessens inhibition by inorganic phosphate (which reacts with the E₂ state). These observations indicate that CTP is a poorer substrate than ATP because it is less effective in promoting conversion of E₂ to E₁, essential for the (Na + K)-dependent reaction mechanism. However, contrary to this rationale, dimethyl sulfoxide stimulated the (Na + K)-CTPase reaction although by other criteria, including inhibition of the (Na + K)-ATPase, the reagent appears to favor the E₂ over the E₁ conformational state.     

穴位埋线联合益肾化痰方对多囊卵巢综合征患者T、E2、LH水平影响

摘要 目的：探讨穴位埋线联合益肾化痰方对多囊卵巢综合征患者睾酮(testosterone,T)、雌二醇(estradiol,E₂)、黄体生成素(luteinizing hormone,LH)水平影响。方法：选取2018年1月至2019年6月我院收治的120例多囊卵巢综合征患者作为研究对象,随机将其分为两组,对照组60例,给予益肾化痰方治疗,研究组60例,在对照组的基础上联合穴位埋线治疗。观察两组治疗后的疗效及不良反应率,检测两组治疗后子宫内膜厚度、成熟卵泡数以及治疗前后T、E₂、LH水平变化情况。结果：研究组治疗的总有效率为 98.33 %,显著高于对照组治疗的总有效率（85.0 %,P＜0.05）。两组治疗后子宫内膜厚度及成熟卵泡数比较,研究组明显高于对照组(P＜0.05)。两组治疗前T、E₂、LH水平指标比较差异无统计学意义（P>0.05）;两组治疗后T、E₂、LH水平指标比较差异有统计学意义（P<0.05）。对照组头痛3例,恶心4例,不良反应率为11.67 %;研究组头痛1例,不良反应率为1.67 %,两组患者不良反应率比较有统计学意义（P<0.05）。结论：埋线联合益肾化痰方治疗多囊卵巢综合征患者,能有效的提高治疗疗效,改善患者T、E2、LH水平,促进排卵,安全可靠,值得临床推广和应用。     

Synthesis and biological activity of hydroxylated derivatives of linoleic acid and conjugated linoleic acids

Allylic hydroxylated derivatives of the C18 unsaturated fatty acids were prepared from linoleic acid (LA) and conjugated linoleic acids (CLAs). The reaction of LA methyl ester with selenium dioxide (SeO₂) gave mono-hydroxylated derivatives, 13-hydroxy-9Z,11E-octadecadienoic acid, 13-hydroxy-9E,11E-octadecadienoic acid, 9-hydroxy-10E,12Z-octadecadienoic acid and 9-hydroxy-10E,12E-octadecadienoic acid methyl esters. In contrast, the reaction of CLA methyl ester with SeO₂ gave di-hydroxylated derivatives as novel products including, erythro-12,13-dihydroxy-10E-octadecenoic acid, erythro-11,12-dihydroxy-9E-octadecenoic acid, erythro-10,11-dihydroxy-12E-octadecenoic acid and erythro-9,10-dihydroxy-11E-octadecenoic acid methyl esters. These products were purified by normal-phase short column vacuum chromatography followed by high-performance liquid chromatography (HPLC). Their chemical structures were characterized by liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance spectroscopy (NMR). The allylic hydroxylated derivatives of LA and CLA exhibited moderate in vitro cytotoxicity against a panel of human cancer cell lines including chronic myelogenous leukemia K562, myeloma RPMI8226, hepatocellular carcinoma HepG2 and breast adenocarcinoma MCF-7 cells (IC₅₀ 10-75 μM). The allylic hydroxylated derivatives of LA and CLA also showed toxicity to brine shrimp with LD₅₀ values in the range of 2.30-13.8 μM. However these compounds showed insignificant toxicity to honeybee at doses up to 100 μg/bee.     

Density functional theory study on (LiNH<Subscript>2</Subscript>)<Subscript>n</Subscript> (<Emphasis Type="Italic">n</Emphasis> = 1–5) clusters

Geometrical structures and relative stabilities of (LiNH₂)_n (n = 1–5) clusters were studied using density functional theory (DFT) at the B3LYP/6-31G* and B3LYP/6-31++G* levels. The electronic structures, vibrational properties, N–H bond dissociation energies (BDE), thermodynamic properties, bond properties and ionization potentials were analyzed for the most stable isomers. The calculated results show that the Li–N and Li–Li bonds can be formed more easily than those of the Li–H or N–H bonds in the clusters, in which NH₂ is bound to the framework of Li atomic clusters with fused rings. The average binding energies for each LiNH₂ unit increase gradually from 142 kJ mol⁻¹ up to about 180 kJ mol⁻¹ with increasing n. Natural bond orbital (NBO) analysis suggests that the bonds between Li and NH₂ are of strong ionicity. Three-center–two-electron Li–N–Li bonding exists in the (LiNH₂)₂ dimer. The N–H BDE values indicate that the change in N–H BDE values from the monomer a1 to the singlet-state clusters is small. The N–H bonds in singlet state clusters are stable, while the N–H bonds in triplet clusters dissociate easily. A study of their thermodynamic properties suggests that monomer a1 forms clusters (b1, c1, d2 and e1) easily at low temperature, and clusters with fewer numbers of rings tend to transfer to ones with more rings at low temperature. E _g, E _HOMO and E _av decrease gradually, and become constant. Ring-like (LiNH₂)_3,4 clusters possess higher ionization energy (VIE) and E _g, but lower values of E _HOMO. Ring-like (LiNH₂)_3,4 clusters are more stable than other types. A comparison of structures and spectra between clusters and crystal showed that the NH₂ moiety in clusters has a structure and spectral features similar to those of the crystal.     

The mechanism of acid-catalyzed conversion of ginsenoside Rf and two new 25-hydroxylated ginsenosides

Ginsenoside Rf is known to have higher chemical stability than other ginsenosides and until lately, the constituents in which it would convert were not known. Only in recent times, it was found that ginsenoside Rf converted to (20E)-Rg₉, (20Z)-Rg₉, Rg₁₀, and 20(R)-Rf. During my continued studies to update the chemical profile of red ginseng, two new ginsenosides converted from ginsenoside Rf, 25-hydroxylated ginsenosides, were discovered. These two new converted ginsenosides, namely (20E),25(OH)-ginsenoside Rg₉ (1), and (20Z),25(OH)-ginsenoside Rg₉ (2), together with ginsenosides (20E)-Rg₉ (3), (20Z)-Rg₉ (4), Rg₁₀ (5), and 20(R)-Rf (6) were isolated from a reaction mixture of ginsenoside Rf in an acid-catalyzed reaction. Their chemical structures (1 and 2) were elucidated by NMR and Mass spectral methods. Compounds 1 and 2 were presumably generated by hydration of (20E)-, and (20Z)-ginsenoside Rg₉. The presence of these six converted ginsenosides was confirmed by UPLC/TOF-MS method in red ginseng. On the basis of these results, I deduced the overall conversion mechanism of ginsenoside Rf and evaluated the significance of ginsenoside Rf as a characteristic mark substance of Panax ginseng.     

Geometric and dosimetric accuracy and imaging dose of the real-time tumour tracking system of a gimbal mounted linac

PurposeTo suggest a comprehensive testing scheme to evaluate the geometric and dosimetric accuracy and the imaging dose of the VERO dynamic tumour tracking (DTT) for its clinical implementation.MethodsGeometric accuracy was evaluated for gantry 0° and 90° in terms of prediction (E_P), mechanical (E_M) and tracking (E_T) errors for sinusoidal patterns with 10 and 20 mm amplitudes, 2–6 s periods and phase shift up to 1 s and for 3 patient patterns. The automatic 4D model update was investigated simulating changes in the breathing pattern during treatment.Dosimetric accuracy was evaluated with gafchromic films irradiated in static and moving phantom with and without DTT. The entrance skin dose (ESD) was assessed using a solid state detector and gafchromic films.ResultsThe RMS of E_P, E_M, and E_T were up to 0.8, 0.5 and 0.9 mm for all non phased-shifted motion patterns while for the phased-shifted ones, E_P and E_T increased to 2.2 and 2.6 mm. Up to 4 updates are necessary to restore a good correlation model, according to type of change.For 100 kVp and 1 mA s X-ray beam, the ESD per portal due to 20 s fluoroscopy was 16.6 mGy, while treatment verification at a frequency of 1 Hz contributed with 4.2 mGy/min.ConclusionsThe proposed testing scheme highlighted that the VERO DTT system tracks a moving target with high accuracy. The automatic update of the 4D model is a powerful tool to guarantee the accuracy of tracking without increasing the imaging dose.     

The Influences of Jasmonic Acid Methyl Ester on Microtubules in Potato Cells and Formation of Potato Tubers

Amides in a CH₂Cl₂ extract from the fruits of Piper retrofractum were detected by HPLC/APCI-MS. Seven new unsaturated amides, together with six known ones, were isolated, and their structures were determined to be N-isobutyl-2E,4E,12Z-octadecatrienamide (1), N-isobutyl-2E,4E,14Z-eicosatrienamide (2), 1-(octadeca-2E,4E,12Z-trienoyl)piperidine (3), 1-(eicosa-2E,4E,14Z-trienoyl)piperidine (4), 1-(octadeca-2E,4E-dienoyl)piperidine (5), 1-(eicosa-2E,4E-dienoyl)piperidine (6), and 1-(eicosa-2E,14Z-dienoyl)piperidine (7) on the basis of chemical and spectroscopic evidence.     

A Refined Prediction Method for Gel Retardation of DNA Oligonucleotides from Dinucleotide Step Parameters: Reconciliation of DNA Bending Models with Crystal Structure Data

Abstract

The development and assessment of a prediction method for gel retardation and sequence dependent curvature of DNA based on dinucleotide step parameters are described. The method is formulated using the Babcock-Olson equations for base pair step geometry (1) and employs Monte Carlo simulated annealing for parameter optimization against experimental data. The refined base pair step parameters define a structural construct which, when the width of observed parameter distributions is taken into account, is consistent with the results of DNA oligonucleotide crystal structures. The predictive power of the method is demonstrated and tested via comparisons with DNA bending data on sets of sequences not included in the training set, including A-tracts with and without periodic helix phasing, phased A₄T₄ and T₄A₄ motifs, a sequence with a phased GGGCCC motif, some “unconventional” helix phasing sequences, and three short fragments of kinetoplast DNA from Crithidia fasiculata that exhibit significantly different behavior on non-denaturing polyacrylamide gels. The nature of the structural construct produced by the methodology is discussed with respect to static and dynamic models of structure and representations of bending and bendability. An independent theoretical account of sequence dependent chemical footprinting results is provided. Detailed analysis of sequences with A-tract induced axis bending forms the basis for a critical discussion of the applicability of wedge models, junction models and non A-tract, general sequence models for understanding the origin of DNA curvature at the molecular level.     

Platinum(II) and palladium(II) complexes with 2-Acetyl pyridine 4N-ethyl thiosemicarbazone able to overcome the cis-Platin resistance. Structure, antibacterial activity and DNA strand breakage

The reactions of Pd(II) and Pt(II) with 2-Acetyl Pyridine N(4)-Ethyl-Thiosemicarbazones, HAc4Et and 2-Acetyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HAc4PiPiz and 2-Formyl Pyridine N(4)-1-(2-pyridyl)-piperazinyl Thiosemicarbazone, HFo4PiPiz afforded the complexes, [Pd(Ac4Et)], 1, [Pd(HAc4Et)₂]Cl₂, 2 and [Pd(Ac4Et)₂], 3[Pt(Ac4Et)], 4, [Pt(HAc4Et)₂]Cl₂, 5, [Pt(Ac4Et)₂], 6 and [Pd(Fo4PipePiz)Cl], 7, [Pd(Fo4PipePiz)₂], 8, [Pd(Ac4PipePiz)Cl], 9 and [Pd(Ac4PipePiz)₂], 10. The crystal structure of the complex [Pt(Ac4Et)₂], 6 has been solved. The platinum(II) atom is in a square planar environment surrounded by two cis nitrogen atoms and two cis sulfur atoms. The ligands are not equivalent, one being tridentate with (N,N,S) donation, the other being monodentate using only the sulfur atom to coordinate to the metal. The tridentate ligand shows a Z, E, Z configuration while the monodentate ligand shows an E, E, Z. Inter-molecular hydrogen bonds stabilize the structure, while the crystal packing is determined by –, and Pt – C interactions. The antibacterial effect of Pd(II) and Pt(II) complexes were studied in vitro. The complexes were found to have effect on Gram(+) bacteria, while the same complexes showed no bactericidal effect on Gram(–) bacteria. The effect of the Pd(II) and Pt(II) complexes on the in vitro DNA strand breakage was studied by agarose gel electrophoresis. The complexes 1-6 were found to exhibit a cytotoxic potency in a very low micromolar range and to be able to overcome the cisplatin resistance of A2780/Cp8 cells (Kovala-Demertzi et al. 2000).     

Effective Cytochrome P450 (CYP) Inhibitors Isolated from Tarragon (Artemisia dracunculus)

Two effective cytochrome P450 (CYP) inhibitors were isolated from tarragon, Artemisia dracunculus. Their structures were spectroscopically identified as 2E,4E-undeca-2,4-diene-8,10-diynoic acid isobutylamide (1) and 2E,4E-undeca-2,4-diene-8,10-diynoic acid piperidide (2). Both compounds had dose-dependent inhibitory effects on CYP3A4 activity with IC₅₀ values of 10.0 ± 1.3 µM for compound 1 and 3.3 ± 0.2 µM for compound 2, and exhibited mechanism-based inhibition. This is the first reported isolation of effective CYP inhibitors from tarragon (Artemisia dracunculus) purchased from a Japanese market.     

Electrochemical behaviour and reactivity of [Os(bpy)2(CO)(OTf)] in halogenated solvents

The dimethylaminopyridine (DMAP) promoted reaction between [Os(bpy)₂(CO)(OTf)]OTf (where ) and methylene chloride is reported. C-Cl bond breaking of a solvent molecule leads to the formation of the [Os(bpy)₂(CO)(Cl)]OTf complex. The reactivity and redox properties of [Os(bpy)₂(CO)(OTf)]OTf were investigated by means of room- and low-temperature electrochemical experiments. In CH₂Cl₂, at low temperature, the complex undergoes two 1e electrochemical and chemical reversible reductions (E_rE_r mechanism), but at room temperature a more complex electrochemical mechanism is observed, leading to the electro-synthesis of [Os(bpy)₂(CO)(Cl)]OTf via electrochemical reversible and chemical irreversible reduction processes (E_rC_i mechanism). The DMAP nucleophilicity was used to produce the new [Os(bpy)₂(CO)(Br)]OTf and [Os(bpy)₂(CO)(I)]OTf complexes which have been fully characterized.     

The effects of long-term estrogen exposure on the induction of sexual behavior and measurements of brain estrogen and progestin receptors in the female rat

The purpose of this study was to investigate long-term effects of estradiol-17β (E₂) on sexual receptivity and to study the molecular basis for estrogen potentiated changes in receptivity. We therefore examined the long-term effects of E₂ on E₂ and progestin receptors in the hypothalamus-preoptic area-septum (HPS) and pituitary (PIT) of the female rat. Twenty-one days following ovariectomy, females received a 5-mm Silastic capsule of E₂ or cholesterol (C) for 1 week (pretreatment). Some animals were sacrificed for chemical analyses (i). The remainder had their capsules removed and 5 days later these animals either were sacrificed for chemical analyses (ii), or received E₂ (reimplantation). Forty-six hours after reimplantation, females either were sacrificed for chemical analyses (iii), or were tested for receptivity. When tested with sexually active males or by a manual stimulation method, animals pretreated with E₂ showed significantly better lordosis scores than animals pretreated with C. The tests for lordosis were carried out after administration of E₂ or E₂ + P to all subjects tested. During E₂ pretreatment, HPS and PIT cytosol progestin receptors increased significantly, while available estrogen receptor levels decreased significantly, as compared with C controls. Five days after E₂ pretreatment, HPS progestin receptor levels had decreased to the level observed in C controls, while PIT progestin receptors were slightly elevated. In HPS and PIT, levels of available E₂ receptor in E₂ and C pretreated animals were indistinguishable from each other. Neither the saturation capacity of the estrogen receptor nor the dissociation constant for binding [³H]E₂ was altered by E₂ pretreatment, as shown by Scatchard equilibrium analysis. Forty-six hours following E₂ reimplantation, progestin HPS and PIT receptor levels in E₂ and C pretreated animals were identical. Long-term potentiation of lordosis by E₂ does not result from a change in estrogen or progestin receptor dynamics in HPS of female rats.