A prospective, observational study of chemotherapy-induced ovarian damage on follicular reserve and maturation.

Background: Chemotherapy negatively affects gonadal function, often resulting in premature ovarian failure (POF) due to ovarian reserve depletion. Mechanisms of gonadotoxicity, such as primordial follicle overactivation and "burnout", remain to be established. Ovarian tissue cryopreservation (OTC) before treatment plays an important role in safeguarding fertility.

Do stage and grade of malignancy impact fertility preservation in breast cancer patients?

Introduction: The impact of cancer on basal fertility and ovarian response to stimulation has not yet been clarified. Evidence on this topic is scarce and conflicting. Aim of this study was to assess the impact of breast cancer stage and grade on the number of retrieved mature oocytes during controlled ovarian stimulation for fertility preservation.

Solid-state nuclear magnetic resonance study of polymorphism in tris(8-hydroxyquinolinate)aluminium.

Tris(8-hydroxyquinolinate)aluminium (Alq ) is a metal-organic coordination complex, which is a widely used electroluminescent material in organic light-emitting diode technology. Crystalline Alq is known to occur in five polymorphic forms (denoted α, β, γ, δ, and ε), although the structures of some of these polymorphs have been the subject of considerable debate. In particular, the structure of α-Alq , which is a model for the local structure in amorphous films used in devices, is highly complex and has never been conclusively solved.

Photochromic Torsional Switch (PTS): a light-driven actuator for the dynamic tuning of π-conjugation extension.

Here we present a molecular architecture that can reversibly change the geometric conformation of its π-system backbone irradiation with two different wavelengths. The proposed 'molecular actuator' consists of a photoswitchable azobenzene orthogonally connected to a π-conjugated bithiophene by both direct and aliphatic linker-assisted bonding. Upon exposure to 350 nm light, the azobenzene moiety isomerizes to its form, causing the bithiophene to assume a semiplanar anti conformation (extended π-conjugation).

Solubility and crystallizability: facile access to functionalized π-conjugated compounds with chlorendylimide protecting groups.

Functional π-conjugated molecules are relevant for the preparation of new organic electronic materials with improved performance. However, their synthesis is often rendered difficult by their inherently low solubility, and the permanent attachment of solubilizing groups may change the properties of the material. Here, we introduced the chlorendylimidyl moiety as a new temporary protecting group for the straightforward large-scale synthesis of protected quarter-, sexi-, octathiophene, and perylene bisimide diamine and dicarboxylic acid derivatives.

Newly-identified receptors for peptide histidine-isoleucine and GHRH-like peptide in zebrafish help to elucidate the mammalian secretin superfamily.

A group of ten hormones in humans are structurally related and known as the secretin superfamily. These hormones bind to G-protein-coupled receptors that activate the cAMP pathway and are clustered as the secretin or B family. We used an evolutionary approach with zebrafish as a model to understand why some of these hormones, such as peptide histidine-methionine (PHM) and pituitary adenylate cyclase-activating polypeptide (PACAP)-related peptide (PRP) in humans lack a receptor.

Astressin-amide and astressin-acid are structurally different in dimethylsulfoxide.

The C-terminally amidated CRF antagonist astressin binds to CRF-R1 or CRF-R2 receptors with low nanomolar affinity while the corresponding astressin-acid has >100 times less affinity. To understand the role of the amide group in binding, the conformations of astressin-amide and astressin-acid were studied in DMSO using NMR techniques. The 3D NMR structures show that the backbones of both analogs prefer an alpha-helical conformation, with a small kink around Gln(26).

Identification of new gonadotrophin-releasing hormone partial agonists.

GnRH agonists or antagonists are currently utilized as therapeutic agents in a number of diseases. A side-effect of prolonged treatment with GnRH analogues is hypoestrogenism. In this study, we tested the in vitro potency of different GnRH analogues originally found to be partial agonists (i.

AlphaA-Conotoxin OIVA defines a new alphaA-conotoxin subfamily of nicotinic acetylcholine receptor inhibitors.

The venoms of cone snails are rich in multiply disulfide-crosslinked peptides, the conotoxins. Conotoxins are grouped into families on the basis of shared cysteine patterns and homologous molecular targets. For example, both the kappaA- and alphaA-conotoxin families share the same Class IV Cys pattern (-CC-C-C-C-C-), but differ in their molecular targets.

Goldfish ghrelin: molecular characterization of the complementary deoxyribonucleic acid, partial gene structure and evidence for its stimulatory role in food intake.

Complementary deoxyribonucleic acid (cDNA) encoding goldfish preproghrelin was identified using rapid amplification of the cDNA ends (RACE) and reverse transcription (RT)-polymerase chain reaction (PCR). The 490 bp cDNA encodes a 103 amino acid preproghrelin which has a 26 amino acid signal region, 19 amino acid mature peptide and a 55 amino acid C-terminal peptide region. The mature peptide region of goldfish ghrelin has two putative cleavage sites and amidation signals (GRR); one after 12 amino acids and the other after 19 amino acids.

Expression, purification, and characterization of a soluble form of the first extracellular domain of the human type 1 corticotropin releasing factor receptor.

The first extracellular domain (ECD-1) of the corticotropin releasing factor (CRF) type 1 receptor, (CRFR1), is important for binding of CRF ligands. A soluble protein, mNT-CRFR1, produced by COS M6 cells transfected with a cDNA encoding amino acids 1--119 of human CRFR1 and modified to include epitope tags, binds a CRF antagonist, astressin, in a radioreceptor assay using [(125)I-d-Tyr(0)]astressin. N-terminal sequencing of mNT-CRFR1 showed the absence of the first 23 amino acids of human CRFR1.

Early expression of pituitary adenylate cyclase-activating polypeptide and activation of its receptor in chick neuroblasts.

To investigate the involvement of pituitary adenylate cyclase- activating polypeptide (PACAP) and GH-releasing factor (GRF) during early chick brain development, we established neuroblast- enriched primary cell cultures derived from embryonic day 3.5 chick brain. We measured increases in cAMP generated by several species-specific forms of the peptides.

Design of potent dicyclic (1-5/4-10) gonadotropin releasing hormone (GnRH) antagonists.

In three earlier papers, the structures and biological potencies of numerous mono- and dicyclic antagonists of GnRH were reported. Among these, two families, each containing two to four members were identified that had very high antagonist potencies in an antiovulatory assay (within a factor of 2 of those of the most potent linear analogues) and high affinities (K(i) < 0.5 nM) for the rat GnRH receptor (rGnRHR).

Design of monocyclic (1-3) and dicyclic (1-3/4-10) gonadotropin releasing hormone (GnRH) antagonists.

Careful analysis of the NMR structures of cyclo(4-10)[Ac-Delta(3)Pro(1),DFpa(2),DTrp(3),Asp(4),DNal (6), Dpr(10)]GnRH, dicyclo(4-10/5-8)[Ac-DNal(1),DCpa(2),DTrp(3), Asp(4), Glu(5),DArg(6),Lys(8),Dpr(10)]GnRH, and dicyclo(4-10/5, 5'-8)[Ac-DNal(1),DCpa(2),DPal(3),Asp(4), Glu(5)(Gly),DArg(6),Dbu(8), Dpr(10)]GnRH showed that, in the N-terminal tripeptide, a type II beta-turn around residues 1 and 2 was probable along with a gamma-turn around DTrp(3)/DPal(3). This suggested the possibility of constraining the N-terminus by the introduction of a cyclo(1-3) scaffold. Optimization of ring size and composition led to the discovery of cyclo(1-3)[Ac-DAsp(1),DCpa(2),DLys(3),DNal(6), DAla(10)]GnRH (5, K(i) = 0.

Design of potent dicyclic (4-10/5-8) gonadotropin releasing hormone (GnRH) antagonists.

With the ultimate goal of identifying a consensus bioactive conformation of GnRH antagonists, the compatibility of a number of side chain to side chain bridges in bioactive analogues was systematically explored. In an earlier publication, cyclo[Asp(4)-Dpr(10)]GnRH antagonists with high potencies in vitro and in vivo had been identified.(1) Independently from Dutta et al.

Corticotropin releasing factor (CRF) agonists with reduced amide bonds and Ser7 substitutions.

Strategies to generate competitive antagonists of bioactive peptides include several possible structural modifications such as the introduction of D-residues and of reduced amide bonds, the substitution of amino acid side chains, dimerization of fragments, and deletion of part of the sequence, among others. Whereas we have identified the two most likely residues responsible for receptor activation in corticotropin releasing factor (CRF) (Ser7 and Leu8)1 and generated potent antagonists by deleting residues 1-8,2,3 the question remained as to whether we could generate CRF antagonists with enhanced affinity after reduction of amide bonds at the N-terminus of CRF or through subtle alteration of those residues' side chains. Reduced amide bond replacements (psi[CH2NH]) between residues 6-9 in oCRF(5-41) (11, 12, 15) analogues consistently yielded potencies of <1% that of oCRF.

Comparison of an agonist, urocortin, and an antagonist, astressin, as radioligands for characterization of corticotropin-releasing factor receptors.

The characteristics of a high-affinity antagonist radioligand are compared with those a high-affinity agonist in binding to the cloned corticotropin-releasing factor receptor type 1 (CRF-R1) and type 2 (CRF-R2) and to the native receptors that exist in rat cerebellum and brain stem. The relative potencies of CRF antagonists and agonists to the two types of cloned CRF receptors overexpressed stably in Chinese hamster ovary cells are determined using the antagonist radioligand 125I- [DTyr1]astressin (Ast*), and the agonist radioligand, 125I -[Tyr0]rat urocortin (Ucn*). The inhibitory binding constants (Ki) of astressin and urocortin are 1 to 2 nM for all receptors and are independent of which radioligand is employed.

Human growth hormone-releasing hormone hGHRH(1-29)-NH2: systematic structure-activity relationship studies.

Two complete and two partial structure-activity relationship scans of the active fragment of human growth hormone-releasing hormone, [Nle27]-hGHRH(1-29)-NH2, have identified potent agonists in vitro. Single-point replacement of each amino acid by alanine led to the identification of [Ala8]-, [Ala9]-, [Ala15]- (Felix et al. Peptides 1986 1986, 481), [Ala22]-, and [Ala28, Nle27]-hGHRH(1-29)-NH2 as being 2-6 times more potent than hGHRH(1-40)-OH (standard) in vitro.

Rat corticostatin R4: synthesis, disulfide bridge assignment, and in vivo activity.

We have synthesized significant amounts of the most potent member of the rat corticostatins that inhibits ACTH-induced corticosteroid and compared its structure to that of the natural hormone. The cystine bridging arrangement that corresponds to that reported for a human defensin (3-31, 5-20, 10-30) was determined. The in vitro corticostatic activity of the synthetic rat corticostatin R4 paralleled that of the natural R4.

[Acute abdomen caused by phlegmonous appendicitis and leukemic infiltration of the cecum in a patient with acute lymphatic leukosis in relapse: clinico-therapeutic aspects].

We report a case of eleven years old child with an acute lymphoblastic leukemia who developed an acute abdomen while in haematological relapse. He had an acute appendicitis with leukemic infiltration of the coecum. The early surgical intervention and the coecum irradiation were successful: the following chemiotherapy achieved remission.

[Effect of factor VIII concentrate on malondialdehyde release by normal human platelets].

It is well known that Factor VIII concentrates affect platelet function both "in vitro" and "in vivo" but the mechanism of their action is poorly understood. Therefore the aim of the present work was to investigate a possible effect of these concentrates on prostaglandin synthesis by platelets, measured as the amount of released malondialdehyde (MDA), which is an index of Thromboxane A2 production. Our data suggest that Factor VIII concentrates have no effect on MDA release by platelets and on its inhibition by aspirin and heparin.