Proposal of a Formal Gynecologic Endoscopy Curriculum

As minimally invasive surgery becomes the standard of care in the United States and around the world, the formal training of endoscopic surgeons is an issue of growing concern. With the implementation of the American Association of Gynecologic Laparoscopists/Society of Reproductive Surgeons (AAGL/SRS)–sponsored fellowship training in gynecologic endoscopy and a growing number of hands-on courses, we have the challenge of credentialing and certifying future gynecologic endoscopists. The objective of this article is to propose and to illustrate a uniform standardized core curriculum for obstetrics and gynecology residents, fellows in AAGL/SRS-sponsored fellowship programs, and participants in postgraduate courses. Consisting of 3 discrete parts, this proposal addresses formal laparoscopic training for gynecologists, already implemented and available to general surgeons, and a novel proposition for core training in hysteroscopy. The curriculum is distributed in a quarterly system with specific educational objectives in each quarter. After quarters 1 and 2, an online examination is given; after quarter 3, participants are required to take and pass a hands-on examination at a specified testing facility; and at the end of quarter 4, participants must demonstrate leadership skills in the operating room and in a teaching capacity, and promote the principles of the AAGL.     

Biomolecular mimicry in the actin cytoskeleton: mechanisms underlying the cytotoxicity of kabiramide C and related macrolides

This study characterizes the interactions between kabiramide C (KabC) and related macrolides and actin and establishes the mechanisms that underlie their inhibition of actin filament dynamics and cytotoxicity. The G-actin-KabC complex is formed through a two-step binding reaction and is extremely stable and long-lived. Competition-binding studies show that KabC binds to the same site on G-actin as Gelsolin domain 1 and CapG. KabC also binds to protomers within F-actin and results in the severing and capping of the (+) end; these studies suggest that free KabC and related macrolides act as biomimetics of Gelsolin. The G-actin-KabC complex binds to the (+) end of a growing filament, where it functions as a novel, unregulated, (+)-end capper and is largely responsible for the inhibition of motility and cytokinesis in approximately 10 -100 nM KabC-treated cells. KabC and related macrolides are useful probes to study the regulation of the actin filament (+) end and may lead to new therapies to treat diseases of the actin cytoskeleton.     

Shape bistability of a membrane neck: a toggle switch to control vesicle content release

Shape dynamics and permeability of a membrane neck connecting a vesicle and plasma membrane are considered. The neck is modeled by a lipid membrane tubule extended between two parallel axisymmetric rings. Within a range of lengths, defined by system geometry and mechanical properties of the membrane, the tubule has two stable shapes: catenoidal microtubule and cylindrical nanotubule. The permeabilities of these two shapes, measured as ionic conductivity of the tubule interior, differ by up to four orders of magnitude. Near the critical length the transitions between the shapes occur within less than a millisecond. Theoretical estimates show that the shape switching is controlled by a single parameter, the tubule length. Thus the tubule connection can operate as a conductivity microswitch, toggling the release of vesicle content in such cellular processes as "kiss-and-run" exocytosis. In support of this notion, bistable behavior of membrane connections between vesicles and the cell plasma membrane in macrophages is demonstrated.     

Rhodopsin phosphorylation: from terminating single photon responses to photoreceptor dark adaptation

Rhodopsin phosphorylation has provided one of the first examples of the ubiquitous regulatory pattern of specific kinases downregulating the activity of G-protein-coupled receptors. However, only recently have studies in living animals allowed us to consider the role of rhodopsin phosphorylation in a broader spectrum of visual functions, ranging from the ability of rods to generate reproducible electrical responses to their ability to adapt to darkness after substantial light exposures.     

Asymmetric sorbents based on mono- and diamines and resolution of racemates by ligand-exchange chromatography

The asymmetric sorbents A, B, C, and D were prepared by interaction of a chloromethylated styrene copolymer of the isoporous macronet type (5,5% of crosslinks) with the chiral amines (S)-1-phenylethylamine, (R)-1,2-propanediamine, and their derivatives. Resins A and B , based on 1-phenylethylamine, do not sorb Cu(II) ions, whereas resins C and D , based on 1,2-propanediamine saturated with Cu(II) ions, were successfully used for ligand-exchange chromatography of amino acids, showing higher affinity to aminodicarboxylic acids than to diaminocarboxylic acids. Sorbent D displays an enantioselectivity of α ≥ 1,5 towards amino acids like Ala, Abu, Ser, or Lys and provides quantitative resolution of enantiomers of some other amino acids. L -amino acids are retained longer by resins C and D than D-isomers.     

Antitumor effect of valorphin in vitro and in vivo: combined action with cytostatic drugs

The action of the cytostatic drugs (epirubicin and vincristine) in combination with the endogenous antiproliferative beta-hemoglobin fragment (33-39), valorphin, was studied in tumor (L929 and A549) cell cultures, primary culture of murine bone marrow cells and in murine model of breast carcinoma in vivo. Simultaneous application of 1 microM valorphin and 1 microM epirubicin, in vitro, did not result in an additive suppressive effect on cell culture growth. Additive effects were achieved with alternating applications of the peptide and the drugs, namely, 0.5 microM (but not 1 microM) epirubicin added 24 h prior to 1 microM valorphin; 1 microM valorphin added 48 h prior to 0.1 microM epirubicin, or 0.1 microM vincristine, or 0.05 microM vincristine, which resulted in 100% cell death in the both series with vincristine and up to 78% cell biomass reduction in the experiments with epirubicin. In the in vivo model (female BLRB mice with subcutaneously inoculated syngeneic mammary carcinoma), simultaneous treatment with 25 mg/m(2) epirubicin and 1 mg/kg valorphin resulted in 42% of tumor growth inhibition, as compared with the negative control group and 22% inhibition as compared with the epirubcin-treated group (at 20th day of treatment). Survival was significantly improved (69% compared to 39% in the group treated with epirubicin only) at day 26 after the treatment beginning.